1.Combination of AAV-delivered tumor suppressor PTEN with anti-PD-1 loaded depot gel for enhanced antitumor immunity.
Yongshun ZHANG ; Lan YANG ; Yangsen OU ; Rui HU ; Guangsheng DU ; Shuang LUO ; Fuhua WU ; Hairui WANG ; Zhiqiang XIE ; Yu ZHANG ; Chunting HE ; Cheng MA ; Tao GONG ; Ling ZHANG ; Zhirong ZHANG ; Xun SUN
Acta Pharmaceutica Sinica B 2024;14(1):350-364
Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.
2.Clinical characteristics and risk factors of patients with uremic encephalopathy
Ziming OU ; Fuhua XIE ; Zhenhui ZHANG ; Weiyan CHEN ; Yichao WEN
Chinese Journal of Emergency Medicine 2021;30(5):602-606
Objective:To analyze and compare clinical characteristics and risk factors of patients with uremic encephalopathy (UE).Methods:A retrospective analysis was performed from January 2014 to January 2019 in our hospital. Seventy patients diagnosed with chronic kidney disease (CKD) at the end stage (according to diagnosis standard of CKD) complicated with UE were classified into the UE group. In principle matching with sex, age and duration of disease, seventy patients with chronic kidney disease at the end stage but without UE were classified into the non-UE group (NUE group). The demographic data, laboratory examination, CT or MRI examination were recorded and analyzed by using t or χ 2 test. In addition, independent risk factors of patients with UE were analyzed by using Logistic model. Results:A total of 70 patients in the UE group and 70 patients in the NUE group were collected. The proportion of patients with a history of alcohol comsumption, chronic obstructive pulmonary disease and polycystic kidney disease were higher in the UE group than in the NUE group ( P<0.05). There were no significant differences in hypertension, diabetes, and coronary artery disease history between the two groups ( P>0.05). The proportion of cerebral focus and lesions for brain white matter revealed by head CT or MRI in the UE group were significantly higher than that in the NUE group ( P<0.05). The serum NLR and UA levels in the UE group were higher than those in the NUE group ( P<0.05), but the serum ALB and FT3 levels in the UE group were lower than those in the NUE group ( P<0.05). Logistic regression analysis showed that serum NLR, ALB and FT3 levels were independent risk factors for UE patients. Conclusions:Cerebral focus and lesions for brain white matter revealed by CT or MRI are typical abnormal in UE patients. The serum NLR, FT3 and ALB levels are independent risk factor for UE patients.
4.Distribution and proportion of M1/M2 macrophages in periodontal tissues in rats with and without periodontitis
LIANG Hongling ; CHEN Bin ; HE Shasha ; XIE Xiaoting ; YAN Fuhua
Journal of Prevention and Treatment for Stomatological Diseases 2018;26(10):627-633
Objective:
To investigate the distribution and proportion of M1/M2 macrophages in the periodontal tissues of rats with and without periodontitis.
Method:
Twelve Sprague-Dawley rats were randomly divided into a chronic periodontitis group (CP, n = 6) and a periodontal health group (PH, n = 6). The periodontitis model was induced at the first mandibular molar using a stainless steel ligature and was confirmed by histological analysis. M1 macrophages were labeled with inducible nitric oxide synthase (iNOS), and M2 macrophages were labeled with CD163. The distributions of M1 and M2 macrophages in the two groups were determined via immunohistochemistry and immunofluorescence, and the M1/M2 ratios were compared between the two groups.
Results :
The M1 type macrophage count in the PH group was 12.17 ± 1.40, and the M1 macrophage count in the CP group was 40.00 ± 3.20; there was a statistically significant difference between the two groups (t = 7.96, P<0.0001). The M2 macrophage count in the PH group was 4.50 ± 1.09, and the M2 type macrophage count in the CP group was 5.33 ± 0.67. There was no statistically significant difference between the two groups (t = 0.65, P = 0.53). The M1/M2 ratio in the CP group was 3.72 ± 1.08, and the M1/M2 ratio in the PH group was 8.31 ± 1.37; there was a statistically significant difference between the two groups (t = 2.63, P= 0.025).
Conclusion
During periodontitis, M1 macrophages increased significantly and were widely distributed; they may be involved in the progression of periodontitis and may be closely related to the destruction of the cementum.
