ObjectiveTo observe ovarian microvascular damage in rats with cold coagulation and blood stasis syndrome and to explore the mechanism by which Liangfang Wenjing decoction improves this condition in rats. MethodsFifty SPF female SD rats were randomly divided into a blank group， a model group， low-dose （8.1 g·kg^-1） and high-dose groups （16.2 g·kg^-1） of Liangfang Wenjing decoction， and a 4-phenylbutyric acid （0.1 g·kg^-1） group， with 10 rats in each group. The ice-water bath method was employed to establish the rat model of cold coagulation and blood stasis syndrome. Concurrent with modeling， Liangfang Wenjing decoction was administered continuously for 21 days， once daily. The rats' syndrome manifestations and estrous cycles were recorded. The enzyme-linked immunosorbent assay （ELISA） was used to detect serum reproductive hormone levels and levels of endothelin-1 （ET-1）， nitric oxide （NO）， thrombomodulin （TM）， and von Willebrand factor （vWF） in ovarian tissue. Prothrombin time （PT）， activated partial thromboplastin time （APTT）， thrombin time （TT）， and fibrinogen （FIB） were measured. The ovarian microcirculatory blood perfusion was detected by laser speckle contrast imaging. Hematoxylin-eosin （HE） staining was performed to observe the ovarian histopathology， flow cytometry to detect ovarian apoptosis rate， and transmission electron microscopy to observe the ultrastructure of ovarian microvascular endothelial cells. Western blot was employed to detect the protein expression of endothelial nitric oxide synthase （eNOS）， phosphorylated eNOS （p-eNOS）， Caspase-3， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， glucose-regulated protein 78 （GRP78）， C/EBP homologous protein （CHOP）， inositol-requiring enzyme1α （IRE1α）， p-IRE1α， apoptosis signal-regulating kinase 1 （ASK1）， p-ASK1， c-Jun N-terminal kinase （JNK）， and p-JNK. Immunofluorescence was used to detect ovarian Bax and Bcl-2 expression in microvascular endothelial cells. ResultsCompared with the blank group， the model group showed signs of cold coagulation and blood stasis syndrome， prolonged estrus cycles， and reproductive hormone disorders. Histopathological results revealed a decrease in follicle counts at all stages and disorganized granulosa cell arrangement. Ovarian microcirculatory perfusion was significantly decreased （P<0.01）. PT， APTT， and TT were reduced （P<0.05， P<0.01）， while FIB levels were increased （P<0.05）. In ovarian tissue， NO content was decreased， while ET-1， vWF， and TM levels were increased significantly （P<0.01）. The apoptosis rate of ovarian cells was markedly increased （P<0.01）. Furthermore， p-eNOS/eNOS and Bcl-2 were decreased （P<0.05）， whereas Bax， cleaved-Caspase-3/Caspase-3， GRP78， CHOP， p-IRE1α/IRE1α， p-ASK1/ASK1， and p-JNK/JNK expression showed significant increases （P<0.05， P<0.01）. Compared with the model group， Liangfang Wenjing decoction intervention alleviated the symptoms of cold coagulation and blood stasis， gradually restored the estrus cycle， and improved ovarian histopathology and endothelial cell ultrastructure. Microcirculatory blood perfusion was significantly elevated （P<0.05）. NO content in ovarian tissue was elevated， while ET-1， vWF， and TM levels were significantly decreased （P<0.05， P<0.01）. The p-eNOS/eNOS ratio and Bcl-2 expression were significantly elevated （P<0.05）， while the expression of Bax， cleaved-Caspase-3/Caspase-3， GRP78， CHOP， p-IRE1α/IRE1α， p-ASK1/ASK1， and p-JNK/JNK was significantly decreased （P<0.05， P<0.01）. ConclusionLiangfang Wenjing decoction may regulate the IRE1α/ASK1/JNK signaling pathway to inhibit endoplasmic reticulum stress， attenuate apoptosis， and improve microvascular endothelial injury in ovaries of rats with cold coagulation and blood stasis syndrome.

