Objective To explore the effects of polyethylene glycol-2-methoxyestradiol(PEG-2ME2/2ME2)nanoparticles on cerebral vascular endothelial RBE4 cells after oxygen glucose deprivation/reperfusion(OGD/R).Methods To construct the PEG-2ME2/2ME2 nanoparticles by solvent evaporation method,and the characterization of nanoparticles was detected by transmission electron microscope(TEM)and laser particle size analyzer;the cellular cytotoxicity of PEG-2ME2/2ME2 nanoparticles was detected by CCK-8.Using OGD/R to simulate the process of ischemia-reperfusion in vitro,to detect the cell activity by CCK-8;Western blot and immu-nofluorescence were used to detect the expression of tight junction proteins,and the barrier function of cerebrovascular endothelial cells was comprehensively evaluated by establishing blood-brain barrier(BBB)model in vitro and measuring fluorescence probe leakage;re-active oxygen species(ROS)probe was used to detect the ROS level of RBE4 cells,and Western blot was used to detect superoxide dis-mutase to identify the redox status of RBE4 cells.Results The results of TEM showed that the spherical morphology of PEG-2ME2/2ME2 nanoparticles was stable,and the results of laser particle size analyzer showed that the size of PEG-2ME2/2ME2 nanoparticles was uniform;the results of CCK-8 assay showed that the PEG-2ME2/2ME2 nanoparticles had no significant cytotoxicity to RBE4 cells with-in 5μmol/L of 2ME2;the results of CCK-8 assay showed that PEG-2ME2/2ME2 nanoparticles rescued the cellular activity of RBE4 cells after OGD/R compared to the 2ME2 alone,inhibited the downregulation of tight junction protein expression,and effectively restored the barrier function of cerebral vascular endothelial cells;the detection results of ROS probe and Western blot showed that PEG-2ME2/2ME2 nanoparticles reduced intracellular ROS levels,restored the expression of superoxide dismutase compared to the 2ME2 alone.Conclusion PEG-2ME2/2ME2 nanoparticles have uniform size and stable morphology,which can protect RBE4 cells against OGD/R,effectively restore the integrity and barrier function of the blood-brain barrier.The PEG-2ME2/2ME2 nanoparticles are expected to be-come potential drugs for the treatment of cerebrovascular endothelial barrier injury after OGD/R.

Objective:To analyze the clinical features and magnetic resonance imaging of non-malignant patients assigned to Prostate Imaging Reporting And Data System (PI-RADS) 5 score.Methods:We performed a retrospective review of 289 patients who underwent magnetic resonance ultrasound targeted combined system biopsy with PI-RADS 5 lesions in the First Affiliated Hospital of Nanjing Medical University between May 2019 and July 2021. The median age 72 (66, 77)years, median body mass index 24.4(22.3, 27.1)kg/m 2, median prostate volume (PV) 37.39(29.39, 48.86) ml, median PSA 22.24(10.91, 62.69) ng/ml, and median PSAD 0.53(0.30, 1.52)ng/ml 2 were recorded. According to the biopsy pathological results, all patients were divided into benign lesion group and prostate cancer group. PSA, PSAD, PV, and apparent diffusion coefficient (ADC) values were compared, and magnetic resonance imaging and clinical characteristics of patients with biopsy benign lesions were analyzed. Results:There were 11 cases (3.8%) with benign lesion and 278 cases (96.2%) with prostate cancer. The characters of 11 negative biopsy cases were displayed as follows: median age 69(66, 79)years, median body mass index 22.0(21.0, 25.5)kg/m 2, median PV 62.90(38.48, 71.96)ml, median PSA 5.55(2.99, 20.52)ng/ml, median PSAD 0.16(0.07, 0.24) ng/ml 2, median ADC 714.47(701.91, 801.26)×10 -6 mm 2/s, abnormal digital rectal and amination in 5 cases, smoking in 7 cases, and alcohol consumption in 4 cases. The median PV [62.90(38.48, 71.96) vs. 37.21(29.22, 47.82)ml, P<0.01], the PSA value [5.55(2.99, 20.52) vs. 23.53(11.14, 65.98)ng/ml, P<0.01], and the PSAD value [0.16(0.07, 0.24) vs. 0.58(0.31, 1.57)ng/ml 2, P<0.01] were significantly different between benign condition group and prostate carcinoma group. Benign condition group included 5 chronic prostatitis, 2 acute prostatitis (1 with focal adenocarcinoma), 2 granulomatous inflammation, and 2 tuberculous granulomatous inflammation. In 7 benign cases, PSA was less than 10 ng/ml, combined with frequent urination, urgency of urination and incontinence were founded. In 8 benign cases, the area of lesion was more than 50% of the total prostate area in the axial position and the imaging of magnetic resonance were diffused, with regular shape and uniform signal. The imaging of symmetrical distribution was in 6 cases. Conclusions:The benign condition with PI-RADS 5 lesions included chronic prostatitis, acute prostatitis, granulomatous inflammation and tuberculous granulomatous inflammation, among which prostatitis was the most common cause. The PSA value were less than 10 ng/ml in most benign cases, with symptoms such as frequent urination, urgency of urination and incontinence. The imaging of magnetic resonance were diffused, symmetrically distributed, with regular shape and uniform signal.

