Ras homolog gene family member A(RhoA)is a small GTPase protein.Rho-associated coiled-coil forming protein kinase(ROCK)can be activated during the occurrence and development of ischemic stroke.RhoA/ROCK signaling pathway is an important regulatory factor in the pathological process of ischemic stroke,and regulation of this signaling pathway has become a research focus in promoting neuronal recovery and improving cerebral ischemia/reperfusion injury after ischemic stroke.However,only Fasudil is currently available as a RhoA/ROCK inhibitor.The rest is still in the stage of research and development or clinical trials,and has broad research prospects.In this paper,the regulatory role and mechanism of RhoA/ROCK signaling pathway in ischemic stroke were analyzed,and the application of inhibitors and regulatory drugs were described,aiming to provide new ideas for the prevention and treatment of ischemic stroke.

Objective:To explore the mechanism of peritoneal dialysis solution (PDS)-induced peritoneal microinflammation through activation of ceramide (CER) in peritoneal dialysis model mice.Methods:Thirty 5-week-old male C57BL/6 mice weighing about 22 g were used to set up peritoneal dialysis models, and then were randomly divided into 4 groups: sham operation group (1.5 ml sterilized water, n=7), high glucose-PDS group (1.5 ml 4.25% PDS, n=8), high glucose-PDS+ acid sphingomyelinase (ASMase) inhibitor desipramine (DES) group (1.5 ml sterilized water+10 mg/kg DES, n=8), high glucose-PDS+Src kinase inhibitor PP2 group (1.5 ml sterilized water +1 mg/kg PP2, n=7), with intraperitoneal injection once a day. After 28 days, the mice were sacrificed to retain peritoneal tissues. HE staining and Masson staining were used to observe the histological changes of peritoneum. Immunohistochemistry was used to detect the Toll-like receptor 4 (TLR4) and macrophages. High performance liquid chromatography, liquid chromatography/mass spectrometry and immunofluorescence were used to detect the expression of ASMase and CER. Real-time quantitative PCR was used to detect the mRNA levels of c-Src, p-Src, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Western blotting was used to detect the protein levels of c-Src, and p-Src. Enzyme-linked immunosorbent assay was used to detect the serum C reactive protein (CRP), IL-6 and TNF-α. Results:(1) High glucose-PDS led to peritoneal hyperplasia, collagen deposition and fibrosis in the peritoneal dialysis mice, indicating successful modeling. Compared with high glucose-PDS group, peritoneal hyperplasia, collagen deposition and fibrosis of mice treated with DES and PP2 were significantly improved (all P<0.05). (2) Compared with sham operation group, ASMase activation and CER level of peritoneal tissues were significantly higher in high glucose-PDS group, and DES could significantly inhibit activated ASMase and increased CER expression caused by high glucose-PDS (both P<0.05). PP2 had no significant effect on ASMase activation and CER level (both P>0.05). (3) Compared with sham operation group, there were more TLR4 and macrophage positive staining cells in peritoneal tissues in high glucose-PDS group, and the mRNA expression levels of IL-6 and TNF-α in peritoneal tissues and serum CRP, IL-6 and TNF-α were higher (all P<0.05). DES and PP2 could significantly inhibit the increased TLR4, macrophages and related inflammatory factors induced by high glucose-PDS (all P<0.05). (4) Compared with sham operation group, c-Src and p-Src mRNA and protein expression levels of peritoneal tissues in high glucose-PDS group were significantly higher (all P<0.05). PP2 significantly inhibited the increased p-Src mRNA and protein levels caused by high glucose-PDS (both P<0.05), but had no significant effect on the mRNA and protein expression levels of c-Src (both P>0.05). DES had no significant effect on the mRNA and protein expression levels of c-Src and p-Src (all P>0.05). Conclusions:High glucose-PDS may enhance the expression of CER through stimulating the activity of ASMase, phosphorylate Src, activate TLR4 and induce inflammatory damage of peritoneum in peritoneal dialysis model mice.

