Objective: To explore the causal relationship between gut microbiota and upper urinary tract stones using Mendelian randomization (MR) analysis，and to investigate the potential mediating role of plasma metabolites. Methods: Data on gut microbiota，plasma metabolites，and upper urinary tract stones were obtained from publicly available Genome-wide Association Studies (GWAS).Bidirectional MR analysis was performed to examine the causal relationship between gut microbiota and upper urinary tract stones.Subsequently，a two-step MR approach was employed to determine whether gut microbiota contribute to upper urinary tract stones through plasma metabolites，and the mediating effects and mediator ratio were calculated.The inverse variance weighted (IVW) method was used as the primary analytical tool，supplemented by Bayesian weighted Mendelian randomization (BWMR)，MR-Egger，and weighted median (WM) analyses.Horizontal pleiotropy and heterogeneity tests were conducted to ensure the robustness of the findings. Results: Bidirectional MR analysis identified causal associations between 7 gut microbial taxa and 6 microbial metabolic pathways with upper urinary tract stones，while the development of upper urinary tract stones affected 13 gut microbial taxa and 5 metabolic pathways.Additionally，43 plasma metabolites (including 27 identified metabolites，8 unidentified metabolites，and 8 metabolite ratios) were causally associated with upper urinary tract stones.The two-step MR analysis identified 11 potential causal pathways.After metabolic pathways and unidentified metabolites were excluded，a causal link mediated by Bacteroides faecis between galactarate and upper urinary tract stones was confirmed，with a mediation proportion of 16.99% (95%CI：5.76%-33.95%，P=0.0371). Conclusion: This study establishes a causal relationship between parabacteroides and upper urinary tract stones，and elucidates the mediating role of galactarate，offering new insights into the pathogenesis and prevention strategies for upper urinary tract stones.

BACKGROUND:Previous studies have shown the correlation between lumbosacral sagittal plane parameters and natural absorption of lumbar disc herniation.However,the lumbosacral sagittal plane parameters included lumbar lordosis angle,lumbosacral joint angle,sacral inclination angle and many other parameters.The effects of each parameter on the natural absorption of the herniated disc were different.In addition,there are few studies on the reabsorption of a specific segment of intervertebral disc herniation at present,and most of the measured data are obtained from digital radiography or CT,while the correlation between lumbosacral sagittal plane parameters measured from MRI and reabsorption after L5/S1 intervertebral disc herniation is rarely reported. OBJECTIVE:To study the corresponding changes of lumbar sagittal plane parameters after L5/S1 intervertebral disc herniation reabsorption and to screen out the lumbosacral sagittal plane parameters with the most significant changes during intervertebral disc reabsorption. METHODS:Totally 57 patients with lumbar disc herniation who had complete MRI image data were selected and met the diagnostic criteria for lumbar disc herniation and only received non-surgical treatment for reabsorption of L5/S1 protrusion segments.MRI measured the protrusion area of the maximum protrusion plane in the coronal plane,lumbosacral sagittal plane parameters[lumbar curvature index,lumbar lordosis(α),L5/S1 disc angle(β),intervertebral height measurement,lumbosacral joint angle,sacral platform angle,sacral inclination angle,and lower lumbar lordosis angle].Besides,lumbosacral sagittal plane parameters were ranked in the importance of variables by random forest model in R software,and then significant variables were fitted with multiple linear regression.The changes between parameters before and after treatment were analyzed and compared by paired sample t-test. RESULTS AND CONCLUSION:(1)A total of 57 patients with L5/S1 lumbar disc herniation were included in this study,and the symptoms and imaging features of the patients were significantly relieved to a large extent.(2)Before treatment,there were 4 cases of grade 1,29 cases of grade 2 and 24 cases of grade 3 according to the Classification of Michigan State University.After treatment,there were 48 cases of grade 1 and 9 cases of grade 2.(3)The random forest model suggested that intervertebral height,lumbar curve index,sacral inclination angle,and lower lumbar lordosis angle changed significantly in L5/S1 disc herniation reabsorption,and the order of their change significance was lumbar curve index>intervertebral space height>sacral inclination angle>lower lumbar lordosis angle.(4)Lumbar curve index,lumbar lordosis and sacral platform angle increased,with statistical significance(P<0.05).There were no significant differences in disc angle,intervertebral height,lower lumbar lordosis angle,sacral inclination angle or lumbosacral joint angle(P>0.05).(5)Lumbar curvature index was the most significant parameter of the lumbosacral sagittal plane in herniated disc reabsorption.In addition,lumbar curve index,sacral inclination angle,and lower lumbar lordosis angle are commonly used clinically to describe the change of lumbar curvature,suggesting that L5/S1 disc herniation reabsorption is correlated with the change of lumbar curvature.It is indicated that in the treatment of lumbar disc herniation,a clinical cure can be achieved by improving or restoring the disordered lumbar curvature.

