Patients with depression are more likely to have chronic gastrointestinal (GI) symptoms than the general population, but such symptoms are considered only somatic symptoms of depression and lack special attention. There is a chronic lack of appropriate diagnosis and effective treatment for patients with depression accompanied by GI symptoms, and studying the association between depression and GI disorders (GIDs) is extremely important for clinical management. There is growing evidence that depression is closely related to the microbiota present in the GI tract, and the microbiota-gut-brain axis (MGBA) is creating a new perspective on the association between depression and GIDs. Identifying and treating GIDs would provide a key opportunity to prevent episodes of depression and may also improve the outcome of refractory depression. Current studies on depression and the microbially related gut-brain axis (GBA) lack a focus on GI function. In this review, we combine preclinical and clinical evidence to summarize the roles of the microbially regulated GBA in emotions and GI function, and summarize potential therapeutic strategies to provide a reference for the study of the pathomechanism and treatment of depression in combination with GI symptoms.
Humans ; Gastrointestinal Microbiome/physiology* ; Depression/microbiology* ; Gastrointestinal Diseases/physiopathology* ; Brain ; Animals ; Brain-Gut Axis ; Gastrointestinal Tract/microbiology*

OBJECTIVES: To investigate the effects of formulated granules of Tianma Gouteng Yin (TGY) on motor deficits in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced subacute Parkinson's disease (PD) and explore the possible molecular mechanisms. METHODS: Ninety C57BL/6 mice were randomized equally into 6 groups, including a control group, a PD model group, a NEC-1 (6.5 mg/kg) treatment group, two TGY treatment groups at 5 and 2.5 g/kg, and a Madopar (76 mg/kg) treatment (positive control) group. Mouse models of PD were established by intraperitoneal injection of MPTP (30 mg/kg) for 5 consecutive days with the corresponding treatments for 15 days. The mice were randomly selected for motor function tests. Western blotting was used to detect the changes in expressions of TH, α-syn, RIPK1, RIPK3 and MLKL in the striatum of the mice. Network pharmacology analysis and molecular docking studies were performed to explore TGY-mediated regulation of the necroptosis pathway for PD treatment. RESULTS: Compared with those in the control group, the PD model mice exhibited obvious motor deficits with significantly increased α-syn protein expression and lowered TH protein expression in the striatum. Treatment with NEC-1 obviously improved motor deficits, inhibited the necroptosis pathway, and alleviated the changes in TH and α‑syn proteins in PD mice. Network pharmacology and molecular docking analyses suggested that the therapeutic effect of TGY in PD was associated with the modulation of RIPK1, a key protein in the necroptosis pathway. In PD mouse models, TGY treatment at the two doses significantly improved motor deficits of the mice, increased TH expression, and decreased the expressions of α-syn and necroptosis-related proteins in the striatum. CONCLUSIONS TGY can effectively inhibit the necroptosis pathway, increase TH expression and decrease α-syn expression in the striatum to improve motor deficits in PD mice.
Animals ; Mice, Inbred C57BL ; Mice ; Necroptosis/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Parkinson Disease/drug therapy* ; Disease Models, Animal ; Male

Objective To evaluate the efficacy of a modified sericin hydrogel scaffold loaded with dexamethasone(SMH-CD/DEX)scaffold for promoting bone defect healing by stimulating anti-inflammatory macrophage polarization.Methods The light-curable SMH-CD/DEX scaffold was prepared using dexamethasone-loaded NH2-β-cyclodextrin(NH2-β-CD)and sericin hydrogel and characterized by scanning electron microscopy(SEM),Fourier transform infrared spectroscopy(FTIR),biocompatibility assessment and drug release test.THP-1 macrophages incubated with the scaffold were examined for protein expressions of iNOS and Arg-1,mRNA expressions of IL-6,Il-10,Arg-1 and iNOS,and surface markers CD86 and CD206 using Western blotting,RT-qPCR,and flow cytometry.In a co-culture system of human periodontal ligament stem cells(HPDLSCs)and THP-1 macrophages,the osteogenic ability of the stem cells incubated with the scaffold was evaluated by detecting protein expressions of COL1A1 and Runx2 and expressions of ALP,Runx2,OCN and BMP2 mRNA,ALP staining,and alizarin red staining.In a rat model of mandibular bone defect,the osteogenic effect of the scaffold was assessed by observing bone regeneration using micro-CT and histopathological staining.Results In THP-1 macrophages,incubation with SMH-CD/DEX scaffold significantly enhanced protein expressions of Arg-1 and mRNA expressions of IL-10 and Arg-1 and lowered iNOS protein expression and IL-6 and iNOS mRNA expressions.In the co-culture system,SMH-CD/DEX effectively increased the protein expressions of COL1A1 and Runx2 and mRNA expressions of ALP and BMP2 in HPDLSCs and promoted their osteogenic differentiation.In the rat models,implantation of SMH-CD/DEX scaffold significantly promoted bone repair and bone regeneration in the bone defect.Conclusion The SMH-CD/DEX scaffold capable of sustained dexamethasone release promotes osteogenic differentiation of stem cells and bone defect repair in rats by regulating M2 polarization.