【Objective】 To elucidate the possible role of arginine and histidine in the pathogenesis of schizophrenia by exploring the serum levels of semi-essential amino acids (arginine and histidine) in patients with schizophrenia and their correlation with psychiatric symptoms. 【Methods】 We selected 72 inpatients with schizophrenia admitted to The First Affiliated Hospital of Xi’an Jiaotong University from March 2021 to October 2022 and 72 healthy volunteers enrolled in Yanta Community during the same period as the research subjects. Serum arginine and histidine levels were measured in patients with schizophrenia and healthy controls using serum liquid chromatography-mass spectrometry (LC-MS). We used the Positive and Negative Symptom Scale (PANSS) to evaluate the mental symptoms of patients with schizophrenia and analyzed the correlation of serum arginine and histidine levels with disease course, frequency of onset, and PANSS score. 【Results】 The levels of serum arginine (P<0.001) and histidine (P=0.011) in the schizophrenia group were significantly lower than those in the control group. The levels of serum arginine and histidine were significantly negatively correlated with the frequency of onset (rs=-0.410, rs=-0.262), total score of PANSS (rs=-0.298, rs=-0.256), positive factors (rs=-0.299, rs=-0.234) and cognitive impairment factors (rs=-0.251, rs=-0.296). In addition, serum arginine levels had significantly negative correlation with anxiety and depression factors (rs=-0.269, P<0.05). 【Conclusion】 The serum levels of arginine and histidine in patients with schizophrenia are significantly lower than those in healthy individuals, and are negatively correlated with overall mental symptoms, severity of positive symptoms and cognitive impairment. The severity of anxiety and depression symptoms is negatively correlated with arginine levels. The detection of serum arginine and histidine can provide reference for the diagnosis and assessment of the severity of schizophrenia in the future.

Objective To investigate the effect of peripheral blood bile acids on the cognitive function of schizophrenia patients.Methods Targeted metabolomics was adopted to analyze the total level of primary and secondary serum bile acid metabolites collected from 23 schizophrenia patients and 23 health control individuals.The MATRICS Consensus Cognitive Battery(MCCB)was adopted to evaluate the subjects'cognitive function in five dimensions.Results We found that the schizophrenia patients had impaired cognitive functions in multiple dimensions including speed of processing,working memory,reasoning and problem solving,and visual learning.Compared with the health control group,serum levels of cholic acid(CA)and chenodeoxycholic acid(CDCA)were significantly lower in patients with schizophrenia,while serum level of glycocholic acid(GCA)was significantly higher,and the ratio of deoxycholic acid(DCA)to CA was higher(3.04 vs.1.16).Speed of processing,working memory,reasoning and problem solving,and visual learning abilities were significantly negatively correlated with serum levels of multiple primary bile acids including taurocholic acid(TCA),GCA,glycochenodeoxycholic acid(GCDCA)and taurochenodeoxycholic acid(TCDCA),after adjustments of age,sex,and body mass index.Conclusion The bile acid profile of schizophrenia patients is obvious,and the decrease in neuroprotective bile acids(namely,CA and CDCA)and the up-regulation of cytotoxic bile acid(i.e.,GCA)may impair the cognitive function of schizophrenia patients.