Objective To observe the changes of liver function,blood cell,and lung function of healthy young and middle-aged men before and after fast-advancing short-term high altitude exposure(FSHAE);and to explore the effects and possible mechanisms of FSHAE on the function of liver,blood cells,and lung tissues.Methods This study included 48 healthy young and middle-aged male volunteers,who collected physiological indicators,tested liver function indicators,blood cell indicators,and lung function-related indicators 1 day before entering the plateau(100m above sea level),and 15 days after FSHAE(3000m above sea level).Differences in the relevant parameters of each system were compared before and after FSHAE.Results Compared with those before entering the plateau,the physiological parameters of young and middle-aged men after 15 days of FSHAE heart rate increased significantly,respiratory rate increased,systolic blood pressure increased,mean arterial blood pressure increased,oxygen saturation decreased(P＜0.01),and diastolic blood pressure increased(P＜0.05),all of which were statistically significant;and the indicators of liver function:glutamic oxaloacetic aminotransferase,glutamic alanine aminotransferase increased(P＜0.01),glutamylamine aminotransferase,glutamate aminotransferase,glutaminase,and pulmonary function were increased(P＜0.01),glutamyl transpeptidase,alkaline phosphatase,and total bile acids were elevated,and total protein decreased(P＜0.05),and the differences were statistically significant.Hemocyte-related indexes:erythrocyte count,erythrocyte pressure volume,mean erythrocyte volume,mean hemoglobin volume,mean hemoglobin concentration,and hemoglobin were elevated,and platelet count decreased(P＜0.01),and the differences were statistically significant.although there was an elevation of leukocyte count(P＞0.05);Lung function-related indexes:decreased exertion lung volume(P＜0.05).There were decreased exertion expiratory volume in the first second,increased one-second rate(P＞0.05).Conclusion FSHAE can lead to oxidative stress in the organism,and acute hypoxic multisystemic injury will occur,with the simultaneous emergence of hypoxic adaptive regulation of various systems,self-compensatory repair of various organs of the organism,and there may be the possibility of interactions between various systems.

Objective:To explore the standardization of totally implantable venous power port of nursing process in CT enhancement and application effect of contrast medium injection, so as to provide a safer and more efficient way for contrast medium injection in CT enhanced examination for patients with malignant tumors.Methods:A non-randomized prospective study was conducted, 358 patients with malignant tumors were selected in Sun Yat-sen Memorial Hospital, Sun Yat-sen University who underwent CT enhanced examination from August 1, 2022 to July 31, 2023, 179 patients who had been implanted totally implantable venous power port were selected as the experimental group, and the standardized nursing procedure was given. The other 179 patients were the control group, using radiology routine high-pressure intravenous indwelling needle as the contrast medium access, with routine peripheral venous nursing process. The incidence of contrast medium extravasation during CT enhanced examination was observed and compared between the two groups.Results:All the patients were included. There were 85 males and 94 females, aged (55.50±11.72) years old in the control group. There were 83 males and 96 females, aged (54.50±12.24) years old in the experimental group. The incidence of contrast medium extravasation was 0 in the experimental group and 3.35%(6/179) in the control group. The difference between the two groups was statistically significant (Fisher exact probability, P<0.05). Conclusions:The application of standardized nursing procedure of totally implantable venous power port to the injection of contrast medium in CT enhanced examination of malignant tumor patients, can significantly reduce the incidence of contrast medium extravasation.

