Objective:To construct a mouse asthma model induced by mugwort pollen and to explore endotyping,providing methods for subsequent precision treatment.Methods:BALB/c mice were intraperitoneally injected with mugwort pollen extract(MPE)to sensitize,following MPE intranasal challenge to construct MPE allergic asthma murine model.Mice were randomly divided into PBS sensitization and PBS challenge(P-P),MPE sensitization and PBS challenge(M-P),MPE sensitization and MPE challenge model(M-M)groups.24 h after final challenge,mice were performed to examine airway responsiveness;bronchoalveolar lavage fluid(BALF)was harvested for cell counting and statistical classification of inflammatory cells through flow cytometry analysis.Pulmonary slides were collected for pathological examination,including HE,PAS,Masson and α-SMA immunohistochemical staining.ELISA was used to detect levels of IFN-γ,IL-4,IL-5,IL-13,IL-17A in lung tissue and serum,as well as serum total IgE and MPE-specific IgE,IgG1,IgG2a levels.Results:Pathological examination showed higher airway reactivity,more inflammatory cells infiltration around airway,obvious goblet metaplasia,thickening of airway smooth muscles and dramatical fibrin deposition around airway in model group.Total cell numbers of BALF were increased from<1×105 cells/ml in P-P group to>5×105 cells/ml in model group,in which eosinophils were predominant cellular type,levels of IL-4,IL-13,IL-17A in lung and IL-5,IL-13 levels in serum were significantly increased,as well as significant increasing levels of total IgE and MPE-specific IgE,IgG1,IgG2a.Conclusion:MPE-sensitized and challenged mice induces typical eosinophilic asthma featured with elevated eosinophils,as well as secretion of inflammatory factors of type 2 and type 17,IgE,IgG1 and IgG2a subtypes soars to high levels.

Objective:To establish an irritant contact dermatitis(ICD)model induced by sodium dodecyl sulfate(SDS)in mice,and explore its endotype to provide an experimental and theoretical basis for subsequent precise treatment.Methods:Mice were randomly divided into two groups(model group and control group),4%SDS was topically applied to induce ICD in mice,saline was used on control group,the dose and frequency were consistent with model group,and the skin lesions of mice were observed.Epidermal thickness and inflammatory cell infiltration were analyzed by HE staining,toluidine blue staining and immunofluorescence staining.Real-time quantitative PCR was performed to investigate mRNA expression levels of cytokines.Results:Compared with control group,mice in ICD model group showed epidermal thickness on the back of neck,and the numbers of inflammatory cells were increased in dermis.The number of neutrophils,macrophages and T cells were increased.Expressions of Il17a and Il17f mRNA levels were increased.Conclusion:SDS-induced ICD model is successfully established,with the elevated infiltration of neutrophils,macrophages and T cells,and secretion of type 17 cytokines.

Hypertensive intracerebral hemorrhage (ICH) is mostly single in basal ganglia, thalamus and pons. Simultaneous hemorrhage in other brain regions is relatively rare, accounting for only 5.6% of all hemorrhagic strokes, while bilateral symmetrical hemorrhage is extremely rare. A case of bilateral basal ganglia symmetrical hemorrhage is reported for clinical reference.

