We prepared gold nanostar (GNS) through seed growth method firstly,then formation of COX-2 siRNA(siCOX-2) and GNS composite modified with polyethylene glyco (PEG),2-amino-2-deoxy-D-glucos (DG) and 9-D-arginin (9R) was prepared.Mterwords,paclitaxel temperature sensitive liposome (PTX-TSL) was prepared by film dispersion method.Finally,siCOX-2 delivery systerm (PTX-TSL-(siCOX-2(9R/DG-GNS)))was obtained by hydrosulfuryl ligand reaction between siCOX-2 (9R/DG-GNS) and PTX-TSL The successful build of siCOX-2 (9R/DG-GNS) was vetified by nuclear magnetic resonance (NMR),sodium dodecyl sulfate polyacryl amide gel electrophoresis (SDS-PAGE),and ultraviolet spectrophotometry and agarose gel electrophoresis method.Particle size of PTX-TSL-(siCOX-2(9R/DG-GNS)) was (292 ± 14) nm and Zeta potential was about -(2.59 ± 0.12) mV,which were measured by Zetasizer Nano ZS90.The morphology of PTX-TSL-(siCOX-2 (9R/DG-GNS)) measured by transmissionelectronmicroscopy showed homogeneous star structure with phospholipid bilayer on the surface,and it showed good thermal conversion efficiency under radiation of 808 nm laser.Differential scanning calorimetry test showed that PTX-TSL phase transition temperature is about 42.6 ℃.The drug loading content(using dialysis method) and encapsulation efficiency of PTX-TSL were about 7.5％ and 95.4％,at the same time,the release process experiment of PTX-TSL showed that it had a good temperature sensitive release performance.It is hopeful that this siCOX-2 system can be used for reducing drug resistance of PTX and improving the treatment effect of PTX through the synergistic antitumor drug resistance effect of siCOX-2.

Objective To get the knowledge of the diagnosis and treatment of acute pulmonary embolism (APE)in primary hospital.Methods The clinical data of the patients diagnosed with APE were retrospectively reviewed.The patients were clarified into different risk-group by revised Geneva score and Wells score according to the clinical records.Results 17 patients were diagnosed with APE in this time slot,in which male 10 cases and female 7 cases,average age was (51.8 ±18.4)years old,and among them,4 cases with 4 scores of revised Geneva score,9 cases with 4 to 10 scores,4 cases with more than 11,6 cases with less than 4 Wells score,11 cases with more than 4,2 cases with low risk and 15 cases with intermediate risk.The length of hospital stay was (10.9 ±5.4)days in average.In this group,one patient was dead,seven cases improved,six cases remarkably improved and three cases were recued.Fourteen patients received anticoagulation agents and three cases without any.Eleven patients were given thrombolystic therapy,one case was operated and six cases were given interventional treatment.Conclusion Clinicians know APE and keep alert gradually.However,it should be improved in respects of treating and following the APE patients.

Objective To evaluate the effect of diabetic peripheral neuropathy on peripheral neurotoxicity induced by local anesthetics in rats.Methods Sixty healthy adult male SPF Sprague-Dawley rats,aged 6 weeks,weighing 150-180 g,were divided into either control group (n =18) or diabetic peripheral neuropathy group (n=42) using a random number table.The rats were fed a high-fat and high-sucrose diet for 8 weeks,and streptozotocin (STZ) 30 mg/kg was injected intraperitoneally to induce diabetes mellitus which was confirmed by blood glucose level≥ 16.7 mmol/L.The mechanical paw withdrawal threshold to yon Frey filament stimulation and thermal paw withdrawal threshold were measured.The decrease in reaction thresholds to thermal and mechanical stimuli (changing from sensitivity to insensitivity) was observed after STZ injection.At 4 weeks after STZ injection,the rats showing a marked hyperalgesia served as early diabetic group.At 8 weeks after STZ injection,the rats showing a marked insensitivity to pain served as late diabetic group.Experiments were carried out in early or late diabetic rats,and ordinary Sprague-Dawley rats of the same age were used as control group.Left sciatic nerve block was performed with 2％ lidocaine 0.2 ml.Before the sciatic nerve block and at 1 week after the sciatic nerve block,the nerve conduction velocity of the left sciatic nerve and F-wave minimal latency were measured,and the sciatic nerve block time was recorded.Results Compared with the baseline before block,the nerve conduction velocity was significantly decreased,and the F-wave minimal latency was prolonged in late diabetic rats (P＜0.05).Compared with control group,the sciatic nerve block time was significantly prolonged in late diabetic group (P＜0.05).Conclusion Diabetic peripheral neuropathy aggravates peripheral neurotoxicity induced by local anesthetics in rats.

