Vision is closely tied to quality of life. Traditional drug delivery routes for clinical therapy of key ocular diseases, such as glaucoma, are topical and systemic administrations, which are less invasive but often face some physiological barriers such as tear film turnover, corneal penetration, and blood-ocular barrier. These barriers may limit penetration and distribution of ophthalmic drugs, resulting in limitation of information about pharmacokinetic characteristics of drugs in human eye. To address this, some ocular based compartment models, including classical ocular compartmental model and physiologically based pharmacokinetic(PBPK)model, have been established to illustrate dispositions of drugs in eyes. For classical ocular compartmental model, cornea or vitreous humor serves as central compartment and other ocular tissues are identified as peripheral compartments. The PBPK model, incorporating dynamic factors such as changes in ocular blood flow, effects of transporters, blood-ocular barrier, may characterize complex ocular physiology structure and dispositions of drugs in eyes. These models can contribute to development of new ophthalmic drugs and therapy strategies for ocular diseases. Here, the characteristics of drugs in eye following administrations via various routes, general ocular compartmental model and PBPK model as well as their applications in the development of new ophthalmic drugs and drug regimen for ocular diseases are reviened.

Objective To observe the value of CT radiomics nomogram for predicting Ki-67 expression of thymus epithelial tumors.Methods Totally 163 patients with thymus epithelial tumor,including 114 patients in training set and 49 patients in validation set were retrospectively enrolled.The patients were further divided into low expression(＜50％)and high expression(≥50％)subgroups according to Ki-67 index.Multivariate logistic regression analysis was performed to screen independent predicting factors of Ki-67 expression in thymus epithelial tumors,and clinical-CT model was constructed.The optimal radiomics features were extracted and screened based on chest plain and venous phase enhanced CT images,respectively.Then radiomics modelplain and radiomics modelenhanced were constructed,and Radscoreplain and Radscoreenhanced were calculated,respectively.The nomogram model was constructed based on clinical-CT model,Radscoreplain and Radscoreenhanced.Receiver operating characteristic curves were drawn,and the area under the curves(AUC)were calculated to evaluate the efficacy of each model for predicting Ki-67 expression of thymus epithelial tumors.Results Patient's gender and enhanced CT value of lesion were both independent predicting factors of Ki-67 expression in thymus epithelial tumors(both P＜0.05).The AUC of clinical-CT model,radiomics modelplain,radiomics modelenhanced and nomogram model for predicting Ki-67 expression was 0.736,0.814,0.836 and 0.857 in training set,which was 0.746,0.746,0.750 and 0.799 in validation set,respectively.Conclusion CT radiomics nomogram could be used to predict Ki-6 7 expression of thymus epithelial tumors.

Objective:To study the relationship between cystathionine β-synthase (CBS) and cystathionine γ-lyase (CTH) genes-related signaling pathways in liver cancer cells.Methods:We conducted a correlation analysis between the clinical features of CBS and CTH gene expression by mining the GEO (Gene Expression Omnibus) and TCGA (The Cancer Genome Atlas) databases of liver cancer. Additionally, liver cancer cell lines were verified by immunoblotting.Results:CBS and CTH expressions were significantly lower in tumors than in non-tumors ( P < 0.05). COX regression result showed that CBS was an independent risk factor for the poor prognosis of liver cancer cells ( HR=0.65, P = 0.02). A univariate logistic regression analysis was performed on the different tumor stages focusing on the CBS gene, which showed that TNM stage II verses I ( P = 0.01, OR=0.50), stage III verses I ( P = 0.03, OR=0.56), T stage T2 verses T1 ( P < 0.01, OR=0.43), and T3 stage verses T1 ( P = 0.02, OR=0.54) were significantly lower in liver cancer. TNM stage III verses I ( P = 0.01, OR=0.50), Edmondson stage II verses I ( P = 0.03, OR=0.48), stage III verses stage I ( P < 0.01, OR=0.30), stage IV verses I ( P = 0.03, OR=0.22), and T stage T3 verses T1( P = 0.03, OR=0.22) of the CTH gene expressions were significantly lower in liver cancer. GSEA enrichment analysis result revealed that the signaling pathway most correlated with the expression of CTH and CBS genes in liver cancer cells was cytochrome P450 (CYP450) (FDR Q < 0.01, FWER P < 0.01). Western blot results showed that the expression of the CTH downstream protein CSE was reduced in HCC cell lines such as HLE and Hep3B cells compared with the human immortalized liver cell line HL-7702. Conclusion:CBS and CTH gene expressions are lower in tumor tissue than in normal tissue groups. The CBS gene is an independent risk factor for poor prognosis in stem cell carcinoma. The cytochrome P450 is the signaling pathway most closely related to the CBS and CTH genes.

