Objective To observe the effect of a new cell delivery tool(MSC exo)on the proliferation of pancreatic cancer by transferring targeted genes.Methods Transmission Electron Microscope(TEM)and Nanoparticle Tracking Analysis(NTA)were used to identify human mesenchymal stem cell exosomes(MSC-exo)and transport miR-450a-5p into CFPAC-1,to explore the effect of miR-450a-5p targeting BZW2 on inhibiting the proliferation of pancreatic cancer cells.Results The expression of miR-450a-5p was low in pancreatic cancer tissue(P<0.05),and the expression of CD63 and TSG101 of MSC-exo-miR-450a-5p in CFPAC-1 cells was higher than that of MSC-exo by Western blot(P<0.05).CCK-8 and EdU results showed that MSC-exo-miR-450a-5p significantly inhibited the proliferation of CFPAC-1 cells(P<0.05).Cell scratch and Transwell experiments showed that MSC-exo-miR-450a-5p can inhibit the migration and invasion of CFPAC-1 cells(P<0.05).Through dual luciferase assay,it was confirmed that miR-450a-5p targets BZW2,and RT-qPCR and Western blotting showed a negative correlation(P<0.05)between miR-450a-5p and BZW2 expression.Overexpression of BZW2,CCK-8,EdU,cell scratch,and Transwell experiments confirmed that pc-BZW2 reversed the anti-cancer function of MSC-exo-miR-450a-5p on CFPAC-1.Western blot detected PCNA,Ki-67,MMP2,MMP9,and the results were consistent with the above experiments(P<0.05).Conclusion hMSC exo is a new delivery system,targeting BZW2 to transport miR-450a-5p to inhibit the biological malignancy of pancreatic cancer cells,which provides an important clue for the research of targeted treatment of pancreatic cancer.

As the most aggressive breast cancer, triple-negative breast cancer (TNBC) is still incurable and very prone to metastasis. The transform growth factor β (TGF-β)-induced epithelial-mesenchymal transition (EMT) is crucially involved in the growth and metastasis of TNBC. This study reported that a natural compound isotoosendanin (ITSN) reduced TNBC metastasis by inhibiting TGF-β-induced EMT and the formation of invadopodia. ITSN can directly interact with TGF-β receptor type-1 (TGFβR1) and abrogated the kinase activity of TGFβR1, thereby blocking the TGF-β-initiated downstream signaling pathway. Moreover, the ITSN-provided inhibition on metastasis obviously disappeared in TGFβR1-overexpressed TNBC cells in vitro as well as in mice bearing TNBC cells overexpressed TGFβR1. Furthermore, Lys232 and Asp351 residues in the kinase domain of TGFβR1 were found to be crucial for the interaction of ITSN with TGFβR1. Additionally, ITSN also improved the inhibitory efficacy of programmed cell death 1 ligand 1 (PD-L1) antibody for TNBC in vivo via inhibiting the TGF-β-mediated EMT in the tumor microenvironment. Our findings not only highlight the key role of TGFβR1 in TNBC metastasis, but also provide a leading compound targeting TGFβR1 for the treatment of TNBC metastasis. Moreover, this study also points out a potential strategy for TNBC treatment by using the combined application of anti-PD-L1 with a TGFβR1 inhibitor.