Objective:To compare the dosimetric difference between intensity-modulated photon radiaotherapy (IMRT) planning and intensity-modulated proton radiotherapy (IMPT) planning for glioma.Methods:The clinical data of 15 glioma patients who underwent IMRT in ion medical center of the First Affiliated Hospital of USTC from November 2020 to April 2022 were retrospectively analyzed. IMRT planning and IMPT planning were designed for the image of each patient in the therapy planning system. Main dosimetric parameters were compared including plan target volume (PTV), coverage index (CI), dose homogeneity index (HI), and maximal dose (D max) and mean dose (D mean) of organs at risk between both plans. Results:There were no significant differences between IMRT planning and IMPT planning in terms of D max and D mean of PTV1 and PTV2, CI and HI (all P > 0.05). Compared with IMRT planning, brainstem D mean [6.92 GyE (0.09 GyE, 12.58 GyE) vs. 24.41 GyE (2.59 GyE, 34.18 GyE)], left optic nerve D max [0.78 GyE (0.04 GyE, 25.18 GyE) vs. 20.42 GyE (6.38 GyE, 37.17 GyE)], left optic nerve D mean [0.10 GyE (0.01 GyE, 11.63 GyE) vs. 9.74 GyE (2.99 GyE, 20.87 GyE)], right optic nerve D mean [1.57 GyE (0.13 GyE, 14.90 GyE) vs. 14.08 GyE (2.66 GyE, 23.67 GyE)], left len D max [0 GyE (0 GyE, 2.91 GyE) vs. 4.84 GyE (1.42 GyE, 5.48 GyE)], left len D mean [0 GyE (0 GyE, 1.73 GyE) vs. 3.84 GyE (1.25 GyE, 4.30 GyE)], right len D max [0.25 GyE (0.04 GyE, 4.55 GyE) vs. 4.28 GyE (1.58 GyE, 5.84 GyE)], right len D mean [0.16 GyE (0.01 GyE, 1.95 GyE) vs. 3.73 GyE (1.04 GyE, 4.86 GyE)], pituitary D max [6.97 GyE (0.18 GyE, 39.70 GyE) vs. 36.60 GyE (2.74 GyE, 45.19 GyE)], pituitary D mean [1.36 GyE (0.06 GyE, 13.85 GyE) vs. 24.74 GyE (2.42 GyE, 32.80 GyE)], hippocampus D max [5.10 GyE (0.24 GyE, 26.52 GyE) vs. 35.83 GyE (5.03 GyE, 46.11 GyE)], hippocampus D mean [0.36 GyE (0.04 GyE, 25.65 GyE) vs. 18.79 GyE (2.37 GyE, 28.10 GyE)] in IMPT planning were lower, and the differences were statistically significant (all P < 0.05). There were no statistical differences in brainstem D max [51.98 GyE (0.66 GyE, 53.43 GyE) vs. 53.29 GyE (3.87 GyE, 53.48 GyE)], right optic nerve D max [9.60 GyE (0.01 GyE, 43.32 GyE) vs. 25.37 GyE (3.45 GyE, 41.25 GyE)] of both plans (all P > 0.05). Conclusion:In the radiotherapy for glioma, IMRT and IMPT can meet the dose demand in clinic. Furthermore, IMPT planning can protect organs at risk and reduce radiation dose in hippocampus, brainstem, optic nerve, lens and pituitary.

Objective:To explore the efficacy and safety of intraarterial microguidewire electrocoagulation in arterial aneurysms.Methods:(1) SilverSpeed, a kind of microguidewire used in clinical intravascular treatment for intracranial aneurysms, was used to conduct in vitro electrolysis gas generation experiment with isolated arterial blood of anticoagulant New Zealand white rabbits as medium, and thrombus attachment on the surface of microguidewire was observed under scanning electron microscope. (2) Rabbit common carotid artery aneurysm models were established by using vein bag transplantation method, and divided into microguidewire electrocoagulation treatment groups ( n=40) and blank control group ( n=10). The number of closured tumor cavity and the quality of formed thrombus were observed after electrocoagulation simulation treatment with SilverSpeed microguidewire (charging at 6, 9, 12, 15, and 18 V voltage, respectively for 1, 3, 6, 9, 12, and 15 min). DSA was used to observe whether there was ruptured aneurysms or thrombosis of parent artery. Twelve h later, head MRI diffusion weighted sequence scan was performed to detect whether there were new cerebral ischemia foci in the distal cerebral blood supply area of the parent artery. DSA was performed again 6 months after surgery to observe whether the aneurysms recurred. Results:(1) Electrolytic gas generation experiment results showed that bubbles were generated after electrification of SilverSpeed microguidewire; the higher the voltage, the more severe the reaction. Scanning electron microscope showed that thrombus attached to the surface of the microguidewire after electrification in isolated blood; and the higher the voltage, the denser the thrombus. (2) Under the same charging time, the higher the voltage, the larger the number of closured tumor cavity in rabbits of the microguidewire electrocoagulation treatment groups. Under the same voltage, the longer the charging time, the better the quality of thrombosis. Ischemic events occurred only in the microguidewire electrocoagulation treatment group with voltage>9 V, and the charging duration was not associated with the incidence of embolic events. When the voltage was 15 V, 2 experimental rabbits died due to aneurysm rupture 3 min after electrification. When the voltage was 18 V, 4 experimental rabbits died of cardiac arrest 9 min after electrification, and another 2 rabbits died of aneurysm rupture 6 min after electrification.Conclusions:High voltage is the main cause of adverse events in the microguidewire electrocoagulation treatment of aneurysms. After setting the appropriate voltage, prolonging the electrification time can improve the electrocoagulation effect without increasing the safety risk.