Objective To evaluate the efficacy of a modified sericin hydrogel scaffold loaded with dexamethasone(SMH-CD/DEX)scaffold for promoting bone defect healing by stimulating anti-inflammatory macrophage polarization.Methods The light-curable SMH-CD/DEX scaffold was prepared using dexamethasone-loaded NH2-β-cyclodextrin(NH2-β-CD)and sericin hydrogel and characterized by scanning electron microscopy(SEM),Fourier transform infrared spectroscopy(FTIR),biocompatibility assessment and drug release test.THP-1 macrophages incubated with the scaffold were examined for protein expressions of iNOS and Arg-1,mRNA expressions of IL-6,Il-10,Arg-1 and iNOS,and surface markers CD86 and CD206 using Western blotting,RT-qPCR,and flow cytometry.In a co-culture system of human periodontal ligament stem cells(HPDLSCs)and THP-1 macrophages,the osteogenic ability of the stem cells incubated with the scaffold was evaluated by detecting protein expressions of COL1A1 and Runx2 and expressions of ALP,Runx2,OCN and BMP2 mRNA,ALP staining,and alizarin red staining.In a rat model of mandibular bone defect,the osteogenic effect of the scaffold was assessed by observing bone regeneration using micro-CT and histopathological staining.Results In THP-1 macrophages,incubation with SMH-CD/DEX scaffold significantly enhanced protein expressions of Arg-1 and mRNA expressions of IL-10 and Arg-1 and lowered iNOS protein expression and IL-6 and iNOS mRNA expressions.In the co-culture system,SMH-CD/DEX effectively increased the protein expressions of COL1A1 and Runx2 and mRNA expressions of ALP and BMP2 in HPDLSCs and promoted their osteogenic differentiation.In the rat models,implantation of SMH-CD/DEX scaffold significantly promoted bone repair and bone regeneration in the bone defect.Conclusion The SMH-CD/DEX scaffold capable of sustained dexamethasone release promotes osteogenic differentiation of stem cells and bone defect repair in rats by regulating M2 polarization.

Objective To train influenza clinical syndrome data using machine learning methods;To obtain an influenza syndrome differentiation model.Methods The medical records of influenza patients who visited the fever clinic of China-Japan Friendship Hospital from December 2019 to March 2022 were collected.The data set system was used for data processing,and the data generated by different data processing processes were stored separately for training.The study selected logistic regression,decision tree,naive Bayes,support vector machine,multi-layer perceptron,lightGBM and random forest as alternative models,and optimized the hyperparameters through Optuna.Models were trained separately in each data set,and the model prediction performance was evaluated,with the macro-F1 score as the core.Results Totally 1 011 training samples were collected,including 453 cases of wind-heat syndrome,152 cases of superficial wind-cold syndrome,and 406 cases of superficial cold and internal heat syndrome;8 data sets were obtained for training,containing 80 copies of data.After training,the macro-F1 scores of logistic regression,decision tree,naive Bayes,support vector machine,multi-layer perceptron lightGBM and random forest model were 0.783 0,0.774 2,0.731 5,0.782 4,0.716 7,0.793 8 and 0.815 3,respectively.Weighted samples could significantly improve the average model performance,while PCA would reduce the average model performance.The prediction performance of the logistic regression model was the best in the single method models,and the random forest model was the best in the integrated method models.Conclusion In the case of a small sample size,it is more appropriate to use logistic regression,decision tree,support vector machine and lightGBM for the TCM influenza syndrome differentiation model.As the sample size increases,logistic regression,support vector machine,lightGBM and random forest may be more suitable.Different data processing methods will affect model performance.Collecting information on the typical degree of syndrome types is beneficial to improving model performance.