In order to improve the yield and simplify the operation, the synthesizing process of JAK3 inhibitor tofacitinib citrate was improved based on the analysis of the methods previously published.Using 2, 4-dichloro-7H-pyrrolo [2, 3-d] pyrimidine and (3R, 4R)-1-benzyl-N, 4-dimethylpiperidin-3-amine dihydrochloride as starting materials, tofacitinib citrate was obtained through four steps of nucleophilic substitution, catalytic transfer hydrogenation, cyanide acetylation and citrate salt, and its crystal form was consistent with the original research.After optimization, the yield was better than those reported in literature, and the mild reaction conditions were suitable for industrial production.

Objective:To investigate the current status of medical record coders and their resignation tendency, and put forward suggestions for the training and team building of medical record coders.Methods:From April to May 2020, a questionnaire survey was conducted among the medical record coders in 27 DRG payment pilot hospitals in Anyang, Henan. Statistical analysis was conducted on the profile of the medical case department, basic personal information, professional quality, job satisfaction and resignation intention. Kendall coefficient was used to analyze the factors related to the resignation intention.Results:There were 98 coders in the surveyed hospitals, including 43 full-time coders and 55 part-time coders. Eighty-three valid questionnaires were recovered, and the effective recovery rate was 84.7%. Among them, 29(34.9%) had education level of junior college or below, 51(61.4%) had junior title or below, 15(18.1%) had medical information or case management as their major, 29(34.9%) coders had not obtained a coding certificate, 31(37.3%) were dissatisfied with the salary system, and 14(16.9%) had a tendency to leave. The medical record coders with lower professional titles, coding certificates and lower salary satisfaction were more likely to have the intention of resignation.Conclusions:Medical record coders in Anyang were challenged with such problems as shortage of manpower, low percentage of coding certificate holders and low salary satisfaction. Title, code certificate issuance and salary satisfaction were correlated with their resignation intention. Hospital managers should strengthen the importance of medical record coding and coders, and establish a reasonable salary, title evaluation and performance incentive system, so as to improve the attractiveness of coder position.

Objective:To evaluate the classification of petroclival meningiomas(PCM), proposed selection of microsurgical approach and therapeutic outcomes.Methods:Retrospectively analyzed clinical data of 179 cases of PCM from Department of Neurosurgery, Xiangya Hospital, Central South University between January 2011 and November 2020. There were 28 males and 151 females with an age of(49.9±10.2) years(range: 22 to 75 years) and the tumor size of(44.8±10.3)mm(range: 15 to 80 mm). The mean duration of symptom ( M( Q R)) was 18.0(40.6)months(range:1 week to 320 months) and the mean preoperative Karnofsky performance scale(KPS) was 78.6±13.3(range: 40 to 100). The PCM were classified into 5 types according to the difference in the origin of dural attachment, involvement of adjacent structures and growth patterns through preoperative MRI. The surgical approaches were selected based on the proposed classification, and the clinical characteristics, surgical record, and follow-up data of each type were reviewed. Results:The PCM were divided into clivus type(CV, 4 cases), petroclival type(PC, 60 cases), petroclivosphenoidal type(PC-S, 62 cases), sphenopetroclival type with 2 subtypes(S-PC, 50 cases) and central skull base type(CSB, 3 cases). All of 176 cases were obtained microsurgical treatment except CSB type. The gross total resection reached in 124 cases(70.5%) with 112 cases of retrosigmoid approach(RSA), 27 cases of subtemporal transtentorial transpetrosal approach, 13 cases of pretemporal trancavernous anterior transpetrosal approach(PTCA), 12 cases of extended pterional transtentorial approach(EPTA) and presigmoid combined supra-infratentorial approach, respectively. The RSA could be adopted in both of CV type and PC type and most of PC-S type(71.0%). S-PC subtype Ⅰ and subtype Ⅱ were mainly underwent EPTA(40.8%) and PTCA(52.2%), respectively. Seventy-two cases(40.9%) gained new neurological dysfunctions mainly with the cranial nerve paralysis. The postoperative morbidity and complications were recovered or improved with conservative and positive symptomatic and supportive treatment. There was no intraoperative and postoperative death case. One hundred and sixty four cases(93.2%) of operative patients were followed with the duration of 24(48)months(range:3 to 108 months). Tumor recurrence and progress were identified in 14 cases(10.4%) and 14 cases(28.6%), respectively. Compared with postoperative neurological status, 89 patients(54.3%) had improved and 38 patients(23.2%) were still suffering various degrees of neurological dysfunctions during the follow-up. The recent KPS was 84.2±11.4(range: 50 to 100) without statistical difference from preoperative KPS ( t=-1.356, P=0.125). As for each type, there were statistically significant differences in brain stem edema (χ 2=3.482, P=0.038), gross total resection (χ 2=9.127, P=0.001), surgical duration( F=8.954, P=0.013), postoperative length of stay( F=3.652, P=0.025), postoperative complications (χ 2=1.550, P=0.024), postoperative KPS( F=2.856, P=0.042) and tumor recurrence/progress (χ 2=4.824, P=0.013). Conclusion:The precise and comprehensive classification of PCM and specific individual treatment strategy are benefit to evaluate the diverse clinical prognosis, choose optimal surgical approaches, elevate gross total resection, diminish neurological dysfunctions and restraint tumor recurrence, so as to improve the quality of life for patients.