Objective:To explore the causal association between inflammatory cytokines and fibromyalgia by Mendelian randomization analysis.Methods:By mining the GWAS Catalog database and FinnGen database, the exposure factor was set as inflammatory cytokines, and the outcome was fibromyalgia. The main analysis method adopted in this study is inverse variance weighted (IVW) method, with MR-Egger, Simple Mode method, weighted median (WM), and Weighted Mode as supplementary statistical methods for Mendelian randomization analysis. Subsequently, by swapping the exposure factors and outcomes, the directionality of the analysis was tested.Results:Among the 91 known inflammatory cytokines, a causal association was found between natural killer cell receptor 2B4 (CD244), monocyte chemotactic protein 2 (MCP-2), C-X-C chemokine 6 (CXCL6), interleukin 12β subunit (IL12B), and fibromyalgia. Among them, CD244, CXCL6, and IL12B were positively correlated with FM [CD244: OR(95% CI)=1.21(1.08, 1.35), P<0.001]. [MCP-2: OR(95% CI)=0.91(0.87, 0.96), P<0.001], [CXCL6: OR(95% CI)=1.15(1.06, 1.24), P<0.001], IL-12B [ OR(95% CI)=1.13(1.06, 1.20), P<0.001]. Sensitivity analysis did not find multiple effects, heterogeneity,or correlation. Conclusion:The increase in the levels of CD244, CXCL6, and IL-12B will increase the risk of FM, while the increase in the level of MCP-2 will reduce the risk of FM disease.

Background and purpose:Colorectal cancer(CRC)is one of the major malignant tumors threatening human health worldwide,with long-term high incidence and mortality rate.Potassium channel modulatory factor 1(KCMF1)is a member of the E3 ubiquitin ligase family.It binds to target proteins through the RING domain and participates in the regulation of a variety of biological processes in vivo.However,the function of KCMF1 in CRC remains unclear.This study aimed to investigate the expression level of E3 ubiquitin ligase KCMF1 in colorectal tumor,and to explore the effects of KCMF1 on the proliferation of CRC cells and its underlying molecular mechanism.Methods:The The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases were used to analyze the expression level of KCMF1 in CRC tissues and adjacent tissues and the association between the KCMF1 expression and the prognosis of CRC patients.Furthermore,immunohistochemical staining was performed to detect the protein level of KCMF1 in 90 paired human CRC tissues and adjacent non-tumor tissues.Lentiviral shRNA delivery system was employed to specifically target the KCMF1 gene(shKCMF1)in HCT116 and HCT15 CRC cell lines.The effects of KCMF1 knockdown on cell proliferation,apoptosis and cell cycle distribution were assessed by methyl thiazoyl terazolium(MTT)assay,colony formation assay,Western blot and flow cytometry.Changes in the transcriptional profile in HCT116 cells upon KCMF1 knockdown were identified by RNA sequencing(RNA-Seq),and the affected signaling pathways were evaluated by bioinformatics analysis.Real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR),Western blot,luciferase reporter assay and cell immunofluorescence assay were utilized to validate the alteration of the affected signaling pathway.Results:The TCGA and GTEx databases and IHC results showed that the mRNA and protein expression levels of KCMF1 in CRC tissues were significantly upregulated compared with adjacent tissues(P＜0.01).KCMF1 expression level was negatively correlated with the survival time of patients with CRC(P＜0.01),and was positively associated with CRC clinical stage(P＜0.05).Compared with control cells,KCMF1 knockdown significantly inhibited the proliferation of HCT116 and HCT15 cells(P＜0.001),induced cell apoptosis(P＜0.001),and led to cell cycle arrest in G1 phase(P＜0.01).RNA-Seq analysis showed that KCMF1 was involved in the regulation of several signaling pathways,including nuclear factor-κB(NF-κB)signaling pathway.KCMF1 knockdown reduced the transcription levels of the target genes of NF-κB signaling pathway,including BCL-XL,XIAP and CIAP(P＜0.05),and suppressed the expression of phosphorylated p65 and nuclear translocation of p65(P＜0.01).Meanwhile,the activity of NF-κB reporter was reduced in tumor cells upon KCMF1 knockdown(P＜0.01).Conclusion:The expression of KCMF1 is significantly upregulated in human CRC tissues and positively associated with advanced clinical stage and poor prognosis.KCMF1 may promote the proliferation of CRC cells by activating the NF-κB signaling pathway.KCMF1 may be a potential new therapeutic target for CRC.

