Background Chronic excessive exposure to fluoride can cause damage to the central nervous system and a certain degree of learning and memory impairment. However, the associated mechanism is not yet clear and further exploration is needed. Objective Using 4D unlabelled quantitative proteomics techniques to explore differentially expressed proteins and their potential mechanisms of action in chronic excessive fluoride exposure induced brain injury. Methods Twenty-four SPF-grade adult SD rats, half male and half male, were selected and divided into a control group and a fluoride group by random number table method, with 12 rats in each group. Among them, the control group drank tap water (fluorine content<1 mg·L⁻¹), the fluoride group drank sodium fluoride solution (fluorine content 10 mg·L⁻¹), and both groups were fed with ordinary mouse feed (fluoride content<0.6 mg·kg⁻¹). After 180 d of feeding, the SD rats were weighed, and then part of the brain tissue was sampled for pathological examination by hematoxylin-eosin (HE) staining and Nissl staining. The rest of the brain tissue was frozen and stored at −80 ℃. Three brain tissue samples from each group were randomly selected for proteomics detection. Differentially expressed proteins were screened and subcellular localization analysis was performed, followed by Gene Ontology (GO) function analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, cluster analysis, and protein-protein interaction analysis. Finally, Western blotting was used to detect the expression levels of key proteins extracted from the brain tissue samples. Results After 180 d of feeding, the average weight of the rats in the fluoride group was significantly lower than that in the control group (P<0.05). The brain tissue stained with HE showed no significant morphological changes in the cerebral cortex of the fluoride treated rats, and neuron loss, irregular arrangement of neurons, eosinophilic changes, and cell body pyknosis were observed in the hippocampus. The Nissl staining results showed that the staining of neurons in the cerebral cortex and hippocampus of rats exposed to fluoride decreased (Nissl bodies decreased). The proteomics results showed that a total of 6927 proteins were identified. After screening, 206 differentially expressed proteins were obtained between the control group and the fluoride group, including 96 up-regulated proteins and 110 down-regulated proteins. The differential proteins were mainly located in cytoplasm (30.6%), nucleus (27.2%), mitochondria (13.6%), plasma membrane (13.6%), and extracellular domain (11.7%). The GO analysis results showed that differentially expressed proteins mainly participated in biological processes such as iron ion transport, regulation of dopamine neuron differentiation, and negative regulation of respiratory burst in inflammatory response, exercised molecular functions such as ferrous binding, iron oxidase activity, and cytokine activity, and were located in the smooth endoplasmic reticulum membrane, fixed components of the membrane, chloride channel complexes, and other cellular components. The KEGG significantly enriched pathways included biosynthesis of secondary metabolites, carbon metabolism, and microbial metabolism in diverse environments. The results of differential protein-protein interaction analysis showed that the highest connectivity was found in glucose-6-phosphate isomerase (Gpi). The expression level of Gpi in the brain tissue of the rats in the fluoride group was lower than that in the control group by Western blotting (P<0.05). Conclusion Multiple differentially expressed proteins are present in the brain tissue of rats with chronic fluorosis, and their functions are related to biosynthesis of secondary metabolites, carbon metabolism, and microbial metabolism in diverse environments; Gpi may be involved in cerebral neurological damage caused by chronic overdose fluoride exposure.

Objective:To investigate factors associated with acute kidney injury(AKI) in postoperative colorectal cancer patients.Methods:The clinical data of 376 colorectal carcinoma (CRC) patients at Department of General Surgery, Affiliated Cancer Hospital of Zhengzhou University from Jan 2018 to Jun 2021 were retrospectively analyzed. Patients were divided into acute kidney injury (AKI) ( n=29) and non-AKI groups ( n=347). The demographic information, perioperative status, laboratory results and other relevant data of the two groups were compared . Binary logistic regression was used to analyze the independent risk factors for postoperative AKI. Results:Twenty-nine CRC patients (7.7%) had postoperative AKI. Binary Logistic regression analysis showed that preoperative hypertension ( OR=3.487, 95% CI: 1.081-11.251, P=0.037), anemia ( OR=3.158, 95% CI: 1.114-8.953, P=0.031), inadequate intraoperative crystalloid infusion ( OR=0.998, 95% CI: 0.997-0.999, P=0.007), low intraoperative mean arterial pressure ( OR=0.915, 95% CI: 0.863-0.970, P=0.003) and moderate to severe postoperative decline in hemoglobin levels ( OR=4.105, 95% CI: 1.487-11.335, P=0.006) were independent risk factors. Conclusion:Preoperative hypertension, anemia, inadequate intraoperative crystalloid infusion, low intraoperative mean arterial pressure, and moderate to severe postoperative decline in hemoglobin levels were independent risk factors for AKI development in colorectal cancer patients.