Objective:To evaluate the classification of petroclival meningiomas(PCM), proposed selection of microsurgical approach and therapeutic outcomes.Methods:Retrospectively analyzed clinical data of 179 cases of PCM from Department of Neurosurgery, Xiangya Hospital, Central South University between January 2011 and November 2020. There were 28 males and 151 females with an age of(49.9±10.2) years(range: 22 to 75 years) and the tumor size of(44.8±10.3)mm(range: 15 to 80 mm). The mean duration of symptom ( M( Q R)) was 18.0(40.6)months(range:1 week to 320 months) and the mean preoperative Karnofsky performance scale(KPS) was 78.6±13.3(range: 40 to 100). The PCM were classified into 5 types according to the difference in the origin of dural attachment, involvement of adjacent structures and growth patterns through preoperative MRI. The surgical approaches were selected based on the proposed classification, and the clinical characteristics, surgical record, and follow-up data of each type were reviewed. Results:The PCM were divided into clivus type(CV, 4 cases), petroclival type(PC, 60 cases), petroclivosphenoidal type(PC-S, 62 cases), sphenopetroclival type with 2 subtypes(S-PC, 50 cases) and central skull base type(CSB, 3 cases). All of 176 cases were obtained microsurgical treatment except CSB type. The gross total resection reached in 124 cases(70.5%) with 112 cases of retrosigmoid approach(RSA), 27 cases of subtemporal transtentorial transpetrosal approach, 13 cases of pretemporal trancavernous anterior transpetrosal approach(PTCA), 12 cases of extended pterional transtentorial approach(EPTA) and presigmoid combined supra-infratentorial approach, respectively. The RSA could be adopted in both of CV type and PC type and most of PC-S type(71.0%). S-PC subtype Ⅰ and subtype Ⅱ were mainly underwent EPTA(40.8%) and PTCA(52.2%), respectively. Seventy-two cases(40.9%) gained new neurological dysfunctions mainly with the cranial nerve paralysis. The postoperative morbidity and complications were recovered or improved with conservative and positive symptomatic and supportive treatment. There was no intraoperative and postoperative death case. One hundred and sixty four cases(93.2%) of operative patients were followed with the duration of 24(48)months(range:3 to 108 months). Tumor recurrence and progress were identified in 14 cases(10.4%) and 14 cases(28.6%), respectively. Compared with postoperative neurological status, 89 patients(54.3%) had improved and 38 patients(23.2%) were still suffering various degrees of neurological dysfunctions during the follow-up. The recent KPS was 84.2±11.4(range: 50 to 100) without statistical difference from preoperative KPS ( t=-1.356, P=0.125). As for each type, there were statistically significant differences in brain stem edema (χ 2=3.482, P=0.038), gross total resection (χ 2=9.127, P=0.001), surgical duration( F=8.954, P=0.013), postoperative length of stay( F=3.652, P=0.025), postoperative complications (χ 2=1.550, P=0.024), postoperative KPS( F=2.856, P=0.042) and tumor recurrence/progress (χ 2=4.824, P=0.013). Conclusion:The precise and comprehensive classification of PCM and specific individual treatment strategy are benefit to evaluate the diverse clinical prognosis, choose optimal surgical approaches, elevate gross total resection, diminish neurological dysfunctions and restraint tumor recurrence, so as to improve the quality of life for patients.