Objective:To evaluate the influence of age factors on dose-effect relationship of oxycodone inhibiting responses to tracheal intubation during induction of general anesthesia in pediatric patients.Methods:American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ pediatric patients of both sexes, aged 6 months-6 yr, with body mass index of 12-22 kg/m 2, scheduled for elective surgery under general anesthesia with tracheal intubation, were divided into 3 groups: infant group (group I, 6-12 months), young children group (group Y, >1-3 yr) and preschooler group (group P, >3-6 yr). Oxycodone was slowly injected intravenously, 2 min later etomidate 0.3 mg/kg and cisatracurium 0.15 mg/kg were intravenously injected, and 3 min later endotracheal intubation was carried out with a visual laryngoscope in all the children. Mean arterial pressure(MAP) and heart rate (HR) immediately before intubation and peak MAP and HR within 3 min after intubation were recorded. The modified Dixon′s sequential method was used. The initial dose of oxycodone was 0.3 mg/kg in each group. If the response to tracheal intubation was positive, the dose of oxycodone was increased by 0.02 mg/kg in the next child; if the response to tracheal intubation was negative, the dose of oxycodone was decreased by 0.02 mg/kg in the next child. Positive response to tracheal intubation was defined as increase in MAP and/or HR and increase in the peak value exceeding 20% of the pre-intubation level within 3 min after tracheal intubation. The aforementioned process was repeated until 7 negative and positive reactions crossed, and then the test was stopped. The median effective dose (ED 50) and 95% confidence interval of oxycodone were calculated by Probit method. Results:The ED 50 (95% confidence interval) of oxycodone inhibiting responses to the tracheal intubation were 0.280 (0.247-0.301) mg/kg, 0.321 (0.304-0.342) mg/kg and 0.354 (0.342-0.368) mg/kg in I, Y and P groups, respectively. The ED 50 of oxycodone inhibiting responses to the tracheal intubation was gradually increased during induction of general anesthesia with increasing age ( P<0.05). Conclusions:For children aged 6 months to 6 yr, the potency of oxycodone in inhibiting responses to the tracheal intubation during general anesthesia induction gradually decreases with increasing age.

Objective:To evaluate the effect of short-chain fatty acids on microglial synapse engulfment in aged rats with postoperative cognitive dysfunction (POCD).Methods:Forty-eight healthy male Sprague-Dawley rats, aged 18 months, weighing 520-650 g, were divided into 4 groups ( n=12 each) using a random number table method: control group (group C), short-chain fatty acids group (group S), POCD group (group P), and POCD+ short-chain fatty acids group (group PS). Rats received short-chain fatty acids (sodium propionate 25.9 mmol/L, sodium butyrate 40 mmol/L and sodium acetate 67.5 mmol/L) in the free drinking water for 28 days in S and PS groups. On day 29, anesthesia was induced with 4%-5% sevoflurane and maintained with 3% sevoflurane, and the tibial fracture internal fixation was performed to prepare a rat model of POCD in P group and PS group. Morris water maze test was performed at day 7 after surgery. The escape latency, times of crossing the original platform, mean swimming speed and time spent in the original platform quadrant were recorded. The rats were sacrificed at the end of Morris water maze test, and the brains were collected to analyze the number and density of dendritic spines in the hippocampal CA1 region (by Golgi staining) and to determine the expression of postsynaptic density 95 (PSD95) and complement 1q (C1q) in the hippocampal CA1 region (by immunofluorescence). Results:Compared with group C, the times of crossing the original platform were significantly decreased, the time spent in the original platform quadrant was shortened, the escape latency was prolonged, the number and density of dendritic spines and the number of intersection points between dendrites and concentric circles were decreased, the expression of PSD95 was down-regulated, and the expression of C1q was up-regulated in P and PS groups ( P<0.05). Compared with group P, the times of crossing the original platform were significantly increased, the time spent in the original platform quadrant was prolonged, the escape latency was shortened, the number and density of dendritic spines and the number of intersection points between dendrites and concentric circles were increased, the expression of PSD-95 was up-regulated, and the expression of C1q was down-regulated in group PS ( P<0.05). Conclusions:The mechanism by which short-chain fatty acids attenuates POCD is related to decreased microglial engulfment of synapses in aged rats.

Objective:To assess the efficacy of high-flow nasal cannula oxygen therapy for the respiratory support after tracheal extubation under general anesthesia in neonates.Methods:This was a prospective randomized controlled study. Ninety-four neonates undergoing general surgery under general anesthesia with endotracheal intubation and endotracheal tube removal following surgery from December 2022 to November 2023 in the Third Affiliated Hospital of Zhengzhou University were selected and divided into 2 groups ( n=47 each) by the random number table method: conventional oxygen therapy group (group C) and high-flow nasal cannula oxygen therapy group (group H). After the endotracheal tube was removed, group H underwent high-flow nasal cannula oxygen therapy: oxygen flow was 2 L·kg -1·min -1, the concentration and humidity of oxygen were both 100%, and the temperature was 37 ℃. Group C underwent conventional mask ventilation with the oxygen flow rate 5 L/min, oxygen concentration 100%, ventilation frequency about 25-35 times/min. The outcome measures were recorded from the time after extubation to the time before discharge from the operating theatre. The main outcome measures were the minimum SpO 2 and hypoxemia (SpO 2<90%), choking, laryngospasm and asphyxia. The secondary outcome measures were respiratory rate (immediate extubation, immediate discharge), minimum HR, and time to discharge from the operating theatre. Results:Compared with group C, the lowest SpO 2 was significantly increased, the incidence of hypoxemia and respiratory rate immediately after discharge from the operating room was decreased ( P<0.05), and no significant changes were found in the incidence of choking, laryngospasm and asphyxia, the lowest heart rate, respiratory rate immediately after tracheal extubation and time to discharge from the operating theatre in group H( P>0.05). Conclusions:High-flow nasal cannula oxygen therapy can improve oxygenation and significantly reduce the risk of hypoxemia when used for the respiratory support after tracheal extubation under general anesthesia in neonates.

