Background The penetration of bacterial agents into the vitreous cavity is difficult because of the existence of blood-retina barrier.So conventional drug therapy is not enough effective on endophthalmitis.Drug delivery systems can decrease drug dose and reduce the drug toxicity.To construct nano controlled-release system of anti-bacterial agents is very important for the treatment of intraocular infectious diseases.Objective This study was to investigate the toxicology and intraocular pharmacoklnetics of intravitreal PNIPAAm-PEO loaded norvancomycin nanoparticles (NV-PNIPAAm-PEO) in normal rabbit eyes.Methods NV-PNIPAAm-PEO was constructed with the drug-loading rate about 22％,and then the drug gelatin solution (20 g/L) was prepared using normal saline solution.Forty-one New Zealand albino rabbits were randomized divided into experimental group and control group.20 g/L drug gelatin solution 0.1 ml was monocularly injected into the vitreous cavity in the experimental group,and the equal volume of sterilized normal saline solution was used in the control group.In 1 day,2,3,7,14,21 and 28 days after injection,ocular anterior and posterior segments were examined by slit lamp microscope and Bsonography,and electroretinogram (ERG) was recorded and the histopathological examination was performed to evaluate the biotoxicity of the drug.Norvancomycin contents in the cornea homogenate,aqueous humor,vitreous,retinochoroid homogenate were detected by high performance liquid chromatography (HPLC) system.Results The anterior and posterior segments were normal by the slit lamp microscope and B-sonography 1-28 days after injection of NV-PNIPAAm-PEO.In 7,14,21 and 28 days after injection,there were no statistically significant difference in the a-wave latency and amplitude of max-ERG between the two groups,as well as the b-wave amplitude(P＞0.05).The histopathological examination showed that the retinal structure was normal in both groups.HPLC assay showed that the norvancomycin level was gradually declined in different eye tissues from 1 day through 28 days after injection.Norvancomycin was undetectable in the cornea during the observing duration.The maximal norvancomycin content in the blood plasma was (0.34 ± 0.11) mg/L in the second day,and norvancomycin content ranged (0.08 ± 0.04)-(2.16±0.07) mg/L in the aqueous humor,(0.11 ±0.22)-(2.54 ±0.38) μg/g in the chorioretina,respectively.The drug concentration was (5.65 ± 1.14)-(406.69 ± 21.05) mg/L in the vitreous,which was higher than the minimal inhibitory concentration (MIC) to the most gram-positive bacteria.Conclusions The intravitreal injection of 22％ NV-PNIPAAm-PEO maintains the therapeutic drug concentration till 21 days in vitreous without the toxic effect on eye tissues,suggesting a great treating potential for intraocular infecting diseases.

Objective To investigate the diagnosis and operation treatment of primary intrahepatic cholangiocelhlar carcinoma (PICC), for improving the level of diagnosis and treament of PICC. Methods The clinical data of 18 cases with PICC confirmed by operation were analyzed retrospectively. Results In the early stage, no specific symptoms was found in all the 18 cases, the positive cases of AFP, CEA, CA199 and live cirrhosis were 2, 4, 3 and 4. The diagnostic rates of ultrasound examination, CT and MRI were 11.1%(2/18), 42.9%(6/14) and 45.5% (5/11 ). Seven cases were diagnosed as suffering from PICC and the others were misdiagnosed. Of all the 18 patients, 8 cases underwent radical resection and 10 cases received palliative excision. Conclusions PICC patients lack clinical features and serum tumor marker,the rato of misdiagnosis is high, but that of radical resection is low. Knowing its clinicopathological features well. Radicalresection is the best way for treatment of PICC.

Objective To observe the impact of heart catheterization on blood and organ function,and create an stable animal model.Methods Ten male Wistar rats were divided into control group undergoing sham operation and experimental group undergoing improved heart catheterization(n=5 in each group).Blood samples were obtained every day from 10 rats before and after operation,and white blood cell(WBC),alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood urea nitrogen(BUN),creatinine(Cr),creatine phosphokinase(CK) and lipopolysaccharide were detected.The pathomorphology of heart,liver and kidney in catheterized rats was observed on postoperative day 7.Results For the catheterized rats,blood cultures were negative of bacteria and the markers above were within normal range except for CK that recovered to normal value in 7 d,while the control rats had no obvious damage.Conclusion Heart catheterization causes no infection and organ function changes in rats.The animal model of heart catheterization for clinical pharmacological research is reliable.

