Objective:To investigate the efficacy of Balanophora involucrata Hook.f.in treatment of hyperuricemia(HUA)based on network pharmacology,molecular docking,and hyperuricemia models in vivo and in vitro,and to clarify the main targets of its active components and related signaling pathway mechanism.Methods:The potential targets of Balanophora involucrata Hook.f.in treatment of HUA were identified by Databases such as the Traditional Chinese Medicine Database in Taiwan,the Chinese Herbal Medicine Identification Database,Professional Chemical Database,TargetNet Database,SwissTargetPrediction Database,GeneCards,Therapeutic Target Database(TTD),DrugBank Database,DisGeNET Database,Online Mendelian Inheritance in Man(OMIM)Database,and Venny Database.STRING Database and Cytoscape software were used to construct the active component-predictive target network and protein-protein interaction(PPI)network for Balanophora involucrata Hook.f.;topological analysis was used to select the main active components and core targets;Gene Ontology(GO)functional and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were performed by R software;AutoDock Vina software was used for molecular docking validation.The NRK-52E cells were divided into blank control group,blank administration group,model group,and different concentrations(2.0,10.0,and 50.0 μmol·L-1)of erythrodiol(EDT)groups.High-performance liquid chromatography culture(HPLC)was used to detect the uric acid(UA)levels in the cell culture supernatants in various groups.The male ICR mice were divided into blank control group,blank administration group,model group,and EDT group;the mice in the last two groups were used to prepare the HUA models;kits were used to detect the levels of UA,creatinine(Cr),and blood urea nitrogen(BUN)in serum of the mice in various groups;the bilateral kidney tissue of the mice was harvested and weighed;the kidney indexes of the mice in various groups were calculated;TUNEL staining was used to observe the apoptosis in kidney tissue of the mice in various groups;Western blotting method was used to detect the expression levels of protein kinase B(AKT),phosphorylated AKT(p-AKT),phosphoinositide 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),and matrix metalloproteinase-9(MMP-9)proteins in kidney tissue of the mice in various groups.Results:Six active components of Balanophora involucrata Hook.f.were identified,involving 116 intersecting targets and 14 core targets.The enrichment analysis yielded 1 828 GO terms and 145 signaling pathways.The molecular docking results showed that EDT had good binding activity with MMP-9.The high uric acid cell experiment results showed that compared with blank control group,the UA level in the cells in model group was significantly increased(P<0.01);compared with model group,the UA levels in the cells in 2.0,10.0,and 50.0 μmol·L-1 EDT groups were significantly decreased(P<0.01).Compared with blank control group,the levels of UA,Cr,and BUN in serum of the mice in model group were increased(P<0.01),and the kidney indexes were significantly increased(P<0.01);compared with model group,the levels of UA,Cr,and BUN in serum of the mice in EDT group were decreased(P<0.05 or P<0.01),and the kidney index was significantly decreased(P<0.05 or P<0.01).Compared with blank control group,the number of apoptotic cells in kidney tissue of the mice in model group was increased;compared with model group,the number of the apoptotic cells in kidney tissue of the mice in EDT group was significantly decreased.Compared with blank control group,the ratios of p-AKT/AKT and p-PI3K/PI3K and expression level of Bcl-2 protein in kidney tissue of the mice in model group were significantly decreased(P<0.05 or P<0.01),while the expression levels of Bax and MMP-9 proteins were significantly increased(P<0.01);compared with model group,the ratios of p-AKT/AKT and p-PI3K/PI3K and expression level of Bcl-2 protein in kidney tissue of the mice in EDT group were significantly increased(P<0.05 or P<0.01),and the expression levels of Bax and MMP-9 proteins were significantly decreased(P<0.01).Conclusion:The active component of Balanophora involucrata Hook.f.,EDT,has a UA-decreasing effect and may inhibit the apoptosis and alleviate the kidney injury by activating the PI3K/AKT signaling pathway.