Objective This study aims to observe the clinical effect of bone plate reduction in combination with a re-sorbable plate on large mandibular cysts.Methods Between October 2017 and September 2022,patients with large mandibular cysts in the presence of labial and buccal cortical bone were involved in the study.Intraoral approach was performed for bone plate reduction.Cone beam computed tomography(CBCT)scan was reviewed at 3,6,and 9 months postoperatively to observe postoperative complications.Osteogenic results were assessed at these times to determine the clinical outcomes of this procedure.Results Eleven cases with large mandibular cysts in the presence of cortical bone were evaluated.The average thickness of the cortical bone on the labial and buccal sides was measured to be about(1.98±0.37)mm before surgery,with a mean value of(0.73±0.17)mm at the thinnest part of the plate and up to 0.51 mm at the thinnest part of the plate.The cystic cavities were well re-vealed during the surgeries,which were completed suc-cessfully.Postoperatively,the wounds healed in one stage without infection.The percentages of cyst shrinkage were 20.01%,41.76%,and 73.41%at 3,6,and 9 months after surgery,respectively.Quantitative measurement of bone mineral density in the jaws by CBCT with MIMICS software.The bone mineral densities of the adult bone were 313.78,555.85,and 657.45 HU at the 3,6,and 9 month time intervals,respectively.No significant change in the patient's maxillofacial appearance were observed from the preoperative period as assessed by the patient's and observer's visual analog scale.Conclusion Bone plate reduction is an effective treatment for large mandibular cysts of the oral and maxillofacial re-gion with the presence of cortical bone.

Objective:To assess the prognostic value of modified Charlson comorbidity index (mCCI) combined with serum albumin for long-term prognosis in peritoneal dialysis (PD) patients.Methods:From January 1, 2007 to June 30, 2015, patients who started PD in Nanjing Drum Tower Hospital were enrolled in this retrospective cohort study. Clinical data including gender, age, underlying diseases, laboratory examination and prognosis were collected. The mCCI at the beginning of PD was calculated. Whether the duration of PD exceeded 5 years was used as an indicator to evaluate the prognosis. The patients were divided into≥5 years group and<5 years group according to the duration of PD, and the data were compared between the two groups. Cox regression model was constructed to analyze the influencing factors of all-cause death in PD patients. Multivariate logistic regression model and receiver operating characteristic (ROC) curve were used to analyze the predictive value of mCCI and serum albumin levels on whether patients could maintain long-term PD.Results:Of the 183 patients included [males 106(57.9%), females 77(42.1%); (53.35±16.50) years old; 162 cases (88.5%) with hypertension, 55 cases (30.1%) with diabetes], 97 cases had PD duration for ≥5 years and 86 cases less than 5 years. The overall 5-year technical survival rate was 65.1%. At the beginning of PD, compared with the dialysis age≥5 years group, the patients in the dialysis age less than 5 years group had older age, higher mCCI, lower serum albumin level, and higher C-reactive protein (CRP) level (all P<0.05), but there were no significant differences in gender, education level, electrolyte, mean arterial pressure, high densitv lipoprotein (HDL), low-density lipoprotein (LDL) and PD adequacy index between the two groups (all P>0.05). Multivariate logistic regression analysis showed that increased age ( OR=1.022, 95% CI 1.000-1.043, P=0.046), increased mCCI ( OR=1.620, 95% CI 1.300-2.018, P<0.001) and decreased serum albumin ( OR=0.807, 95% CI 0.730-0.893, P<0.001) were independent predictors for the duration of PD<5 years. ROC curve analysis showed that the area under ROC curves ( AUC) of mCCI, serum albumin level and combined prediction probability of the two for the duration of PD<5 years were 0.647(95% CI 0.568-0.727), 0.655(95% CI 0.577-0.734), and 0.767(95% CI 0.700-0.835), respectively, indicating that the accuracy of combined parameters to predict survival outcome was higher than that of any single parameter. Multivariate Cox analysis showed that increased age ( HR=1.073, 95% CI 1.046-1.100, P<0.001), increased mCCI ( HR=1.198, 95% CI 1.044-1.375, P=0.010) and decreased serum albumin ( HR=0.904, 95% CI 0.843-0.969, P=0.004) were independent influencing factors for all-cause death in PD patients. Conclusions:Old age, high mCCI and low serum albumin level are influencing factors for dialysis age<5 years and all-cause death in PD patients. mCCI combined with serum albumin level can improve the accuracy of predicting the long-term dialysis in PD patients.