Objective To study the safety and efficacy of ultrasound-guided puncture combined with surgical resection for liquefied cavitary hepatic alveolar echinococcosis (HAE).Methods A retrospective study was conducted on 17 patients who had liquefied cavitary HAE and were treated at the Affiliated Hospital of Qinghai University from January 2014 to August 2016.Ten patients were treated with ultrasound-guided puncture combined with surgical resection (the case group),and 7 patients were treated with resection (the control group).The basic characteristics,operation time,blood loss during operation,preoperative and postoperative laboratory tests and complications were compared between the 2 groups.Results There were no significant differences between the 2 groups in basic characteristics,such as age,gender,and lesion diameter (P ＞ 0.05).The operation time and blood loss during operation showed significant differences between the 2 groups,(308.0 ± 23.0) min (389.0 ± 95.7) min and (1 360.0 ± 182.9) ml vs.(1 607.1 ± 205.0) ml,respectively (all P ＜ 0.05).The prothrombin time (PT) after day 3 of operation and alanine aminotransferase level after day 5 of operation showed significant differences between the 2 groups,(13.8 ±0.9) s vs.(15.5 ±1.7) s and (81.9 ±20.9) U/L vs.(108.1 ±29.5) U/L,respectively (all P ＜ 0.05).There was no significant difference in postoperative complications between the 2 groups.Conclusions Ultrasound-guided puncture combined with surgical resection shortened the operation time,reduced blood loss and avoided serious complications after surgery.This treatment is efficacious and safe for liquefied cavitary HAE.

Objective To preliminarily study the use of indocyanine green in hepatic alveolar echinococcosis surgery.Methods The data of 13 patients with hepatic alveolar ecbinococcosis treated at the Affiliated Hospital of Qinghai University from May 2017 to May 2018 with laparotomy and intraoperative indocyanine green injection were retrospectively studied.Images were collected by the fluorescence acquisition system.Results There were 7 females and 6 males,with an average age of (37.9±14.7) years.The mean weight was (57.4±11.3) kg.Except for one patient of Han nationality,the rest were Tibetans.The lesions were not visualized but normal liver tissues emitted green fluorescence.One patient had a slightly enhanced fluorescence circle around the lesion.The fluorescence intensity of some areas were between normal liver tissues and the lesion,which were suspected to be the marginal zone (which needed to be confirmed by pathology).Three patients (23.1％,3/13) had small lesions on the liver surface,2 were not found by imaging examination,and 1 showed strip calcification on CT.No residual lesions in the liver (except for the microwave ablated lesions) were found after resection.No postoperative complications occurred in all the patients.Seven patients were followed up and no recurrence was found.Conclusions Fluorescence imaging of indocyanine green has the advantages of detecting small and residual lesions in surgery carried out for hepatic alveolar echinococcosis.More studies are needed to confirm the findings.

ObjectiveTo investigate the correlation between systemic immune-inflammation index (SII) and prognosis in patients with hepatic alveolar echinococcosis. MethodsA retrospective analysis was performed for the clinical data of 242 patients who were admitted to Department of Hepatopancreatobiliary Surgery, Qinghai University Affiliated Hospital, from January 2015 to December 2018 and underwent surgery for hepatic alveolar echinococcosis, and SII was calculated. The chi-square test was used for comparison of categorical data between two groups, and a Spearman correlation analysis was performed. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value of SII; the Kaplan-Meier method was used to plot survival curves and analyze overall survival time in the two groups, and the log-rank test was used for comparison of survival rates between the two groups; univariate and multivariate Cox regression analyses were used to identify the influencing factors for the prognosis of patients with hepatic alveolar echinococcosis. ResultsThe Spearman correlation analysis showed that SII was positively correlated with the postoperative fatality rate of patients with hepatic alveolar echinococcosis (r=0.267, P＜0.001). The ROC curve showed that the optimal cut-off value of SII before surgery was 758.92, and based on this, 242 patients with hepatic alveolar echinococcosis were divided into low SII (SII ≤758.92) group with 126 patients and high SII (SII ＞758.92) group with 116 patients. The low SII group had 1-, 3-, and 5-year survival rates of 98.20%, 88.47%, and 6610%, respectively, and the high SII group had 1-, 3-, and 5-year survival rates of 90.80%, 53.05%, and 27.40%, respectively. The low SII group had a cumulative survival rate of ＞50% and a mean survival time of 55.584 months (95% confidence interval［CI］: 53550-57.617), while the high SII group had a cumulative survival rate of ＜50%, a mean survival time of 39.384 months (95% CI: 35.070-43.698), and a median survival time of 43 months (95% CI: 34.694-51.306). The low SII group had a significantly better survival rate than the high SII group, and there was a significant difference in overall survival rate between the two groups (χ2=46.979, P＜005). The univariate analysis showed that SII ＞758.92 (hazard ratio ［HR］=5.907, 95% CI: 3.386-10.306, P=0.001) was an influencing factor for the overall survival time of patients with hepatic alveolar echinococcosis, and the multivariate Cox regression analysis showed that preoperative peripheral blood SII (HR=3.507, 95% CI: 1.911-6.435, P=0.001) was an independent risk factor for the overall survival rate of patients with hepatic alveolar echinococcosis. ConclusionPreoperative SII level is clearly correlated with the prognosis of patients with hepatic alveolar echinococcosis and can thus be used as a clinical indicator to evaluate the prognosis of patients. The higher the peripheral blood SII before surgery, the worse the prognosis of patients.