Objective To study the influence of GM1 on hyperbilirubinemia-induced brain injury in neonatal rats and its possible mechanism.Method A total of 120 7-day-old Sprague-Dawley (SD) rats were randomly assigned into normal control group (n =40),hyperbilirubinemia group (n =40) and GM1 group (n =40).According to the different duration of hyperbilirubinemia,each group was further assigned into 5 subgroups,6 h,12 h,24 h,48 h and 72 h group (n =8).The model of neonatal rat with hyperbilirubinemia was established injecting bilirubin solution (100 μg/g) intraperitoneally.GM1 (10 mg/kg) was injected intraperitoneally immediately after the model was established in GM1 group.Immunohistochemical method was used to determine the expression of Bax in hippocampus.TUNEL method was used to measure the neural cell apoptosis index (AI) in the brain.Result Six hours after the hyperbilirubinemia model was set up,the expression of Bax and AI in hyperbilirubinemia group and GM1 group were examined.The median of AI were 33.5％ and 15.4％ respectively and the average grey value of Bax positive cells were 157.4 ± 2.8 and 162.9 ± 2.3.Both apoptosis cells and the expression of Bax were gradually increasing,and peaked at 72 h after the model was established.The median of AI were 55.5％ and 35.5％ respectively,and the average grey value of Bax positive cells were 127.8 ± 3.6 and 141.5 ±2.7 in hyperbilirubinemia group and GM1 group.And the expressions of Bax and AI in the control group were nearly undetectable.The expression of Bax and AI in GM1 group were lower than hyperbilirubinemia group,but higher than the control group,the differences were statistically significant (P ＜ 0.001).Conclusion Brain cells apoptosis is influenced by hyperbilirubinemia-induced brain injury and Bax may be involved in the process.GM1 may reduce the brain damage by inhibiting the expression of Bax to reduce the apoptosis of the brain cells.

Objective To retrospectively analyze the prognostic factors for locoregionally recurrent early?stage extranodal nasal?type natural killer/T?cell lymphoma ( NKTCL) . Methods A total of 56 patients with early?stage extranodal nasal?type NKTCL, who had locoregional recurrence after initial treatment and then received salvage treatment from 1995 to 2014, were enrolled as subjects. The effects of salvage treatment on the overall survival ( OS) rate were analyzed after initial treatment and recurrence. Univariate and multivariate prognostic analyses were performed on the OS rate after recurrence. Results The median follow?up time was 35. 9 months after initial treatment and 14. 8 months after recurrence. The 3?year OS rate was 73% after initial treatment and 58% after recurrence. Compared with chemotherapy alone, radiotherapy?containing salvage treatment significantly improved the OS rates after initial treatment and recurrence ( P=0. 040, 0. 009 ) , and re?irradiation also significantly improved the OS rates after initial treatment and recurrence (P=0. 018, 0. 019). Most (84%) of the acute and late adverse reactions after re?irradiation were grade 1?2 ones. The univariate and multivariate analyses showed that the Karnofsky Performance Status score, radiotherapy in initial treatment, and radiotherapy in salvage treatment were influencing factors for the OS rate after recurrence. Conclusions Radiotherapy achieves improved survival and tolerable toxicities, making it indispensable in the treatment of locoregionally recurrent extranodal nasal?type NKTCL.

