Increased prevalence of CFTR variants and susceptibility to CRS: A real-world study based on Chinese children.

Background: Chronic Rhinosinusitis is a common disease in children. The main function of CFTR is to maintain the thickness of the mucous layer on the surface of the nasal mucosa. CFTR disease-causing variant can cause CFTR protein dysfunction and induce or aggravate chronic infection. However, the carrying status of the CFTR variants in the Chinese population is not clear. Objective: To study the frequency and variants of CFTR in Chinese children with CRS and to analyze the CFTR variants and the clinical characteristics and susceptibility to CRS. Methods: Whole Exome Sequencing was performed to analyze the CFTR genes in a total of 106 CRS children from the Chinese mainland area. The CFTR variants, frequency and clinical data were summarized and analyzed. Results: A total of 31 CFTR variants were detected, of which the carrying rate of 7 sites was significantly higher than that of the population database. 88 patients carried more than 2 variants. 37 people carried variants (MAF < 0.05), of which 91.89% had a history of recurrent upper respiratory infections, 16 had nasal polyps, 5 had bronchiectasis, and 1 was diagnosed with CF-related disorders. Conclusion: The carrying rate of CFTR variants in Chinese CRS children increased, and the highest rates of variants (MAF < 0.05) are p.I556V, p. E217G, c.1210-12[T]. Carrying multiple CFTR variants, especially p.E217G, p.I807 M, p.V920L and c.1210-12[T] may lead to increased susceptibility to CRS. There are CF-related disorders in patients with CRS.

Long non-coding RNA HOXA11-AS regulates ischemic neuronal death by targeting miR-337-3p/YBX1 signaling pathway: protective effect of dexmedetomidine.

Cerebral ischemia/reperfusion (I/R) is a common neurological disease. Homeobox A11 antisense RNA (HOXA11-AS), a long non-coding RNA (lncRNA), has been demonstrated as an important regulator in diverse human cancers. However, its function and regulatory mechanism in ischemic stroke remains largely unknown. Dexmedetomidine (Dex) have received wide attraction because of its neuroprotective effects. This study aimed to explore the possible link between Dex and HOXA11-AS in protecting neuronal cells from by ischemia/reperfusion-induced apoptosis. We used oxygen-glucose deprivation and reoxygenation (OGD/R) in mouse neuroblastoma Neuro-2a cells and middle cerebral artery occlusion (MACO) mouse model to test the link. We found that Dex significantly alleviated OGD/R-induced DNA fragmentation, cell viability and apoptosis, and rescued the decreased HOXA11-AS expression after ischemic damage in Neuro-2a cells. Gain-/loss-of-function studies revealed that HOXA11-AS promoted proliferation, inhibited apoptosis in Neuro-2a cells exposed to OGD/R. Knockdown of HOXA11-AS decreased the protective effect of Dex on OGD/R cells. HOXA11-AS was found to transcriptionally regulate microRNA-337-3p (miR-337-3p) expression as evidenced by luciferase reporter assay, while miR-337-3p expression was upregulated following ischemia in vitro and in vivo. Besides, knockdown of miR-337-3p protected OGD/R-induced apoptotic death of Neuro-2a cells. Furthermore, HOXA11-AS functioned as a competing endogenous RNA (ceRNA) and competed with Y box protein 1 (Ybx1) mRNA for directly binding to miR-337-3p, which protected ischemic neuronal death. Dex treatment protected against ischemic damage and improved overall neurological functions in vivo. Our data suggest a novel mechanism of Dex neuroprotection for ischemic stroke through regulating lncRNA HOXA11-AS by targeting the miR-337-3p/Ybx1 signaling pathway, which might help develop new strategies for the therapeutic interventions in cerebral ischemic stroke.

Bath-plug technique for the endoscopic management of cerebrospinal fluid leaks in children.