Objective: Sex differences have been observed in many aspects of schizophrenia, including cognitive deficits. Despite extensive research into the relationship between metabolic factors and cognitive deficits in schizophrenia, few studies have explored the potential sex difference in their association. Methods: We recruited 358 schizophrenia patients and 231 healthy controls. The participants underwent measurements of body mass index (BMI), waist circumference, blood pressure, triglycerides, high-density lipoprotein cholesterol, and fasting blood glucose. Metabolic risk factors included abdominal obesity, hypertension, hyperglycemia, and dyslipidemia. A collection of these metabolic risk factors has been defined as metabolic syndrome. These diagnoses were based on the criteria of the National Cholesterol Education Program’s Adult Treatment Panel III. Cognitive performance was measured using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). A descriptive analysis, difference analysis, and linear regression model were used to identify the metabolic risk factors for cognitive function in schizophrenia. Results: Our findings revealed sex differences in the rate of abdominal obesity and hypertension in schizophrenic patients. Additionally, we observed sex differences in the association between metabolic risk factors and cognitive impairment in schizophrenia. Specifically, hyperglycemia was associated with the immediate memory index score of RBANS in male patients, while dyslipidemia was associated with language, attention, delayed memory index scores, and RBANS total score in female patients. Conclusion Our results suggest that sex should be considered when evaluating the impact of metabolic disorders on the cognitive function of schizophrenic patients. Moreover, our study identifies hyperglycemia and dyslipidemia as potential targets for precise treatment by sex stratification, which could benefit the improvement of cognitive impairment in schizophrenic patients.

BACKGROUND:The recovery of function after spinal cord injury depends on the functional remodeling of the motor cortex.However,the anatomical evidence underlying the functional remodeling of the motor cortex is still illusive.Analyzing the anatomical changes in the motor cortex after spinal cord injury can provide new ideas and research directions for regulating functional recovery and rehabilitation after spinal cord injury. OBJECTIVE:To analyze the neural circuit structural basis of functional remodeling of the primary motor cortex after spinal cord injury. METHODS:C57BL/6J mice were randomly divided into a sham operation group and a spinal cord injury group.The adeno-associated virus vectors expressing the fusion protein of Cre recombinase were injected into C4 of mice of both groups.The adeno-associated virus vectors with Cre recombinase-inducible expression of avian sarcoma/leukosis envelope glycoprotein receptor TVA and rabies glycoprotein were injected into the primary motor cortex.Fourteen days later,a C6 dorsal hemisection mice model was established in the spinal cord injury group.The pseudotyped rabies virus was injected into the primary motor cortex of mice of both groups.After 7 days,brain samples were collected and frozen sections were made.The distribution of input neurons innervating corticospinal motor neurons in the brain was observed and analyzed quantitatively. RESULTS AND CONCLUSION:Fluorescence microscopy observation and quantitative analysis found that input neurons innervating corticospinal motor neurons of the primary motor cortex in mice of both groups were distributed in the cerebral cortex,thalamus and midbrain.Among them,in the sham operation group,the number of input neurons in the mouse cerebral cortex accounted for(84.0±3.6)%of total brain input neurons;that in the thalamus accounted for(10.6±2.3)%,and that in the midbrain accounted for(0.7±0.4)%.Direct synaptic input neurons in the spinal cord injury group accounted for(81.7±1.0)%,(13.1±0.5)%,and(1.6±0.8)%in the cerebral cortex,thalamus and midbrain,respectively.The proportion and number of primary motor cortex input neurons in the three regions of the spinal cord injury group did not differ significantly from that of the sham operation group.After spinal cord injury,the number of input neurons innervating corticospinal pyramidal motor neurons in various brain regions did not change significantly,suggesting that functional remodeling of the motor cortex after spinal cord injury may not only depend on changes in synaptic input related to injured corticospinal motor neurons,but also on transcriptional regulation changes within the injured neurons themselves.

