Objective To investigate the beneficial effect of Kai-Xin-San combined with fluoxetine in improving depression-like behaviors on chronic unpredictable mild stress(CUMS)induced depression model mice.Methods The present study aimed to assess the potential of Kai-Xin-San in combination with fluoxetine to ameliorate depression-like behaviors in a CUMS induced mouse depression model.Behavioral tests,such as the sucrose preference test were employed to evaluate the efficacy of the treatment.Additionally,the levels of suppressed stress factors were measured using the ELISA method.The morphology of hippocampal tissue was evaluated using the HE staining method,Nissl Staining and TUNEL staining methods.Furthermore,western blotting analysis was utilized to determine the expression levels of proteins such as Caspase-3,and Caspase-9.Results The co-administration of Kai-Xin-San and fluoxetine resulted in a significant increase in sucrose preference rate in model mice.This effect was comparable to that of fluoxetine alone at the standard clinical dose.Furthermore,the combination treatment up-regulated the levels of suppressed stress factors,reduced the apoptosis of hippocampus induced by depression and regulated the apoptosis signaling pathway in hippocampus.Conclusion The combination of Kai-Xin-San and fluoxetine has been shown to be an effective treatment for depression-like behavior in animal models,resulting in a reduction in the required clinical dosage of fluoxetine.This effect may be attributed to the up-regulation of neurotransmitter expression,inhibition of stress axis activation,and central nervous inflammation.

OBJECTIVE To evaluate the ameliorative effect of Juanbi Tongluo Oral Liquid on sciatic neuronal apoptosis in Type 2 diabetic model mice.METHODS The Type 2 diabetes mouse model was established by feeding with high-fat and high-sugar diet combined with intraperitoneal injection of streptozotocin(STZ).The mice were treated with metformin(200 mg·kg-1·d-1),low dose(3.9 g·kg-1·d-1)and high dose(7.8 g·kg-1·d-1)Juanbi Tongluo Oral Liquid for 35 days.The latency of response to thermal stimu-lation was detected by hot plate,and the values of blood glucose insulin and glycosylated hemoglobin were determined.Biochemical kits were used to detect the expression of serum total cholesterol(T-CHO),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-Px)and oxidation product malondialdehyde(MDA).The expression of tumor cytokine α(TNF-α),interleukin(IL)-1β,IL-6 and IL-10 in serum of mice were detected by ELISA method;the injury of sciatic nerve of model mice was detected by HE staining;the apoptosis of sciatic nerve was detected by TUNEL method;and the expression of neurofilament protein NF-L,apoptosis(cleaved Caspase-3,Caspase-3)and oxidative stress(Nrf2,HO-1)signal pathway proteins in sciatic nerve of model mice were detected by Western blot method.RESULTS High-dose Juanbi Tongluo Oral Liquid shortened the latent period of heat pain response in model mice(P<0.01);downregulated fasting blood glucose and glycated hemoglobin(P<0.01),and upregulated fasting plasma insulin in model mice(P<0.01);downregulated serum T-CHO,TG,and LDL-C levels(P<0.01),upregulated HDL-C levels(P<0.01);downregulated serum pro-inflammatory factors TNF-α,IL-1β and IL-6 levels(P<0.05),upregulated the anti-inflammatory cyto-kine IL-10 level(P<0.01);inhibited sciatic nerve structural damage and apoptosis(P<0.05);downregulated the ratio of cleaved Caspase-3 to Caspase-3 in the apoptosis pathway(P<0.01);upregulated the expression of neurofilament proteins NF-L and NF-H in sciatic nerve tissue(P<0.05,P<0.01);and upregulated the expression of antioxidant stress proteins Nrf2 and HO-1(P<0.01).CONCLUSION Juanbi Tongluo Oral Liquid can improve sciatic neuronal apoptosis of Type 2 diabetic mice,which may be related to its effect on improving oxidative stress and inflammatory stress.