Objective:To explore the effect of hydrogen sulfide (H 2S) on modulating the subunit Kir6.2 of adenosine triphosphate sensitive potassium channels via the cyclic guanosine monophosphate-dependent protein kinase (cGMP/PKG) signaling pathway in epileptic rat models. Methods:Sixty adult male SD rats were randomly divided into the following six groups (10 rats in each group) by random number table method: control, epileptic, H 2S donor, H 2S donor+epileptic, KT5823 (one inhibitor of the cyclic guanosine monophosphate-dependent protein kinase)+H 2S donor+epileptic, and glibenclamide (one inhibitor of the adenosine triphosphate sensitive potassium channels)+H 2S donor+epileptic groups. Except the control group, SD rats were intraperitoneally injected with plentylenetetrazole to make the kindling models and their behaviours were recorded including the latency period, the grade, and the duration of the first epileptic seizure according to the Racine′s standard. The waveforms of electroencephalogram (EEG) in hippocampus were also recorded during the seizure. The mRNA and protein levels of PKG and Kir6.2 in hippocampus were evaluated by Western blotting and quantitative real-time polymerase chain reaction, and the hippocampal concentrations of cGMP and phosphorylation of cyclic guanosine monophosphate-dependent protein kinase (p-PKG) were detected by enzyme linked immunosorbent assay. Results:Rats in the epileptic group showed Ⅳ-Ⅴ grade of epileptic seizure [4.500 (4.000, 4.875)], short latency period [(10.37±8.21) min] but long duration [(69.50±24.37) s] of seizure. Compared to the epileptic group, rats in the H 2S donor group showed Ⅱ-Ⅲ grade of epileptic seizure ( P=0.004), significantly longer latency period ( P<0.001), and shorter duration of seizure ( P<0.001). Compared to the H 2S donor+epileptic group, rats in the KT5823+H 2S donor+epileptic group showed Ⅲ-Ⅳ grade of epileptic seizures, significantly shorter latency period ( P<0.001), and longer duration of seizure ( P<0.001). The results of EEG showed that the wave patterns in the epileptic group were spike or sharp waves and the amplitudes were largest [(190.570±23.590) μV]. Compared with the epileptic group, amplitudes were reduced ( P<0.001) in the H 2S donor+epileptic group. PKG mRNA and PKG protein were expressed differently among all groups (PKG mRNA: n=5, H=26.714, P<0.001; PKG protein: n=5, F=30.597, P<0.001). Compared with the control group, the expression of both PKG mRNA and PKG protein was decreased (PKG mRNA: 1.000±0.001 vs 0.782±0.064, P=0.023; PKG protein: 0.550±0.037 vs 0.145±0.020, P=0.042) in the epileptic group. Besides, Kir6.2 mRNA and Kir6.2 protein were expressed differently among all groups (Kir6.2 mRNA: n=5, H=27.761, P<0.001; Kir6.2 protein: n=5, F=60.659, P<0.001). Compared with the control group, the expression of both Kir6.2 mRNA and Kir6.2 protein was decreased (Kir6.2 mRNA: 1.000±0.001 vs 0.897±0.033, P=0.004; Kir6.2 protein: 0.384±0.035 vs 0.215±0.016, P=0.024) in the epileptic group. And the concentrations of cGMP and p-PKG were decreased (cGMP: P<0.001; p-PKG: P<0.001) in the epileptic group. The results in the H 2S donor+epileptic group were up-regulated (PKG mRNA: P=0.047; PKG protein: P<0.001; Kir6.2 mRNA: P=0.011; Kir6.2 protein: P<0.001; cGMP: P<0.001; p-PKG: P<0.001) compared with the epileptic group. However, the results in the KT5823+H 2S donor+epileptic group were down-regulated (PKG mRNA: P=0.015; PKG protein: P=0.027; Kir6.2 mRNA: P=0.013; Kir6.2 protein: P=0.017; cGMP: P=0.005; p-PKG: P<0.001) compared with the H 2S donor+epileptic group. Conclusion:A possible mechanism is that H 2S prevents the epileptic seizure from modulating the subunit Kir6.2 of ATP sensitive potassium channels via the cGMP/PKG signaling pathway.