Objective:To investigate the clinical characteristics and prognostic factors of primary urethral cancer.Methods:The clinical data of 35 patients with primary urethral cancer admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to April 2022 were retrospectively analyzed. There were 12 males (34.3%) and 23 females (65.7%). The average age was 61.1 ± 13.0 years old. The clinical symptoms included 13 cases of urethral obstruction (37.1%), 7 cases of hematuria (20.0%), 6 cases of urethral bleeding (17.1%), 5 cases of urinary tract irritation (14.3%), 1 case of Urinary incontinence (2.9%), 1 case of low back pain (2.9%), 1 case of scrotal ulcer (2.9%), and 1 case (2.9%) by self examination. All patients underwent cystourethroscopy and tissue biopsy. The biopsy pathology showed 16 cases of urothelial carcinoma, 7 cases of squamous carcinoma, 4 cases of adenocarcinoma, 3 cases of malignant melanoma, 1 case of urothelial carcinoma with squamous carcinoma, 1 case of Signet ring cell carcinoma, 1 case of sarcomatoid carcinoma, 1 case of embryonic Rhabdomyosarcoma, and 1 case of epithelioid angiosarcoma. The tumors were located in the proximal urethra in 13 cases (37.1%) and in the distal urethra in 22 cases (62.9%). There were 14 cases (40.0%) with a maximum diameter of less than 3 cm, 16 cases (45.7%) with a diameter of ≥ 3 cm, and 5 cases (14.3%) with mucosal abnormalities. There were 12 cases of T 1 stage, 9 cases of T 2 stage, 7 cases of T 3 stage, and 7 cases of T 4 stage in tumor staging. Imaging evaluation of lymph nodes showed 25 cases of N 0 stage, 2 cases of N 1 stage, and 8 cases of N 2 stage; A total of 11 cases of lymph node biopsy were performed (including 8 cases of intraoperative lymph node dissection and 3 cases of preoperative lymph node biopsy), of which 6 cases had lymph node metastasis, and 1 case was initially diagnosed with distant metastasis. Thirty-one cases underwent surgical treatment, of which 16 cases underwent radical urethrectomy, and 8 cases underwent intraoperative pelvic and bilateral inguinal lymph node dissection, 8 cases underwent resection of urethral tumors, and 7 cases underwent transurethral resection of tumors. Four cases did not undergo surgical treatment, while 1 case had epithelioid angiosarcoma and received radiotherapy combined with chemotherapy, 2 cases received chemotherapy with GC (Gemcitabine+ cisplatin) regimen, and 1 case received immunotherapy with immune checkpoint inhibitors. The risk factors that affected patient prognosis were analyzed. Results:All 35 cases in this group were followed up, with a median follow-up time of 22 (2, 122) months. Seventeen cases survived, 18 cases died, and the overall median survival duration was 23 (13 to not reached) months. The overall 5-year survival rate was 45%. The results of univariate analysis showed that clinical T-stage ( P=0.019), maximum tumor diameter ( P=0.016), and tumor location ( P=0.006) were independent risk factors affecting patient prognosis. Result of multivariate analysis showed that the maximum diameter of the tumor ≥ 3 cm ( HR=2.673, P=0.029) and the proximal location of the tumor ( HR=3.064, P=0.023) were independent risk factors affecting patient survival. Gender, age, treatment method, lymph node dissection, adjuvant radiotherapy, adjuvant chemotherapy, clinical manifestations, pathological type, clinical N staging, and pathological N staging had no significant impact on patient survival rate ( P>0.05). Single factor analysis was conducted on female patients separately, and only tumor location was found to be a prognostic factor ( χ2=17.246, P<0.01). Conclusions:Primary urethral cancer is a rare disease with various symptoms and poor prognosis. The maximum diameter of the tumor ≥3 cm and the tumor located at the proximal end of the urethra are clinical risk factors affecting the prognosis of patients with primary urethral cancer.

