OBJECTIVE To explore the mechanism of improvement effect of Chanbao zhichuang suppository （CBZCS） on hemorrhoids in rats through network pharmacology and metabolomics. METHODS A hemorrhoid model was established by subcutaneous injection of rhododendron oil to induce anal swelling. SD rats were divided into blank group （NC group， 0.32 g/kg vaseline）， model group （Model group， 0.32 g/kg vaseline）， CBZCS low-， medium-， and high-dose groups （CBZCS-L， CBZCS- M， CBZCS-H groups， with dosages of 0.16， 0.32， and 0.64 g/kg respectively）， and Mayinglong musk hemorrhoids suppository group （Positive group， 0.32 g/kg）， with 9 rats in each group. Anal administration was performed at 6， 12， 24， 48， and 72 hours after modeling. After the last administration， the pathological changes of the anal tissues in rats were observed， and the serum levels of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in rats were detected. Differential metabolite analysis and enrichment analysis were conducted by metabolomics methods， and the target proteins of CBZCS in treating hemorrhoids were obtained by network pharmacology. The core metabolic pathways were screened by interaction and enrichment analysis of differential metabolites and proteins， and the core proteins were experimentally verified. RESULTS Compared with the NC group， the anal tissues of the Model group showed obvious lesions， and the levels of IL-6 and TNF- α in the serum were significantly increased （P＜0.05）； compared with the Model group， the pathological damage of the anal tissues in the treatment groups was alleviated to varying degrees， and serum levels of IL-6 in CBZCS-H group， CBZCS-M group， and Positive group as well as serum levels of TNF-α in CBZCS-H group were significantly reduced （P＜0.05）. The metabolomics results showed that 34 differential metabolites were screened from the anal tissues of rats， and 22 of them showed a return after CBZCS administration. The differential metabolites mainly enriched in arachidonic acid metabolism， histidine metabolism， and glycerophospholipid metabolism. Through the network pharmacology， 138 intersection genes of CBZCS against hemorrhoids were determined. The analysis results showed that differential metabolites and target proteins were mainly enriched in the arachidonic acid metabolism pathway， and the regulation of this pathway might be related to cyclooxygenase-2 （COX-2）， Myc proto-oncogene protein （c-MYC）， cytochrome P450 1B1 （CYP1B1）， interleukin-1β （IL-1β）， and IL-6 protein expression. The experimental verification results showed that the expression levels of key proteins （COX-2， c-MYC， CYP1B1， IL-6， IL-1β） in the anal tissues of the Model group were significantly higher than those in the NC group （P＜0.05）， and the levels of the above proteins in the anal tissues of CBZCS-H group and Positive group were significantly lower than those in the Model group （P＜0.05）. CONCLUSIONS The mechanism of CBZCS in treating hemorrhoids may be to inhibit the expression of COX-2， c-MYC and CYP1B1 proteins， thereby inhibiting arachidonic acid metabolism and reducing the release of inflammatory factors IL-6 and IL-1β.

Objective:To investigate whether vestibular-evoked myogenic potentials (VEMP) can be used to assess brainstem and its supplementary diagnostic value in patients with early-stage Parkinson′s disease (PD).Methods:A total of 123 patients with early-stage PD (PD group) diagnosed in the Department of Neurology of the Second Affiliated Hospital of Soochow University from January 2019 to January 2022 were consecutively enrolled, and 122 healthy controls (healthy control group) were included. Cervical VEMP (cVEMP) and ocular VEMP (oVEMP) examinations were performed on all subjects. VEMP parameters between the 2 groups were compared, and receiver operating characteristic curve was used to evaluate the auxiliary diagnostic efficacy of VEMP for early-stage PD. Correlations between VEMP parameters and motor and non-motor symptoms such as autonomic dysfunction were analyzed in the PD group using Spearman correlation analysis.Results:Bilateral latencies of cVEMP [left P1 latency (Lp13): 19.0 (16.4, 20.9) ms vs 13.1(12.0, 14.2) ms, Z=-11.18, left N1 latency (Ln23): 27.4 (24.6, 29.9) ms vs 21.2 (19.8, 23.0) ms, Z=-10.14; right P1 latency (Rp13): 18.8 (16.2, 20.9) ms vs 13.0 (11.7, 14.1) ms, Z=-10.84, right N1 latency (Rn23): 27.7 (24.3, 29.7) ms vs 21.1 (19.6, 22.9) ms, Z=-10.50] and bilateral latencies of oVEMP [left N1 latency (Ln10): 12.7 (10.7, 14.4) ms vs 10.4 (9.7, 11.4) ms, Z=-8.02, left P1 latency (Lp15): 16.5 (15.1, 18.3) ms vs 14.5 (13.4, 15.3) ms, Z=-7.96; right N1 latency (Rn10): 12.8 (11.4, 14.0) ms vs 10.5 (9.7, 11.5) ms, Z=-8.85, right P1 latency (Rp15): 16.7 (15.3, 18.3) ms vs 14.4 (13.3, 15.1) ms, Z=-9.39] of the PD group significantly prolonged compared to the healthy control group (all P<0.001). Compared to the healthy control group, the area under the curve (AUC) values of Lp13, Ln23, Rp13 and Rn23 of cVEMP in the PD group were all greater than 0.7, and the AUC values of Lp13 and Rp13 in the PD group were greater than 0.9 (all P<0.001); the AUC values of Ln10, Lp15, Rn10, and Rp15 of oVEMP in the PD group were all greater than 0.7 (all P<0.001). The Rn10-p15 corrected amplitude in PD patients was positively correlated with levodopa equivalent dose ( r=0.21, P=0.020). The Rn10 in PD patients was positively correlated with the Non-Motor Symptoms Questionnaire scores ( r=0.21, P=0.023). The Lp13-n23 corrected amplitude was negatively correlated with the Scale for Outcomes in Parkinson′s Disease-Autonomic scores ( r=-0.20, P=0.023). There was no significant correlation between VEMP parameters and Unified Parkinson′s Disease Rating Scale part Ⅲ score ( P>0.05). Conclusion:VEMP, especially cVEMP, as a non-invasive neuroelectrophysiological index, is an objective marker for brainstem damage and could be used for screening early-stage PD patients.