OBJECTIVE To investigate the potential of low-frequency, low-power ultrasound to enhance the transdermal absorption and efficacy of ketoprofen gel. METHODS Ketoprofen gel was used as a model drug to compare the in vitro transdermal permeation of ultrasound treated group and untreated group. Additionally, a rat model of collagen-induced inflammation provided a basis for evaluating pharmacodynamic differences. Pharmacokinetic studies further elucidated the effects of ultrasound on ketoprofen gel's penetration process. RESULTS Ultrasound treatment enhanced the cumulative transdermal permeation of ketoprofen gel by 3.5-fold over 24 hours compared to untreated. Significant pharmacokinetic improvements in AUC0-t from (4289.02±763.58)ng·h·mL−1 to (11301.10±3386.30)ng·h·mL−1 and a reduction in Tmax from (6.0±1.4)h to (3.0±2.0)h. Ultrasound notably improved the gel's anti-inflammatory effects in the rat model, effectively and rapidly reducing inflammation-induced swelling. CONCLUSION Low-frequency, low-power ultrasound can significantly improve the amount and rate of transdermal absorption of ketoprofen gel and enhance its pharmacological potency, from the aspects of skin permeation tests, pharmacodynamic evaluation, and pharmacokinetic studies, which is an effective penetration enhancer for transdermal administration of ketoprofen gel.

ObjectiveTo analyze the gender differences in the pathogen distribution and drug susceptibility of bacteria causing urinary tract infection among psychiatric inpatients in a hospital in Guangzhou， and to provide a basis for clinical diagnosis and rational use of drugs in treatment. MethodsClinical data of 326 psychiatric patients complicating urinary tract infection in a hospital in Guangzhou from 2019 to 2020 were retrospectively analyzed， including 126 males and 200 females. Data including gender， age， identification results of urinary tract pathogens from urine samples and drug susceptibility results were collected. The differences in bacterial distribution and drug resistance rate of urinary tract infection pathogens in patients of different genders were analyzed. ResultsA total of 326 strains of urinary tract infection bacteria were isolated， including 103 strains （31.60%） of multi-drug resistant bacteria. Male and female urinary tract infection in patients with multi-drug resistant bacteria were detected 52 strains （41.27%） and 51 strains （25.50%）， the detection rate of multi-drug resistant bacteria in female patients was significantly higher than that in male patients， with statistical difference （χ²=8.895， P<0.01）. In terms of bacterial distribution， the composition ratio of Escherichia coli in female patients was higher than that in male patients （χ²=14.794）， while the composition ratio of Acinetobacter baumannii and Pseudomonas aeruginosa was lower than that in male patients （χ²=13.665， 4.054）， with statistical difference （P<0.05 or 0.01）. The drug susceptibility results showed that Escherichia coli isolated from female patients were less resistant to various antibiotics such as ampicillin/sulbactam， aztreonam， cefepime， ceftazidime， levofloxacin， imipenem and meropenem than those from male patients （χ²=5.028~17.680， P<0.05 or 0.01）. ConclusionThe prevalence rate and bacterial distribution of psychiatric patients complicating urinary tract infection differ between patients of different genders， furthermore， the rate of drug resistance for Escherichia coli is lower in female patients than that in male patients.

Objective:To compare the leaf open time (LOT) parameters and γ passing rates between the 4.0.4 and 4.2.3 helix Tomotherapy planning systems and evaluate the improvement.Methods:Retrospective comparison of the treatment plans of 345 cases selected by 4.0.4 and 4.2.3 versions was performed. The Machine Specific Sinogram of each plan was extracted from the archived plan file to calculate the LOT. The evaluated LOT parameters included the projection time, the maximum LOT, the mean non-zeros time, the time difference between the projection time and the maximum LOT, the relative count of leaves with LOT greater than maximum LOT minus 5 ms, the relative count of leaves with LOT lower than 100 ms and the beam on time. The γ passing rate (criteria: 3 mm/3%, 10% threshold and global error) and the LOT parameters between two version systems were evaluated with the independent t-test. The relationship between the LOT parameters and γ passing rate was analyzed by the multiple linear regression method. Results:The γ passing rate of the Ver 4.0.4 system was 97.86%, significantly lower than 98.6% of the Ver 4.2.3 system ( P<0.001). The time gap between the projection time and the maximum LOT of the Ver 4.2.3 system was significantly less than that of the Ver 4.0.4 system (1 ms vs. 11 ms, P<0.001). For the Ver 4.0.4 system, the multiple linear regression method showed that the maximum LOT ratio and the beam on time were negatively correlated with the γ passing rate (both P<0.001). However, for the Ver 4.2.3 system, only the beam on time showed a negative correlation with the γ passing rate ( P<0.001). Conclusion:The γ passing rate of the Ver 4.2.3 system is significantly higher than that of the Ver 4.0.4 system. The decrease of γ passing rate caused by the leaves near the maximum LOT is properly resolved in the new version system.