5.The characteristics of pancreatic ductal adenocarcinoma with single-source dual energy spectral CT imaging
Huanhuan XIE ; Xiaozhu LIN ; Qingrou WANG ; Nan CHEN ; Haipeng DONG ; Kemin CHEN ; Fuhua YAN
Chinese Journal of Radiology 2017;51(3):170-173
Objective To explore the quantitative characteristics of pancreatic ductal adenocarcinoma(PDAC) in single-source dual energy spectral CT imaging. Methods From January 2013 to December 2014, 113 patients underwent dual phase contrast-enhanced gemstone spectral imaging(GSI) on Discovery CT 750 HD. All diagnoses were pathologically confirmed by surgery or biopsy. The spectral HU curves of PDAC were observed, the monochromatic CT values, the effective atomic number(Zef ), the iodine concentration(IC), water concentration(WC), and the corresponding normalized values(normalized monochromatic CT values, normalized Zef , normalized IC, normalized WC)of the lesion and the pancreatic parenchyma in late arterial phase(AP) and portal venous phase(PP) were recorded . The measurements were performed three times repeatedly. Paired t test (normal distribution) or Wilcoxon test (non-normal distribution) were used for analyzing the differences between the two phases and between PDAC and pancreatic parenchyma. Results The monochromatic CT values of PDAC in AP were lower than in PP at each energy level and the difference was more marked at lower energy. The normalized monochromatic CT values increased with the increase of energy level in both AP and PP and the difference was more distinct at lower energy. The Zef , IC and normalized IC of PDAC all had significant differences(P<0.05), while the WC, normalized Zef , and normalized WC had no difference between AP and PP. The Zef and IC of pancreatic parenchyma had significant differences(P<0.05), while the WC had no difference between AP and PP. The differences of Zef , IC, and WC between PDAC and pancreatic parenchyma were significant in both two phases (P<0.05). Conclusions Dual phase CT spectral imaging showed characteristic quantitative parameters of pancreatic ductal adenocarcinoma. The monochromatic CT values, Zef , and iodine concentration of PDAC were lower than those of pancreatic parenchyma in both AP and PP. The monochromatic CT values, Zef , and iodine concentration of PDAC in late arterial phase were lower than those in portal venous phase. The differences were all more distinct at lower energy.
6.Preoperative diagnosis of pancreatic neuroendocrine neoplasms with computed tomography and magnetic resonance imaging
Xiaozhu LIN ; Huanhuan XIE ; Qingrou WANG ; Weimin CHAI ; Nan CHEN ; Fei MIAO ; Kemin CHEN ; Fuhua YAN
Chinese Journal of Digestion 2017;37(5):308-312
Objective To assess the value of computed tomography (CT) and magnetic resonance imaging (MRI) in the diagnosis of pancreatic neuroendocrine neoplasms (PNEN) and to analyze the factors influencing thepreoperative imaging diagnosis of PNEN.Methods From January 2016 to November 2016, patients with PNEN diagnosed by surgery and biopsy were collected. CT and MRI data of them were analyzed. The CT values or signal intensity of the lesions and the pancreatic parenchyma were measured and the contrast-to-noise ratio (CNR) of the lesion was calculated. Detecting sensitivity and diagnosis accuracy of CT and MRI were compared. Detecting sensitivity of different MRI sequences was also analyzed. Diagnosis accuracy of non-functional PNEN and functional PNEN was compared and analyzed. Lesion CNR was compared between arterial phase and portal venous phase of the contrast enhanced CT. The sensitivity, accuracy and constituent ratio were compared by nonparametric analysis. Independent sample t test and one-way analysis of variancewere performed for the quantitative parameters comparison. Results A total of 54 patients with 56 lesions of PNEN were included for two of whom had two lesions each. CT and MRI were both performed in 44 patients (46 lesions).Detecting sensitivity and diagnosis accuracy of CT were 97.8% (45/46) and87.0% (40/46), respectively. Detecting sensitivity of MRI were 97.8% (45/46) and89.1% (41/46), respectively. There was no significant difference in detecting sensitivity and diagnosis accuracy between CT and MRI (both P>0.05). The CNR of lesion in arterial phase was higher than that of portal venous phase(4.7±3.8 vs 3.4±2.5), and the difference was statistically significant (t=2.949, P<0.05). Detecting rates of T1 weighted imaging with fat suppression (T1WI-FS) image, T2 weighted imaging with fat suppression (T2WI-FS) image, diffusion weighted imagingand dynamic contrast enhanced T1WI-FS image were 90.0% (45/50), 88.0%(44/50), 86.0%(43/50), and 91.7% (44/48), respectively. There was no significant difference in detecting rate among these images sequences (Q=2.526, P=0.510). Tumor diameter in non-functional PNEN was significantly larger than that in functional PNEN ((2.9±1.6) cm vs (1.7±0.7) cm)(t=3.479,P<0.05). The overall diagnosis rate of non-functional PNEN with CT and MRI before operation was 70.8% (17/24), which was significantly lower than that of functional PNEN (100.0%, 31/31) (χ2=10.360,P=0.002).Conclusions CT and MRI are both sensitive in detectingPNEN, and they were two complementary modalities. CT image in arterial phase delineated the lesion better than that in portal venous phase. MRI images with different sequences can becomplementary and there is no significant difference in detecting sensitivity for PNEN among different sequences. CT and MRI play an equal rolein the diagnosis of PNEN before operation. Because of atypical CT and MRI findings, the diagnosis of non-functional PNEN is more difficult thanfunctional PNEN.