Importance: The safety and efficacy of the bath-plug technique for the closure of cerebrospinal fluid (CSF) leaks in children remain unknown. Objective: We undertook this study to ascertain whether the bath-plug technique was safe and effective for the repair of CSF leaks. Methods: We retrospectively reviewed patients who underwent endoscopic repair of CSF leaks with the fat graft as a plug-in at Beijing Children's Hospital from March 2016 to May 2020. Demographic data, medical history, defect sites and sizes, interventions, and clinical outcomes were analyzed. One representative clinical case was additionally selected to highlight the procedure and the healing process. Results: A total of 18 pediatric patients were included in this study. The group was composed of 11 boys and seven girls, aged from 5 to 123 months. The etiologies included congenital CSF leaks (n = 9) and head trauma (n = 9). Among all patients, 12 fistulas (66.7%) were located at the cribriform plate area, two (11.1%) at the roof of the ethmoid sinuses, two (11.1%) in the sphenoid sinus, and two (11.1%) at the frontal sinus. The maximum diameters of fistulas ranged from 5 to 20 mm, with a median value of 8 mm. Encephaloceles were identified in 14 (77.8%) patients. No hydrocephalus was recognized. All CSF leaks were successfully repaired with a bath-plug technique. Follow-up ranged from 50 to 70 months. No surgical complications were encountered in any patient. Interpretation: Bath-plug technique is safe and reliable for the endoscopic management of CSF leaks in children. Meticulous peri-operative preparations are important for pediatric patients.

NPAS2 promotes aerobic glycolysis and tumor growth in prostate cancer through HIF-1A signaling.

BACKGROUND: Prostate cancer (PCa), one of the common malignant tumors, is the second leading cause of cancer-related deaths in men. The circadian rhythm plays a critical role in disease. Circadian disturbances are often found in patients with tumors and enable to promote tumor development and accelerate its progression. Accumulating evidence suggests that the core clock gene NPAS2 (neuronal PAS domain-containing protein 2) has been implicated in tumors initiation and progression. However, there are few studies on the association between NPAS2 and prostate cancer. The purpose of this paper is to investigate the impact of NPAS2 on cell growth and glucose metabolism in prostate cancer. METHODS: Quantitative real-time PCR (qRT-PCR), immunohistochemical (IHC) staining, western blot, GEO (Gene Expression Omnibus) and CCLE (Cancer Cell Line Encyclopedia) databases were used to analyze the expression of NPAS2 in human PCa tissues and various PCa cell lines. Cell proliferation was assessed using MTS, clonogenic assays, apoptotic analyses, and subcutaneous tumor formation experiments in nude mice. Glucose uptake, lactate production, cellular oxygen consumption rate and medium pH were measured to examine the effect of NPAS2 on glucose metabolism. The relation of NPAS2 and glycolytic genes was analyzed based on TCGA (The Cancer Genome Atlas) database. RESULTS: Our data showed that NPAS2 expression in prostate cancer patient tissue was elevated compared with that in normal prostate tissue. NPAS2 knockdown inhibited cell proliferation and promoted cell apoptosis in vitro and suppressed tumor growth in a nude mouse model in vivo. NPAS2 knockdown led to glucose uptake and lactate production diminished, oxygen consumption rate and pH elevated. NPAS2 increased HIF-1A (hypoxia-inducible factor-1A) expression, leading to enhanced glycolytic metabolism. There was a positive correlation with the expression of NPAS2 and glycolytic genes, these genes were upregulated with overexpression of NPAS2 while knockdown of NPAS2 led to a lower level. CONCLUSION: NPAS2 is upregulated in prostate cancer and promotes cell survival by promoting glycolysis and inhibiting oxidative phosphorylation in PCa cells.

Percutaneous nephroscopy combined with the laser used for right kidney bullet extraction: A case report.

RATIONALE: Wounds caused by firearms are intractable problems in treating war traumas and clinical management. Conventional open surgery inflicts large injury and leads to slow recovery. At the same time, most patients suffer from compound injuries with the critical condition and poor operation tolerance. Thus, it is crucial to probe into the minimally invasive surgical removal of residual kidney bullets. PATIENT CONCERNS: We report a case where a bullet remained in the right renal parenchyma on the patient, with penetrating injury in his liver. DIAGNOSIS: Obviously the patient has suffered gunshot wound with a bullet stuck in his kidney, while his liver function was impacted. INTERVENTIONS: Six months after the injury, we performed the minimally-invasive procedures on the patient with percutaneous nephroscope technology and laser technology under the guidance of ultrasound localization. The bullet and ammunition granulation and scar surrounding tissue were fully removed. Intraoperative bleeding was little, while the incision was small. The patient could leave the bed and walk on the 1st postoperative day. The drainage tube was removed on the 3rd postoperative day, after which the patient was discharged on the 4th postoperative day. OUTCOMES: The patient recovered well after surgery and was followed up for 5 years. The latest examination of his liver and kidney function was as follows: alanine aminotransferase 61IU/L, aspartate aminotransferase 33 IU/L, albumin/globulin 46.6/26.0, total bilirubin 19.1µmol/L, direct bilirubin 4.9µmol/L, indirect bilirubin 14.2µmol/L, alkaline phosphatase 111 IU/L, creatinine 57µmol/L, urea 5.16mmol/L, cystatin 0.73mg/L. The plain computed tomography scan showed a few calcifications in the liver and a patchy low-density shadow in the right kidney. It was proved that the liver and kidney function of the patient recovered well, and his living qualify has come back to the track, with no postoperative complications. LESSONS: Innovative integration of percutaneous nephroscopy technology and laser was used to remove kidney foreign bodies and developed the optimal surgical plan, small trauma, fast recovery, and the treatment of kidney foreign bodies was newly explored.