Objective:To explore the value and technique details of the overlay reconstruction technique of angiography in surgical planning of scalp arteriovenous fistulas.Methods:The clinical data of patients admitted from February 2014 to April 2020 in the Neurosurgical Department of Second Affiliated Hospital of Soochow University with scalp arteriovenous fistulas were analyzed retrospectively. Preoperative angiography was carried out in all patients for diagnosis, and the angiographical data was obtained without injection of the contrast agent by the mode of XperCT Cereb. Fast HD followed by three-dimension rotation angiography (3DRA) with the contrast agent. The overlay reconstruction was achieved for surgical planning to demonstrate feeding arteries and drainage veins surrounding the fistula. Surgeries were conducted by resection or devascularization of the lesion. All patients were followed up in the out-patient clinic to assess the healing and to detect the symptomatic recurrence and scalp necrosis. The pathological changes of the lesion were observed by HE staining.Results:Five patients were enrolled in this study, including three males and two females aged from 10 to 60 years old (average 34.2-year-old). Pulsatile mass of local scalp was presented in all patients, one with a thin scalp. Five patients suffered from five scalp arteriovenous fistulas, including three on the right side and two on the left. Feeding arteries mainly originated from the superficial temporal artery were confirmed in four cases, and the posterior auricular artery in one case. Single venous drainage was noted in two cases, as well as multiple drainage veins in three cases. Three lesions were supplied by unilateral feeding arteries, while bilateral feeding arteries supplied the rest lesions. Two fistulas were treated by resection, two were treated by devascularization, and one was treated by resection with skin grafting. One lesion was fed by a single artery, three lesions were fed by two arteries, and one lesion was fed by three arteries. Three lesions were fed by unilateral arteries, and two lesions were fed by bilateral arteries. Single fistula was detected in one lesion and multiple fistulas in four lesions. Single drainage was confirmed in two lesions, doubled drainages in two lesions, and tripledrainages in one lesion. All patients experienced surgical treatment in one stage.Two patients underwent complete resection of the lesion, two with complete devascularization, and one with autologous thigh skin grafting after resection. Postoperative pathological examination demonstrated dilated and congested vascular lumen, which was consistent with arteriovenous fistula. All patients healed well after surgery. With13-87 months follow-up, no recurrence and necrosis were noted. Two were reexamined by cerebral angiography, which showed no recurrence.Conclusions:Digital subtraction angiography facilitates the diagnosis of scalp arteriovenous fistula accurately and effectively. The overlay reconstruction technique of angiography is crucial for precise localization of fistula shunt and the surrounding feeders and drainages, which is helpful for surgical planning.

