Network pharmacology and molecular docking were employed to predict the mechanism of Zhizhu Decoction in regulating macrophage polarization to reduce adipose tissue inflammation in obese children, and animal experiments were then carried out to validate the prediction results. The active ingredients and targets of Zhizhu Decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The inflammation related targets in the adipose tissue of obese children were searched against GeneCards, OMIM, and DisGeNET, and a drug-disease-target network was established. STRING was used to construct a protein-protein interaction(PPI) network and screen for core targets. R language was used to carry out Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. AutoDock was used for the molecular docking between core targets and active ingredients. 24 SPF grade 6-week C57B/6J male mice were adaptively fed for 1 week, and 8 mice were randomly selected as the blank group. The remaining 16 mice were fed with high-fat diet for 8 weeks to onstruct a high-fat diet induced mouse obesity model. After successful modeling, the 16 mice were randomly divided into model group and Zhizhu Decoction group, with 8 mice in each group. Zhizhu Decoction group was intervened by gavage for 14 days, once a day. Blank group and model group were given an equal amount of sterile double distilled water(ddH_2O) by gavage daily. After the last gavage, serum and inguinal adipose tissue were collected from mice for testing. The morphology of inguinal adipose tissue was observed by hematoxylin-eosin(HE) staining, the levels of inflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA), and the protein expression of macrophage marker molecule nitric oxide synthase(iNOS) and epidermal growth factor like hormone receptor 1(F4/80) was detected by immunofluorescence staining. Network pharmacology predicted luteolin, naringenin, and nobiletin as the main active ingredients in Zhizhu Decoction and 15 core targets. KEGG pathway enrichment analysis revealed involvement in the key signaling pathway of nuclear factor κB(NF-κB). Molecular docking showed that the active ingredients of Zhizhu Decoction bound well to the core targets. Animal experiment showed that compared with the model group, Zhizhu Decoction reduced the distribution of inflammatory cytokines in the inguinal adipose tissue of mice, lowered the levels of TNF-α and IL-6 in the serum(P<0.05, P<0.01), and down-regulated the expression of iNOS and F4/80(P<0.05). The results showed that the active ingredients in Zhizhu Decoction, such as luteolin, naringenin, and nobiletin, inhibit the aggregation of macrophages in adipose tissue, downregulate their classic activated macrophage(M1) polarization, reduce the expression of inflammatory factors IL-6 and TNF-α, and thus improve adipose tissue inflammation in obese mice.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Molecular Docking Simulation ; Adipose Tissue/immunology* ; Mice ; Male ; Humans ; Network Pharmacology ; Macrophages/immunology* ; Mice, Inbred C57BL ; Child ; Protein Interaction Maps/drug effects* ; Obesity/genetics* ; Inflammation/drug therapy*

PURPOSE: Hand-sewn anastomosis as the gold standard of vascular anastomosis cannot fully meet the requirements of vascular anastomosis in speed and quality. Various vascular couplers have been developed to ameliorate this situation. Most of them are mainly used for venous anastomosis rather than arterial anastomosis. Although it is generally acknowledged that in almost all operations involving vascular reconstruction, it is the arteries that need to be anastomosed faster and more accurately and not the veins. A dedicated device is needed for creating arterial anastomosis in an easy, timesaving, less damaging but reliable procedure. Therefore, we plan to develop a novel arterial coupler device and test pre-clinical safety and effectiveness. METHODS: In this cohort study, the rationality of this novel arterial coupler was preliminarily tested by finite element analysis before it was manufactured. Several factors restrict the use of vascular couplers in arterial anastomosis, such as arterial eversion, fixation, etc. The manufactured arterial couplers underwent in vitro and in vivo experiments. In vitro, isolated arteries of beagles were anastomosed with the assistance of an arterial coupler, and the anastomosed arteries were evaluated through anti-traction tests. In animal experiments, the bilateral femoral arteries of 5 beagles served as a control group. After dissection, the femoral artery on one side was randomly selected to be anastomosed with a quick arterial coupler (QAC) (QAC