Objective:To explore the pathogenesis and potential biomarkers of atrial fibrillation based on bioinformatics.Methods:Differentially expressed genes and module genes related to atrial fibrillation were obtained from GSE41177 and GSE79768 datasets(Chinese-origin tissue samples)through differential expression analysis and weighted gene co-expression network analysis.Candidate hub genes were obtained by taking intersections,and hub genes were obtained after gender stratification.Subsequently,functional enrichment analysis and immune infiltration analysis were performed.Four machine learning models were constructed based on the hub genes,and the optimal model was selected to construct a prediction nomogram.The prediction ability of the nomogram was verified using calibration curves and decision curves.Finally,potential therapeutic drugs for atrial fibrillation were screened from the DGIdb database.Results:A total of 67 differentially expressed genes and 65 module genes related to atrial fibrillation were identified.Functional enrichment analysis indicated that the pathogenesis of atrial fibrillation was closely related to inflammatory response,immune response,and immune and infectious diseases.Four common hub genes(TYROBP,FCER1G,EVI2B and SOD2),and two genes specifically expressed in male(PILRA and SLC35G3)and female(HLA-DRA and GATP)patients with atrial fibrillation were obtained after gender-segregated screening.The extreme gradient boosting model had satisfactory diagnostic efficiency,and the nomogram constructed based on the hub genes,male significant variables(PILRA,SLC35G3 and SOD2),and female significant variables(FCER1G,SOD2 and TYRO BP)had satisfactory predictive ability.Immune infiltration analysis demonstrated a disturbed immune infiltration microenvironment in atrial fibrillation with a higher abundance of plasma cells,neutrophils,and γδT cells,with a higher abundance of neutrophils in males and resting mast cells in females.Two potential drugs for the treatment of atrial fibrillation,valproic acid and methotrexate,were obtained by database and literature screening.Conclusions:The pathogenesis of atrial fibrillation is closely related to inflammation and immune response,and the microenvironment of immune cell infiltration of cardiomyocytes in the atrial tissue of patients with atrial fibrillation is disordered.TYROBP,FCER1G,EVI2B and SOD2 serve as potential diagnostic biomarkers of atrial fibrillation;PILRA and SLC35G3 serve as potential specific diagnostic biomarkers of atrial fibrillation in the male population,which can effectively predict the risk of atrial fibrillation development and are also potential targets for the treatment of atrial fibrillation.

Purpose To explore the application of contrast-enhanced ultrasound in evaluating the local muscle microcirculation before and after acupuncture at Zusanli point in normal people.Materials and Methods A total of 72 healthy volunteers who visited the Department of Ultrasound,the Second Affiliated Hospital of Fujian Medical University from September 2018 to May 2020 were prospectively collected,all subjects performed ultrasound contrast before acupuncture,acupuncture with strongest deqi,and two hours after acupuncture to observe the blood flow perfusion of the microvessels in the tibialis anterior muscle.The pre-selected areas of interest the small arteries,muscle tissues and venules in the middle were analyzed to obtain the time-intensity curve and contrast transit time(CTTs)perfusion parameters.Needle sensation was evaluated using objective scoring criteria for acupuncture combined with moxibustion recipients.Gastrin,plasma gastrin,cholecystokinin,and secretin were measured in all subjects before acupuncture,when acupuncture had the strongest deqi,and two hours after acupuncture.Results ①CTTs of arterial-muscle,muscle-venous and arterial-venous of the tibialis anterior muscle at acupuncture with strongest deqi were significantly shorter than those at before acupuncture and two hours after acupuncture(all P<0.001),and there was no significant difference in CTTs before and after acupuncture and moxibustion(P>0.05);②when acupuncture deqi was strongest,serum gastrin,plasma prokinetics,cholecystokinin,and secretin were significantly increased compared with those before acupuncture and two hours after acupuncture,with statistically significant difference(all P<0.001),while there was no significant difference in these parameters between before acupuncture and two hours after acupuncture(P>0.05);③when acupuncture had the strongest deqi,there were positive correlations between gastrin,plasma prokinetic hormone,cholecystokinin,and secretin values and CTTs of arterial-muscle,muscle-venous,and arterial-venous(r=0.360-0.702,P<0.001).Conclusion Acupuncture of the Zusanli,when it gains the strongest deqi,can cause changes in the microcirculation around the skeletal muscle,leading to a significant shortening of CTTs,and also promotes the secretory function of the gastrointestinal tract.