Objective:To explore the value and technique details of the overlay reconstruction technique of angiography in surgical planning of scalp arteriovenous fistulas.Methods:The clinical data of patients admitted from February 2014 to April 2020 in the Neurosurgical Department of Second Affiliated Hospital of Soochow University with scalp arteriovenous fistulas were analyzed retrospectively. Preoperative angiography was carried out in all patients for diagnosis, and the angiographical data was obtained without injection of the contrast agent by the mode of XperCT Cereb. Fast HD followed by three-dimension rotation angiography (3DRA) with the contrast agent. The overlay reconstruction was achieved for surgical planning to demonstrate feeding arteries and drainage veins surrounding the fistula. Surgeries were conducted by resection or devascularization of the lesion. All patients were followed up in the out-patient clinic to assess the healing and to detect the symptomatic recurrence and scalp necrosis. The pathological changes of the lesion were observed by HE staining.Results:Five patients were enrolled in this study, including three males and two females aged from 10 to 60 years old (average 34.2-year-old). Pulsatile mass of local scalp was presented in all patients, one with a thin scalp. Five patients suffered from five scalp arteriovenous fistulas, including three on the right side and two on the left. Feeding arteries mainly originated from the superficial temporal artery were confirmed in four cases, and the posterior auricular artery in one case. Single venous drainage was noted in two cases, as well as multiple drainage veins in three cases. Three lesions were supplied by unilateral feeding arteries, while bilateral feeding arteries supplied the rest lesions. Two fistulas were treated by resection, two were treated by devascularization, and one was treated by resection with skin grafting. One lesion was fed by a single artery, three lesions were fed by two arteries, and one lesion was fed by three arteries. Three lesions were fed by unilateral arteries, and two lesions were fed by bilateral arteries. Single fistula was detected in one lesion and multiple fistulas in four lesions. Single drainage was confirmed in two lesions, doubled drainages in two lesions, and tripledrainages in one lesion. All patients experienced surgical treatment in one stage.Two patients underwent complete resection of the lesion, two with complete devascularization, and one with autologous thigh skin grafting after resection. Postoperative pathological examination demonstrated dilated and congested vascular lumen, which was consistent with arteriovenous fistula. All patients healed well after surgery. With13-87 months follow-up, no recurrence and necrosis were noted. Two were reexamined by cerebral angiography, which showed no recurrence.Conclusions:Digital subtraction angiography facilitates the diagnosis of scalp arteriovenous fistula accurately and effectively. The overlay reconstruction technique of angiography is crucial for precise localization of fistula shunt and the surrounding feeders and drainages, which is helpful for surgical planning.

Purpose: Accumulating evidence has suggested that toll-like receptor 4 (TLR4) is critically involved in the pathogenesis of asthma. The aim of this study was to investigate the role of TLR4 in toluene diisocyanate (TDI)-induced allergic airway inflammation. Methods: TLR4−/− and wild-type (WT) C57BL/10J mice were sensitized and challenged with TDI to generate a TDI-induced asthma model. B-cell lymphoma 2 (Bcl-2) inhibitors, ABT-199 (4 mg/kg) and ABT-737 (4 mg/kg), were intranasally given to TDI-exposed TLR4−/− mice after each challenge. Results: TDI exposure led to increased airway hyperresponsiveness (AHR), granulocyte flux, bronchial epithelial shedding and extensive submucosal collagen deposition, which were unexpectedly aggravated by TLR4 deficiency. Following TDI challenge, TLR4−/− mice exhibited down-regulated interleukin-17A and increased colony-stimulating factor 3 in bronchoalveolar lavage fluid (BALF), while WT mice did not. In addition, TLR4 deficiency robustly suppressed the expression of NOD-like receptor family pyrin domain containing 3 and NLR family CARD domain containing 4, decreased caspase-1 activity in TDI-exposed mice, but had no effect on the level of high mobility group box 1 in BALF. Flow cytometry revealed that TDI hampered both neutrophil and eosinophil apoptosis, of which neutrophil apoptosis was further inhibited in TDI-exposed TLR4−/− mice, with marked up-regulation of Bcl-2. Moreover, inhibition of Bcl-2 with either ABT-199 or ABT-737 significantly alleviated neutrophil recruitment by promoting apoptosis. Conclusions These data indicated that TLR4 deficiency promoted neutrophil infiltration by impairing its apoptosis via up-regulation of Bcl-2, thereby resulting in deteriorated AHR and airway inflammation, which suggests that TLR4 could be a negative regulator of TDI-induced neutrophilic inflammation.

