Objective To observe the therapeutic effects of urolithin A(UA)on respiratory syncytial virus(RSV)-induced lung infection in neonatal mice and explore the underlying mechanisms.Methods Babl/c mice(5-7 days old)were subjected to nasal instillation of RSV and received intraperitoneal injection of saline or 2.5,5 and 10 mg/kg UA 2 h after the infection and then once daily for 2 weeks.Bronchoalveolar lavage fluid(BALF)was then collected for detection of inflammatory cells and mediators,and lung pathology was evaluated with HE staining.RSV-infected BEAS-2B cells were treated with 2.5,5 or 10 μmol/L UA.Inflammatory factors,cell viability,apoptosis and autophagy were analyzed using ELISA,CCK-8 assay,TUNEL staining,flow cytometry,Western blotting and immunofluorescence staining.The cellular expressions of miR-136 and Sirt1 mRNAs were detected using qRT-PCR.A dual-luciferase reporter system was used to verify the binding between miR-136 and Sirt1.Results In neonatal Babl/c mice,RSV infection caused obvious lung pathologies,promoted pulmonary cell apoptosis and LC3-Ⅱ/Ⅰ,Beclin-1 and miR-136 expressions,and increased the total cell number,inflammatory cells and factors in the BALF and decreased p62 and Sirt1 expressions.All these changes were alleviated dose-dependently by UA.In BEAS-2B cells,RSV infection significantly increased cell apoptosis,LC3B-positive cells and miR-136 expression and reduced Sirt1 expression(P<0.01),which were dose-dependently attenuated by UA.Dual-luciferase reporter assay confirmed the binding between miR-136 and Sirt1.In RSV-infected BEAS-2B cells with UA treatment,overexpression of miR-136 and Ex527 treatment both significantly increased the inflammatory factors and cell apoptosis but decreased LC3B expression,and these changes were further enhanced by their combined treatment.Conclusion UA ameliorates RSV-induced lung infection in neonatal mice by activating miR-136-mediated Sirt1 signaling pathway.

Objective To observe the therapeutic effects of urolithin A(UA)on respiratory syncytial virus(RSV)-induced lung infection in neonatal mice and explore the underlying mechanisms.Methods Babl/c mice(5-7 days old)were subjected to nasal instillation of RSV and received intraperitoneal injection of saline or 2.5,5 and 10 mg/kg UA 2 h after the infection and then once daily for 2 weeks.Bronchoalveolar lavage fluid(BALF)was then collected for detection of inflammatory cells and mediators,and lung pathology was evaluated with HE staining.RSV-infected BEAS-2B cells were treated with 2.5,5 or 10 μmol/L UA.Inflammatory factors,cell viability,apoptosis and autophagy were analyzed using ELISA,CCK-8 assay,TUNEL staining,flow cytometry,Western blotting and immunofluorescence staining.The cellular expressions of miR-136 and Sirt1 mRNAs were detected using qRT-PCR.A dual-luciferase reporter system was used to verify the binding between miR-136 and Sirt1.Results In neonatal Babl/c mice,RSV infection caused obvious lung pathologies,promoted pulmonary cell apoptosis and LC3-Ⅱ/Ⅰ,Beclin-1 and miR-136 expressions,and increased the total cell number,inflammatory cells and factors in the BALF and decreased p62 and Sirt1 expressions.All these changes were alleviated dose-dependently by UA.In BEAS-2B cells,RSV infection significantly increased cell apoptosis,LC3B-positive cells and miR-136 expression and reduced Sirt1 expression(P<0.01),which were dose-dependently attenuated by UA.Dual-luciferase reporter assay confirmed the binding between miR-136 and Sirt1.In RSV-infected BEAS-2B cells with UA treatment,overexpression of miR-136 and Ex527 treatment both significantly increased the inflammatory factors and cell apoptosis but decreased LC3B expression,and these changes were further enhanced by their combined treatment.Conclusion UA ameliorates RSV-induced lung infection in neonatal mice by activating miR-136-mediated Sirt1 signaling pathway.