7.Value of CT spectral imaging in demonstration of pancreatic ductal adenocarcinoma
Huanhuan XIE ; Xiaozhu LIN ; Qingrou WANG ; Nan CHEN ; Haipeng DONG ; Kemin CHEN ; Fuhua YAN
Journal of Practical Radiology 2017;33(5):750-753
Objective To explore the value of CT spectral imaging in the demonstration of pancreatic ductal adenocarcinoma (PDAC).Methods 113 patients were scanned by CT spectral,and gemstone spectral imaging (GSI) was performed in late arterial phase (AP) and portal venous phase (PP).All diagnosis were pathologically confirmed.The ROIs were placed on the lesion and on the pancreatic parenchyma.The ROI files including the CTmono values and the normalized CTmono values (normalized to pancreatic parenchyma) were saved.The works were performed three times repeatedly.CNR values ranged from 40 keV to 140 keV and the optimal keV in AP and PP were calculated.The differences of CTmono values, normalized CTmono values,and CNR were compared between the optimal keV and 70 keV(equivalent to conventional 120 kVp energy level).Paired t-test and Wilcoxon signed rank test were performed.P<0.05 was considered statistically significant.Results The optimal monochromatic energy of PDAC were 40 keV in both AP and PP.The optimal CNR values(mean±standard) were 2.31±1.02 and 2.38±1.02 in AP and PP,while the corresponding values of 70 keV were 2.08±0.98 and 2.12±0.96.The CNR of 40 keV was higher than that of 70 keV in both AP and PP.The CTmono values of PDAC were (58±13) HU and (71±19) HU at 70 keV and were (111±44) HU and (155±57) HU at 40 keV in AP and PP.The CTmono value in PP was higher than in AP.The median of normalized CTmono values of PDAC at 40 keV were 47.0% and 53.9% in AP and PP, and were lower than those of 70 keV,which were 57.7% and 61.8%.The differences of normalized CTmono values between 40 keV and 70 keV were significant.Conclusion CT spectral imaging manifests that PDAC is hypovascular both in AP and PP and is progressively enhanced form AP to PP.There is maximal conspicuity of tumor in AP, and the optimal monochromatic imaging can improve the conspicuity of PDAC lesion.
8.Impacting factors on the professional identity of railway young workers and the relationship with the professional identity and subjective well-being
Fuhua KUANG ; Dongjie XIE ; Ligang WANG ; Xiaolan FAN ; Wenbin GAO
Chinese Journal of Behavioral Medicine and Brain Science 2014;23(3):254-257
Objective To investigate the impacting factors on the professional identity of railway young workers and the relationship of the professional identity and subjective well-being.Methods The sample consisting of 5 762 young workers was selected from railway enterprises by stratified and random sampling according to the proportion.Occupational professional identity Scale and Index of Well-being,Index of General Affect Scale were used.The affect of the variable,such as sex,age,working years,educational background and income on professional identity were studied.Moreover,the relationship between professional identity and subjective well-being was reported.Results (1) Professional identity ascended witb the increase of ages,and there was significance between three groups(F=6.667,P<0.05).(2)Professional identity ascended with the increase of length of service (F=5.147,P<0.01),but it dropped at the point of 9-12 years.(3) The professional identity of workers with bachelor degree was higher than that with junior college education background.and there was significance between three groups (F=3.538,P<0.05).(4)The workers who had more than 3 500 RMB monthly salary was regarded on the top in professional identity,while those whose monthly salary were under 2 500 RMB was in the lowest level (F=42.275,P<0.01).(5)The result of linear regression indicated that the degree of professional identity can forecast the degree of subjective well-being(R =0.534,P<0.01).Conclusion The professional identity of railway young works was affected by their ages,the length of service,the educational degree and salary,The professional identity can forecast subjective well-being.