Objective:To explore the clinicopathological features and prognosis of renal mucinous tubular spindle cell carcinoma (MTSCC).Methods:The clinical data of 16 patients with MTSCC admitted to the First Affiliated Hospital of Zhengzhou University from July 2013 to July 2022 were retrospectively analyzed. There were six male cases and ten female cases. The mean age was (56.4±11.4) years old. Among them, 10 cases were asymptomatic, two complained of hematuria, three complained of lumbar pain, and one complained of lower limb pain. Twelve cases underwent preoperative enhanced CT examination, 6 cases of ultrasound examination, 3 cases of MRI examination, and 1 case of bone scan. Imaging manifestations showed that the masses were round or round-like with clear borders. Two cases combined with hemorrhage and three cases combined with calcification. Five cases showed exophytic growth, 10 cases partially exophytic, and 1 case completely endophytic. The maximum diameter of the tumor was (65.7±27.4) mm. The tumors were located in the left kidney in 11 cases and in the right kidney in 5 cases. The tumors were mildly delayed-enhancing under enhanced CT, long/short T1 signal mixed with long/short T2 signal under MRI, and diffusion-limited high signal under DWI. The tumors were hypoechoic masses without obvious blood flow signals under ultrasound. Twelve cases were diagnosed as renal occupying neoplasms, 2 cases were suggested as lack of blood supply renal tumor, and one was considered renal tumor rupture and bleeding. In one case, a bone scan suggested metastasis to the thoracic spine and pelvis. The metastatic renal tumor was diagnosed, and a renal puncture was performed to clarify the pathology. Eleven patients underwent laparoscopic radical nephrectomy, and 4 patients underwent partial nephrectomy. One case was metastasized without surgery and treated with apatinib mesylate and zoledronic acid.Results:The postoperative pathological specimens showed grayish, grayish-yellow, or grayish-red masses with a soft or medium texture. No perinephric, ureteral, or adrenal invasion was seen in all tumors. Microscopically, the tumor cells were round and ovoid. The tumor cells were arranged in tubular and striated shapes, and mucus pools were locally visible. No sarcomatous component was seen in all tumors. There were 9 patients with pT 1N 0M 0, 6 patients with pT 2N 0M 0, and 1 patient with pT 1N 0M 1. After operation, 2 patients with pT 2N 0M 0, who underwent laparoscopic radical nephrectomy were treated with pazopanib and sunitinib, respectively. All patients were followed up for a median of 50.7(25.8, 75.0)months, 15 patients were free of recurrent metastases, and 1 patient with pre-puncture metastasis died due to tumor progression of multiple pulmonary and bone metastases, with a survival of 16.9 months. Conclusions:Renal MTSCC is rare, mostly found on physical examination, with female patients predominantly, and imaging shows a lack of blood supply tumor. Surgery is the primary treatment method. Partial nephrectomy or radical nephrectomy could be chosen according to the tumor stage, kidney function, and patient's underlying condition, and patients have a good prognosis.

BackgroundCompared with adult-onset schizophrenia， patients with adolescent-onset schizophrenia experience a high genetic susceptibility， severe negative symptoms， high recurrence rate， poor prognosis and social function recovery. And clarifying the brain functional alterations in adolescent-onset schizophrenia is of great significance for further elucidating the pathogenesis of the disease and exploring personalized and precise treatment. ObjectiveTo investigate the altered functional and effective connectivity of bilateral precuneus in first-episode patients with adolescent-onset schizophrenia based on resting-state functional magnetic resonance imaging （rs-fMRI）， thus providing reliable imaging evidence in guiding the study on mechanism involved in adolescent-onset schizophrenia. MethodsTwenty-one drugnaïve first-episode patients with adolescent-onset schizophrenia who met the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） criteria for schizophrenia were enrolled， and another 21 psychiatrially healthy controls matched on age， educational background and gender were concurrently selected. The schizophrenic subjects were evaluated using the Psychotic Symptom Rating Scales （PSYRATS） and Positive and Negative Symptom Scale （PANSS）. All participants underwent rs-fMRI scans， and the whole-brain seed-based functional and effective connectivity analyses were conducted in bilateral cuneus region. Then the correlation between functional connectivity strength and clinical symptoms of patients was discussed. ResultsIn terms of functional connectivity， the functional connectivity of bilateral precuneus and left middle temporal gyrus was increased in patient group compared with healthy control group ［P<0.01， family-wise error （FWE） correction at cluster level， P<0.05］. In terms of effective connectivity， patient group responded to negative feedback with greater activation of seed region and left middle frontal gyrus than healthy control group. Correlation analysis within patient group denoted that the decreased effective connectivity of bilateral precuneus and left middle frontal gyrus was positively correlated with the total PANSS score （r=0.450， P<0.05）. ConclusionThe resting-state functional and effective connectivity of bilateral precuneus is abnormally alerted in drugnaïve first-episode patients with adolescent-onset schizophrenia， and the decreased effective connectivity of bilateral precuneus and left middle frontal gyrus may be related to the development of clinical symptoms. ［Funded by National Key Research and Development Program of China （number， 2022YFC2009901， 2022YFC2009900）］