Purpose: The poor retention and ambiguous differentiation of stem cells (SCs) within corpus cavernosum (CC) limit the cell application in erectile dysfunction (ED). Herein, the effects and mechanism of microRNA-145 (miR-145) gene modification on modulating the traits and fate of bone marrow-derived mesenchymal stem cells (BMSCs) were investigated. Materials and Methods: The effects of miR-145 on cell apoptosis, proliferation, migration, and differentiation were determined by flow cytometry, cell counting kit-8, transwell assays and myogenic induction. Then, the age-related ED rats were recruited to four groups including phosphate buffer saline, BMSC, vector-BMSC, overexpressed-miR-145-BMSC groups. After cell transplantation, the CC were harvested and prepared to demonstrate the retention and differentiation of BMSCs by immunofluorescent staining. Then, the target of miR-145 was verified by quantitative real-time polymerase chain reaction and immunohistochemical. After that, APTO-253, as an inducer of Krüppel-like factor 4 (KLF4), was introduced for rescue experiments in corpus cavernosum smooth muscle cells (CCSMCs) under the co-culture system. Results: In vitro, miR-145 inhibited the migration and apoptosis of BMSCs and promoted the differentiation of BMSCs into smooth muscle-like cells with stronger contractility. In vivo, the amount of 5-ethynyl-2′-deoxyuridine (EdU)+cells within CC was significantly enhanced and maintained in the miR-145 gene modified BMSC group. The EdU/CD31 co-staning was detected, however, no co-staining of EdU/α-actin was observed. Furthermore, miR-145, which secreted from the gene modified BMSCs, dampened the expression of KLF4. However, the effects of miR-145 on CCSMCs could be rescued by APTO-253. Conclusions Overall, miR-145 modification prolongs the retention of the transplanted BMSCs within the CC, and this effect might be attributed to the modulation of the miR-145/KLF4 axis. Consequently, our findings offer a promising and innovative strategy to enhance the local stem cell-based treatments.

Objective:To investigate the effect of hepatitis B virus (HBV) infection in patients with hepatic alveolar echinococcoisis after surgical resection and determine the differences of liver function between patients with different HBV-DNA levels.Methods:Patients were selected from January 2014 to July 2018 in the Affiliated Hospital of Qinghai University. Twenty-eight patients with hepatitis B and hepatic alveolar echinococcoisis were included in the experimental group, and 20 patients with hepatic alveolar echinococcoisis but without hepatitis B virus were included in the control group. Based on HBV-DNA level, the experimental group was divided into low-level group (HBV-DNA level<200 IU/ml, n=6), intermediate-level group (HBV-DNA level 200-20 000 IU/ml, n=15) and high level group (HBV-DNA level>20 000 IU/ml, n=7). Comparison of complications and liver function after liver resection in two groups.Univariate and multivariate logistic regression were used to analyze the influential factors of postoperative complications in patients.Comparison of postoperative liver function indexes in patients with different HBV-DNA levels. Results:In the control group, postoperative total bilirubin 10.6(8.3, 16.9) μmol/L, direct bilirubin 5.3(3.4, 10.0) μmol/L, prothrombin time 13.6(13.0, 15.8)s, and the incidence of complications 25.0%(5/20), were better than the experimental group 12.6(8.4, 46.9) μmol/L, 6.7(3.1, 26.4) μmol/L, 15.4(13.5, 18.1)s, 78.6% (22/28), the differences were statistically significant significance (all P<0.05). Multivariate logistic analysis showed that patients with HBV infection ( OR=4.593, 95% CI: 1.128-18.708) and intraoperative blood loss ≥1 000 ml ( OR=2.200, 95% CI: 1.106-4.378) were the hepatic alveolar echinococcoisis independent risk factors for postoperative complications. There were no significant differences in total bilirubin and albumin between the three groups of patients with different HBV-DNA levels ( P>0.05). Conclusion:Patients with HBV and hepatic alveolar echinococcoisis have worse liver function and are more prone to complications after surgical resection, but there is no significant difference in liver function among patients with different HBV-DNA levels.