[ ABSTRACT] AIM:To investigate the effect of triptolide on the inhibition of microglial activation in 1-methyl-4-phenyl pyridinium ( MPP+)-induced hemiparkinson disease rats.METHODS:The rat model of Parkinson disease was es-tablished by intranigral injection of MPP +.The rats were randomly divided into sham group, MPP+group, triptolide group and vehicle group.The survival of dopaminergic neurons was detected by the immunofluorescence of tyrosine hydroxylase ( TH) in the substantia nigra ( SN) .The activation of microglia was determined by immunofluorescence of OX-42 ( micro-glia marker) in the SN.The expression of chemokine receptor CX3CR1 in SN was measured by Western blotting.RE-SULTS:Intranigral injection of MPP+increased the fluorescence intensity of the microglial marker, and promoted DA neu-ron degenerative death.Immunohistological analysis showed that the OX-42 density was decreased (P<0.01) and tyrosine hydroxylase (TH) positive neurons were increased in the triptolide group (P<0.01).The expression of CX3CR1 was lower in triptolide group than that in model group (P<0.05).CONCLUSION:Triptolide may improve PA neurons func-tion in MPP+-induced rats through inhibiting CX3CR1 expression and microglial activation.

Objective To evaluate the clinical value of ultrasound breast imaging reporting and data system (BI‐RADS) in small solid breast masses with diameter ≤1 cm. Methods The ultrasound features of 230 solid breast masses with diameter ≤ 1 cm were described by ultrasound BI‐RADS, the relationship between ultrasound features, BI‐RADS final assesment and pathology were analyzed. Results Of these 230 masses, 72 (31 3.% ) were pathologically confirmed to be malignant and 158 (68 7.% ) to be benign. The ultrasound BI‐RADS features of mass shape, margin, orientation, posterior acoustic features, and microcalcificaition were significantly different between malignant and benign masses( P < 0.05). Irregular shape, noncircumscribed, nonparallel orientation, postrior shadowing, microcalcifications were regarded as malignant ultrasound features, their positive predictive values(PPV), sensitivity, specificity and accuracy for malignancy were 53 3.% -100%, 2 8.% -75 0.%, 82 3.% -100%, 69 6.% -80 9.%, respectively. One hundred and fifty‐two(66.1% ), 62(27 0.% ), 16(7 0.% ) masses were classified into grade 3, 4, and 5, respectively. The PPV for grade 3, 4 and 5 were 10 5.%, 64 5.%, 100% respectively. Among BI‐RADS grade 3 cases, 87 5.%malignant masses were intraductal carcinoma in situ and special type of invasive cancer, among pathological benign BI‐RADS grade 4 masses, 90 9.% were hyperplasia and intraductal papilloma. Conclusions In small breast masses with diameter ≤ 1 cm, due to the sensitivity of malignant signs are not high, the overlap between signs of benign and malignant lesions, pathological type and other factors, the positive predictive value of BI‐RADS grade 3 is higher than criteria of American College of Radiology, so BI‐RADS classification requires further detailed study.

Aim To investigate the effect of sphingo-sine kinase 1 (SphK1 )on unilateral ureteral obstruc-tion(UUO)-induced tubulointerstitial fibrosis and ex-plore the possible mechanism.Methods The CD-1 mice were randomly divided into four groups:sham-op-eration group(Sham),PF-543 treatment control group (Sham +PF-543),model group(UUO)and PF-543 treatment group(UUO +PF-543).On 1 ,3,7 and 1 4 d after operation,eight mice were selected randomly from each group and sacrificed.The protein expressions of SphK1 ,mature TGF-β1 ,FN,ColⅠ,LC3,Beclin1 ,Atg5 and Atg1 2 were observed by Western blot.The histo-logical changes were examined by Masson′s trichrome stain.Immunhistochemistry was performed to measure the levels of expression of SphK1 ,FN and Col Ⅰ. Transmission electron microscope was used to observe the autophagic body.Results SphK1 expression and autophagy were both upregulated in a mouse model of kidney fibrosis induced by UUO. Meanwhile, in-creased mature TGF-β1 and deposition of extracellular matrix(ECM)were observed in tubulointerstitial areas compared with sham-operated mice.After intraperito-neal injection with the SphK1 specific inhibitor PF-543 in UUO mice,enhanced expression of SphK1 and acti-vated autophagy were significantly abrogated.Howev-er,aggravation of renal fibrosis was detected when SphK1 inhibitor PF-543 was applied to suppress SphK1 expression in UUO mice.Conclusion SphK1 activa-tion is renoprotective through the induction of autoph-agy in the pathogenesis of kidney fibrosis.

