ObjectiveTo investigate the antitumor effect and mechanism of Guiqi Yiyuan ointment on Lewis lung cancer mice based on the extracellular regulatory protein kinase （ERK） signaling pathway. MethodsA Lewis lung cancer mouse model was established. Except for the blank group， the model mice were randomly divided into the model group， Guiqi Yiyuan ointment low， medium， and high dose groups， and the extracellular ERK1/2 inhibitor group， with 10 mice per group. The Guiqi Yiyuan ointment was administered by gavage at doses of 1.75， 3.5， 7.0 g·kg^-1·d^-1 for the low， medium， and high dose groups， respectively. The ERK1/2 inhibitor group was given the ERK1/2 inhibitor LY3214996 （100 mg·kg^-1·d^-1） by gavage. The treatment was administered for 14 consecutive days， after which samples were collected. Tumor histopathological changes were observed using hematoxylin-eosin （HE） staining. Transmission electron microscopy was used to observe ultrastructural changes in tumor cells. Immunofluorescence was performed to measure the phosphorylation of ERK1/2 （p-ERK1/2） and the expression of programmed cell death ligand-1 （PD-L1） in tumor tissues. Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of p-ERK1/2， PD-L1， the autophagy marker Beclin-1， the autophagic protein p62， and the microtubule-associated protein light chains LC3Ⅰ and LC3Ⅱ at both the protein and gene levels. ResultsCompared with the model group， the average tumor weight was significantly reduced in the low and medium dose groups of Guiqi Yiyuan ointment （P<0.05）， and markedly reduced in the high dose and inhibitor groups （P<0.01）. Tumor cells in all treatment groups became progressively irregular， with ruptured nuclei and expanded areas of cell disintegration and necrosis. The number of organellar ablations in tumor tissues increased， and the number of autophagic vesicles also increased in all groups. The mean fluorescence intensity of p-ERK1/2 and PD-L1 was reduced in the low and medium dose groups of Guiqi Yiyuan ointment （P<0.05）， and significantly reduced in the high dose and inhibitor groups （P<0.01）. The mRNA expression of ERK1/2， PD-L1， Beclin-1， and p62 was reduced in the medium dose group （P<0.05）， while LC3Ⅰ/Ⅱ mRNA expression was elevated （P<0.05）. In the high dose and inhibitor groups， mRNA expression of ERK1/2， PD-L1， Beclin-1， and p62 was significantly reduced （P<0.01）， while LC3Ⅰ/Ⅱ mRNA expression was significantly increased （P<0.01）. Protein expression of p-ERK1/2， PD-L1， Beclin-1， and p62 was reduced in the medium dose group （P<0.05）， and LC3Ⅰ/Ⅱ protein expression was elevated （P<0.05）. In the high dose and inhibitor groups， protein expression of p-ERK1/2， PD-L1， Beclin-1， and p62 was significantly reduced （P<0.01）， while LC3Ⅰ/Ⅱ protein expression was significantly elevated （P<0.01）. ConclusionGuiqi Yiyuan ointment may inhibit the activation of the ERK signaling pathway， downregulate the expression of p-ERK1/2， promote autophagic flux in tumor cells， and regulate the expression of PD-L1， thereby exerting an inhibitory effect on tumor growth in Lewis lung cancer mice.

Objective:To investigate the efficacy of microsurgical treatment in cavernous sinus tumors.Methods:The clinical data of 87 patients with cavernous sinus tumor treated by microsurgery from January, 2010 to August, 2019 were analysed retrospectively. The surgical approaches and microsurgical skills for common tumors in Cavernous Sinus region were discussed. The follow-up included outpatient and telephone follow-ups, and the follow-up results were evaluated by KPS score.Results:Among the 87 cases, 57 were totally resected (65.5%), 14 were subtotal resected (16.1%) and 16 were major resected (18.4%). Hospitalisation ranged from 14 to 98 days, with an average of 29 days. Postoperative complications occurred in 30 cases with cranial nerve injury, 2 brain stem injury, 4 postoperative bleeding, 5 cerebrospinal fluid leakage, 4 infection, 1 Pituitary damage and 1 death. Prognosis and follow-up analysis showed 68 cases with KPS>60 and 66 with KPS>80 at 1 month after surgery; 74 with KPS>70 and 72 with KPS>80 at 3 months after surgery; 78 with KPS>80 by 12 months after surgery. During the follow-up period of 6-120 months, 3 cases died. Recurrence: 6 of incomplete resection of meningioma, were in 1-6 years after the surgery, 4 of incomplete resection of schwannoma in 1-8 years, 2 of pituitary adenoma respectively in 13 and 16 months after the surgery. There was no recurrence after reoperation. Two cases of chondrosarcoma, 3 of chordoma and 3 of germinoma were treated with radiotherapy, and during the follow-up, there was no progress of the focus. No tumor progression or recurrence was found in other cases during follow-up.Conclusion:Surgery of cavernous sinus tumor is difficult due to frequent postoperative complications. Reasonable preoperative plan, surgical approach and precise microsurgical techniques are the keys in reduction of postoperative complications and in the improvement of prognosis.