group), and the femoral artery on the other side was anastomosed by the same person using an end-to-end suture technique with a 6-0 Prolene suture (suture group). The bilateral femoral arteries of 5 beagles were used for coupler-assisted anastomosis and hand-sewn anastomosis in vivo, respectively. Success rate, blood loss, anastomotic time, clamp time, total operation time, and patency rate were recorded. The patency of anastomosed arteries was assessed using vascular Doppler ultrasound, electromagnetic flowmeter, and pathological examination (6 weeks after surgery). RESULTS: As a novel arterial coupler, QAC was successfully designed and manufactured by using poly lactic-co-glycolic acid raw materials and 3-dimensions printing technology. Its rationality was preliminarily tested through finite element analysis and related mechanical analysis methods. The isolated arteries were successfully anastomosed with the assistance of QAC in vitro testing, which showed good anti-traction properties. In animal studies, QAC-assisted arterial anastomosis has superior profiles compared to hand-sewn anastomosis in anastomotic time (7.80 ± 1.41 vs. 16.38 ± 1.04 min), clamp time (8.80 ± 1.41 vs. 14.14 ± 1.57 min), and total operation time (46.64 ± 2.38 vs. 51.96 ± 3.65 min). The results of electromagnetic flowmeter, vascular Doppler ultrasound, and pathological examination showed that QAC-assisted anastomotic arteries were superior to hand-sewn arteries in terms of postoperative blood flow (16.86 ± 3.93 vs. 10.36 ± 0.92 mL/min) and vascular patency in 6 weeks after surgery. CONCLUSION QAC is a well-designed and easily maneuverable device specialized for end-to-end arterial anastomosis. Application of this device may decrease thermal ischemia time and improve the patency of anastomotic arteries, thus, improving outcomes.
Animals ; Anastomosis, Surgical/instrumentation* ; Dogs ; Femoral Artery/surgery* ; Vascular Surgical Procedures/instrumentation* ; Finite Element Analysis

Objective To explore the effects of chronic stress and stress cessation on hypothalamic appetite regulators in mice,and to explore the stress-dependent mechanism of appetite change.Methods A total of 32 male C57BL/6 mice were randomly divided into control(Ctrl)group(n=16)and chronic unpredictable mild stress(CUMS)group(n=16).The mice in the CUMS group were given CUMS to establish the stress model,and those in the Ctrl group were fed normally.The food intake and weight of mice were recorded.The CUMS model was verified through tail suspension experiments and forced swimming experiments.Eight mice in the Ctrl group and 8 mice in the CUMS group were randomly sacrificed at the 12th week.The Ctrl group was re-grouped into the cessation-control(C-Ctrl)group(n=8),the CUMS group was re-grouped into the cessation-stress(C-CUMS)group(n=8),and the mice were sacrificed at the 15th week.The mRNA and protein levels of appetite-regulating factors,including orexin 1 receptor(OX1R),leptin receptor(LEPR)and agouti-related protein(AgRP)in the hypothalamus,were detected by quantitative polymerase chain reaction and immunochemistry.Results From week 2 to week 11 of stress,the food intake of the mice in the CUMS group was significantly higher than that in the Ctrl group(all P＜0.05),while there was no significant difference in body weight between the 2 groups within 11 weeks(all P＞0.05).Compared with the Ctrl group,the immobility durations of forced swimming and tail suspension of the CUMS group were markedly longer after 11 weeks(both P＜0.01),indicating successful modeling.AgRP and OX1R mRNA expression in the hypothalamus of the CUMS group was significantly increased(both P＜0.01),while LEPR mRNA expression was significantly decreased(P＜0.01);AgRP protein in the hypothalamic arcuate nucleus of the CUMS group was significantly higher than that of the Ctrl group(P＜0.05),and LEPR protein was markedly lower than that of the Ctrl group(P＜0.01).However,after 3 weeks of stress cessation,the C-CUMS group had less food intake and lower body weight than the C-Ctrl group(both P＜0.05).The LEPR mRNA of the C-CUMS group was significantly increased(P＜0.01),while AgRP and OX1R mRNA were not significantly different(both P＞0.05).There was no significant difference in AgRP protein levels between the C-CUMS group and the C-Ctrl group(P＞0.05),while LEPR protein level of the C-CUMS group was significantly higher than that of the C-Ctrl group(P＜0.01).Conclusion CUMS can lead to increased appetite in mice,which may involve the functional regulation of LEPR and AgRP.After the stress cessation,the appetite decreases,which may involve the functional regulation of LEPR.