Objective To study the diagnostic value of glycosylated hemoglobin(HbA1c)combined with ho-meostasis model assessment of insulin resistance( HOMA-IR)in obese children with prediabetes. Methods Five hundred and ninety-five obese children diagnosed at Outpatient Department of Pediatrics,Tianjin Medical University General Hospital were enrolled in the study from October 2012 to March 2016. Oral glucose tolerance test(OGTT)and HbA1c test were performed after fasting 8 to 10 hours for all the subjects. According to the World Health Organization (WHO)criteria,the obese children were divided into non-prediabetes group(483 cases)and prediabetes group(112 cases). The levels of HOMA-IR and HbA1c were compared between 2 groups. The receiver operating characteristic (ROC)curve was drawn for screening prediabetes,and the diagnosis value of area under curve( AUC)and different cutoff value were calculated. Logistic regression model was used to analyze the combined diagnosis of prediabetic AUC with preserved probability as a single variable and ROC curve. Z test was used to compare the statistical differences of each AUC. Results The levels of HbA1c and HOMA-IR of the prediabetes obese children group[(5. 65 ± 0. 36)%and 11. 60 ± 8. 86]were all higher than those of the non-prediabetes obese children group[(5. 47 ± 0. 32)% and 6. 49 ± 4. 61],and there were significant differences between 2 groups(all P<0. 01). The AUC of HbA1c ROC for prediabetes was 0. 633. When the cutoff was 5. 585%,the sensitivity and specificity were 0. 584 and 0. 601,respective-ly. The AUC of HOMA-IR ROC for prediabetes was 0. 758. When the cutoff was 7. 244,the sensitivity and specificity were 0. 779 and 0. 669,respectively. When combined with HOMA-IR and HbA1c,the AUC was 0. 764. Compared with HbA1c,there were significant differences in AUC of ROC curve between HOMA-IR alone or HOMA-IR com-bined with HbA1c in the diagnosis of prediabetes mellitus(all P<0. 01). There was no significant difference in AUC of ROC curve between HOMA-IR alone and HOMA-IR combined with HbA1c in the diagnosis of prediabetes melli-tus(P>0. 05). Conclusions Only HOMA-IR or HOMA-IR combined with HbA1c may be the optimal indexes for diagnosing obese children with prediabetes.

Objective To investigate the effect of 1α, 25-dihydroxyvitamin D3 [1α,25-(OH)2 D3] on tumor necrosis factor-α ( TNF-α) induced activation of human umbilical vein endothelial cells ( HUVECs ) . The mechanism involved in this process was also studied. Methods HUVECs were cultured and treated with TNF-α( 40 ng/ml), 1α,25-(OH)2D3(10-8 mol/L), and SN50 as indicated. Vascular cell adhesion molecule (VCAM) and E-selectin were used as markers of endothelial activation, which were detected by Western blotting and realtime PCR (RT-PCR). NF-κB signaling pathway was investigated to study the mechanism. Western blotting, RT-PCR, immunofluorescence assay, and chromatin immunoprecipitation ( ChIP ) method were used to evaluate the effects of 1α,25-( OH) 2 D3 on its early activation, nuclear transport, and binding to VCAM and E-selectin promoters. Results (1) Western blotting and RT-PCR showed that TNF-α could significantly up-regulate the expression of VCAM and E-selectin in HUVECs, which can be inhibited by specific NF-κB blocker SN50. 1α,25-( OH) 2 D3 down-regulated the expression of VCAM and E-selectin induced by TNF-α. ( 2 ) Western blotting showed that TNF-α induces I-κBαphosphorylation, thereby activating NF-κB p65 subunit. Immunofluorescence showed that 1α, 25-( OH ) 2 D3 significantly inhibited the nuclear translocation of NF-κB p65 subunit. ChIP analysis revealed that 1α,25-( OH) 2 D3 inhibited the binding of NF-κB p65 to VCAM and E-selectin promoters and thus affected gene expression. Conclusions TNF-αenhanced the expression of E-selectin and VCAM in HUVECs via NF-κB signaling pathway. 1α,25-( OH) 2 D3 may inhibit NF-κB early activation, nuclear transport and the binding of NF-κB p65 to VCAM and E-selectin promoters, thereby inhibiting TNF-α-induced endothelial cell activation.