Objective:To investigate the effect of deviation from the isocenter point on the quality of CT images at the same radiation dose.Methods:A 160-layer CT scanner was used to scan the phantom at isocenter and deviations of 3, 6, 9, 12 and 15 cm. CT was performed with the following parameters: 120 kVp; 400 mAs; slice thickness, 1 mm; and slice increment, 1 mm. Images were reconstructed using the filtered back projection algorithm. Noise power spectrum (NPS), task transfer function (TTF) and detectability index (d′) were measured. NPS peak was used to quantify the noise magnitude and TTF 50% was used to quantify the spatial resolution. NPS, TTF and d′ were compared using one-way ANOVA. Results:The NPS average spatial frequency, spatial resolution and d′ values gradually decreased as the offset distance increased and the amount of noise increased. NPS peak at isocenter and deviations of 3 cm, 6 cm, 9 cm, 12 cm and 15 cm were (94.31±1.48), (104.25±1.46), (131.44±1.96), (171.86±1.91), (224.05±1.37), (286.51±2.09)HU 2·mm 2, respectively ( F=37 241.91, P<0.001). And d′ values of 2 mm low-contrast lesions were 3.51±0.06, 3.31±0.04, 3.01±0.04, 2.59±0.06, 2.21±0.03, 1.88±0.03, respectively. The reduction in spatial resolution was more pronounced for high contrast, and the d′ values decreased to a similar extent for various types of lesions. The noise was increased by about 82%, the high contrast spatial resolution was decreased by about 12%, and the d′ value was decreased by about 26% at 9 cm from the isocenter point (all P<0.05). The noise was increased by about 204%, the high contrast spatial resolution was decreased by about 27%, and the d′ value was decreased by about 45% at 15 cm from the isocenter (all P<0.05). Conclusion:The CT image quality was decreased with the increase of the offset distance from the CT isocenter point. The image quality was severely compromised at offset distances greater than 9 cm.

Objective To discuss the clinical diagnosis,treatment and prognosis of malignant melanoma of urinary system.Methods The clinical data of 5 patients with primary malignant melanoma of urinary system were retrospectively analyzed.There were 2 cases of primary melanona of the urethra,3 cases of primary malignant melanoma of the bladder.The diameter of the tumor ranged from 0.9 to 5.1 cm with an average of 3.1 cm.Results Two cases of urethral patients underwent radical resection of urethra.Among 3 cases of bladder,1 cases were in poor condition,and underwent laparoscopic partial cystectomy.In 1 young men,radical resection was refused and only transurethral resection of the bladder tumor was performed.Radical resection of bladder was done in 1 cases.Postoperative pathology showed that the tumor cells of 4 cases were fusiform under microscope,1 case was polygonal.5 cases showed melanin in the cytoplasm and diffuse proliferation of tumor cells,with obvious heterogeneity,cell proliferation index Ki-67 10％-30％.During the follow-up period of 7-30 months (median 19 months),3 patients died of metastasis.Conclusions Malignant melanona of urinary system is rare,with high malignancy and poor prognosis.Targeted therapy and immune therapy has become a new treatment option,which could improve the prognosis of patients.