Objective To explore the role of the SerpinB5 and β-catenin in occurrence and development of the primary hepatocellular carcinoma (HCC). Methods The expressions of SerpinB5 and β-catenin protein and mRNA in carcinoma tissues and paracancerous tissues of 60 patients with primary HCC were detected by immumohistochemistry and real-time quantitative reverse transcriptional polymerase chain reaction (RT-PCR) methods. Results The positive expression rate of SerpinB5 protein and SerpinB5 mRNA in carcinoma tissues were significantly lower than those in paracancerous tissues:25.0%(15/60) vs. 63.3%(38/60) and 1.12 ± 0.43 vs. 5.19 ± 0.39, and there were statistical differences (P<0.01). The positive expression rate of β-catenin protein and β-catenin mRNA in carcinoma tissues were significantly higher than those that in paracancerous tissues: 65.0%(39/60) vs. 31.7%(19/60) and 4.23 ± 0.25 vs. 1.19 ± 0.17, and there was statistical difference (P<0.01). Decreased SerpinB5 expression was associated with higher serumα-fetoprotein level, larger tumor size, poor differentiation, advanced TNM stage, capsule invasion and tumor thrombosis (P < 0.01 or 0.05). Increased β-catenin expression was associated with poor differentiation, advanced TNM stage, capsule invasion and tumor thrombosis (P < 0.01 or < 0.05). The correlation analysis result showed that SerpinB5 had negative correlation withβ-catenin (carcinoma issues:r=-0.346, P=0.001;paracancerous tissues:r=-0.258, P = 0.024). Conclusions The abnormal expression of SerpinB5 and β-catenin may contribute to the progression and biologically malignant behavior of primary HCC, and SerpinB5 and β-catenin exists synergistic effect in the occurrence and development of primary HCC.

Objective To evaluate the clinical application of multimodality treatment of brain arteriovenous malformation (BAVM) with Onyx embolization and microsurgery.Methods There were 48 patients with BAVM treated by combination of Onyx embolization and microsurgery.The clinical features,therapeutic process,complications and discharge status (by MRI,DSA and Glasgow outcome scale,GOS) were recorded in detail.The prognosis was estimated by modified Rankin scale (mRS) with 6-42 months' follow-up.Results The total resection rate was 97.9％.The therapy-related complications happened in 8 patients (16.7％).Among them,4 cases had dysfunction of central nervous system (8.3％),2 cases with intra-cerebral hemorrhage (4.2％),and 2 suffered from severe cerebral edema (4.2％).Good recovery was seen in 38 cases (79.2％) evaluated by GOS when discharged from hospital.The follow-up result mRS ＜ 3 was 97.9％.Conclusion Multimodality treatment of BAVM with Onyx embolization and microsurgery should be a good therapeutic strategy.

Objective To investigate the clinical features and therapeutic strategies of one patient with meningioangiomatosis ( MA ) complicated with intracranial aneurysm formation. Methods The clinical data of one patient with aneurysm-formed MA admitted to the Department of Neurosurgery,the First Affiliated Hospital of Sun Yat-sen University was analyzed retrospectively. The patient received emergency craniotomy and middle cerebral artery aneurysm clipping and evacuation of intracranial hematoma. The meningeal tissue around the aneurysm was taken for pathological examination. Results Microscopy revealed meningeal thickening in the patient with MA accompanied with intracranial aneurysm. Spindle cells around the meninges and perivascular tissue of cortical hyperplasia formed an annular and fence-like structure. The results of immunohistochemistry showed the hyperplastic vessels and perivascular fibroblast like spindle cells diffuse vimentin-positive;the hyperplastic vascular endothelial cells CD99,CD34 were positive;and the residual glial cells in the lesions showed glial fibrillary acidic protein positive. Conclusion MA complicated with intracranial aneurysm is rare. The vascular condition is poor. The shape of aneurysm is irregular,and the risk of bleeding is high. Excise the involved meningeal tissue and clip the aneurysm with microsurgical operation is the resonable treatment.