Objective To study the mechanism of central nervous system (CNS) injury in chronic fluorosis and the neuroprotective effect of chondroitin sulfate (CS).Methods Forty-eight female Sprague-Dawley rats weighting 90-120 g were divided into 8 groups according to body weight by random number table,6 rats in each group:control group,drinking tap water freely;low dose and high dose fluoride groups,freely drinking tap water with fluoride content of 10 and 50 mg/L,respectively;control + normal saline (NS),low dose fluoride + NS,and high dose fluoride + NS groups,each group was fed for 180 d,and treated with intraperitoneal injection of 0.66 mg/kg NS for 5 d (once a day);low dose fluoride + CS and high dose fluoride + CS groups,each group was fed for 180 d,0.66 mg/kg CS was injected intraperitoneally for 5 d (once a day).All groups were fed standard nutritive animal feed for 185 d and dissected for brain tissue.The pathologic change was observed after hematoxylin-eosin (HE)staining;the expression levels of phosphorylated extracellular signal-regulated protein kinase 1/2 (phospho-Erk1/2)and glutamate receptors 1,2 (GluR1,GluR2) in the brain cortex were detected by immunohistochemistry;the protein levels of Erk1/2,phospho-Erk1/2,GluR1,and GluR2 in the brain cortex were detected by Western blotting.Results Brain cortex of all rats in the fluoride groups showed eosinophilic degeneration,loss and disordered arrangement of neurons,and the brain morphological changes in each fluoride + CS groups were significantly improved compared with those in the fluoride groups.Immunohistochemistry results showed that compared with the control group [(0.44 ± 0.09)％,(1.49 ± 0.05)％,(2.51 ± 0.54)％],the expression levels of phospho-Erk1/2 [(1.47 ±0.09)％,(1.03 ± 0.05)％],and GluR2 [(2.37 ± 0.06)％,(3.38 ± 0.12)％] in the low dose and high dose fluoride groups were increased,and the expression levels of GluR1 [(1.49 ± 0.02)％,(0.99 ± 0.19)％] were decreased (P ＜ 0.05).Western blotting results showed that compared with the control group (1.00 ± 0.12,1.76 ± 0.33),the protein levels of Erk1/2 (3.10 ± 0.76,1.99 ± 0.01) and phospho-Erk1/2 (3.27 ± 0.25,2.67 ± 0.05) in low dose and high dose fluoride groups were significantly increased (P ＜ 0.05);compared with low dose fluoride group,the protein levels of Erk1/2,and phospho-Erk1/2 (1.30 ± 0.31,2.20 ± 0.34) in low dose fluoride + CS group decreased significantly (P ＜0.05).Compared with control group (1.86 ± 0.47,1.17 ± 0.27),the protein levels of GluR1 (1.09 ± 0.26,0.61 ± 0.14) in low dose and high dose fluoride groups decreased significantly,while the protein level of GluR2 (1.99 ± 0.42,3.38 ±0.27) increased significantly (P ＜ 0.05);compared with low dose and high dose fluoride groups,the protein levels of GluR2 in low dose fluoride + CS and high dose fluoride + CS groups (1.53 ± 0.41,2.65 ± 0.32) decreased significantly (P ＜ 0.05).The protein level of phospho-Erk1/2 was negatively correlated with GluR1 protein level (r =-0.975,-0.991,P ＜ 0.05) in low dose and high dose fluoride groups,and it was positively correlated with the protein level of GluR2 (r =0.986,0.993,P ＜ 0.05).Conclusion The CNS injury caused by chronic fluorosis may be related to GluR1 and GluR2 activated Erk1/2 signaling pathway,and CS has certain protection to the injury.