Objective To evaluate the role of NOX2 in bupivacaine-induced production of reactive oxygen species (ROS) in nerve cells.Methods SH-SY5Y cells were seeded in culture plates and divided into 4 groups (n =11 each) using a random number table:small interfering RNA (siRNA) negative control group (group NC),siRNA negative control plus bupivacaine group (group NC +B),NOX2 siRNA group and NOX2 siRNA plus bupivacaine group (group NOX2 siRNA + B).In NC and NOX2 siRNA groups,the cells were transfected with negative siRNA and NOX2 siRNA,respectively,and then incubated in the culture medium for 24 h.In NC+B and NOX2 siRNA+B groups,cells were transfected with negative siRNA and NOX2 siRNA,respectively,new plates were used,the cells were incubated for 3 h with bupivacaine at the final concentration of 1.5 mmol/L,the culture medium was then replaced,and the cells were incubated until 24 h.The level of intracellular ROS was measured using the fluorogenic probe dihydroethidium,the cell apoptosis was determined by TUNEL,and the expression of activated caspase-3 and caspase-9 was detected using Western blot.Apoptosis rate was calculated.Results Compared with group NC,the level of ROS and apoptosis rate were significantly increased,and the expression of activated caspase-3 and caspase-9 was up-regulated in group NC+B (P＜ 0.05),the level of ROS was significantly increased,and the expression of activated caspase-3 and caspase-9 was up-regulated (P＜0.05),and no significant change was found in apoptosis rate in group NOX2 siRNA+B (P＞0.05),and no significant change was found in the level of ROS or apoptosis rate (P＞0.05),and the expression of activated caspase-3 and caspase-9 was significantly up-regulated in group NOX2 siRNA (P＜ 0.05).Compared with group NC+B,the level of ROS and apoptosis rate were significantly decreased,and the expression of activated caspase-3 and caspase-9 was down-regulated in group NOX2 siRNA+B (P＜0.05).Conclusion NOX2 is involved in the pathophysiological mechanism of bupivacaine-induced burst production of ROS in nerve cells.

Objective To prepare the rat model of type 2 diabetes mellitus (T2DM), and to ob-serve the characteristics of peripheral neuropathy. Methods High fat and high sugar diets were fed for 8 weeks to induce insulin resistance and then low dose streptozotocin ( STZ) was injected intraperitoneally to induce type 2 diabetes mellitus models in Sprague Dawley rats. Blood glucose and serum insulin levels con-tinuous were monitored. Tactile allodynia in response to von Frey ( VF) filament stimulation of the plantar hind paws and paw withdrawal thermal latency ( PWTL) to plantar test were used as the criterion for diabetic neuropathy. Instruments AD was used to detect nerve conduction velocity ( NCV) of sciatic nerve in rat and the morphological and pathological changes of sciatic nerve were detected by electron microscope. Results The characteristics of T2DM rats by peripheral neuropathy in this method were that 50％ force withdrawal threshold and PWTL were measured. Both values of diabetic rats were decreased from the day of STZ injec-tion until 4 weeks after STZ injection, and then increased 8 weeks after STZ injection (50％ force withdraw-al threshold values, (11.8 ±0.8)g, (8.4 ±0.7)g and (16.2 ±1.4)g; PWTL (10.2 ±0.9)s, (8.3 ± 1. 2)s and (13. 2 ± 1. 0)s. These results indicated that tactile sensation changed from hypersensitive to hy-posensitive. Compared to the NC group, the sciatic nerve motor and sensory conduction velocity were signifi-cantly decreased at 4 and 8 weeks in DM group, respectively. Compared to DM group at 4 weeks, the sciat-ic nerve motor and sensory conduction velocities were further decreased in the DM group at 8 weeks. Con-clusively, sciatic nerve showed obvious demyelination and axonal collapse. Conclusions T2DM rat model was successfully induced by high fat and sugar diet combined with small dose of STZ injection. The rat mod-el has typical pathological change of peripheral nerve. It might provide a particularly advantageous tool for investigations of diabetes and its chronic complications.