Objective To investigate the clinical features and treatment strategy of brain arteriovenous malforma-tions(AVM) associated with arterial aneurysms. Methods The clinical manifestation, imaging data, treatment and out-come of the patients with AVM were retrospectively analyzed in 38(10.4%) of these 364 patients. Results Hemorrhage was the most common clinical manifestation (60.5%). The hemorrhage risk was higher in AVM associated with arterial an-eurysms than in single AVM(χ2=5.956,P<0.05). The most common type of associated aneurysms was feeding artery an-eurysm (69.4%). Hemorrhage more frequently occurred within the aneurysm.(χ2=8.869,P<0.05). The bleeding lesions and 43 associated aneurysms of the 37 patients were treated effectively by endovascular treatment and/or craniotomy. Thirty-four patients had excellent or good outcomes, six patients had complications, 3 patients had neurological deficits. Postoperative digital subtraction angiography (DSA) examination showed the complete disappearance of arteriovenous malformation and aneurysm in sixteen cases. Conclusions The AVM associated with aneurysms is common in patients with AVM. AVM associated with aneurysms has a higher risk of hemorrhage than single AVM. The aneurysm within AVM has a higher rate of hemorrhage. The treatment priority should be given to the bleeding lesions and aneurysms.

Objective To investigate the difference of expression and distribution of Toll-like receptor 4 (TLR4)between acquired immunodeficiency syndrome (AIDS)-related Kaposi sarcoma (AIDS-KS)and classic Kaposi sarcoma (KS).Methods The subjects were collected from The First Teaching Hospital of Xinjiang Medical University from January 2010 to January 2012,including 11 patients with AIDS-KS,7 patients with classic KS,7 human immunodeficiency virus (HIV)infective patients without KS and 7 healthy volunteers.Clinical data and biopsy specimens were collected.The expression of TLR4 was detected by immunohistochemical method.Statistical analysis of mean between two groups was conducted by using t test.Statistical analysis of ranked data was conducted by using U test.Comparison between groups was analyzed with one-way ANOVA.Results The expressions of TLR4 were both strongly positive in patients with AIDS-KS and classic KS,and mainly in alien vascular endothelial cells (VEC)and tumor cells.TLR4 was located on cell membrane and cytoplasm,and also in the nucleus. TLR4 was rarely expressed in the skin tissue in HIV infective patients without KS and healthy volunteers. The expressions of TLR4 in AIDS-KS,classic KS,HIV infective patients and healthy volunteers were 0.242±0.443,0.208±0.059,0.072±0.042 and 0.065 ±0.031 ,respectively (F =33.70,P <0.01 ). The expressions of TLR4 were lower in HIV infective (AIDS ) patients without KS and healthy volunteers.The expression level of TLR4 was significantly higher in KS patients compared with non-KS patients (t=4.097,P =0.003).However,TLR4 expression had no significant difference between AIDS-KS and classic KS patients (t =0.480,P =0.638).The expression of TLR4 was significantly higher in AIDS-KS patients compared with HIV infective patients (t=2.900,P =0.010).Conclusions The study identifies that TLR4 is highly expressed in patients with AIDS-KS or classic KS.It is suggested that TLR4 may play an important role in occurrence and development of KS.