Objective To investigate the clinicopathologic characteristics and relevance of main and minor lesions of synchronous multiple early gastric cancers ( SMEGC) and gastric high grade intraepithelial neoplasia ( GHGIN) . Methods Thirty-two patients with SMEGC or/and GHGIN who were diagnosed and treated with endoscopic submucosal dissection in Nanjing Drum Tower Hospital from July 2012 to September 2016 were enrolled in this study. Their clinicopathologic characteristics were summed up, and the correlation between main and minor lesions on the size, location, endoscopic classification, pathologic type, invasion depth and vascular invasion were analyzed. Results Among the 32 patients, with mean age of 66. 19±7. 46 years, 90. 62％(29/32) were male, 17 cases (53. 3％) had family history of gastric cancer, 25 (78. 13％) had smoking history, and 22 ( 68. 75％) were alcohol users. There were 30 cases ( 93. 75％) and 31 cases ( 96. 88％) with mucosal atrophy and intestinal metaplasia, respectively. The size of main and minor lesions showed a positive correlation (r=0. 4167, P=0. 018). The endoscopic classification of major and minor lesions had no statistical significant consistency ( P=0. 314 ) , but the pathologic type and invasion depth between major and minor lesions demonstrated a moderate significant positive correlation ( P<0. 05 ) . The comparison of location between the main and minor lesions did not show correlation. However, it showed a significant correlation between major lesion which on the upper 1/3 of stomach and minor lesion on the lower 1/3 of stomach ( r=0. 463,P=0. 003) . Further more, when the main lesion was at posterior gastric wall, the minor lesions on lesser curvature were increased, which showed a positive correlation( r=0. 417,P=0. 009) . Conclusion Old-age male with long-term smoking and alcohol history whose lesions combined with surrounding mucosa merger atrophy and intestinal metaplasia are considered as a high risk group in patients with SMEGC or/and GHGIN. Therefore, clinicians must keep high vigilant and make carefully observations on this group of patients during endoscopic examination, and consider the correlation between main and minor lesions to avoid misdiagnosis.

Objective To analyze the clinical features,treatment methods,and prognostic factors for early primary pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma.Methods A retrospective analysis was performed on the clinical data,treatment outcomes,and survival of 32 patients with early pulmonary MALT lymphoma from March 2001 to September 2013.The median age of those patients was 56 years.Twenty-three patients had stage ⅠE disease and nine had stage Ⅱ E disease.According to the marginal zone B-cell lymphoma prognostic index (MZLPI),twenty-three patients were scored as 0 and nine as 1.Nine patients received radiotherapy,eight patients underwent surgery alone,three patients underwent surgery plus chemotherapy,and twelve patients received chemotherapy alone.The Kaplan-Meier method was adapted for calculating the OS,PFS and the log-rank test was used for survival difference analysis and univariate prognostic analysis.Results The 5-year sample size was 22.The 5-year overall survival (OS) and progression-free survival (PFS) rates were 84.5％ and 73.2％,respectively.Radiotherapy yielded an overall response rate of 100％,including a complete response rate of 66.7％ and a partial response rate of 33.3％.The univariate analysis showed that non-radiotherapy treatment was a prognostic factor for poor PFS.The patients treated with radiotherapy had significantly higher 5-year PFS rates than those treated without radiotherapy (100％ vs.63.0％,P=0.029),while there was no significant difference in 5-year OS rate between these two groups (100％ vs.78.8％,P=0.129).Age older than 60 years,an ECOG score of 2,and an MZLPI score of 1 were prognostic factors for poor PFS (P=0.041,0.018,and 0.044) and OS (P=0.001,0.001,and 0.003).Conclusions The prognostic factors for early pulmonary MALT lymphoma include age,ECOG score,and MZLPI score.Low-dose involved-field radiotherapy (24-30 Gy) can improve local control and survival.