Objective:To evaluate the sensitivity of the ArcCheck dosimetry system in detecting the leaf open time errors during the center and off-center helical tomotheray delivery quality assurance (DQA).Methods:Nine nasopharyngeal carcinoma (NPC) patients were selected in this study. Two DQA plans were created for each patient: the" center" plan was created by moving the image of the ArcCheck phantom to place the high dose region on the phantom center and the " off-center" plan was created by offsetting the phantom and putting several diodes through a higher does region. Leaf open time errors of 2, 4, 6, 8 and 10 ms were introduced to the Sinogram which was modified using Matlab. Each intentional error plan and original (no error) plan for each patient were measured using both " center" and " off-center" DQA methods, the γ analysis was performed to evaluate the DQA results. The different dose and distance error criteria of 3%/3 mm, 3%/2 mm and 2%/2 mm were selected, and different thresholds of 5%, 10% and 15% were selected for γ analysis. The gradient and the minimum detectable error approach were taken to quantitatively analyze the sensitivity. The correlation between different dose distance error criteria and different thresholds was also evaluated by Pearson correlation analysis. Results:The absolute value of γ gradient of the " center" DQA plans were larger than those of the " off-center" plans in all different γ criteria (all P<0.05). The stricter the γ criteria were adopted, the more sensitive DQA results of leaf open time error were obtained. The minimum detectable error was 2 ms in all different γ criteria for the " center" DQA plan. The minimum error detectability of the " off-center" DQA plan was weaker than that of the " center" DQA plan. The γ passing rates of three different dose distance error criteria were significantly strongly correlated for the " center" DQA plan ( R2>0.9). For the " off-center " DQA plan, only the 3%/3 mm and 3%/2 mm criteria were significantly strongly correlated ( R2>0.9). Significant strong correlation was observed in the γ passing rate at different thresholds between the " off-center" and " center" DQA plans. Conclusions:The " center" DQA plan method is more sensitive than the " off-center" DQA plan method in all γ criteria, and the γ passing rates in different γ criteria are strongly correlated for the " center" DQA plan. The " center" DQA plan method is recommended.

OBJECTIVE：To investigate the effects of Periplaneta americana extract on the proliferation and apoptosis of human non-small cell lung cancer A 549 cells as well as its possible mechanism. METHODS ：The dry bodies of P. americana were soaked with 90％ ethanol and eluted with gradient water-methanol by polyamide column chromatography. The 20％，30％，40％， 50％，60％，70％，80％，90％ methanol elution sites （YS-A-H）were obtained. MTT method was used to screen the active site ， and the inhibition rate of different doses of active site was detected. Flow cytometry was adopted to detect cell apoptosis ，cell cycle and mitochondrial membrane potential of cells after treated with different doses of active site. RESULTS ：Half inhibition concentrations of YS-A-H were （95.25±8.42），（129.93±7.24），（221.28±12.68），（275.39±14.87），（276.76±16.32），（31.90± 5.34），（163.15±6.97），（122.81±8.36）μg/mL，respectively. YS-F had the strongest activity. After treated with 3，9，27，81 μg/mL YS-F for 24，48，72 h，cell proliferation inhibitory rate was increased significantly at different time points ；after treated for 48，72 h，that was significantly higher than same group after treated for 24 h；after 72 h treatment ，that was significantly higher than same group after 48 h treatment （P＜0.01）. There was no significant effect of 24 h treatment of 3 μg/mL YS-F and 72 h treatment of 9 μg/mL YS-F on the percentage of cells in the late stage of necrosis，24 h treatment of 3 μg/mL YS-F on the percentage of cells in G2/M phase and 48 h treatment of 3 μg/mL YS-F on the reduction rate of mitochondrial membrane potential（P＞0.05）. The percentage of cells in the early stage of apoptosis ，the late stage of apoptosis and the early stage of necrosis ，the late stage of necrosis，as well as the percentage of cells in the Sub-G 0/G1 and S phase at each time point were significantly increased in other different doses groups ，while the percentage of cells in G 0/G1 and G 2/M phase was decreased significantly （P＜0.01）. In each dose group，the percentage of cells in the early stage of apoptosis ，the late stage of apoptosis and the early stage of necrosis ，the late stage of necrosis （except for the percentage of cells in the late stage of necrosis treated with YS-F 9 μg/mL for 72 h）and the percentage of cells in Sub-G 0/G1 phase，G2/M phase （except for YS-F 27，81 μg/mL for 48 h）after treated for 48，72 h were significantly higher than same group after 24 h of treatment ；the percentage of cells in G 0/G1 phase，S phase and G 2/M phase （except for YS-F 9 μg/mL for 48 h）after treated for 48，72 h were significantly lower than same group after 24 h of treatment （P＜0.01）；the percentage of cells in the early stage of apoptosis ，the late stage of apoptosis and the early stage of necrosis ，the late stage of necrosis （except for the percentage of cells in the late stage of apoptosis and early stage of necrosis when treated with YS-F 27 μg/mL for 72 h，the percentage of cells in the late stage of necrosis when treated with YS-F 3，9 μg/mL for 72 h were decreased significantly ）and the percentage of cells in S phase （except for YS-F 3 μg/mL for 72 h）and Sub-G 0/G1 phase after treated for 72 h were significantly higher than same group after 48 h of treatment ，while the percentage of cells in G 0/G1 and G 2/M phase were significantly lower than same group after 48 h of treatment （P＜0.01）. After treated with YS-F 9，27，81 μg/mL for 48 h，the reduction rate of cell mitochondrial membrane potential was increased significantly ；YS-F 27，81 μg/mL groups were significantly higher than YS-F 9 μg/mL group，and YS-F 81 μg/mL group was significantly higher than YS-F 27 μg/mL group. CONCLUSIONS：YS-F can inhibit the proliferation and promote the apoptosis of A 549 cells by preventing cell transformation from S phase to G 2/M phase ，and reducing mitochondrial membrane potential ，in time-dependent or dose-dependent manner.