Objective: To explore the risk factors for hyperlipidemic acute pancreatitis (HTGP). Methods: The clincial data of 169 HTGP cases admitted in Capital Medical University Attached Xuanwu Hospital from September 2012 to December 2018 were retrospectively analyzed. Patients were divided into severe HTGP group (n=63) and mild or moderately severe HTGP group (n=106). Clinical data were compared between two groups and variables with statistically significance and clinical values were chosen and included for binary logistic regression to explore the independent risk factors for severe HTGP. Results: Severe HTGP patients′ heart beat and respiratory rate were significantly higher than moderately severe or mild HTGP cases, while the percentage of patients with previous AP history in severe HTGP group was obviously lower than moderately severe or mild HTGP cases. There were no statistically significant differences on other baseline data and previous history. Severe HTGP patients had significantly higher white blood cell, mean platelet volume, erythrocyte sedimentation rate, total protein, C-reaction protein on first day, C-reaction protein on third day, amylase, lipase, triacylglycerol, prothrombin time, D-dimer, fibrinogen, CTSI, APACHEⅡ score and Ranson score than those in moderately severe or mild HTGP cases; the lymphocyte count, albumin-globulin ratio, uric acid, apolipoprotein-A1, blood calcium, prothrombin activity were obviously lower than those in moderately severe or mild HTGP cases; and all the differences were statistically significant. Triglyceride and CRP on the first and third day, CTSI, APACHEⅡ score and Ranson score were included for binary logistic regression model, and the results showed that triglyceride on the first day (OR=1.08, 95% CI 1.02-1.14, P=0.01), C-reaction protein on the third day (OR=1.01, 95% CI 1.00-1.01, P<0.01), CTSI score(OR=1.51, 95% CI 1.06-2.13, P=0.02), APACHEⅡ score(OR=1.22, 95% CI 1.07-1.40, P<0.01)were the risk factors of severe HTGP, while triglyceride on the third day (OR=0.8, 95% CI 0.69-0.91, P=0.00)was the protective factor of severe HTGP. Conclusions Triglyceride on the first day, C-reaction protein on the third day, CTSI score and APACHEⅡ score were the risk factors of severe HTGP, which deserve special attention.

ETS-1 is a transcription factor that is a member of the E26 transformation-specific (ETS) family. Galanin receptor 2 (GalR2), a subtype of receptors of the neuropeptide galanin, has been shown to have an antidepressant-like effect after activation in rodents. Our previous study has shown that overexpression of ETS-1 increases the expression of GalR2 in PC12 phaeochromocytoma cells. However, whether ETS-1 has an antidepressant-like effect is still unclear. In this study, we found that chronic mild stress (CMS) decreased the expression of both ETS-1 and GalR2 in the ventral hippocampus of rats. Meanwhile, we demonstrated that overexpression of ETS-1 increased the expression of GalR2 in primary hippocampal neurons. Importantly, we showed that overexpression of ETS-1 in the ventral hippocampus counteracted the depression-like behaviors of CMS rats. Furthermore, we found that overexpression of ETS-1 increased the level of downstream phosphorylated extracellular signal-regulated protein kinases 1 and 2 (p-ERK1/2) of GalR2 in the ventral hippocampus of CMS rats. Taken together, our findings suggest that ETS-1 has an antidepressant-like effect in rats, which might be mediated by increasing the level of GalR2 and its downstream p-ERK1/2 in the ventral hippocampus.

Objective: To explore the correlation of apolipoprotein levels with the severity of hyperlipidemic acute pancreatitis. Methods: Clinical date of 169 patients with hyperlipidemic acute pancreatitis (AP) admitted in our hospital from September 2012 to December 2018 were retrospectively analyzed. Apolipoprotein (Apo) AⅠ, Apo B, Apo B/Apo AⅠ ratio were compared among hyperlipidemic AP patients with different severity. Pearson correlation analysis was conducted to explore the correlation of Apo AⅠ, Apo B, Apo B/Apo AⅠ with Atlanta classification, CTSI score, APACHE-Ⅱscore, RANSON score and C-reaction protein level. The optimal cut-off point of apolipoproteins for predict the severe hyperlipidemic AP was determined by ROC curve. The local and systemic complications of pancreatitis patients with different Apo levels were compared with chi-square test. Results: There were no significant differences in general conditions among patients with severe AP (SAP), median-severe AP (MSAP) and mild AP (MAP). The Apo AⅠ levels of SAP [ (0.89±0.36) g/L] were lower than those of MSAP [(1.07±0.40)g/L, t=2.07, P=0.04] and MAP [(1.14±0.70) g/L, t=2.55, P=0.01]. Apo AⅠ was negatively correlated with Atlanta classification (r=-0.24, P<0.01). The optimal cut-off point of Apo A Ⅰ to predict SAP was 0.8 g/L, with the sensitivity of 0.877, specificity of 0.674 and Youden index of 0.55. The area under curve (AUC) was 0.623 (P<0.01). The proportions of SAP patients [52.94% (27/51) vs. 30.51%(36/118), χ²=7.66, P<0.01] and the patients of APACHE-Ⅱscore>8 [70.59%(36/51) vs. 55.08%(65/118), χ²=3.56, P=0.04] in patients with Apo AⅠ≤0.8 g/L were higher than those in patients with Apo AⅠ>0.8 g/L. Conclusion Apolipoprotein AⅠ level is negatively correlated with Atlanta classification and Apo AⅠ level can be used to predict severity of hyperlipidemic acute pancreatitis.