Objective:To explore the feasibility of the clinical implementation of intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) plans with 6MV photon on two Elekta Linacs (Versa HD and Synergy) after beam matching.Methods:The images of 12 patients with nasopharyngeal carcinoma, central lung cancer and prostate cancer were randomly selected, and the IMRT and VMAT plans were designed. Two different dose tools of ionization chamber and three-dimensional detector ArcCheck were used to verify the individualized radiation treatment of 6MV photon beams on two Linacs and compare the differences.Results:The deviations between the doses of two Linacs (Versa HD and Synergy) measured by the ion chamber and treatment planning system were (0.32±1.32)% and (0.54±1.29)%. The differences of all plans were within the range of ±3%, and the deviations of the point dose between two Linacs were within the range of ±2% with no statistical significance (both P>0.05). The γ analysis of verification using ArcCheck showed that the passing rates of all plans under the 2mm/3% and 3mm/3% with 10% threshold conditions were over 95%, respectively. The average differences between two Linacs were 0.19%(2mm/3%) and 0.09%(3mm/3%). Conclusions:The results of performing IMRT/VMAT plans on two Linacs meet the clinical requirements and the differences between two Linacs are small. Hence, the same plans can be implemented interchangeably on different Linacs.

Objective: To study the dosimetric characteristics and plan quality of PTV-based intensity modulated proton radiotherapy (IMPT) and volumetric-modulated arc therapy (VMAT) plans for prostate cancer, so as to provide a reference for clinical application. Methods: A total of 10 prostate cancer cases were included in this retrospective study. IMPT and RapidArc plans were designed by RayStation and Eclipse TPS based on PTV, respectively. For each case, IMPT plans were generated using multiple field optimization (MFO) technique with two parallel-opposed lateral fields, whereas RapidArc plans were generated using double-arc technique (two full arcs). Final dose calculation of IMPT was conducted by pencil beam(PB) and Monte Carlo (MC) algorithm, respectively, with adopted data model from the pencil beam scanning (PBS) proton therapy system of IBA Protues Plus(IBA Group, Belgium); The data model originated from the linear accelerator of Varian Clinac iX (Varian Medical Systems, America) was used for RapidArc plans. Dosimetric parameters of DVH and dose distribution were used to compare the dose differences in targets and organs at risk (OARs) between these two treatment techniques. Results: For targets, HIs of PB-IMPT and MC-IMPT were slightly better than that of RapidArc , but CI of IMPT was slightly lower than that of RapidArc; D_1% of PB-IMPT was significantly better than those of MC-IMPT and RapidArc (Z=-2.805, -2.803, P<0.05). PB-IMPT and MC-IMPT achieved better protection than RapidArc on rectum V₃₀(Z=-2.191, -1.988, P<0.05)and D_mean(Z=-2.599, -2.497, P<0.05), bladder V₃₀(Z=-2.701, -2.701, P<0.05), V₄₀(Z=-2.395, -2.395, P<0.05)and D_mean(Z=-2.701, -2.701, P<0.05). There was no significant difference between PB-IMPT and MC-IMPT plans for prostate cancer, except for the D_1% [(73.86±67.34) Gy vs.(75.45±2.01) Gy] (RBE) and HI [(0.040±0.010) vs. (0.058±0.020)] of the target. Conclusions Both techniques can meet the clinical requirements, but IMPT showed significant dosimetric advantages compared with RapidArch by reducing the dose to OARs and improving the plan quality.