Objective To evaluate the dosimetric characteristics of the TomoDose diode and its application in detecting the couch velocity and assessing the beam Profile stability for convenient and efficient quality control of Tomotherapy.Methods Fundamental properties of the TomoDose detector,such as dose linearity,dose per pulse dependence,directional dependence and field size dependence were tested by the water-equivalent phantom and the results were statistically compared with those measured by the ion-chamber (0.057 cm3,A 1SL).Five different couch velocities with a time interval of 0.0005 s were designed to test the sensitivity of TomoDose for detecting the couch velocity,and then the clinical data of 7 patients with different couch velocities were selected to verify the test accuracy.The beam profile of three different jaws of 1.0,2.5 and 5.0 cm were measured using TomoDose with water-equivalent phantom in the x and y directions under the same conditions as water tank with an underwater depth of 15,50,100,150 and 200 mm,respectively.The Profile data obtained by water tank and TomoDose were evaluated using the Gamma (γ) evaluation method with the 2％/1 mm criterion.Results The dose linearity of the TomoDose and ion chamber was in a linear pattern within the beam-on-time ≤ 30 s.The difference between the TomoDose and ion chamber was less than 2％ for the dose per pulse dependence,and the response trends of them were consistent.TomoDose showed angular response dependence with a maximum difference of 2.53％ for the gantry angle of ±60°.For the field size dependence,the response difference between the TomoDose and ion chamber was increased with the decreasing field size when the Jaw was 5.0 cm,and the maximum deviation was 0.78％ when the field size was 5.0 cm×2.5 cm.TomoDose could detect the couch distance error of 0.5 mm,and determine the couch velocity deviation of＜ 0.6％.For the Profile stability testing:In the x direction,there was always γ＜1 at the underwater depth of 15 mm for all values of Jaw;when the underwater depth was not 15 mm,there was always γ＜ 1 in the main beam region (off-axis distance＜ 200 mm),whereas in the penumbra region (off-axis distance＞ 200 mm),the value of γ was larger and even with γ＞ l.In the y direction,all comparison results of Profile under three field width demonstrated that γ index was larger on the edge of beam,whereas γ＜1 was found in all cases.Conclusions TomoDose is suitable f or the quality control of Tomotherapy,which can accurately measure the couch velocity,precisely monitor the stability of beam Profile of Tomotherapy and complete the quality control process in a convenient and efficient manner.