OBJECTIVES: To investigate the mechanism of comorbidity between non-alcoholic fatty liver disease (NAFLD) and atherosclerosis (AS) based on metabolomics and network pharmacology. METHODS: Six ApoE^－/－ mice were fed with a high-fat diet for 16 weeks as a comorbid model of NAFLD and AS (model group). Normal diet was given to 6 wildtype C57BL/6J mice (control group). Serum samples were taken from both groups for a non-targeted metabolomics assay to identify differential metabolites. Network pharmacology was applied to explore the possible mechanistic effects of differential metabolites on AS and NAFLD. An in vitro comorbid cell model was constructed using NCTC1469 cells and RAW264.7 macrophage. Cellular lipid accumulation, cell viability, morphology and function of mitochondria were detected with oil red O staining, CCK-8 assay, transmission electron microscopy and JC-1 staining, respectively. RESULTS: A total of 85 differential metabolites associated with comorbidity of NAFLD and AS were identified. The top 20 differential metabolites were subjected to network pharmacology analysis, which showed that the core targets of differential metabolites related to AS and NAFLD were STAT3, EGFR, MAPK14, PPARG, NFKB1, PTGS2, ESR1, PPARA, PTPN1 and SCD. The Kyoto Encyclopedia of Genes and Genomes showed the top 10 signaling pathways were PPAR signaling pathway, AGE-RAGE signaling pathway in diabetic complications, alcoholic liver disease, prolactin signaling pathway, insulin resistance, TNF signaling pathway, hepatitis B, the relax in signaling pathway, IL-17 signaling pathway and NAFLD. Experimental validation showed that lipid metabolism-related genes PPARG, PPARA, PTPN1, and SCD were significantly changed in hepatocyte models, and steatotic hepatocytes affected the expression of macrophage inflammation-related genes STAT3, NFKB1 and PTGS2; steatotic hepatocytes promoted the formation of foam cells and exacerbated the accumulation of lipids in foam cells; the disrupted morphology, impaired function, and increased reactive oxygen species production were observed in steatotic hepatocyte mitochondria, while the formation of foam cells aggravated mitochondrial damage. CONCLUSIONS Abnormal lipid metabolism and inflammatory response are distinctive features of comorbid AS and NAFLD. Hepatocyte steatosis causes mitochondrial damage, which leads to mitochondrial dysfunction, increased reactive oxygen species and activation of macrophage inflammatory response, resulting in the acceleration of AS development.
Animals ; Mice ; Non-alcoholic Fatty Liver Disease/metabolism* ; Cyclooxygenase 2/metabolism* ; PPAR gamma/metabolism* ; Reactive Oxygen Species/metabolism* ; Mice, Inbred C57BL ; Hepatocytes ; Macrophages/metabolism* ; Liver