Objective To evaluate the therapeutic effect of Huangqin Decoction(HQD)on ulcerative colitis(UC)in mice and explore its mechanism.Methods Male Balb/c mice were randomly divided into normal control group,model group,mesalazine group(5-ASA,200 mg/kg),and low-,medium-and high-dose HQD groups(2.275,4.55 and 9.1 g/kg,respectively).With the exception of those in the normal control group,all the mice were exposed to 3%DSS solution in drinking water for 7 days to establish UC models.After treatment with the indicated drugs,the mice were assessed for colon injury and apoptosis using HE,AB-PAS and TUNEL staining,and the expression levels of inflammatory factors were detected with ELISA.Western blotting,immunohistochemistry and qRT-PCR were used to detect the changes in protein expressions associated with the intestinal chemical barrier,mechanical barrier and endoplasmic reticulum stress(ERS).Results HQD treatment significantly reduced DAI score and macro score of UC mice,decreased colonic epithelial cell apoptosis,lowered expressions of IL-6,TNF-α,IL-1β and IL-8,and enhanced the expressions of MUC2 and TFF3.HQD treatment also upregulated the protein expressions of claudin-1,occludin and E-cadherin,reduced the expressions of GRP78,CHOP,caspase-12 and caspase-3,decreased the phosphorylation levels of PERK,eIF2α and IRE1α,and increased the Bcl-2/Bax ratio in the colon tissues of UC mice.Conclusion HQD inhibits colonic epithelial cell apoptosis and improves intestinal barrier function in UC mice possibly by reducing ERS mediated by the PERK and IRE1α signaling pathways.

Objective To evaluate the therapeutic effect of Huangqin Decoction(HQD)on ulcerative colitis(UC)in mice and explore its mechanism.Methods Male Balb/c mice were randomly divided into normal control group,model group,mesalazine group(5-ASA,200 mg/kg),and low-,medium-and high-dose HQD groups(2.275,4.55 and 9.1 g/kg,respectively).With the exception of those in the normal control group,all the mice were exposed to 3%DSS solution in drinking water for 7 days to establish UC models.After treatment with the indicated drugs,the mice were assessed for colon injury and apoptosis using HE,AB-PAS and TUNEL staining,and the expression levels of inflammatory factors were detected with ELISA.Western blotting,immunohistochemistry and qRT-PCR were used to detect the changes in protein expressions associated with the intestinal chemical barrier,mechanical barrier and endoplasmic reticulum stress(ERS).Results HQD treatment significantly reduced DAI score and macro score of UC mice,decreased colonic epithelial cell apoptosis,lowered expressions of IL-6,TNF-α,IL-1β and IL-8,and enhanced the expressions of MUC2 and TFF3.HQD treatment also upregulated the protein expressions of claudin-1,occludin and E-cadherin,reduced the expressions of GRP78,CHOP,caspase-12 and caspase-3,decreased the phosphorylation levels of PERK,eIF2α and IRE1α,and increased the Bcl-2/Bax ratio in the colon tissues of UC mice.Conclusion HQD inhibits colonic epithelial cell apoptosis and improves intestinal barrier function in UC mice possibly by reducing ERS mediated by the PERK and IRE1α signaling pathways.

Objective To systematically evaluate the adult intraoperatively acquired pressure injury risk prediction model.Methods Related study on IAPI risk prediction model in Chinese and English databases such as CBM,CNKI,PubMed and Web of Science were searched.The language is limited to Chinese and English,and the search time is until November 4,2022.Two researchers independently screened the literature and extracted the data,and applied the bias risk assessment tool of prediction model research to analyze the bias risk and applicability of the included literature.Results 13 articles were included,including 17 models(operation time,age,diabetes,BMI and serum albumin are the most commonly used predictors).Among the 17 models,the area under the curve of 14 models was 0.616 to 0.984,and the other study did not report the AUC results.Among the 13 studies,10 had good applicability,while the remaining 3 had unclear applicability.13 studies have a high risk of bias,mainly because the included studies are retrospective studies,the predictive factors are screened based on univariate analysis,and the predictive outcomes are not defined by guidelines or standardization.Conclusions The existing IAPI risk prediction model for adults has good applicability,but the risk of bias is high,and the construction is not perfect.It is necessary to pay attention to the effectiveness of different risk assessment methods in the later construction,so as to get a better and more accurate risk prediction model and provide some reference and basis for formulating relevant prevention strategies.