Acquired CFTR dysfunction and dense distribution of ionocytes in nasal mucosa of children with CRS.

BACKGROUND: Ionocytes are rare cells in airway epithelium characterized by a high expression of CFTR. OBJECTIVES: To investigate the morphology and distribution of ionocytes and the function of CFTR in the nasal mucosal epithelium of children. METHODS: The exfoliated cells of nasal mucosa from 101 children were detected using flow cytometry to analyze the number of ionocytes and CFTR and the difference of CFTR function. Nasal mucosa and polyps were collected from 10 children with CRSwNP. The RNAscope of FOXI1 and CFTR was detected in pathological paraffin sections. The expression and distribution of ionocytes and CFTR in nasal mucosa and polyp epithelium were observed. RESULTS: In CRS patients, the number of ionocytes in the nasal epithelium was lower and the number of ionocytes that did not express CFTR was higher, and the function of CFTR was also decreased. The expression of CFTR in the nasal mucosa of CRS showed the characteristics of local dense distribution and increased as the inflammation expanded. The ionocytes were "tadpole-shaped" in the epithelium and gathered in the area of high CFTR expression, the intracellular CFTR was expanded in clusters. Ionocytes that did not express CFTR was more common in the nasal polyps. CONCLUSIONS: The number of ionocytes and the function of CFTR in nasal mucosa of CRS patients decreased. With the expansion of inflammation, CFTR and ionocytes showed more obvious dense distribution. Some ionocytes lost the expression of CFTR and did not show the "tadpole" shape, which may be related to the occurrence of polyps.

Changes in Pre- and Post-adenoidectomy Bacterial Profile in Children With Chronic Rhinosinusitis.

OBJECTIVE: We aimed to investigate the difference between the bacterial profiles of the nasal cavities and adenoid surfaces of children with chronic rhinosinusitis (CRS). We also intended to determine and analyze the potential correlation between the pre- and post-adenoidectomy differences in the nasal bacterial profile and clinical prognosis. METHODS: The clinical information of pediatric patients was collected. All the children underwent adenoidectomy (with or without tonsillectomy), and swab samples were collected during the operation. Visual analog scales (VAS) were used at 3, 6, and 12 months postoperatively. At the 12-month follow-up examination, swab samples were collected again. PCR amplification was performed of the v3-v4 variable regions of 16S rRNA of the collected specimens, as well as high-throughput sequencing using the Illumina platform. The species information was obtained by OTUs clustering, species annotation, and α-diversity analysis. RESULTS: Twenty-two male and eight female pediatric patients were included in the investigation The most abundant genus level bacterial representatives on the nasal surface before adenoidectomy were Moraxella catarrh, Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus, whereas on the surface of adenoids, they were Streptococcus pneumonia, Haemophilus influenza, Nucleobacter, and Moraxella catarrhalis. One year postoperatively, the bacteria with the highest abundance on the nasal surface at the genus level were Moraxella catarrhalis, Streptococcus pneumonia, Staphylococcus aureus, and non-culturable Dolosigranulum. One year postoperatively, the bacterial richness in the nasal cavity was significantly higher than at baseline (P < .05). Furthermore, the subjective nasal score of all children significantly decreased at 3, 6, and 12 months postoperatively (P < .01). CONCLUSION: The preoperative bacterial abundance of the nasal cavity and the adenoid surfaces was similar, showing a clear correlation. No single specific bacterium was established to be a dominant species associated with the development of CRS in children. The post-adenoidectomy bacterial richness in the nasal cavity was significantly increased, which may be closely related to the relief of postoperative sinusitis symptoms.