BACKGROUND: Breast cancer patients who are positive for hormone receptor typically exhibit a favorable prognosis. It is controversial whether chemotherapy is necessary for them after surgery. Our study aimed to establish a multigene model to predict the relapse of hormone receptor-positive early-stage Chinese breast cancer after surgery and direct individualized application of chemotherapy in breast cancer patients after surgery. METHODS: In this study, differentially expressed genes (DEGs) were identified between relapse and nonrelapse breast cancer groups based on RNA sequencing. Gene set enrichment analysis (GSEA) was performed to identify potential relapse-relevant pathways. CIBERSORT and Microenvironment Cell Populations-counter algorithms were used to analyze immune infiltration. The least absolute shrinkage and selection operator (LASSO) regression, log-rank tests, and multiple Cox regression were performed to identify prognostic signatures. A predictive model was developed and validated based on Kaplan-Meier analysis, receiver operating characteristic curve (ROC). RESULTS: A total of 234 out of 487 patients were enrolled in this study, and 1588 DEGs were identified between the relapse and nonrelapse groups. GSEA results showed that immune-related pathways were enriched in the nonrelapse group, whereas cell cycle- and metabolism-relevant pathways were enriched in the relapse group. A predictive model was developed using three genes ( CKMT1B , SMR3B , and OR11M1P ) generated from the LASSO regression. The model stratified breast cancer patients into high- and low-risk subgroups with significantly different prognostic statuses, and our model was independent of other clinical factors. Time-dependent ROC showed high predictive performance of the model. CONCLUSIONS A multigene model was established from RNA-sequencing data to direct risk classification and predict relapse of hormone receptor-positive breast cancer in Chinese patients. Utilization of the model could provide individualized evaluation of chemotherapy after surgery for breast cancer patients.
Humans ; Female ; Breast Neoplasms/genetics* ; East Asian People ; Neoplasm Recurrence, Local/genetics* ; Breast ; Algorithms ; Chronic Disease ; Prognosis ; Tumor Microenvironment

As one of the classic prescriptions of traditional Chinese medicine， Didangtang is an effective prescription for breaking and expelling blood stasis. It was considered that Didangtang damage the healthy qi and contained toxic Chinese medicinal materials such as leeches and gadflies， and thus it was rarely used. However， as the attention to classic prescriptions increases， Didangtang has been widely used in clinical practice and demonstrated definite efficacy in treating diabetes mellitus and its complications， malignant tumors， Alzheimer's disease， stroke， renal diseases， cardiovascular diseases， peripheral vascular diseases， gynecological disease， and male diseases according to the disease location， pathogenesis， symptoms， and pharmacological effects. Didangtang has the effects of mitigating insulin resistance， improving microvascular and peripheral vascular circulation， delaying diabetic macrovascular lesions， preventing vascular fibrosis， improving immunity， inhibiting tumor growth， protecting the brain tissue， nerve cells， vascular endothelial function， and kidney， reducing inflammation， and delaying aging. This paper summarizes the clinical application of Didangtang and initially explores the underlying mechanism.

Objective:To introduce the therapeutic effect of forearm radial artery perforator propeller flap for repair of hand and wrist soft tissue defects.Methods:The clinical data of patients with soft tissue defects of hand and wrist who received the treatment with forearm radial artery perforator propeller flap in Northern Jiangsu People’s Hospital from January 2018 to September 2020 were collected. The radial artery of the forearm was projected on the skin surface as the axis, and the nearest perforator was selected as the rotation point according to the location of the soft tissue defect. The radial artery perforator propeller flap was designed based on the location, area and shape of soft tissue defect. The length of the large paddle of the flap is equal to the distance between the proximal side of the wound edge and the rotation point plus the length of the wound, and the length of the small paddle of the flap is equal to the distance between the proximal side of the wound edge and the rotation point. The donor site was closed directly or with full-thickness skin graft from the ipsilateral upper arm. The survival, appearance of the flap and skin graft, hand and wrist function and patients satisfactory rate were observed and recorded.Results:A total of 6 patients were included, including 4 males and 2 females; the mean age was 40.5 years (range, 25-65 years ). There were 1 case on the palm side of the hand, 1 case on the dorsal side of the hand, 3 cases on the volar side of the wrist, and 1 case on the dorsal side of the wrist. The area of soft tissue defect after debridement was 2 cm × 3 cm-7 cm × 10 cm. The forearm radial artery perforator propeller flap ranged from 3 cm × 4 cm to 8 cm × 11 cm. The donor site was closed directly in 3 cases, and with full-thickness skin graft in 3 cases. The flaps in all 6 patients survived completely with primary healing. The skin grafts for the donor site in 3 cases survived completely. The patients were followed up for 3 months to 1 year, with an average of 5 months. The function of the hand and wrist recovered well. The texture of the flap was similar to that of the surrounding tissue with good appearance, no swelling or slight swelling, no obvious color difference. The donor site healed well without scar hyperplasia. The patients were satisfied with the surgical results.Conclusion:Propeller flap pedicled with forearm radial artery perforator is a simple and effective method to repair soft tissue defects of wrist and hand with reliable recovery of appearance and function. The patients’ satisfactory rate is also high.