Objective To use the cognitive reinforcement comprehensive intervention program constructed by our team to intervene in patients with spinal cord injury and evaluate its clinical application effect.Methods A non-randomized trial design was adopted to select 97 patients with spinal cord injury from November 2021 to September 2022.Forty-four patients from March to September 2022 in a Grade A hospital in Hefei City were included in the experimental group,and 53 patients from November 2021 to February 2022 were included in the control group.The cognitive reinforcement comprehensive intervention program was used to intervene in the experimental group,and the conventional rehabilitation nursing was used to intervene in the control group.The intervention lasted for 12 weeks in both groups.The Changsha Montreal Scale,Social Support Rating Scale,Rehabilitation Exercise Self-efficacy Scale,Spinal Cord Injury Independence Rating Scale and Hamilton Anxiety Scale were used to measure the two groups before intervention,1 month after intervention and 3 months after intervention.Results 40 cases in the experimental group and 48 cases in the control group completed the study.Repeated measurement ANOVA showed that the temporal,interactive and intergroup effects of cognitive function scores and anxiety scores were statistically significant(P＜0.05).The time effect and interaction effect of the subjective support dimension score,coping self-efficacy dimension score of the two groups were statistically significant(P＜0.05).One month after the intervention,the cognitive function scores of test group were higher than before intervention and control group,and the anxiety scores were lower than before intervention and control group(P＜0.05).Three months after the intervention,the scores of cognitive function,subjective support dimension and coping self-efficacy dimension of experimental group were higher than those before intervention and control group,and the scores of anxiety level were lower than those before intervention and control group(P＜0.05).Conclusion Comprehensive intervention of cognitive reinforcement can improve the cognitive function of patients with spinal cord injury,delay the process of cognitive impairment,enhance self-confidence,relieve anxiety,and promote physical and mental rehabilitation of patients.

Objective:To summarize the best evidence for spasticity management in spinal cord injury patients, so as to provide references for clinical practice.Methods:PubMed, Embase, CLINICAL, BMJ Best Clinical Practice website, JBI Evidence-based Health Care Center database, National Institute for Health and Clinical Excellence, Ontario Guidelines Network, US National Guidelines Network, Scottish Interhospital Guidelines Network, UpToDate, Cochrane Library, CNKI, Wanfang Database, Medlive, China Biology Medicine disc and professional association websites were syatematically searched for clinical decisions, guidelines, evidence summary, systematic reviews and expert consensus or opinions on spasm management. The quality of the included studies was evaluated and the evidence content was extracted. The search period was from the establishment of the databases to February 28, 2023.Results:A total of 15 articles were included, including 2 clinical decision-making articles, 1 guideline, 3 expert consensus or opinions articles and 9 systematic evaluations. A total of 18 pieces of evidence were summarized from 4 aspects, such as regular evaluation, intervention measures, intervention principles, and effectiveness evaluation of patients with spinal cord injury.Conclusions:This study summarizes the best evidence for spasticity management in patients with spinal cord injury and provides an evidence-based basis for clinical work. It is recommended that when applying the evidence, an individualized spasticity treatment plan should be developed according to the needs of the patient and the actual clinical situation.

bcl-2 inhibitor of transcription 1 (Bit1) is an anoikis effector that can play a role of caspase-independent apoptosis by down-regulating bcl-2 expression. Previous studies have found that Bit1 affects cell survival and apoptosis through Erk and FAK-PI3K-Akt-NF-κB pathways. It is worth noting that the expression of Bit1 has shown the obvious tumor specificity in different tumors, and it is closely related to TNM stage, differentiation and prognosis of the tumor. This review summarizes the expression, main mechanism, and significance of Bit1 in different tumors.

Objective To investigate the beneficial role of synbiotics in the intestinal microbiota of patients with chronic functional constipation (CFC).Methods According to the inclusion and exclusion criteria,6 patients with CFC were enrolled with their fresh fecal samples collected,after a continuous treatment of one month their fresh fecal samples collected again.Meanwhile,6 healthy volunteers were enrolled as the control group with their fresh fecal samples collected.All samples were transported with ice and stored in -80 ℃ refrigerator,and were analyzed by metagenomics sequencing.Results After 4 weeks of symbiotic treatment,the intestinal microbiota had changed in species in patients with CFC.Bacteria of Escherichia_ coli,Clostridium_ sp._ SS2/1 and Clostridium_ sp._ 7_ 3_ 54FAA,which were rich in the people with constipation,decreased in abundance after the treatment.Bacteria of Lactobacillus_ oris and Bifidobacterium _ animalis,which were rich in the healthy people,increased in content after the treatment.Bacteria of Veillonella_ parvula,Veillonella_ sp._ 6_ 1_ 27,Veillonella_ sp._ 3 _ 1_ 44 which were rich in the healthy people,decreased in content after the treatment.LEfSe analysis showed that Parabacteroides distaso nis,Escherichia_ coli and Enterobacter-cloacae were the specific species of the three groups respectively.Conclusion Synbiotics can change the intestinal microbiota showing therapeutic effect,thus can be used as a novel clinical treatment method.