Objective To assess the value of preoperative neutrophil-lymphocyte ratio ( NLR) for predict the prognosis in patients with high grade T1 bladder.Methods From January 2004 to December 2014, the data of 307 patients diagnosed as bladder cancer of Stage 1 and high grade after undergoing TURBT were analyzed, including gender, age, smoking status, tumor number and size, hydronephrosis, intravesical instillations and preoperative blood transfusion of 307 patients diagnosed as bladder cancer of stage 1 and high grade after undergoing TURBT were analyzed retrospectively.All patients were primary urothelial carcinoma.According to preoperative NLR,patients were divided into the low NLR group( NLR≤2.42,n=197) and the high NLR group(NLR >2.42,n =110).Recurrence-free survival (RFS) and progression-free survival ( PFS) were calculated according to the Kaplan-Meier model and compared by the log-rank model.Cox regression models were used for multivariate analyses of the association between NLR and bladder cancer, then the prognostic factors affecting RFS and PFS were evaluated.Result of these 307 patients, the low NLR group accounted for 64.2%(197/307), and the high NLR group accounted for 35. 8%(110/307).The mean follow-up period was 71(range, 1-123)months.The recurrence rate in the low NLR group and the high NLR group recurrence rate were 19.2%( 38/197 ) and 34.5%( 38/110 ) respectively, RFS were 73.0(range, 2-123)months and 67.5(range, 1-122)months respectively.The progression rates were 4.1%(8/197) and 10.9%(12/110) respectively.The recurrence and progression rates in the high NLR group is higher than those in the low NLR group(P<0.01 and P=0.008), and RFS was shorter( P=0.002).Multivariable Cox regression analysis showed that NLR>2.42(P=0.007,HR=1.912)and hydronephrosis (P<0.01, HR =2.485 ) are associated with higher risk of recurrence.Conclusion Elevated preoperative NLR is an independent predictor of RFS and PFS in patients with high grade T1 bladder cancer.

Objective:To study the infiltration mode of local immune cells in prostate cancer and to explore the role of immune cells in the development of prostate cancer.Methods:Gene expression profile chip dataset of normal prostate and prostate cancer tissues were downloaded from Gene Expression Omnibus (GEO) database. The proportion of 22 immune cells in the two groups was calculated by using R and SPSS software; the differences in the proportion of immune cells between the two groups were compared. The correlation coefficients among immune cells in prostate cancer tissues were calculated.Results:The dataset GSE62872 was downloaded, and a total of 424 samples were obtained, including 160 normal prostate tissues and 264 prostate cancer tissues. There were 20 228 mRNA detected in each sample. Deconvolution algorithm was used to obtain the proportion data of 22 kinds of immune cells after data correction. The samples were screened with P < 0.01, and 63 normal prostate tissues and 57 prostate cancer tissues were obtained. The immune cells with higher expression included CD8 + T cells [(23.48±6.16)%], plasma cells [(18.46±5.74)%], monocytes [(12.15±3.82)%] and activated NK cells [(11.11±2.97)%]. The immune cells with higher constituent ratio correlation coefficient included CD8 + T cells and unactivated memory CD4 + T cells ( r = -0.609, P < 0.01), M 0 macrophages and M 2 macrophages ( r = -0.596, P < 0.01). Compared with normal tissues, the infiltration degree of M 1 macrophages and unactivated dendritic cell was increased, and the difference was statistically significant ( Z = -2.783, P = 0.005; Z = -2.129, P = 0.033). Conclusions:The infiltrated immune cells in the tumor microenvironment of prostate cancer are mainly CD8 + T cells, plasma cells, monocytes and activated NK cells. With the effect of the tumor microenvironment, M 0 macrophages mainly differentiate into M 2 macrophages cells, which may be involved in the occurrence and development of prostate cancer, providing new clues to find potential immunotherapy targets.

Objective:To analyze the influencing factors of short-term efficacy of 125I seed implantation for recurrent cervical metastatic lymph nodes of esophageal squamous cell carcinoma after external beam radiation therapy (RESCC). Methods:From January 2013 to March 2019, 47 patients (42 males, 5 females; age: 47-77 years) with RESCC who underwent CT guided 125I seed implantation in Hebei General Hospital were retrospectively analyzed. Patients were divided into effective group (complete remission (CR)+ partial remission (PR)) and ineffective group (stable disease (SD)+ progressive disease (PD)) according to response evaluation criteria in solid tumors (RECIST) at 3 months after implantation. Multivariate logistic regression was used to analyze the independent influencing factors of short-term efficacy. Cut-off values were determined by ROC curve. Results:Of 47 patients, 26 were effective (3 were CR and 23 were PR) and 21 were ineffective (7 were SD, 14 were PD). Multivariate regression analysis showed that tumor diameter, immediate postoperative dose delivered to 90% gross tumor volume ( D90), recurrence interval time were independent influencing factors of short-term efficacy (odds ratio ( OR; 95% CI): 4.240(1.220-14.737), 0.999(0.999-1.000), 0.989(0.979-1.000), Wald values: 5.163, 5.043, 3.956, all P<0.05). ROC curve showed that the AUC of tumor diameter, D90 and recurrence interval time were 0.782, 0.786 and 0.838 respectively, with cut-off values of 4.85 cm, 115.78 Gy and 297.5 d respectively. Conclusions:The short-term efficacy of 125I seed implantation for RESCC is mainly related to the tumor diameter, immediate postoperative D90 and recurrence interval time. Patients with tumor diameter <4.85 cm, immediate postoperative D90>115.78 Gy and recurrence interval time >297.5 d have better efficacy.