Primary Aneurysmal Bone Cyst of Nasal Cavity and Sinuses in a Child: Case Report and Literature Review.

INTRODUCTION: Aneurysmal bone cysts (ABCs) are a rare benign bone lesion, which are divided into primary and secondary categories, and occur mainly in the vertebra and the long tubular bones. Primary ABCs in the nasal cavity and the sinuses are rare. CASE PRESENTATION: We reported on a one-year-old boy who suffered from progressive nasal obstruction and intermittent nosebleeds over a period of approximately 1 month. The patient had no history of trauma or surgery. Physical examination showed a red tumor in his right nasal cavity. A magnetic resonance imaging scan showed a multicystic lesion arising from the ethmoid sinus. The lesion was resected under a nasal endoscope without any complications. Histological evaluation confirmed that the lesion was an aneurysmal bone cyst. Because an osteoma was found during the surgery on the cyst, the lesion was considered secondary clinically. However, fluorescence in situ hybridization testing showed a rearrangement of the USP6 (ubiquitin-specific protease 6) oncogene on chromosome 17. No recurrence was observed after 1 year. CONCLUSION: An ABC of the nasal cavity and sinuses in such a young child is very rare and needs to be further analyzed according to postoperative pathology and combined with a genetic examination to make a diagnosis. Endoscopic sinus surgery is an effective method of treatment for this kind of disease.

[Clinical analysis of 59 cases of pediatric nasal dermal sinus cysts with midfacial infection as the first symptom].

Objective:To review the clinical and radiological presentation and management of infected nasal dermal sinus cysts（NDSC） in children. Methods:Clinical data were collected from 59 NDSC children with secondary fronto-orbital area infection who presented to Beijing Children's Hospital from January 2007 to December 2021. All patients underwent preoperative imaging workup, including MRI and CT. All patients underwent endoscopic excision of a NDSC under general anesthesia. Results:A total of 59 patients were included in the study,while 58 presented with a sinus, 1 presented with a cyst.The main lesions of NDSC included nasal root in 20 cases （33.9%）, nasal bridge in 34 cases （57.6%）, nasal tip in 4 cases （6.8%）, and nasal tip and nasal root in 1 case （1.7%）. The depth of lesions included 6 cases （10.2%） of superficial type of nasal frontal bone, 33 cases （55.9%） of nasal frontal bone, 19 cases （32.2%） of intracranial epidural type, and 1 case （1.7%） of intracranial epidural type. The main sites of infection included inner canthus in 15 cases （25.4%）, nasal dorsum in 22 cases （37.3%）, nasal root in 16 cases （27.1%）, and forehead in 6 cases （10.2%）. Among 59 cases, 7 cases （11.9%） were complicated with other diseases, and 4 cases（6.8%） had external nasal deformities. Surgical approaches included transverse incision in 12 cases（20.3%）, minimal midline vertical incision in 41 cases （69.5%）, external rhinoplasty in 4 cases （6.8%） and bicoronal incision with vertical incision in 2 cases （3.4%）. The range of lesions was completely consistent with MRI results.All cases were successfully operated without one-stage nasal dorsum reconstruction. All patients were followed up from 7 to 173 months（average 52.2 months）. There were 6 cases of recurrence, all of which were in situ recurrence. The operation was performed again, and no recurrence has occurred since the follow-up, No nasal deformity was noted, and cosmetic outcome were favorable for all patients. Conclusion:NDSC infection in children with midfacial infection as the first symptom is rare in clinical practice, and its manifestations are diverse. Early diagnosis and rational treatment are very important to improve the cure rate.Preoperative high resolution MRI combined with CT scanning is of great significance in judging the course of NDSC, especially the intracranial extension. The treatment goal is to achieve minimally invasive and individualized treatment under the premise of complete excision of the lesion, and take into account the cosmetic needs.

Photodynamic therapy for prostate cancer: Recent advances, challenges and opportunities.