Objective To investigate the application of preoperative autologous blood donation (PABD) in selective operation.Methods Retrospective investigations and analysis were carried out in clinical datas of 1 026 patients of PABD in selective operation from January 2016 to may 2017,comparing with those who had not performed PABD in the same time.Results ①The surgeries of PABD were mainly neurosurgery,urology,orthopedics,gynecology and hepatobiliary surgery,respectively,which accounted for 5.97％,4.90％,3.78％,3.76％ and 3.55％ of the patients in the same period;②The rate of transfusion of allogeneic red blood cells of selective operation in PABD group of neurosurgery,urology,orthopedics,gynecology and hepatobiliary surgery were 5.66％,2.51％,4.89％,0 and 4.88％,respetively,while not performed PABD group were 25.46％,28.58％,24.77％,10.62％ and 17.54％,respetively;③The rate of transfusion of the group of hemoglobin (Hb)＜ 120 g/L is significantly higher than those Hb is (120-129.9) g/L,(130-139.9)g/L and ≥ 140 g/L(7.65％vs 2.44％,3.66％ and 2.70％,P＞0.05).Conclusion ①PABD is mainly carried out in neurosurgery,urology,orthopedics,gynecology and hepatobiliary surgery;②The group of Hb＜ 120 g/L has a high rate transfusion of allogeneic erythrocyte in selective operations;③Only the PABD is improved can patients make benefit from it.

Purpose To analyze the imaging manifestations of solitary fibrous tumors (SFT) so as to improve its diagnosis. Materials and Methods The CT and MRI findings of 24 patients with SFT confirmed pathologically were analyzed retrospectively and compared respectively with their pathological results in terms of lesion's location, size, shape, density (signal), type of enhancement and relationship with the surrounding tissues. Seven patients underwent MRI scan, 5 were with enhanced scan; 17 patients were carried out plain CT scan and 11 were with enhanced CT scan. Results The lesions in the 23 cases were solid and 1 was solid and cystic. Through the imaging diagnosis, 20 cases were diagnosed as benign tumors, 2 cases were diagnosed as malignancies, and 2 benign tumors were misdiagnosed, which showed that the diagnose accordance rate was 91.7%(22/24). On plain CT scans, 5 lesions (maximum diameter<4 cm) showed homogeneous density; 7 cases (maximum diameter>5 cm) showed heterogeneous density, 4 of which had calcification and 7 had necrosis; the shapes were round-like or lobulated. On enhanced CT scans, 5 cases presented progressive enhancement pattern, 5 cases showed fast-in and slow-out pattern, 1 case showed slight enhancement pattern. On MRI scan, 4 cases of the solid part of tumors showed isointensity signals on T1WI and isointensity or slight hyperintensity signals on T2WI, 3 cases showed isointensity or low signals on T1WI and low, isointensity or slight hyperintensity signals on T2WI, and slight hyperintensity signal on DWI, the solid part of tumors were strongly enhanced. Two malignant tumors presented features like heterogeneous density, unclear boundary, invasive growth and progressive enhancement pattern. The pathological findings demonstrated that the tumor tissues mainly consisted of spindle cells with rich fibers and vessels. Conclusion The imaging findings of benign and malignant SFT have certain features, malignant SFT have invasive growth signs. The obvious progressive enhancement of solid component which shows isointensity and hyperintensity on T1WI or T2WI may be helpful in the diagnosis of SFT; however, the final diagnosis should be confirmed with histopathology.

Lectin-likeoxidizedLDLreceptor-1(LOX-1)isoneofthemajorreceptorsoftheoxidized low-density lipoproteins (oxLDL). Recent research suggests that LOX-1 can not only bind, neutralize and degrade oxLDL, but also bind some non-oxidized lipoproteins and apoptotic blood cel s. LOX-1 is involved in the process of atherosclerosis through a variety of w ays, such as activating platelet, inducing inflammatory reaction, promoting the proliferation and migration of vascular smooth muscle cels. This article reviews the related research progress from the relationship betw een the structure and function of the LOX-1 and its lipid metabolism and the pathogenesis of atherosclerosis.