Objective:To introduce the therapeutic effect of forearm radial artery perforator propeller flap for repair of hand and wrist soft tissue defects.Methods:The clinical data of patients with soft tissue defects of hand and wrist who received the treatment with forearm radial artery perforator propeller flap in Northern Jiangsu People’s Hospital from January 2018 to September 2020 were collected. The radial artery of the forearm was projected on the skin surface as the axis, and the nearest perforator was selected as the rotation point according to the location of the soft tissue defect. The radial artery perforator propeller flap was designed based on the location, area and shape of soft tissue defect. The length of the large paddle of the flap is equal to the distance between the proximal side of the wound edge and the rotation point plus the length of the wound, and the length of the small paddle of the flap is equal to the distance between the proximal side of the wound edge and the rotation point. The donor site was closed directly or with full-thickness skin graft from the ipsilateral upper arm. The survival, appearance of the flap and skin graft, hand and wrist function and patients satisfactory rate were observed and recorded.Results:A total of 6 patients were included, including 4 males and 2 females; the mean age was 40.5 years (range, 25-65 years ). There were 1 case on the palm side of the hand, 1 case on the dorsal side of the hand, 3 cases on the volar side of the wrist, and 1 case on the dorsal side of the wrist. The area of soft tissue defect after debridement was 2 cm × 3 cm-7 cm × 10 cm. The forearm radial artery perforator propeller flap ranged from 3 cm × 4 cm to 8 cm × 11 cm. The donor site was closed directly in 3 cases, and with full-thickness skin graft in 3 cases. The flaps in all 6 patients survived completely with primary healing. The skin grafts for the donor site in 3 cases survived completely. The patients were followed up for 3 months to 1 year, with an average of 5 months. The function of the hand and wrist recovered well. The texture of the flap was similar to that of the surrounding tissue with good appearance, no swelling or slight swelling, no obvious color difference. The donor site healed well without scar hyperplasia. The patients were satisfied with the surgical results.Conclusion:Propeller flap pedicled with forearm radial artery perforator is a simple and effective method to repair soft tissue defects of wrist and hand with reliable recovery of appearance and function. The patients’ satisfactory rate is also high.

Increased microglial activation and neuroinflammation within autonomic brain regions such as the rostral ventrolateral medulla (RVLM) have been implicated in stress-induced hypertension (SIH). Prorenin, a member of the brain renin-angiotensin system (RAS), can directly activate microglia. The present study aimed to investigate the effects of prorenin on microglial activation in the RVLM of SIH rats. Rats were subjected to intermittent electric foot-shocks plus noise, this stress was administered for 2 h twice daily for 15 consecutive days, and mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were monitored. The results showed that MAP and RSNA were augmented, and this paralleled increased pro-inflammatory phenotype (M1) switching. Prorenin and its receptor (PRR) expression and the NLR family pyrin domain containing 3 (NLRP3) activation were increased in RVLM of SIH rats. In addition, PLX5622 (a microglial depletion agent), MCC950 (a NLRP3 inhibitor), and/or PRO20 (a (Pro)renin receptor antagonist) had antihypertensive effects in the rats. The NLRP3 expression in the RVLM was decreased in SIH rats treated with PLX5622. Mito-tracker staining showed translocation of NLRP3 from mitochondria to the cytoplasm in prorenin-stimulated microglia. Prorenin increased the ROS-triggering M1 phenotype-switching and NLRP3 activation, while MCC950 decreased the M1 polarization. In conclusion, upregulated prorenin in the RVLM may be involved in the pathogenesis of SIH, mediated by activation of the microglia-derived NLRP3 inflammasome. The link between prorenin and NLRP3 in microglia provides insights for the treatment of stress-related hypertension.