OBJECTIVE： To investigate the acute toxicity， long-term toxicity， skin irritation and anaphylaxis of Bee venom （BV） plastics， and to evaluate its preclinical safety. METHODS： The acute toxicity of BV plastics to rats was investigated after administration of high-dose， medium-dose and low-dose （144， 96， 48 mg/kg） of BV plastics. The long-term toxicity of BV plastics was investigated by continuous administration of high-dose， medium-dose and low-dose （72， 48， 24 mg/kg） of BV plastics for 28 days. The irritation of intact and damaged skin in rabbits with 8 mg/kg BV plastics was investigated by using the self-control method of left and right homologous body. The skin anaphylaxis of guinea pig were investigated after sensitized with 15 mg/kg BV plastics on the left back （on 0， 7th， 14th day） and stimulated with 15 mg/kg BV plastics on the right back. RESULTS： During the acute toxicity experiment with BV plastic，the weight of rats and the changes of viscera were normal，and there was no relevant toxic reaction. Long-term toxicity test results showed that no significant pathological changes were observed at 24 h after the last administration； the spleen index  of rats in BV low-dose group， testicular index in middle-dose group and epididymis index in high-dose and middle-dose groups were significantly increased， while PT in plasma of rats in BV medium-dose and low-dose groups was significantly prolonged （P＜0.05）. There were no abnormal changes in organ appearance， other organ index， coagulation index and blood biochemical index. All above indexes became normal at the end of 2-week recovery period. Skin irritation test showed that BV plastics could cause slight erythema and obvious scab on the skin of rabbits which along with little irritation on intact or damaged skin. Skin anaphylaxis test showed that BV plastics produced mild erythema in the skin of guinea pigs， belonging to light allergy. CONCLUSIONS： No acute or long-term toxicity is observed after transdermal administration of BV plastics， which is safe and only causes mild irritation and irritability to skin， indicating there is good safety of the plastic under experiment doses.

Objective This study was to evaluate the long-term clinical efficiency of allogeneic corneal intrastromal lenticule inlay for correction of moderate and high hyperopia.Methods A prospective self-controlled case series study was adopted.Twenty-nine hyperopic patients (53 eyes) were performed with allogeneic corneal intrastromal lenticule inlays.The range of preoperative spherical equivalent was +3.75 to + 10 D,with the mean value of (+6.84±2.95)D.All the cases were followed up for 1 year.Uncorrected and best corrected visual acuity and refraction were compared between before and after operation.Corneal topography and optical coherence topography were used to examine corneal topography.Ocular response analyzer was used to evaluate the shifts of corneal hysteresis.This study followed the Helsinki declaration,and the research process was approved by the Ethic Committee of Beijing Tongren Hospital,and informed consent was signed by each donor and receptor.Results Compared with the before surgery,the uncorrected distance visual acuity (UDVA) and uncorrected near visual acuity (UNVA) were obviously improved and the spherical equivalent (SE) was obviously decresed in 3 months,6 months and 1 year after surgery,with significant differences between them (all at P＜0.05),but no significant differences were found between each postoperative time points (all at P＞0.05).One year after surgery,14 eyes (26.4％) gained one line of best corrected distance visual acuity (BCDVA),and 12 eyes (22.6％) gained two lines of BCDVA.Only 2 patients (5.66％) lost lines due to opaque lenticules,and no eye lost lines after changing the opaque lenticules.There was no obvious hyperopic fallback phenomenon.Compared with the before surgery,the average corneal curvature value (Avek) was obviously improved,the surface regularity index (SRI),surface asymmetry index (SAI) and central corneal thickness (CCT) were obviously increased in 3 months,6 months and 1 year after surgery,with significant differences between them (all at P＜0.05),but no significant differences were found between each postoperative time points (all at P ＞ 0.05).The cornea optical coherence tomography (OCT) examination showed that,after the operation,the corneal stromal implant was in place and clear.One year after surgery,the dividing line of corneal graft was still clearly visible.No significant changes of corneal hysteresis (CH) and corneal resistance factor (CRF) were seen among different time points before and after surgeries (F =1.443,P =0.216;F =1.744,P =0.128).Conclusions Allogeneic corneal small incision intrastromal lenticule inlays can be used to correct moderate and high hyperopic eye with good safety,effectiveness and predictability.It provides a new choice for hyperopic patients.

Objective:To explore Toll-like receptor 2 (TLR2) and TLR4 polymorphism in Han people from Hunan region and its association with coronary atherosclerotic heart disease.Methods:Sanger sequence and statistical analysis were performed to identify the polymorphism of TLR2 and TLR4 genes in 347 unrelated Hunan Han subjects,including 180 healthy people (control group) and 167 patients with coronary atherosclerotic heart disease (coronary atherosclerotic heart disease group).Results:There was no significant difference in the genotype frequency and allelic frequency for TLR2 SNP2258G＞A and TLR4 SNP896A＞G between the 2 groups (P＞0.05),while there was significant difference in the TLR4 SNP1196C＞T between the 2 groups (P＜0.05).Conclusion:TLR4 SNP 1196C ＞T polymorphism is associated with coronary atherosclerotic heart disease in Chinese Han populationin in Hunan region.