9.Efficacy analysis of different therapeutic methods in low-risk patients with clinical stage Ⅰ nonseminomatous germ cell testicular tumors
Gang FAN ; Yu XIE ; Weiqing HAN ; Zhiqiang JIANG ; Ke YANG ; Fuhua ZENG ; Xiaming PEI
Chinese Journal of Urology 2014;35(8):611-615
Objective To evaluate the effects of rigorous surveillance and retroperitoneal lymph node dissection (RPLND) in the treatment of low-risk patients with clinical stage Ⅰ nonseminomatous germ cell testicular tumors (NSGCT) after radical orchiectomy.Methods The data of 71 patients with clinical stage Ⅰ NSGCT were analyzed retrospectively in Hunan Provincial Tumor Hospital,Xiangya Third Hospital of Central South University and Hunan Provincial People's Hospital between Feb,2001 and Apr,2012.Excluding lymphatic and vascular invasion,percentage of embryonal carcinoma>50% and increasing tumour markers (AFP/β-HCG) following orchiectomy,46 low-risk patients out of 71 patients with clinical stage Ⅰ NSGCT were selected and divided into rigorous surveillance group (30 cases) and RPLND group (16 cases) according to different therapeutic methods after radical orchiectomy.Univariate analysis was used to confirm variables associated with disease progression,and the disease free survival rates (DFSR) were compared by using Kaplan-Meier analysis.Results Five cases were lost,and 41 cases were followed up for an average of 61 months (range,15-147 months),with 58 months in rigorous surveillance group (range,19-147months) and 65 months in RPLND group (range,15-144 months).The survival rate was 100% in 2 groups.The DFSR was 89% (24/27) and 86% (12/14),respectively,and there was no significant difference between the 2 groups (x2 =0.08,P=0.78).The DFSR was 83% in patients with small amout of embryonal (percentage of embryonal carcinoma < 50%),and 92% in patients without embryonal carcinoma,and there was no significant difference between the 2 groups (x2=1.07,P=0.30).Also there was no significant difference between the patients less than 15 years and patients more than 15 years (x2=1.59,P =0.21).Conclusions There is no significant difference in recurrence rate and DFSR between rigorous surveillance group and RPLND group.Low-risk patients with clinical stage Ⅰ NSGCT may achieve satisfactory prognosis with surveillance after radical orchiectomy.
10.The diagnosis and treatment of acute renal infarction
Zhenyu YANG ; Jun LI ; Fuhua Lü ; Qier XIA ; Chang SHENG ; Ping XIE ; Xu ZHANG ; Qiang FU ; Qinghua QU ; Dawei WANG ; Ximing GONG ; Xiande YE
Chinese Journal of Urology 2012;33(8):593-597
Objective To evaluate the clinical diagnosis and treatment of acute renal infarction.Methods Two cases (3 sides) of acute renal infarction were reported.The patients were 1 male and 1 female,with the age of 62 and 54 years.Case 1 presented acute left flank pain,and enhanced CT showed a non-enhanced area in the upper and mid pole of the left kidney.The diagnosis of focal renal infarction was made and treated with low-molecular heparin (6000 U ).Case 2 presented acute both right abdominal and flank pain,and enhanced CT showed right renal artery embolism and right renal complete infarction.Digital subtraction angiography (DSA) and catheter thrombolytic therapy was applied.4 months later,the patient presented acute left flank pain,and enhanced CT showed a low density area in left kidney without enhanced by contrast,and DSA and catheter thrombolytic therapy was applied again.Results In case 1,contrastenhanced MRI showed a still low signal area like enhanced CT after 2 days of treatment.The renal function remained normal in the follow-up of 36 months.In case 2,the right kidney resorted to moderate blood flow but became atrophy later.In the follow-up of 4 months,a recurrent focal infarction was confirmed in left kidney by enhanced CT.The left kidney also resorted to moderate bloodflow after DSA and catheter thrombolytic therapy.The renal function became normal after follow-up of 10 months and no new infarction was observed.Conclusions The diagnosis of acute renal infraction could be made by enhanced CT or MRI.Early diagnosis and location of the infraction renal artery is critical for recovery of the impaired renal function.Acute renal infraction should be suspected in patients with unexplained persistent and steady flank or abdominal pain in emergence department.


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