Objective To evaluate the effect of emergent microsurgery in treatment of patients with hematoma-type anterior circulation ruptured aneurysm.Methods The clinical data and therapeutic effect of emergency microsurgery for 32 patients with hematoma-type anterior circulation ruptured aneurysm were analyzed retrospectively.Results Finally 32 patients underwent emergency craniotomy clipping and hematoma removal in 24 h.Among them,15 cases underwent decompressive craniectomy.One week after the operation,CTA revealed that all aneurysms were completely clipped.One patient with communicating hydrocephalus were treated with ventriculoperitoneal shunt,and 6 patients had different degrees of cerebral infarction.After 6 months of follow-up,the Glasgow outcome scale (GOS) showed that there were 5 cases of grade 5 (15.6％),12 cases of grade 4 (37.5 ％),12 cases of grade 3 (37.5％),2 cases of grade 2 (6.3％) and 1 case of grade 1 (6.3％).The prognosis satisfaction rate was 53.1％ (17/32).Conclusion Emergent microsurgery is effective in the treatment of patients with hematoma-type anterior circulation ruptured aneurysm.

Objective To evaluate the effect of emergent microsurgery in treatment of patients with hematoma-type anterior circulation ruptured aneurysm.Methods The clinical data and therapeutic effect of emergency microsurgery for 32 patients with hematoma-type anterior circulation ruptured aneurysm were analyzed retrospectively.Results Finally 32 patients underwent emergency craniotomy clipping and hematoma removal in 24 h.Among them,15 cases underwent decompressive craniectomy.One week after the operation,CTA revealed that all aneurysms were completely clipped.One patient with communicating hydrocephalus were treated with ventriculoperitoneal shunt,and 6 patients had different degrees of cerebral infarction.After 6 months of follow-up,the Glasgow outcome scale (GOS) showed that there were 5 cases of grade 5 (15.6％),12 cases of grade 4 (37.5 ％),12 cases of grade 3 (37.5％),2 cases of grade 2 (6.3％) and 1 case of grade 1 (6.3％).The prognosis satisfaction rate was 53.1％ (17/32).Conclusion Emergent microsurgery is effective in the treatment of patients with hematoma-type anterior circulation ruptured aneurysm.

Objective To evaluate the effect of electrical stimulation of the pelvic floor muscles combined with bladder training on urinary dysfunctionafter incomplete spinal cord injury.Methods Sixty-two incomplete spinal cord injury patients who had received an operation between November 2009 and December 2014 were enrolled and divided randomly into a control group (n=32) and a treatment group (n =30).Both groups were treated with conventional intermittent catheterization,while the treatment group was additionally given electrical stimulation of the pelvic floor muscles combined with bladder training.The residual urine volume was recorded before and after the treatment.Uurodynamic examinations were conducted,and the rate of successful catheter extraction and of urinary tract infection on the 15th and 30th day of treatment,were recorded and analyzed.Results All of the patients were followed-up for an average of 18.5 months.Significant improvement was observed in the residual urine volume,the maximum or average urinary flow rate,and the detrusor pressure at peak flow of both groups.However,at the end of follow-up the treatment group recorded significantly better results on all these measures than the control group.The successful catheter extraction rate of the treatment group (96.7％) was significantly higher than that of the control group and their average number of catheterization days was significantly fewer.The urinary tract infection rates on the 15th and 30th day of treatment were 16.7％ and 6.7％ in the treatment group,significantly lower than in the control group.Conclusions Electrical stimulation of the pelvic floor combined with bladder training significantly improves urination function after an operation for incomplete spinal cord injury,decreases the days of catheterization and lowers the rate of urinary tract infection.Such combined therapy is worth promoting in clinical practice.

Objective To accumulate operating experience and background data for housing mice in individually ventilated cages (IVC).Methods 5 weeks old Balb /c male mice(n =80) were allocated to 8 groups(n =10), which then housed in 5 or 10 per cage in 3 IVC systems(30,50 and 70 air changes /h, respectively) and one open-top cages (OTC) shelf for 8 weeks.Body weight was assessed at the initial date and every week .By the end of the experiment, necropsy was done and organs were separated and weighed .Excelland SPSS software statistics was made to draw the growth curve, and comparative analysis of body weight and organ coefficients was performed between the groups .Results 1.The growth curves of 5-mice per cage were better than that of 10-mice per cage.2.In the IVC groups, the curves trend and fluency of 50 air changes /h were more similar to that of 5-mice housed OTC group.3.The previously mentioned differences were statistically not significant (P >0.05).4.In the liver coefficients, there was a statistically significant difference between the 10-mice housed OTC group and 5-mice housed IVC group with 30 air changes /h(P <0.05), there wasn`t any other significant statistically difference with the organ coefficients between groups (P >0.05).Conclusions Based on the results of this study, the air change frequency on 50 times per hour and keeping 5 Balb/c mice per cage is recommended as the best condition for mouse housing in IVC .