Objective To investigate the related risk factors for dyed cornea of orthokeratology, and to analyze the related risk factors, and to determine the independent risk factors, Provide evidence for intervention measures. Methods The clinical date were investigated for 990 patients with fitting orthokeratology lens between may.2014 and may.2016 in our hospital,through access to medical records, follow-up visit,questionnaire investigation to find out the cause of orthokeratology adverse reactions, the related risk factors were analyzed by univariate and multivariate Logistic regression analysis, using SPSS17.0 statistical processing. Results The incidence rate of dyed cornea of orthokeratology lens fitting in was 14.55%(144 in 990 patients); the single factor analysis found gender, age, region, refraction, lens position, family members, no significant difference . Eye disease combined (χ2= 28.73, P＜0.01), Schirmer I test (χ2=17.68, P＜0.01), lens activity (χ2=67.1, P＜0.01), Lens deposit(χ2=64.29, P＜0.01), lens wearing time (χ2=43.25, P＜0.01), health habits (χ2=38.01, P＜0.01) and water resources (χ2=3.81, P＜0.05), the difference was statistically significant; Logistic Logistic regression analysis found that Schirmer I test ( OR=4.126, P=0.003), lens activity ( OR=1.733, P=0.104), Lens deposit( OR=3.723, P=0.038), lens wearing time ( OR=5.034, P=0.002), health habits ( OR=6.544, P=0.002) and water resources ( OR=7.501, P=0.002) were independent risk factors for adverse reactions of orthokeratology. Conclusions Intervention measures that improve the fitting technology, complete removal of lens depositthe, Control wearing time, improve the health behaviors of the patients with the habit, use saline and professional cleaning are of great significance to reduce the incidence of adverse reactions of orthokeratology.

Objective To investigate the influencing factors of the cognitive deficits in schizophrenic patients with diabetes.Methods 578 inpatients with schizophrenia and 400 healthy adults were collected.578 schizophrenic patients were divided into schizophrenia group with type 2 diabetes (combined group,n=277) and schizophrenia without type 2 diabetes (single disease group,n=301).The cognitive function of all subjects were examined by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).The clinical symptoms of patients with schizophrenia were measured with the Positive and Negative Syndrome Scale (PANSS).Fasting glucose,lipids,hemoglobin A1c (HbA1c) and insulin levels were measured.Results The total score and factor scores of RBANS in the combined group were lower than those in the healthy control group (total score (70.51 ± 14.43) vs (80.04 ± 15.14),immediate memory (62.65 ± 16.81) vs (75.66± 17.33),visual span(83.60±20.81) vs (87.61 ± 15.61),verbal function(85.58± 14.64) vs (93.88± 13.10),attention function (73.66± 17.52) vs (87.42±20.37),delayed memory(75.27± 17.80) vs (86.27± 15.27),all P＜0.05).The total score of RBANS,immediate memory and attention function factor were lower in the combined group than that in the single disease group ((70.51±14.43) vs (75.02±15.25),(62.65±16.81) vs (67.37±19.12),(73.66±17.52) vs (84.17±15.22),all P＜0.05).Multiple linear stepwise regression analysis showed that education,negative symptoms,positive symptoms,BMI,HbAc 1,course of disease and antipsychotic type were the influencing factors of cognitive impairment in schizophrenic patients with diabetes.Conclusion The cognitive impairment of schizophrenic patients with diabetes is more serious and affected by many factors.Targeted early intervention can help reduce cognitive impairment.