OBJECTIVE: To investigate the early effectiveness of transiliac-transsacral screws internal fixation assisted by augmented reality navigation system HoloSight (hereinafter referred to as "computer navigation system") in the treatment of posterior pelvic ring injuries. METHODS: A retrospective analysis was made in the 41 patients with posterior pelvic ring injuries who had been treated surgically with transiliac-transsacral screws between June 2022 and June 2023. The patients were divided into navigation group (18 cases, using computer navigation system to assist screw implantation) and freehand group (23 cases, using C-arm X-ray fluoroscopy to guide screw implantation) according to the different methods of transiliac-transsacral screws placement. There was no significant difference in gender, age, body mass index, causes of injuries, Tile classification of pelvic fracture, days from injury to operation, usage of unlocking closed reduction technique between the two groups ( P>0.05). The time of screw implantation, the fluoroscopy times, the guide wire adjustment times of each screw, and the incidence of complications were recorded and compared between the two groups. The position of the transiliac-transsacral screw was scanned by CT within 2 days after operation, and the position of the screw was classified according to Gras standard. RESULTS: The operation was successfully completed in both groups. The time of screw implantation, the fluoroscopy times, and the guide wire adjustment times of each screw in the navigation group were significantly less than those in the freehand group ( P<0.05). There were 2 cases of incision infection in the freehand group, and the incision healed by first intention after active dressing change; there was no screw-related complication in the navigation group during operation and early period after operation; the difference in incidence of complications between the two groups (8.7% vs. 0) was not significant ( P=0.495). According to the Gras standard, the screw position of the navigation group was significantly better than that of the freehand group ( P<0.05). CONCLUSION Compared with the traditional freehand method, the computer navigation system assisted transiliac-transsacral screws internal fixation in the treatment of posterior pelvic ring injuries has advantages of improving the accuracy of screw implantation and reducing radiation damage and the time of screw implantation.
Humans ; Retrospective Studies ; Surgical Wound Infection ; Replantation ; Body Mass Index

【Objective】 To investigate dynamic regional homogeneity (dReHo) abnormality in end-stage renal disease (ESRD) patients by using resting-state functional magnetic resonance imaging (rs-fMRI). 【Methods】 A total of 26 ESRD patients and 26 healthy controls (HC) matched in gender, education level and age were included. Rs-fMRI scanning was performed in all subjects. All the subjects were tested by using auditory verbal learning test Huashan version (AVLT-H) and Montreal Cognitive Assessment (MoCA) to assess cognitive function before collection of MRI data. T-test was used to observe the difference in dReHo at global level between the two groups. Pearson and Spearman correlation analyses were made to estimate the correlation between abnormal brain regions and clinical scales. 【Results】 Compared with HC group, the dReHo value in ESRD patients reduced on the bilateral superior margin gyrus, left insula, left posterior central gyrus, and left putamen (P<0.05, replacement test correction). The dReHo values of left superior margin gyrus (r=-0.534, P=0.005) and left insula in ESRD patients (r=-0.422, P=0.032) were negatively correlated with the LR-S score, and the dReHo value of the left margin was negatively correlated with the SR-S score (r=-0.468, P=0.016). 【Conclusion】 There are abnormal dReHo values in several brain regions in ESRD patients during resting state, which is related to the patients’ cognitive function. The variation of dReHo value provides a new objective imaging basis for evaluating the cognitive function of ESRD patients.