Objective To analyze the clinical features of AIDS-related Kaposi's sarcoma (AIDSKS) patients in Xinjiang uygur autonomous region,and to evaluate the efficacy of highly active antiretroviral therapy (HAART) and systemic chemotherapy.Methods Clinical data on 70 AIDS-KS patients admitted in Sixth People' s Hospital of Xinjiang Uygur Autonomous Region from January 2008 to June 2013 were reviewed.The demographic characteristics,progress of KS,extent of lesions,treatment and prognosis of these patients were retrospectively studied.The efficacy of different therapies and the prognosis were compared using t or x2 test.Results The average age of 70 AIDS-KS patients was (40 ± 10) years,and the ratio of male and female was 2.5 ∶ 1.Sixty-six out of 70 (94.29％) patients were Uyghur ethnic.Among 70 patients,23 cases (32.9％) were rapidly progressed.Lesions often progress to plaques and nodules affecting head,neck,trunk,limbs and internal organs.Among 64 evaluable cases,the fatality rate in treatment group was 7.7 (4/52),which was significantly lower than that in patients who did not receive treatment (4/12,x2 =5.861,P ＜ 0.05).After 6-month of HAART or HAART sequenced by chemotherapy,CD4+ T lymphocyte counts were significantly increased (t =35.258 and 42.528,P ＜0.01),while it was decreased or remained in low level in patients received other treatments or untreated.HAART sequenced by chemotherapy,chemotherapy sequenced by HAART,and chemotherapy alone were effective for all AIDS-KS patients,while the effective rate in patients received HAART alone was 86.4％ (19/22),and immune reconstitution inflammatory syndrome (IRIS) was appeared in 45.5％ (10/22)patients.Conclusions AIDS-KS more frequently occurs in young Uighur males.The lesion may affect various organs,and some progress rapidly.HAART plus chemotherapy may reduce the incidence of IRIS and improve the prognosis.

Objective To investigate the relationship between glycemic index (GI) of mixed foods and glucose and lipid metabolism index in elderly patients with diabetes mellitus, and to analyze the effects of CI response with regard to sex and obesity. Methods Forty-three patients with diabetes mellitus were divided into two groups with randomly crossover methods: high CI group and low GI group. Mixed meals were given for ten weeks (washing time:2 weeks). The biochemistry index and anthropometric index at baseline,before and after the first and second phase were measured. At the same time,fasting blood glucose(FBG)and postprandial 2 h blood glucose (2hBG) were supervised thrice a week and the daily energy, three macronutrients, and GI were calculated during trial. Results GI was positively correlated with FBG, 2hBG, homeostasis model assessment of insulin resistance ( HOMA-IR) ,body mass index ( BMI), and low-density lipoprotein cholesterol ( r = 0. 097-0. 423, P = 0. 000 1-0.01). GI value was a strong associated factor for FBG and 2hBG in overweight male patients. Conclusions The GI of mixed foods can better reflect the level of glucose response, especially in obese men. And it had good correlations with other metabolic indexes.

Objective To study the effect of PUMA gene mediated by recombinant adenovirus vector combined with radiation on the pancreatic carcinoma. Methods The PANC-1 cells were infected with Ad-PUMA (MOI = 10, 50 and 100, respectively) for 48 h. The expression of PUMA mRNA and protein was detected by RT-PCR and Western blot, respectively. PANC-1 cells were divided into 4 groups: control group, transfection group, irradiation group and combined treatment group. The cell growth inhibition rate and apoptotic rate of PANC-1 cells were assessed by MTT assay and flow cytometry. Human pancreatic carcinomas were transplanted subcutaneously in nude mice, which were randomized into 4 groups: control group, transfection group, irradiation group and combined treatment group. Tumor growth rate and apoptotie index at different time points were recorded in 35 days. Results The expression of PUMA mRNA and protein was increased with the increase of MOI of Ad-PUMA, which was does-dependant (MOI = 10, mRNA = 0.46 ± 0.02, protein = 0. 75 ±0.09;MOI=50, mRNA= 1.12±0.09, protein = 1.01 ±0.18;MOI= 100, mRNA= 1.50±0.08, protein=1.80 ± 0.15 ;P < 0.05). The proliferation of PANC-1 cells was suppressed significantly when transfected by Ad-PUMA in a dose-dependent manner(r = -0.986 55), which was more significant combined with radiation (r = -0.971 26, P < 0.05). Meanwhile, the apoptotie rate was increased in the same manner [for pre- and post-irradiation,which was (45.4 ± 5.26) % and (73.2 ± 6.62) %, respectively, P < 0.05]. From 7 to 35 d after PUMA gene transfection and radiotherapy, the tumor growth was significantly slower than those of irradiation group, transfection group and control group [35 d after therapy, the volume of tumor was (19.82 ± 6.45)mm3 ,(39.5 ± 9.23)mm3 , (33.6 ±3 10.3)mm3 and (52.0 ± 11.43)mm3 , respectively, P < 0.05]. And the apoptotic index was increased in the same manner (AI = 0.43 ± 0.05, 0.29 ± 0.10, 0.24 ± 0.05 and 0.00 ± 0.00, respectively, P < 0.05). Conclusions Recombinant adenoviral-mediated PUMA gene combined with irradiation could increase the cell-killing effect on pancreatic carcinoma. It is better than that of either one kind of therapy.