Objective:To investigate the correlation between cardiac polyps and gastroesophageal flap valve (GEFV).Methods:The clinical, endoscopic and pathological data of 349 patients with cardiac polyps (the cardiac polyp group) visiting Affiliated Hospital of Yangzhou University from January 1, 2016 to December 31, 2021 were retrospectively collected, and the same number of non-cardiac polyp patients (the non-cardiac polyp group) were matched in the same period as control according to the propensity score. The clinical, endoscopic and pathological data of the two groups were compared.Results:After matching with propensity score, there were 296 patients in each group, with no significant differences in smoking, acid reflux, heartburn, Helicobacter pylori infection, bile reflux, reflux esophagitis or pancreatitis between the two groups ( P>0.05). Compared with the non-cardiac polyp group, the risk of cardiac polyps increased in GEFV Ⅱ patients ( OR=3.046, 95%CI: 2.100-4.419, P<0.001) and GEFV Ⅲ patients ( OR=4.202, 95%CI: 2.299-7.681, P<0.001). Compared with the non-cardiac polyp group, the risk of cardiac polyps increased in patients with GEFV abnormalities ( OR=2.822, 95%CI: 1.615-4.931, P<0.001). GEFV abnormalities was associated with the cardiac polyp site ( χ2=22.169, P=0.003) and was not significantly associated with cardiac polyp size, number, morphology, intestinal metaplasia of the surrounding mucosa or intraepithelial neoplasia ( P>0.05). Conclusion:The occurrence of cardiac polyps is related to GEFV, and the patients with GEFV abnormalities are more likely to develop cardiac polyps.

Objective:To explore the effect and mechanism of diosmetin (Dio) on neuronal ferroptosis in rats with bacterial meningitis (BM).Methods:Male SD rats aged 6-7 weeks of SPF grade were selected for the experiment. The BM model was established by injecting group B hemolytic streptococcus into the cisterna magna of cerebellum. Sixty BM model rats were successfully modeled and divided into model group, low-dose Dio group, medium-dose Dio group, high-dose Dio group and inhibitor group according to the random number table method, with 12 rats in each group. Another 12 weight-matched rats were taken as the control group.The rats in the low-dose Dio group, medium-dose Dio group, high-dose Dio group and the inhibitor group were intragastrically administered with Dio at 50 mg/kg, 100 mg/kg, 200 mg/kg and 200 mg/kg, respectively. The rats in the control group were intragastrically administered with an equal volume of 0.9 % sodium chloride solution. On the day of intragastric administration, the rats in the inhibitor group were intraperitoneally injected with SIRT1 pathway inhibitor EX527 (10 mg/kg), and the rats in the other groups were injected with an equal volume of 0.9% sodium chloride solution. The above interventions were performed once a day for 28 consecutive days. Loeffler neurological score was used to evaluate the neurological impairment in rats. Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in cerebrospinal fluid of rats were detected by ELISA. The number of white blood cells in cerebrospinal fluid was detected by a blood cell analyzer. Glutathione (GSH) was detected by micro-enzyme labeling method, malondialdehyde (MDA) was detected by thiobarbituric acid colorimetric method, reactive oxygen species(ROS) was detected by colorimetry, and Fe 2+ level was detected by ferrozine method. Hematoxylin-eosin staining, Prussian blue staining and TUNEL staining were used to observe the pathological damage, iron accumulation and apoptosis in the hippocampus, respectively.Western blot was applied to measure the expression of transferrin (Tf), proliferating cell nuclear antigen (PCNA), Bcl-2-associated X protein (Bax), caspase-3 and SIRT1/Nrf2/HO-1/Gpx4 signaling pathway proteins. Graphpad Prism 9.0 was used for data analysis. One-way ANOVA was used for statistical analysis, and SNK- q test was used for further pairwise comparisons. Results:(1) There was a statistically significant difference in neurological function scores among the 6 groups of rats ( F=125.451, P<0.001). The neurological function score of the model group was lower than that of control group, while the neurological function scores of the low-dose Dio group, medium-dose Dio group, and high-dose Dio group were higher than those of the model group (all P<0.05). The neurological function score of the inhibitor group ((2.57±0.26)) was lower than that of high-dose Dio group ((4.34±0.48)) ( P<0.05). (2) There were statistically significant differences in the levels of IL-6, TNF-α and the number of white blood cells in the cerebrospinal fluid of rats among the 6 groups ( F=127.817, 102.413, 180.967, all P<0.001). The levels of IL-6, TNF-α and the number of white blood cells in model group were higher than those of control group(all P<0.05). The levels of IL-6, TNF-α and the number of white blood cells in low-dose Dio group, medium-dose Dio group and high-dose Dio group were lower than those of model group (all P<0.001), and those in inhibitor group were all higher than those in high-dose Dio group(all P<0.001). (3) There were statistically significant differences in iron deposition rate and neuronal apoptosis rate among the 6 groups of rats ( F=90.857, 88.835, both P<0.001). The iron deposition rate ((18.37±3.14)%) and neuronal apoptosis rate ((27.58±2.63)%) in the inhibitor group were higher than those in the high-dose Dio group ((6.35±1.08)%, (14.02±1.87)%) (both P<0.05). (4) The levels of GSH, ROS, MDA, and Fe 2+ in the hippocampus of the 6 groups of rats showed statistically significant differences ( F=54.465, 106.453, 55.969, 105.457, all P<0.001). The GSH content in the inhibitor group ((103.48±8.76) mmol/g) was lower than that in the high-dose Dio group ((133.97±10.54) mmol/g), while the contents of ROS, MDA, Fe 2+ ((225.17±16.32) μmol/mg, (10.73±1.58) μmol/mg, (62.71±5.43) μg/g) were higher than those of the high-dose Dio group ((131.87±11.67) μmol/mg, (4.35±0.87) μmol/mg, (34.86±2.95) μg/g) (all P<0.05). (5)There were statistically significant differences in the protein levels of Tf, PCNA, Bax, caspase-3, SIRT1, Nrf2, HO-1 and Gpx4 in the hippocampus of the 6 groups of rats ( F=120.179, 107.568, 157.265, 98.031, 90.932, 52.283, 59.424, 114.539, all P<0.001). The protein levels of Tf, Bax and caspase-3 in the hippocampus of inhibitor group were higher than those of the high-dose Dio group, while the protein levels of PCNA, SIRT1, Nrf2, HO-1, Gpx4 were lower than those of the high-dose Dio group (all P<0.05). Conclusion:Diosmetin can activate SIRT1/Nrf2/HO-1/Gpx4 signaling pathway, thereby inhibiting neuronal ferroptosis in BM rats.