Objective:To compare the long-term prognosis between open versus closed reduction and internal fixation in the treatment of unstable pelvic fractures.Methods:The data of 402 consecutive patients with unstable pelvic fracture were retrospectively analyzed who had been treated at The First Medical Center and The Fourth Medical Center, PLA General Hospital, and Strategic Support Force Specialty Medical Center from March 2011 to March 2017. This cohort was divided into 2 groups according to the reduction methods. In the open group of 194 cases subjected to open reduction and internal fixation, there were 133 males and 61 females with a median age of 43.0 (30.7, 51.0) years, and 35 cases of type B and 159 cases of type C by the Tile classification. In the closed group of 208 cases subjected to closed reduction and internal fixation, there were 115 males and 93 females with a median age of 45.5 (32.0, 56.0) years, and 40 cases of type B and 168 cases of type C by the Tile classification. The 2 groups were compared in terms of 12-items Short Form Health Survey (SF-12) scores [physical component summary (PCS) and mental component summary (MCS)] at the last follow-up, time from injury to operation, frequency of intraoperative X-ray fluoroscopy, intraoperative and postoperative blood transfusion, operation time, and quality of postoperative fracture reduction.Results:There was no statistically significant difference between the 2 groups in the preoperative general data except for the gender, showing the 2 groups were comparable ( P>0.05). This cohort of 402 patients was followed up for 7.8(6.2, 8.8) years. At the last follow-up, the PCS [49.9 (45.4, 55.4) points] and MCS [53.1 (46.4, 57.6) points] in the closed group were significantly higher than those in the open group [48.2 (41.4, 52.7) and 46.5 (40.6, 53.6) points] ( P<0.05). The closed group incurred significantly shorter time from injury to operation [6 (5, 8) d] and operation time [180 (126, 260) min] than the open group [9 (6, 13) d and 240 (165, 334) min], significantly less intraoperative and postoperative blood transfusion [1.5 (0, 4.0) U] than the open group [5.0 (2.9, 8.0) U], significantly higher frequency of intraoperative X-ray fluoroscopy [104.5 (85.0, 132.0) times] than the open group [21.0 (18.0, 26.0) times], and a significantly higher excellent and good rate of postoperative fracture reduction (92.8%, 193/208) than the open group (86.6%, 168/194) (all P<0.05). Conclusion:In the treatment of patients with unstable pelvic fractures, compared with open reduction and internal fixation, closed reduction and internal fixation can not only significantly shorten the waiting time and operation time of patients, reduce the transfusion during operation, but also achieve better fracture reduction to ultimately improve the quality of life of patients.

Objective:To investigate the long-term survival and safety in patients with muscle-invasive bladder cancer (MIBC) who experienced a noninvasive down-staging (≤pT 1)after transurethral resection of bladder tumor (TURBT) plus systemic chemotherapy and received bladder-sparing treatment. Methods:The records of patients with MIBC who underwent maximal TURBT plus systemic chemotherapy-guided bladder-sparing treatment were reviewed retrospectively from Dec 2013 to Dec 2020. Eventually, 22 patients who achieved noninvasive down-staging underwent conservative management. The total patient cohort contained 10 males and 12 females. A majority of patients had single lesion and stage T2 disease. The median age of the patients was 66 years and the median tumor size was 3.0 cm. All patients underwent maximal TURBT to resect all visible diseases and followed by 3-4 cycles platinum-based systemic chemotherapy. After achieving noninvasive down-staging, 14 patients received concurrent chemoradiotherapy, and the other 8 patients underwent surveillance. Overactive bladder symptom score (OABSS) was used to assess the bladder function after treatment.Results:Twelve patients achieved pT 0 and 10 patients were down-staged to cT a-T 1. At a median follow-up of 36.7 months, 90.9%(20/22) patients retained their bladder function successfully. Among the 14 patients who received concurrent chemoradiotherapy, 4 had grade 3 or 4 adverse events. Among the 8 patients who underwent surveillance, 3 had grade 3 or 4 adverse events after systemic chemotherapy.Nine patients experienced tumor recurrence in the bladder, and 2 patients died of bladder cancer. Seven (31.8%) patients experienced Ⅲ/Ⅳ grade complications. The 5-year recurrence-free survival (RFS) and overall survival (OS) in patients achieved pT0 were 66.7% and 100.0%, respectively. The 5-year RFS and OS in patients achieved cTa-T1 were 40% and 72%, respectively. The OABSS score of 20 patients who retained their bladder successfully was (1.00±1.03). Conclusions:MIBC patients who achieved noninvasive down-staging might be candidates for the bladder-sparing treatment with maximum TURBT followed by systemic chemotherapy.The patients who achieved pT 0 might have better prognosis with functional bladder.