Purpose: Accumulating evidence has suggested that toll-like receptor 4 (TLR4) is critically involved in the pathogenesis of asthma. The aim of this study was to investigate the role of TLR4 in toluene diisocyanate (TDI)-induced allergic airway inflammation. Methods: TLR4−/− and wild-type (WT) C57BL/10J mice were sensitized and challenged with TDI to generate a TDI-induced asthma model. B-cell lymphoma 2 (Bcl-2) inhibitors, ABT-199 (4 mg/kg) and ABT-737 (4 mg/kg), were intranasally given to TDI-exposed TLR4−/− mice after each challenge. Results: TDI exposure led to increased airway hyperresponsiveness (AHR), granulocyte flux, bronchial epithelial shedding and extensive submucosal collagen deposition, which were unexpectedly aggravated by TLR4 deficiency. Following TDI challenge, TLR4−/− mice exhibited down-regulated interleukin-17A and increased colony-stimulating factor 3 in bronchoalveolar lavage fluid (BALF), while WT mice did not. In addition, TLR4 deficiency robustly suppressed the expression of NOD-like receptor family pyrin domain containing 3 and NLR family CARD domain containing 4, decreased caspase-1 activity in TDI-exposed mice, but had no effect on the level of high mobility group box 1 in BALF. Flow cytometry revealed that TDI hampered both neutrophil and eosinophil apoptosis, of which neutrophil apoptosis was further inhibited in TDI-exposed TLR4−/− mice, with marked up-regulation of Bcl-2. Moreover, inhibition of Bcl-2 with either ABT-199 or ABT-737 significantly alleviated neutrophil recruitment by promoting apoptosis. Conclusions These data indicated that TLR4 deficiency promoted neutrophil infiltration by impairing its apoptosis via up-regulation of Bcl-2, thereby resulting in deteriorated AHR and airway inflammation, which suggests that TLR4 could be a negative regulator of TDI-induced neutrophilic inflammation.

Objective: To investigate the value of neuronavigation system in the keyhole microsurgical operation for distal intracranial artery aneurysms(DIAA). Methods: The clinical data of 16 cases with DIAA who were treated by via keyhole approaches, from January, 2013 to December, 2018, were analyzed retrospectively. Ten aneurysms located in anterior cerebral artery(ACA), 3 in posterior inferior cerebellum artery(PICA) and 3 in perforator artery(PA). The optimal skin incision and craniotomy were designed with assistence of neuronavigation system preoperatively, and lesions were located precisely under the guidance of neuronavigation system during microsurgery before clipping or resection. Angiography was performed before discharge, and clinic followed-up was conducted monthly till 6 months after surgery. Results: The systematic error of neuronavigation system ranged from 0.5 mm to 1.0 mm, with an average of 0.6 mm. All 16 aneurysms were explored and managed successfully with the guidance of neuronavigation system without aneurysm premature rupture nor neuronavigation-related complications. Absolute occlusion of all aneurysms was documented angiographically after surgery. Of all cases, 2 experienced shunt procedure due to delayed hydrocephalus. During 6 months follow-up period, all 16 cases recovered well. Conclusion Neuronavigation system can precisely locate the deep-seated DIAA, contribute to the preoperative planning of microsurgery via keyhole approaches and avoid evitable injury during excessive manipulation. The noninvasive, rapid and contrast-enhanced CT images of head was an ideal data source for the neuronavigation system.