Objective To investigate the neurodevelopmental toxicity of ACR by studying the expression of DCX and GAP-43 in the hippocampal dentate gyrus of rats after maternal exposure to acrylamide. Methods Pregnant rats were randomly divided into low-dose ACR(4.5 mg/kg),medium-dose(9 mg/kg),high dose groups(18 mg/kg)and the control group(0 mg/kg),8 in each group,and were exposed to toxicant from gestation-al day 15 to postnatal day 13. All rats and their pups were killed on postnatal day 14. ABC immunohistochemistry was used to detect the expression of GFAP in the hippocampus of mother rats and offspring. Results Compared with the control group,the expression of DCX and GAP-43 in hippocampus dentate gyrus of the pregnant rats in middle and high dose groups was significantly decreased(P < 0.05). Conclusion ACR may interfere with the growth and development of neurons by reducing the expression of DCX and GAP-43.

Objective To investigate the influence of glomerular filtration rate (GFR)of living donor on recovery of graft function after transplantation.Methods Clinical data of 108 pairs of donors and recipients undergoing living donor renal transplantation at the Organ Transplantation Center of First Affiliated Hospital of Kunming Medical University from 2009 to 2013 were retrospectively studied.The objects were divided into G1 group (GFR <40 ml/min),G2 group(GFR 40 ~45 ml/min),G3 group(GFR 46 ~50 ml/min)and G4 group (GFR >50 ml/min)according to GFR of the donor kidneys.Changes in serum creatinine (Scr)at 1 week,2 weeks,3 weeks,1 month,3 months,6 months and 1 year after transplantation as well as survival conditions of patient and kidney within 1 year after transplantation of each group were compared.Results Compared with G1 group,Scr at 2 weeks,3 weeks,1 month after transplantation was lower in G2 group,G3 group and G4 group,and the difference had statistical significance (all in P <0.05).As for survival conditions of patient and kidney within 1 year after transplantation,one patient in G1 group developed graft failure due to hyperacute rejection and one patient in G1 group died of severe pulmonary infection.One patient in G2 group developed graft failure due to acute rejection.One patient in G3 group died of severe pulmonary infection.One patient in G4 group died of severe pulmonary infection. Other patients and grafts survived during the follow-up.Conclusions Low GFR of living kidney donor has certain influence on recovery of graft function in the early stage (within one month)after renal transplantation.