Purpose: Reduced quality of life after cystectomy has made bladder preservation a popular research topic for muscle-invasive bladder cancer (MIBC). Previous research has indicated significant tumor downstaging after neoadjuvant chemotherapy (NAC). However, maximal transurethral resection of bladder tumor (TURBT) was performed before NAC to define the pathology, impacting the real evaluation of NAC. This research aimed to assess real NAC efficacy without interference from TURBT and apply combined modality therapies guided by NAC efficacy. Materials and Methods: Patients with cT2-4aN0M0 MIBC were confirmed by cystoscopic biopsy and imaging. NAC efficacy was assessed by imaging, urine cytology, and cystoscopy with multidisciplinary team discussion. Definite responders (≤ T1) underwent TURBT plus concurrent chemoradiotherapy. Incomplete responders underwent radical cystectomy or partial cystectomy if feasible. The primary endpoint was the bladder preservation rate. Results: Fifty-nine patients were enrolled, and the median age was 63 years. Patients with cT3-4 accounted for 75%. The median number of NAC cycles was three. Definite responders were 52.5%. The complete response (CR) was 10.2%, and 59.3% of patients received bladder-sparing treatments. With a median follow-up of 44.6 months, the 3-year overall survival (OS) was 72.8%. Three-year OS and relapse-free survival were 88.4% and 60.0% in the bladder-sparing group but only 74.3% and 37.5% in the cystectomy group. The evaluations of preserved bladder function were satisfactory. Conclusion After stratifying MIBC patients by NAC efficacy, definite responders achieved a satisfactory bladder-sparing rate, prognosis, and bladder function. The CR rate reflected the real NAC efficacy for MIBC. This therapy is worth verifying through multicenter research.

Objective:To evaluate the value of 68Ga-labeled prostate-specific membrane antigen( 68Ga-PSMA PET/CT)in the diagnosis of prostate cancer(PCa) and determination of the strategy on neurovascular bundle(NVB)preservation and lymphadenectomy before surgery. Methods:We retrospectively analyzed the clinical data of 46 patients with newly diagnosed PCa who underwent 68Ga-PSMA PET/CT from June 2018 to October 2019. The median age was 66.50 (60.00, 69.25) years old and the median PSA was 15.97(8.58, 33.10)ng/ml. Forty-one patients were diagnosed PCa and 5 were diagnosed with benign prostatic hyperplasia or prostatitis by 68Ga-PSMA PET/CT, 6 were diagnosed with lymph nodes metastasis. Forty patients underwent mpMRI, 33 were diagnosed PCa, and 6 were diagnosed with lymph nodes metastasis. Seventeen patients underwent 11C-choline PET/CT, 12 were diagnosed PCa, and 4 were diagnosed with lymph nodes metastasis. Among the 41 patients which were diagnosed PCa by 68Ga-PSMA PET/CT, 26 were confirmed with PCa by needling biopsy, 12 did not undergo the needling biopsy and 3 had negative biopsy; 22 were in the high-risk group, and 19 were in the low- and medium-risk group. All 41 patients underwent radical prostatectomy. The strategy of NVB preservation was determined by the position of the PCa reported by 68Ga-PSMA PET/CT. If the tumor was close to the unilateral prostate capsule, the healthy part of the NVB would be preserved. And if the tumor was limited in the prostate gland, bilateral NVB would be preserved. The NVB was preserved in 16 cases(6 cases unilateral and 10 cases bilateral). In addition to routine lymph node dissection for patients in the high-risk group, lymph node dissection was also performed on patients with 68Ga-PSMA PET/CT that showed positive lymph nodes in the low- and medium-risk groups. The paired chi-square or Fisher exact test was used to compare the sensitivity and specificity of 68Ga-PSMA PET/CT, mpMRI, and 11C-choline PET/CT for lesion detection. Spearman analysis was used to examine the correlation between the SUV max, Gleason score, and the PSA value before treatment. Results:Forty-one patients undergoing radical resection were diagnosed PCa by postoperative pathology, and no cancer tissue was observed at the surgical margin; the median Gleason score was 8(7, 9); 20 cases (48.8%) had a pathological stage ≤pT 2c; 21 cases (51.2%)≥pT 3; 7 cases were N+ (11 positive lymph nodes). Seven cases (17.1%) had complications of Clavien-Dindo ≤ grade 2 within 30 days after surgery, and there was no complication above grade 3 after surgery. The median follow-up time of the 41 patients was 16(12, 20). The rate of urinary control was 46.3%, 95.1%, and 100% after 1 month, 6 months, and 12 months follow-up respectively. Among the five patients that did not undergo surgery, the PSA value of 4 decreased after antibiotic treatment, and biopsy was performed in 1 case without PSA decreasing, and no carcinoma was found. The sensitivity of 68Ga-PSMA PET/CT on the primary PCa was 100%(41/41), which was significantly better than that of 11C-choline(80%, 12/15, P=0.016)and mpMRI (83.7%, 31/37, P=0.009), while no statistical significance was observed between the specificity of 68Ga-PSMA PET/CT (5/5)and 11C-choline PET/CT(2/2, P=1.000), 68Ga-PSMA PET/CT and mpMRI(1/3, P=0.107). Of the 41 patients that were diagnosed with PCa, the sensitivity of 68Ga-PSMA PET/CT to lymph nodes metastases(71.4%, 5/7) had a significant difference with that of mpMRI(16.7, 1/6, P=0.016), but no statistical difference with 11C-choline (75%, 3/4, P=1.000). Analysis of the relationship between SUV max of 68Ga-PSMA PET/CT, Gleason score, and PSA value before treatment revealed that the SUV max of 68Ga-PSMA PET/CT in patients with Gleason score ≥8 and <8 score were 19.60(9.58, 24.38) and 8.55 (5.18, 12.88); SUV max of patients with PSA values ≥20 ng/ml and <20 ng/ml before treatment were 19.40 (13.00, 23.50) and 8.40 (5.35, 13.95), respectively, the differences were statistically significant (all P<0.05). Conclusions:68Ga-PSMA PET/CT had high sensitivity and specificity for the diagnosis of primary prostate cancer lesions, but the sensitivity for the diagnosis of lymph node metastasis was not enough to guide the preoperative decision of whether to remove the lymph node and the scope of the removal. However, the treatment strategy of whether to retain NVB could be formulated according to the tumor location displayed by 68Ga-PSMA PET/CT before surgery.