This study examined the impact of astragalus polysaccharide synbiotics on fecal scores and blood indices in calves suffering from E.coli-induced diarrhea.Twenty Holstein calves,aged 6-9 days and weighing approximately(44.56±5)kg,were randomly divided into a control group and an experimental group.The experiment lasted 10 days.Both control and experimental group calves received daily intramuscular injections of borlococci(1 mg/kg)and enrofloxacin(20 mg/kg)dur-ing experimental period.In addition to the standard treatment regimen,calves in the experimental group were given 20 g of Astragali polysaccharide synbiotics in their milk each day.Fecal scoring was conducted daily at 9:00 a.m.,and jugular blood was collected at the end of experiment to eval-uate relevant blood parameters.Results indicated a 17％reduction in diarrhea rates in the experi-mental group compared to the control group,although there was no statistically significant differ-ence in fecal scores.Compared to the control group,the experimental group showed a significant in-crease in the levels of immunoglobulin A(IgA)and immunoglobulin M(IgM)by 54.81％and 60.40％,respectively(P＜0.01).Immunoglobulin G(IgG)and interleukin-10(IL-10)levels increased by 50.89％and 46.80％,respectively(P＜0.05).while interleukin-6(IL-6),interleukin-1β(IL-1 β),and tumor necrosis factor-α(TNF-α)decreased by 28.99％,20.88％,and 37.10％,re-spectively(P＜0.01).The experimental group showed a significant reduction in the level of D-lac-tic acid(D-LA)and endotoxin(LPS)by 47.46％and 65.31％compared to the control group,re-spectively(P＜0.01),and diamine oxidase(DAO)activity was 30％lower(P＜0.01).Total su-peroxide dismutase(T-SOD)content increased by 12.78％(P＜0.05),and catalase(CAT)and glutathione peroxidase(GSH-Px)contents increased by 53.09％,and 60.57％,respectively(P＜0.01).Furthermore,malondialdehyde(MDA)content decreased by 33.29％(P＜0.01)in the ex-perimental group.In conclusion,administering astragalus polysaccharide synbiotics could reduce in-testinal mucosal damage in calves with E.coli diarrhea,enhance their immunity and antioxidative stress response,and mitigate the impact of pathogenic bacteria and oxidative stress on intestinal mucosal permeability.

OBJECTIVE: To identify phytochemical constituents present in the extract of flowers of Xanthoceras sorbifolia and evaluate their anti-oxidant and anti-hyperglycemic capacities. METHODS: The AlCl₃ colorimetric method and Prussian Blue assay were used to determine the contents of total flavonoids and total phenolic acids in extraction layers, and the bioactive layers was screened through anti - oxidative activity in vitro. The Waters ACQUITY UPLC system and a Waters ACQUITY UPLC BEH C₁₈ column (2.0 mm × 150 mm, 5 μm) were used to identify the ingredients. And anti-oxidative ingredients were screened by off-line UPLC-QTOF-MS/MS-free radical scavenging. The ameliorative role of it was further evaluated in a high-fat, streptozotocin-induced type 2 diabetic rat model and the study was carried out on NADPH oxidase (PDB ID: 2CDU) by molecular docking. RESULTS: Combined with the results of activity screening in vitro, the anti - oxidative part was identified as the ethyl acetate layer. A total of 24 chemical constituents were identified by liquid chromatography-mass spectrometry in the ethyl acetate layer and 13 main anti-oxidative active constituents were preliminarily screened out through off-line UPLC-QTOF-MS/MS-free radical scavenging. In vivo experiments showed that flowers of X. sorbifolia could significantly reduce the blood glucose level of diabetic mice and alleviate liver cell damage. Based on the results of docking analysis related to the identified phytocompounds and oxidase which involved in type 2 diabetes, quercetin 3-O-rutinoside, kaempferol-3-O-rhamnoside, isorhamnetin-3-O-glucoside, and isoquercitrin showed a better inhibitory profile. CONCLUSION The ethyl acetate layer was rich in flavonoids and phenolic acids and had significant anti-oxidant activity, which could prevent hyperglycemia. This observed activity profile suggested X. sorbifolia flowers as a promising new source of tea to develop alternative natural anti-diabetic products with a high safety margin.