Background::Long non-coding RNAs (lncRNAs) plays an important role in the progression of gastric cancer (GC). Their involvement ranges from genetic regulation to cancer progression. However, the mechanistic roles of RP11-789C1.1 in GC are not fully understood.Methods::We identified the expression of lncRNA RP11-789C1.1 in GC tissues and cell lines by real-time fluorescent quantitative polymerase chain reaction. A series of functional experiments revealed the effect of RP11-789C1.1 on the proliferation of GC cells. In vivo experiments verified the effect of RP11-789C1.1 on the biological behavior of a GC cell line. RNA pull-down unveiled RP11-789C1.1 interacting proteins. Western blot analysis indicated the downstream pathway changes of RP11-789C1.1, and an oxaliplatin dosing experiment disclosed the influence of RP11-789C1.1 on the drug sensitivity of oxaliplatin. Results::Our results demonstrated that RP11-789C1.1 inhibited the proliferation of GC cells and promoted the apoptosis of GC cells. Mechanistically, RP11-789C1.1 inhibited checkpoint kinase 1 (CHK1) phosphorylation by binding ataxiatelangiectasia mutated and Rad3 related (ATR), a serine/threonine-specific protein kinase, promoted GC apoptosis, and mediated oxaliplatin sensitivity.Conclusion::In general, we discovered a tumor suppressor molecule RP11-789C1.1 and confirmed its mechanism of action, providing a theoretical basis for targeted GC therapy.

Objective To study the effect of evidence-based nursing in patients with cerebral apoplexy in ICU by blind bedside spiral nasointestinal tube application.Methods To choose between September 2016 and September 2017 in our hospital ICU were 140 cases of patients with cerebral apoplexy as analysis object,randomly divided into two groups,two groups all use bedside blind spiral nose long intestinal tube technology,the control group using conventional nursing method for nursing,observation group using evidence-based nursing intervention,compared two groups of a success rate of catheter,accident to take off the tube (unscheduled decannulation rate),reflux hiccups,vomiting incidence of aspiration and patient satisfaction.Results The success rate of catheterization in the observation group was higher than that in the control group,and the incidence of accidental catheterization was lower than that in the control group.The incidence of reflux hiccup and vomiting aspiration was significantly lower than that in the control group,and the patient satisfaction was higher than that in the control group (all P＜0.05).Conclusion For patients with cerebral apoplexy in the ICU bed of blind plug spiral nasal bowel technology combined evidence-based nursing intervention,clinical effect is remarkable,improve the success rate of catheter,reduces the surprise success rate of tube,unscheduled tube drawing number,reduces the incidence of reflux hiccups,vomiting aspiration,improve patient satisfaction and quality of life.

Objective To evaluate the therapeutic outcome of horizontal bone augmentation by using the modified split crest technique of piezosurgery in mandible molar area. Methods The present study reviewed the record of 15 patients from 2016 January to 2017 March in the department of oral implantology center of Stomato-logical Hospital of Southern Medical University,who underwent the modified split crest technique of piezosurgery in mandible molar area. Preoperative CBCT was performed to determine the bone thickness of the toothless alveo-lar crest of the mandibular posterior region,and the bone thickness was less than 3 mm. The modified split crest technique of piezosurgery was performed for the horizontal bone augmentation at mandibular posterior region. Meanwhile,GBR and the postoperative CBCT were performed to determine the bone width increments,followed with 1-week anti-inflammatory therapy postoperation. Three months after the operations,the bone width incre-ment was examined by CBCT. SPSS13.0 software was used to analyze the collected data. Results The modified split crest technique of piezosurgery in mandible molar area was successfully established,resulting in the mini-mal operative wounds and the slight postoperative reaction,without obvious infection. The postoperative crest width increase achieved 6.05 ± 0.65 mm. At 3 months after operation,the crest width increase reduced to(5.81 ± 0.61)mm. There were significant differences of the alveolar ridge thickness between the preoperative and post-operative patients(P<0.05). There were significant differences between the preoperative crest width and the 3 months after treatment(P<0.05). Conclusion Horizontal bone augmentation of the modified split crest tech-nique of piezosurgery was efficient,which could be performed in very narrow alveolar ridge,and which was rela-tively safe and accurate,with less trauma. No damage was observed to the soft tissue,and the cutting direction can be well controlled.

Generally speaking,the organism can maintain the stability of T cells.The lymphopeniainduced homeostatic proliferation of T cells could be driven by the recognition of autoantigen including tumor antigen in the absence of foreign antigens or inflammatory signals.This process can break tumor-induced immune tolerance and induce a powerful antitumor immunity.It is confirmed that some negative immune molecules are recruited during the homeostatic proliferation,then the antitumor immunity will be impaired.