Objective To investigate the accuracy of real-time continuous glucose monitoring(RT-CGM)system in the type 2 diabetes mellitus(T2DM). Methods A total of 318 subjects hospitalized between 2013 May to 2014 August were recruited. Each subject received a RT-CGM system. In order to calibrate the interstitial glucose level, finger-stick blood glucose were measured at least four times every day. Patients were divided into three groups according to their finger-stick blood glucose level:≤6.99 mmol/L, 7.0-10.0 mmol/L and≥10.01 mmol/L. Pearson correlation was used to analyze the relationship between the finger-stick glucose and interstitial glucose gained from RT-CGM. Clarke error grid analysis was used to analyze the accuracy of RT-CGM. Results (1)A total of 2, 815 glucose meter values from finger-stick were com?paired with glucose from RT-CGM. A positive relationship(r=0.847)were found between CGM and finger-stick blood glu?cose. The correlation was closer with higher finger-stick blood glucose levels(r=0.457, 0.648 and 0.852 respectively in≤6.99 mmol/L group, 7.0-10.0 mmol/L group and≥10.01 mmol/L group. P<0.001).(2)The Clarke error grid analysis re?vealed that 76.69%of the readings from RT-CGM were clinical perfect (zone A), 20.28%were acceptable (zone B), 3.03%were unacceptable (zone C-E). Clinical perfect rate was lower when the finger-stick glucose≤6.99 mmol/L , compared with that when it is between 7.0-10.0 or≥10.01 mmol/L group(73.12%vs 78.63%&79.28%,P<0.05), there was no significant difference between group of 7.0-10.0 mmol/L with group≥10.01 mmol/L (P>0.05). Conclusion RT-CGM provides accu?rate blood glucose values to guide the treatment of diabetes, and the accuracy is more reliable in high glucose environment.

BACKGROUNDHerpes simplex virus thymidine kinase phosphorylates ganciclovir to ganciclovir monophosphate, which is then converted to ganciclovir triphosphate by endogenous cellular nucleoside kinases. The ganciclovir triphosphate acts as a DNA chain terminator due to the lack of a functional 3'-OH group and terminates the process of DNA replication, hence leading to cell apoptosis. At present, HSVtk gene usually acts as suicide gene to kill tumor cells. The aim of this study was to investigate the selective cytotoxicity of the herpes simplex virus thymidine kinase/ganciclovir (HSVtK/GCV) suicide gene system controlled by the a-fetoprotein (AFP) promoter on hepatocellular carcinoma (HCC) cells in vitro.

METHODSpAFP-HSVtk-IRES2-EGFP recombinant plasmid vectors driven by the AFP promoter were constructed. HL-7702 liver cells, HUH-7 HCC, and HepG2 HCC were transfected with the recombinant plasmids. HSVtK gene expression was detected using Western blotting analysis. HepG2 cells line stably expressing HSVtk gene was selected by G418 reagent. The cytotoxicity of HSVtK/GCV suicide gene system on hepatoma cells was measured by CCK-8 reagents when different doses of ganciclovir were added.

RESULTSPlasmid pAFP-TK-IRES2-EGFP-expressed HSVtk gene was constructed successfully. HSVtk gene expression level was significantly higher in AFP-positive hepatoma cells than in AFP-negative liver cells. After G418 selection, a HepG2 cells line stably expressing HSVtk gene was acquired. With the increase of the dose of ganciclovir the optical density at 450 nm of HepG2 cells stably expressing HSVtk gene gradually decreased (P < 0.05).

CONCLUSIONThe HSVtK gene-specific expression in hepatoma cells as well as the cytotoxicity of the suicide gene system in HepG2 cells provided the basis for the targeted gene therapy of HCC.

Apoptosis ; drug effects ; genetics ; Carcinoma, Hepatocellular ; genetics ; Cell Line, Tumor ; Fetal Proteins ; genetics ; Ganciclovir ; analogs & derivatives ; pharmacology ; Hep G2 Cells ; Humans ; Liver Neoplasms ; genetics ; Promoter Regions, Genetic ; genetics ; Transfection

Objective To investigate the effects of different doses Alpha-Linolenic acid ( ALA ) on the expressions of fatty acid synthesis-related genes in HepG2 cells.Methods HepG2 cells were divided into two groups, normal control group (NC) and high fat group (HF) in which cells were firstly cultured for 36h in the medium contained 0.5mmol/L stearic acid.Real-time quantitative PCR was taken to detect mRNA expression of genes SREBP1C, FAS and ACC which are related to fatty synthesis.While there are significant differences in fatty synthesis, 10%, 20%, 50%, 70% and 100%ALA took the place of stearic acid, 36h later, real-time quantitative PCR and Western blotting were taken to detect mRNA and protein expression of genes related to fatty synthesis.Results SREBP1C mRNA expression of ALA substitution groups were significantly lower than the high-fat group ( P <0.001) .The FAS of 0.5 mmol/L ALA group and 0.35 mmol/L ALA group were significantly lower than the high-fat group (P <0.001).ACC genes mRNA level was not significantly different from high-fat group.SREBP1C and FAS protein expression were significantly lower than the high-fat group, but ACC showed no significant difference.Conclusions Saturated fatty acids promote hepatocyte fatty acid synthesis, ALA abates fatty acid synthesis by inhibiting FAS and SREBP1C gene expression.