Over the past two decades, there has been a tendency toward early diagnosis of prostate cancer due to raised awareness among the general public and professionals, as well as the promotion of prostate-specific antigen (PSA) screening. As a result, patients with prostate cancer are detected at an earlier stage. Due to the risks of urine incontinence, erectile dysfunction, etc., surgery is not advised because the tumor is so small at this early stage. Doctors typically only advise active surveillance. However, it will bring negative psychological effects on patients, such as anxiety. And there is a higher chance of cancer progression. Focal therapy has received increasing attention as an alternative option between active monitoring and radical therapy. Due to its minimally invasive, oncological safety, low toxicity, minimal effects on functional outcomes and support by level 1 evidence from the only RCT within the focal therapy literature, photodynamic treatment (PDT) holds significant promise as the focal therapy of choice over other modalities for men with localized prostate cancer. However, there are still numerous obstacles that prevent further advancement. The review that follows provides an overview of the preclinical and clinical published research on PDT for prostate cancer from 1999 to the present. It focuses on clinical applications of PDT and innovative techniques and technologies that address current problems, especially the use of nanoparticle photosensitizers in PDT of prostate cancer.

Heterogeneous spectrum of CFTR gene mutations in Chinese patients with CAVD and the dilemma of genetic blocking strategy.

In brief: The genetic heterogeneity of CFTR gene mutations in Chinese patients with congenital absence of the vas deferens (CAVD) differs from the hotspot mutation pattern in Caucasians. This paper reviews and suggests a more suitable screening strategy for the Chinese considering the dilemma of CFTR genetic blocking. Abstract: Congenital absence of the vas deferens (CAVD) is a major cause of obstructive azoospermia and male infertility, with CFTR gene mutation as the main pathogenesis. Other genes such as ADGRG2, SLC9A3, and PANK2 have been discovered and proven to be associated with CAVD in recent studies. Multiple CFTR hotspot mutations have been found in Caucasians in several foreign countries, and relevant genetic counseling and preimplantation genetic diagnosis (PGD) have been conducted for decades. However, when we examined research on Chinese CAVD, we discovered that CFTR mutations show heterogeneity in the Chinese Han population, and there is currently no well-established screening strategy. Therefore, we have reviewed the literature, combining domestic and international research as well as our own, aiming to review research progress on the CFTR gene in China and discuss the appropriate scope for CFTR gene detection, the detection efficiency of other CAVD-related genes, and the screening strategy applicable to the Chinese Han population. This study provides more valuable information for genetic counseling and a theoretical basis for PGD and treatment for couples with CAVD when seeking reproductive assistance.

ELOVL2 restrains cell proliferation, migration, and invasion of prostate cancer via regulation of the tumor suppressor INPP4B.

BACKGROUND: Prostate cancer is one of the most common malignancies in men. Members of the elongation of the very-long-chain fatty acid (ELOVL) gene family have been reported to participate in the occurrence and development of various cancers. However, the function of ELOVL gene family members (ELOVLs) in prostate cancer has not been fully elucidated. METHODS: The mRNA expression and prognostic value of ELOVLs in prostate cancer were analyzed using the GEPIA database. The Oncomine database and PrognoScan database were used to further verify the mRNA expression level and prognostic value of ELOVL2 in prostate cancer. RT-qPCR and Western blotting were used to validate the expression levels of ELOVL2 in four prostate cancer cell lines. Immunohistochemistry was performed to detect the ELOVL2 protein expression levels in prostate cancer tissues. Coexpression analysis in the cBioPortal database and enrichment analysis in Kyoto Encyclopedia of Genes and Genomes (KEGG), CCK8, colony formation, and transwell assays were used to identify the functions and mechanisms of ELOVL2. RESULTS: ELOVL2 expression was upregulated in prostate cancer tissues compared with normal tissues. High expression of ELOVL2 indicated a better prognosis in prostate cancer patients. ELOVL2 expression was negatively correlated with Gleason score. Knockdown of ELOVL2 promoted cell proliferation, colony formation, migration, invasion, and the growth of subcutaneous xenografts and activated the PI3K/Akt signaling pathway by downregulating INPP4B, while overexpression of ELOVL2 reversed these effects. In addition, overexpression of INPP4B blocked the promoting effect of sh-ELOVL2 on cell proliferation, colony formation, migration, invasion, and the PI3K/Akt signaling pathway. CONCLUSIONS: Our findings suggest that ELOVL2 might be a prognostic biomarker and therapeutic target for prostate cancer.

Young Children Allergic Rhinitis Questionnaire is a novel tool for allergy screening in children.