Purpose: Cavernous nerve injury induced erectile dysfunction (ED) is a refractory complication with high incidence in person under radical prostatectomy. Studies have shown that relaxin-2 (RLX-2) plays a vital role of endothelial protection, vasodilation, anti-fibrosis and neuroprotection in a variety of diseases. However, whether penile cavernous erection can benefit from RLX-2 remains unknown. The purpose of the experiment was to explore the effects of RLX-2 on ED in the rat suffering with bilateral cavernous nerve injury (BCNI). Materials and Methods: The rats were divided into three groups: Sham group was underwent sham operation, BCNI+RLX group or BCNI group was underwent bilateral cavernous nerve crush and then randomly treated with RLX-2 (0.4 mg/kg/d) or saline by continuous administration using a subcutaneously implanted micro pump for 4 weeks respectively. Then, erectile function was evaluated by electrical stimulation of cavernous nerves. Cavernous nerves and penile tissues and were collected for histological evaluation. Results: Erectile function of rats with BCNI was partially improved after RLX-2 treatment. The BCNI group had lower expression of relaxin family peptide receptor (RXFP) 1, p-AKT/AKT, p-eNOS/eNOS ratios than sham operation rats, but RLX-2 could partially reversed these changes. Histologically, the BCNI+RLX group had a significant effect on preservation of neurofilament, neuronal glial antigen 2 of penile tissue and nNOS of cavernous nerves when compared with BCNI group. RLX-2 could inhibited the lever of BCNI induced corporal fibrosis and apoptosis via regulating TGFβ1-Smad2/3-CTGF pathway and the expression of Bax/Bcl-2 ratio, caspase3. Conclusions RLX-2 could improve erectile function of BCNI rats by protecting cavernous nerve and endothelial function and suppressing corporal fibrosis and apoptosis via RXFP1 and AKT/eNOS pathway. Our findings may provide a promising treatment for refractory BCNI induced ED.

Objective: To analyze the factors influencing the short-term efficacy of CT-guided ¹²⁵I seeds implantation in the treatment of recurrent and metastatic tumors in head and neck. Methods: A total of 73 patients (61 males, 12 females; age: (59.1±11.5) years) with head and neck tumors recurrence and metastasis treated by ¹²⁵I seeds implantation in Hebei General Hospital from January 2015 to April 2019 were retrospectively enrolled. The implanted seeds activity was 11.1-29.6 MBq, and the prescription dose was 80.0-145.0 Gy. CT examination was conducted 3 months after ¹²⁵I seeds implantation. According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, short-term efficacy was classified as effective (complete remission (CR), partial remission (PR)) and ineffective (stable disease (SD), progressive disease (PD)). Univariate analysis of factors affecting short-term effect (gender, age, history of radiation therapy, Karnofsky performance status (KPS) scores, pathological type, the longest diameter of tumor, implantation patterns, seeds activity, immediate postoperative dose delivered to 90% gross tumor volume (D₉₀), and with adjuvant chemotherapy post-surgery or not) were conducted. Variables with P<0.2 were enrolled in logistic multivariate regression analysis. In addition, artificial neural network (ANN) was constructed with all influencing factors as independent variables and short-term efficacy as dependent variables. Finally, receiver operating characteristic (ROC) curve analysis was performed for the common influencing factors in logistic regression analysis and ANN analysis. Results: There were 34 with effective results and 39 with ineffective results. Logistic regression analysis indicated that the longest diameter of tumor, immediate postoperative D₉₀, with adjuvant chemotherapy post-surgery or not had significant impacts on the short-term efficacy (Wald values: 6.950, 4.804, 4.790, all P<0.05); According to results of ANN analysis, the top 5 in order of importance for short-term efficacy prediction were immediate postoperative D₉₀, the longest diameter of tumor, age, seeds activity and gender. ROC curve analysis indicated that the longest diameter of tumor and immediate postoperative D₉₀ were the best predictors for short-term efficacy, with the threshold of 5.25 cm and 110.05 Gy respectively, and the area under the curve (AUC) was 0.843 and 0.847 respectively (both P<0.001). Conclusions The short-term efficacy of ¹²⁵I seeds implantation in the recurrence and metastasis of head and neck tumors is mainly related to the longest diameter of tumor and immediate postoperative D₉₀. Patients with the longest diameter of tumor <5.25 cm and with D₉₀>110.05 Gy can achieve better efficacy.