Objective To investigate the potential clinical prognostic factors of severe traumatic brain injury.Methods Two hundred and thirteen severe traumatic brain injury patients,admitted to our hospital from May 2013 to July 2015,were chosen in our study.Their clinical data were retrospectively analyzed;prognostic factors,including age,gender,mGCS scores (movement GCS scores),improved CT scores,brain hernia,volume of intracranial hematoma,range of cerebral contusion and laceration,and location of intracranial hematoma,were estimated using Chi square test,and after the Chi square test,the factors enjoying statistical significance were analyzed by COX proportional hazards regression model.Results The mortality rate was 15.9％ (34/213).Death occurred within 30 days of admission,and death mostly occurred within 10 days of admission (1-10 d:23 patients;11-20 d:9 patients;20-30 d:2 patients).Cox proportional hazards regression analysis indicated that age,GCS scores (movement GCS scores),improved CT scores,and brain hernia were the prognostic risk factors in patients with severe traumatic brain injury,while gender,volume of intracranial hematoma,range of cerebral contusion and laceration,and location of intracranial hematoma were not.Conclusion Age,mGCS scores (movement GCS scores),improved CT scores,and brain hernia dare important factors affecting the prognosis of patients with severe traumatic brain injury.

Prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), plasma fibrino-gen (FIB), platelet aggregation rate and blood clots-fibrinolytic dynamic figure were taken as indexes in the evalua-tion of anticoagulant activity in vivo of active component F2-2 from Eupolyphaga seu Steleophaga. After 5 days of hypodermic injection of adrenaline, the rat model of acute blood stasis was established. Indexes were determined af-ter the model rats were treated with an intragastric administration of F2-2 for 9 days. The results showed that com-pared with the model group, PT/APTT was prolonged, FIB content was decreased, platelet aggregation rate and the largest of blood coagulation were declined after 9 days of intragastric administration in the model group. However, there was no difference on TT. It was concluded that the anticoagulant component F2-2 separated from E. seu Steleophaga showed favorable anticoagulant activity in vivo. However, its mechanism remained unknown and request-ed further researches.

Objective To evaluate the effect of 131 iodine(131I) therapy in medium and large goiter with hyperthyroidism in order to investigate the influence of pretreatment with antithyroid drugs (ATD) methimazole(MMI) and propylthiouracide (PTU) on 131I therapy.Methods A total of 338 hyperthyroidism patients (136 cases for male,202 cases for female) with thyroid mass greater than 40 grams were treated with 131I in the People's Hospital of Sichuan Province.Thyroid function,thyroid 131I uptake ratio and thyroid imaging were measured before treatment were measured 1-3 months later after administration of 131I,and they were followed up for 6 months to 4 years.Results There were statistical difference between pretreatment and 3 months later of 131I therapy in terms of free triiodothyronine (FT3),(Free thyroxine) FT4.The level of FT3 decreased from (31.9 ± 16.2) pmol/L to (7.8 ±8.5) pmol/L(t =23.9,P =0.000) and level of FT4 decreased from (58.8 ± 22.2) pmol/L to (19.4 ± 16.9) pmol/L(t =25.4,P =0.000).Among 338 patients,109 patients (32.2％) were developed hypothyroidism,and 91 patients (26.9％) were cured,91patients (26.9％) with improved state,20 patients(5.9％) with ineffective and 27 patients(8.0％) with relapse after administration of 131I.The total effective rate was 94.1％ (318/338).Thyroid weight,levels of FT3,FT4,thyroglobulin antibody(TGA),thyroid microsomal antibody(MCA) in effective group were (49.8 ± 9.97) g,(32.5 ± 16.3) pmol/L,(59.5 ± 22.2) pmol/L,(43.6 ± 35.3) ％,(30.1 ± 22.6) ％ respectively,and were (56.9±15.7) g,(22.8 ± 12.8) pmol/L,(47.9 ±20.3) pmol/L,(22.8±30.0)％,(15.3 ±20.5)％ respectively in ineffective group.There were statistically significant differences between the ineffective group and effective group (t =2.932,2.602,2.287,2.501,2.766 ; P =0.000,0.010,0.023,0.013,0.006).Logistic regression analysis was showed that weight of thyroid and serum FT3 were the most important factors in affecting 1131 therapy.Conclusion 131 I therapy for medium and large-sized goiter with hyperthyroidism is safe and effective.ATD may not reduce the effectiveness of subsequent 131I of hyperthyroidism.Thyroid weight and FT3 are the key influential factors in affecting 131I.