Objective To investigate biological markers associated with psychotic symptoms in patients with bipolar disorder(BD)based on electronic medical records of patients,and to develop an interpretable risk prediction model that supports the identification of high-risk individuals and that facilitates decision-making for providing clinical intervention in a timely manner.Methods A total of 2 352 patients diagnosed with BD and admitted to West China Hospital,Sichuan University were enrolled using the electronic medical records system of the hospital.The participants were divided into two subgroups,the bipolar disorder depression(BDD)group and the bipolar disorder mania(BDM)group.The logistic regression algorithm was used to train and validate the prediction model,and interpretability methods were used to analyze the contribution of each feature to individuals and the effect of the features on specific target prediction decisions.Results The logistic regression model demonstrated robust predictive performance across the BD,BDD,and BDM cohorts,with areas under the curve(AUC)of the receiver operating characteristic curves always exceeding 81.6%.The core predictive features included platelet distribution width(PDW),fibrinogen(FIB),platelet large cell ratio(P-LCR),activated partial thromboplastin time(APTT),prothrombin time(PT),and triglyceride(TG).The logistic regression model exhibited strong interpretability and was combined with nomograms for intuitive risk quantification and individualized prediction.Conclusion The logistic regression model enables rapid and simple screening of BD patients with psychotic symptoms.Distinct patterns of changes observed in blood biomarkers of BDD and BDM subgroups enrich the understanding of the underlying pathophysiological mechanisms and highlight the importance of considering subtypes in the intervention and management of patients.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Nanozymes, a groundbreaking discovery by Chinese scientists, represent a novel and remarkable property of nanomaterials. They not only exhibit catalytic activity comparable to natural enzymes, but also boast exceptional stability, tunable reactivity, and the ability to catalyze reactions under mild conditions. The identification of nanozymes has unveiled the biocatalytic potential of inorganic nanomaterials. In parallel, inorganic minerals have long been regarded as pivotal catalysts in the origin of life, driving the synthesis of early biomolecules. These minerals not only facilitate redox reactions that convert simple inorganic compounds into organic molecules but also enable chiral selection, the synthesis of biomacromolecules, and radioprotective functions via their surface structures. Recent advances suggest that inorganic nanomaterials can delicately catalyze the formation of biomolecules, aid in macromolecular assembly, and provide radiation shielding. Furthermore, nanominerals are found in abundance across Earth and extraterrestrial environments. This paper seeks to explore the potential of nanozymes as catalytic agents in the processes that gave rise to life, integrating the catalytic roles of inorganic minerals with the unique attributes of nanozymes, which will provide a new perspective for research of origin of life.

Objective:To compare the safety of radial artery puncture in elderly patients aged 75 years and older who are undergoing neurointerventional procedures.Methods:A single-center retrospective study was conducted, involving 350 elderly patients aged 75 years and older who received neurointerventional treatment at Beijing Tiantan Hospital, Capital Medical University, from June to December 2022.The participants were divided into two groups based on the puncture site: femoral artery puncture and radial artery puncture.The safety indicators compared between the two groups included puncture failure, changes in puncture site, general puncture complications(such as subcutaneous bleeding, puncture site hematoma, and vasospasm), severe puncture complications(including distal limb ischemia and pseudoaneurysm), and lower limb venous thrombosis.Multivariate Logistic regression analysis was conducted to evaluate the impact of different puncture methods on the occurrence of complications.Results:Among the 350 patients, 280 underwent femoral artery puncture, while 70 underwent radial artery puncture.There were no statistically significant differences in baseline characteristics between the two groups(all P>0.05).The proportions of patients using antiplatelet drugs prior to surgery, puncture failure rates, rates of change in puncture sites, and the incidence of severe complications-including distal limb ischemia and pseudoaneurysm-were not significantly different between the two groups( χ2=2.051, 0.075, 0.588, 3.175; P=0.152, 0.784, 0.443, 0.075).In the femoral artery puncture group, 20.4%(57 cases)of patients experienced general puncture complications(including subcutaneous bleeding, puncture site hematoma, and vasospasm), whereas only 8.6%(6 cases)in the radial artery puncture group experienced such complications, revealing a statistically significant difference between the two groups( χ2=5.720, P=0.022).Multivariate Logistic regression analysis indicated that, compared to femoral artery puncture, radial artery puncture was associated with a reduced risk of all complications( OR=0.272, 95% CI: 0.139-0.532, P<0.001), general puncture complications( OR=0.375, 95% CI: 0.153-0.919, P=0.032)and lower limb venous thrombosis( OR=0.219, 95% CI: 0.050-0.954, P=0.043). Conclusions:In elderly patients aged 75 years and older who are undergoing neurointerventional procedures, radial artery puncture is associated with a reduced incidence of general puncture complications and lower limb venous thrombosis when compared to femoral artery puncture, indicating a superior safety profile.