In order to affirm the cardioactive components in Fuzi, we identified a group of aminoalcohol- diterpenoid alkaloids in Fuzi using ultra high-performance liquid chromatography coupled with electrospray ionization mass spectrometer (UPLC-ESI-MS) method. Among a total of forty-one isolated ingredients, thirteen major aminoalcohol-diterpenoid alkaloids were identified by comparing their retention times and MS spectra with those of the reference substances. Moreover, Fuzi samples from different places of origin and with different processing methods were examined and their components displayed a pattern of high similarity, though the relative abundance varies probably due to their different processing methods. Furthermore, the cardiac effect of each identified alkaloid was individually evaluated using the isolated bullfrog heart perfusion experiment. Among the thirteen aminoalcohol diterpenoid alkaloids tested, six of them significantly enhanced the amplitude rates. Taken together, we affirm that the cardioactive components in Fuzi are aminoalcohol-diterpenoid alkaloids, shedding light on future studies of the mechanisms and development of these cardioactive compounds.

Objective To analyze the risk factors of esophageal and gastric variceal bleeding (EGVB) in patients with cirrhosis.Methods A retrospective study was conducted in 638 hospitalized patients with cirrhosis from 2002 to 2009,who were divided into study group as having EGVB (n =286) and control group as not having EGVB (n =352).Differences between 2 groups were analyzed with univariate analysis and multivariate logistic regression.Results Child-pugh classification,serum albumin,prothrombin time,portal vein diameter and spleen thickness were significantly different between 2 groups (P ＜ 0.05).Univariate analysis showed that serum albumin(OR =0.944,P =0.000),prothrombin time (OR =1.067,P =0.007),portal vein diameter (OR =3.423,P =0.007) and spleen thickness (OR =1.276,P =0.007) were correlated with EGVB.Multivariate logistic regression analysis showed that serum albumin (OR =0.936,P =0.000),portal vein diameter (OR =4.098,P =0.013) and spleen thickness (OR =1.275,P =0.000) were independent risk factors for EGVB in patients with cirrhosis.Conclusion Low serum albumin level,increased portal vein diameter and spleen thickness are the risk factors for EGVB in patients with cirrhosis,which can be important predictors.To some extent,increasing serum albumin might reduce the risk of EGVB.

ObjectiveTo assess the balance between regulatory T (Treg) cells and T helper 17 (Th17) cells in patients with serofast syphilis.MethodsBlood samples were collected from 26 patients with serofast syphilis and 23 normal human controls.Flow cytometry was performed to determine the proportion of Treg and Th17 cells in peripheral blood and to quantify the expression of specific transcription factors Foxp3 and ROR-γt in CD4+ T cells of these subjects.Correlation analysis was carried out.ResultsThe proportion of Treg cells in CD4+ T cells in the patients with serofast syphilis was 33.28％ ± 11.84％,significantly higher than that in the normal controls(22.13％ ± 7.79％,P ＜ 0.01 ),while the proportion of Th17 cells was significantly lower in the patients than in the normal controls(3.17％ ± 2.32％ vs.8.87％ ± 2.00％,P ＜ 0.01 ).Enhanced expression of Foxp3 and attenuated expression of ROR-γt were observed in CD4+ T cells from the patients compared with the controls(2994.86 ± 1099.18 vs.2539.72 ± 1086.96,P ＜ 0.05; 1473.12 ± 752.20 vs.1778.34 ± 388.13,P ＜0.05).There was a negative correlation between the expression of Foxp3 and ROR-γt in CD4+ T cells from all the subjects (r =-0.481,P ＜ 0.01 ).ConclusionThe Treg/Th17 cell balance is abnormal in peripheral blood of patients with serofast syphilis.