OBJECTIVE: To explore the effect of ROCK inhibitor Y-27632 on the matrix metalloproteinase 2 and 9 (MMP2 and MMP9) gene expression and activity in tumor necrosis factor α (TNF-α)-treated human umbilical vein endothelial cell (HUVEC).
 METHODS: HHUVEC was divided into 3 groups, a control group, a TNF-α group, and a TNF-α plus Y-27632 group. The expressions of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), MMP2 and MMP9 were examined by real-time PCR. The MMP2/9 activity was measured by gelatin zymography.
 RESULTS: Compared to the control group, the mRNA expressions of ICAM-1, VCAM-1, MMP2 and MMP9 were increased TNF-α-treated cells, which were suppressed by ROCK inhibitor (P<0.01). The MMP2/9 activity was elevated in TNF-α-treated cells, which was reversed by ROCK inhibitor (P<0.05).
 CONCLUSION ROCK inhibitor can suppress TNF-α-induced inflammation in endothelial cells through down-regulation of MMP2/9.
Amides ; Cells, Cultured ; Down-Regulation ; Endothelial Cells ; Humans ; Intercellular Adhesion Molecule-1 ; Matrix Metalloproteinase 2 ; Matrix Metalloproteinase 9 ; Pyridines ; Signal Transduction ; Tumor Necrosis Factor-alpha ; Umbilical Veins ; Vascular Cell Adhesion Molecule-1 ; rho-Associated Kinases

OBJECTIVE: To evaluate the prescription behavior for outpatients in primary health care institutions of Yiyang and to provide scientific basis for promoting the rational use of drugs.
 METHODS: A multi-stage random sampling method was conducted in 21 primary health care institutions from Yiyang. Fifteen prescriptions were randomly selected in every month from each institution and a total of 3780 prescriptions were eventually collected in a year.
 RESULTS: Both the number of drugs and percentage of injection in a prescription were greater than the international standards. Children were more likely to be prescribed by multiple prescriptions, antibiotics prescriptions, hormones and injections prescriptions. The utilization of essential drug was more frequent in female. Antibiotics and hormones were more frequently used in summer and autumn season. Polypharmacy, antibiotics, injections and essential drugs were more frequently used in hospitals of small town. The skin and subcutaneous tissue diseases were often treated with multiple prescriptions, while the respiratory diseases were often treated with antibiotics, hormones and injections. Most primary health care institutions were at the upper limit of rational drug use.
 CONCLUSION The usage of prescription drug in most primary health care is rational, but some still surpass international standards. Thus, primary health care physicians should strictly control their prescriptions behavior.
Anti-Bacterial Agents ; Drug Prescriptions ; statistics & numerical data ; Drug Utilization Review ; Drugs, Essential ; Hormones ; Humans ; Injections ; Outpatients ; Practice Patterns, Physicians' ; Primary Health Care

Background: Nasal?type extranodal natural killer/T?cell lymphoma (ENKTCL) originates primarily in the nasal cavity or extra?nasal sites within the upper aerodigestive tract. However, it is unclear whether the primary site can serve as an independent prognostic factor or whether the varying clinical outcomes observed with different primary sites can be attributed merely to their propensities of regional lymph node involvement. The aim of this study was to investigate the prognostic implications of the primary site and regional lymph node involvement in patients with early?stage nasal?type ENKTCL. Methods: To develop a nomogram, we reviewed the clinical data of 215 consecutively diagnosed patients with early?stage nasal?type ENKTCL who were treated in Sun Yat?sen University Cancer Center with chemotherapy and radiotherapy between 2000 and 2011. The predictive accuracy and discriminative ability of the nomogram were determined using a concordance index (C?index) and calibration curve. Results: The 5?year overall survival (OS) and progression?free survival (PFS) rates of patients with nasal ENKTCL were higher than those of patients with extra?nasal ENKTCL (OS: 68.2% vs. 46.0%, P = 0.030; PFS: 53.4% vs. 26.6%, P = 0.010).The 5?year OS and PFS rates of patients with Ann Arbor stage IE ENKTCL were higher than those of patients with Ann Arbor stage IIE ENKTCL (OS: 66.3% vs. 59.2%, P = 0.003; PFS: 51.4% vs. 40.3%, P = 0.009). Multivariate analysisshowed that age >60 years, ECOG performance status score nasal primary site, and regional lymph node involvement were significantly associated with lower 5?year OS rate;≥2, elevated lactate dehydrogenase (LDH) level, extra?age >60 years, elevated LDH level, extra?nasal primary site, and regional lymph node involvement were significantly associated with lower 5?year PFS rate. The nomogram included the primary site and regional lymph node involve?ment based on multivariate analysis. The calibration curve showed good agreement between the predicted and actual 5?year OS and PFS rates, and the C?indexes of the nomogram for the OS and PFS rates were 0.697 and 0.634, respectively. Conclusions: The primary site and regional lymph node involvement are independent prognostic factors for early?stage ENKTCL treated with chemotherapy followed by definitive radiotherapy.