Degenerative cervical spondylosis is a common spinal disorder in the elderly. During its progression, structural changes such as intervertebral disc degeneration, vertebral osteophyte formation, and facet joint degeneration directly impact neural structures, resulting in neuropathic pain. Moreover, the release of inflammatory mediators can further exacerbate pain, and increased neuronal excitability is considered one of the key pathological mechanisms of neuropathic pain. Current diagnostic and assessment methods for neuropathic pain associated with degenerative cervical spondylosis include clinical evaluation, imaging techniques (such as X-ray, computed tomography, and magnetic resonance imaging), and neurophysiological examinations (including electromyography and nerve conduction studies). Treatment options primarily involve pharmacological therapy, physical therapy, and surgical intervention, which have shown promising short-term outcomes. Despite progress made through the combined use of various treatment modalities, their long-term efficacy and safety remain to be further investigated. Personalized and multimodal treatment strategies are essential for improving patients' quality of life. Future research should continue to explore pain mechanisms and develop innovative therapeutic techniques to optimize clinical management.
Humans ; Spondylosis/therapy* ; Neuralgia/diagnosis* ; Combined Modality Therapy ; Cervical Vertebrae ; Intervertebral Disc Degeneration/complications* ; Physical Therapy Modalities

Objective To investigate the effect of Xiao Chaihu Decoction and Xiangsha Liujunzi Decoction on the changes of gastric mucosal pathological score and gastrointestinal hormones in patients with chronic atrophic gastritis(CAG)of liver stagnation and spleen deficiency type.Methods A total of 156 cases of CAG patients with liver stagnation and spleen deficiency syndrome were randomly divided into a control group and an observation group,78 cases in each group.The control group was treated with conventional western medicine,and the observation group was treated with Xiao Chaihu Decoction and Xiangsha Liujunzi Decoction on the basis of treatment for the control group.The course of treatment covered four weeks.The changes in the scores of traditional Chinese medicine(TCM)symptoms such as epigastric distention and pain,poor appetite,loose stools,limb weakness,belching and acid regurgitation,gastric mucosal pathological scores and serum levels of gastrointestinal hormones of motilin(MTL)and gastrin(GAS)in the two groups were observed before and after treatment.The negative conversion rate of Helicobacter pylori(Hp)in the two groups was compared,and the clinical efficacy and safety of the two groups were evaluated.Results(1)After four weeks of treatment,the total effective rate of the observation group was 93.59％(73/78),which was significantly higher than 82.05％(64/78)of the control group,and the difference between the two groups was statistically significant(P＜0.05).(2)After treatment,the scores of TCM symptoms such as epigastric distention and pain,poor appetite,loose stool,limb weakness,belching and acid regurgitation in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.05).(3)After treatment,the pathological scores of gastric mucosa in the two groups were significantly decreased when compared with those before treatment(P＜0.05),and the decrease in the observation group was more significant than that in the control group(P＜0.01).(4)After four weeks of treatment,the negative conversion rate of Hp in the observation group was 91.03％(71/78),which was significantly higher than that in the control group(75.64％,59/78),and the difference between the two groups was statistically significant(P＜0.05).(5)After treatment,the level of serum GAS in the two groups was significantly decreased(P＜0.05)and the serum MTL level was significantly increased compared with that before treatment(P＜0.05);the decrease of serum GAS level and the increase of serum MTL level in the observation group were significantly superior to those in the control group(P＜0.05).(6)There were no obvious abnormalities in the routine test of blood,urine,stool,kidney function,and liver function,electrocardiograph and other safety indicators during the treatment of the two groups of patients,no adverse reactions such as dizziness,rash and chest distress occurred either,with high safety.Conclusion Xiao Chaihu Decoction combined with Xiangsha Liujunzi Decoction exerts a significant therapeutic effect on GAS of liver stagnation and spleen deficiency type,which can effectively relieve the clinical symptoms,improve the pathological changes of gastric mucosa and promote Hp negative conversion.The therapeutic mechanism may be related to the regulation of gastrointestinal hormone levels.