This study was aimed to investigate the antitussive,expectorant,antiasthmatic and anti-inflammatory effect of Ju-Hong Tan-Ke (JHTK) liquid.The methods of cough induced by ammonia in mice and cough induced by citric acid in guinea pigs were used to observe the antitussive effects.The mouse phenolsulfonphthalein excretion method,rat capillary expectoration method and the rabbit tracheal cilia movement influence experiment were used to observe the expectorant effect.An experiment of allergen induced rats' asthma was used to observe the antiasthmatic effects.The anti-inflammatory effect was observed by mouse peritoneal capillary permeability test and xylene induced ear swelling in mice.The results showed that JHTK liquid could inhibit cough induced by ammonia in mice,decrease the frequency of cough induced by citric acid in guinea pig and prolong the latent period of cough.The medicine could also obviously increase phenol red output of trachea in mice,promote expectoration in rats,accelerate the movement of cilium of tracheal transparently and prolong the latent period of asthma induced by allergens in rats,inhibit capillary permeability and lighten ear edema in mouse model.It was concluded that JHTK liquid could inhibit the reflex cough caused by hypersensitivity of airway sensor.It is peripheral antitussive rather than central antitussive,which has significant antitussive,expectorant,antiasthmatic and anti-inflammatory effects.Its efficacy is superior or equivalent to positive chemical control medicine.

OBJECTIVETo optimize the experimental model of nitric oxide (NO) production in mouse peritoneal macrophages in response to lipopolysaccharides (LPS) stimulation.

METHODSMouse resident peritoneal macrophages were collected by lavaging the peritoneal cavity of mice with Hank's solution and stimulated with Pseudomonas aeruginosa LPS for NO production. NO concentration in the culture supernatants was measured with Griess Reagent. The influences of cell density, LPS concentration, LPS stimulation duration and culture medium volume on NO production were investigated. Finally, the feasibility of the model was confirmed with specific anti-inflammatory drugs.

RESULTSThe density of macrophages produced the most significant effect on NO production (P<0.001), and optimal results were obtained at the macrophage density of 6×10(6) cells/ml with a volume of 100 µl in each well in 96-well plate. At a LPS concentration below 1 µg/ml, NO production increased proportionally with the increment of LPS concentration (P<0.001), but the increment of NO production declined obviously at LPS concentrations beyond 1 µg/ml, and the peak NO production occurred at a LPS concentration of 10 µg/ml. NO production also increased significantly with the prolongation of LPS stimulation (P<0.05), and the increments were greater within 24-48 h than those in 48-72 h. NO content in the culture supernatant was associated with the medium volume, and the highest level occurred in a system volume of 100 µl. Aspirin (1 mmol/L), dexamethasone (10 µmol/L), and cyclosporin A (10 µmol/L) all significantly inhibited LPS-stimulated production of NO in mouse resident peritoneal macrophages (P<0.001).

CONCLUSIONSMacrophage density, LPS concentration, and the duration of LPS stimulation are the main factors affecting LPS-stimulated NO production in mouse resident peritoneal macrophages. The optimal results can be obtained with a macrophage density of 5×10(6) cells/ml (100 µl per well), LPS concentration of 10 µg/ml, LPS stimulation duration of 24 h or 48 h, and a culture medium volume of 100 to 200 µl.

Animals ; Cells, Cultured ; Female ; Lipopolysaccharides ; pharmacology ; Macrophages, Peritoneal ; drug effects ; secretion ; Male ; Mice ; Mice, Inbred Strains ; Nitric Oxide ; biosynthesis