Objective To analyze how enterovirus D68 (EV-D68) protease 2A affects the anti-vi-ral interferon typeⅠ(IFN-Ⅰ) pathway in 293T cells following infection. Methods Western blot was used to detect the expression of recombinant protease 2A, IFN-α and signal transducers and activators of tran-scription 1 (STAT1) at protein level. Expression of EV-D68 viral protein (VP1) and protease 2A was ana-lyzed by immunofluorescence at different time points. Cytopathic effects were recorded to calculate 50％ cell culture infective dose ( CCID50 ) . Expression of the genes involved in the anti-viral IFN-Ⅰ pathway was measured by real-time PCR (RT-PCR). Results The recombinant plasmid pCLIPf-2A was successfully constructed and the expression of recombinant protease 2A could be detected by Western blot 24 h after transfection. The recombinant protease 2A promoted the proliferation of EV-D68 at the late stage of infection and induced the production of IFN-α. Expression of the genes involved in the anti-viral IFN-Ⅰ pathway at mRNA level was up- or down-regulated to different degrees with various trends in different groups following infection. Expression of STAT1 was enhanced in all groups. Conclusions EV-D68 protease 2A promoted the activation of anti-viral IFN-Ⅰpathway in response to viral infection and enhanced the proliferation of virus at the late stage of infection.

Zebrafish is an emerging animal model for studies on auditory system.This model presents high comparability with humans,good accessibility to the hearing organ,and high throughput capacity.To better utilize this animal model,methodologies need to be used to quantify the hearing function of the zebrafish.Zebrafish displays a series of innate and robust behavior related to its auditory function.Here,we reviewed the advantage of using zebrafish in auditory research and then introduced three behavioral tests,as follows:the startle response,the vestibular-ocular reflex,and rheotaxis.These tests are discussed in terms of their physiological characteristics,up-to-date technical development,and apparatus description.Test limitation and areas to improve are also introduced.Finally,we revealed the feasibility of these applications in zebrafish behavioral assessment and their potential in the high-throughput screening on hearing-related genes and drugs.