BACKGROUND: There are a limited number of validated questionnaires available for use in the clinical screening for allergic rhinitis (AR) in children ≤3 years old. We developed a novel self-reported questionnaire and assessed its accuracy and reliability. METHODS: After establishing a pool of items, which were screened by experts, the Young Children Allergic Rhinitis Questionnaire (YCAR-Q) was administered to a birth cohort in the Shunyi District (Beijing, China). The electronic version of the YCAR-Q was distributed through the online community. Children were invited to visit a physician for examination. The diagnostic criteria included symptoms, physical examination findings, and specific serum immunoglobulin E tests. Each item on the questionnaire was evaluated, and the questionnaire's internal consistency, content validity, criterion-related validity, and diagnostic accuracy were assessed. RESULTS: The six-item YCAR-Q was distributed to 7423 parents, and 3037 valid questionnaires were recovered. In total, 1521 children visited a physician for examination, of which 82 were found to have AR. In terms of internal consistency, Cronbach's coefficient was 0.777 and all six questionnaire items were retained. The average scale-level content validity index value was 1. The area under the curve was 0.759. The total scores ranged from 0 to 6, and the cutoff value for diagnosing AR was 3, with a sensitivity of 68.29% and a specificity of 76.58%. CONCLUSIONS: This cross-sectional study indicated that the YCAR-Q could detect AR in children ≤3 years old. This brief and simple test may be used effectively in clinical practice.

Predictive Significance of Enhanced Level of Angiogenesis and Tissue Neutrophils for Antrochoanal Polyps Recurrence in Children.

BACKGROUND: The pathologic features and potential predictive biomarkers for recurrence of antrochoanal polyps (ACPs) in children are not fully understood. OBJECTIVES: To identify the pathologic differences between recurrent and nonrecurrent group and to explore potential clinical markers which predict recurrence of ACPs in children. MATERIAL AND METHODS: A total of 11 recurrent and 21 nonrecurrent ACPs children were enrolled into this retrospect study. Clinical basic information was collected before the first surgery. The counts of vessels were evaluated by hematoxylin-eosin (HE) staining, and CD34 was detected by immunohistochemistry. Meanwhile, the percentage of each tissue inflammatory cells (eosinophils, neutrophils, lymphocytes, and plasma cells) was assessed by HE staining. RESULTS: No statistical significance was observed between the 2 groups in the basic clinical features. Moreover, both the counts of blood vessels and the tissue neutrophils percentage were enhanced significantly in group with ACPs recurrence (P < .05). According to the receiver operating characteristic curves, the area under the curve for the counts of blood vessels and tissue neutrophils percentage in the prediction of ACPs' recurrence was 0.779 (P = .0105) and 0.989 (P < .0001) respectively. CONCLUSIONS AND SIGNIFICANCE: It was concluded that the counts of blood vessels and the percentage of tissue neutrophils appeared to be potential excellent predictors of ACPs recurrence in children.

Establishment and prospective validation of an SUVmax cutoff value to discriminate clinically significant prostate cancer from benign prostate diseases in patients with suspected prostate cancer by 68Ga-PSMA PET/CT: a real-world study.

Background and Aims: The aims of this study were to establish a maximum standardized uptake value (SUVmax) cutoff to discriminate clinically significant prostate cancer (csPCa) from benign prostate disease (BPD) by 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA-11) positron emission tomography/computed tomography (PET/CT) in patients with suspected prostate cancer (PCa), and to perform a prospective real-world validation of this cutoff value. Methods: The study included a training cohort to identify an SUVmax cutoff value and a prospective real-world cohort to validate it. A retrospective analysis assessed 135 patients with suspected PCa in a large tertiary care hospital in China who underwent 68Ga-PSMA-11 PET/CT. All patients were suspected of having PCa based on symptoms, digital rectal examination (DRE), total prostate-specific antigen (tPSA) level, and multiparameter magnetic resonance imaging (mpMRI). The 68Ga-PSMA PET/CT results were evaluated using histopathological results from transrectal ultrasound-guided 12-core biopsy with necessary targeted biopsy as references. Patients with Gleason scores (GS) ≥7 from the biopsy results were diagnosed with csPCa, and patients with negative biopsy and follow-up results were diagnosed with BPD. Receiver operating characteristic (ROC) curve analysis was used to identify the optimal SUVmax cutoff value. The cutoff value was prospectively validated in 58 patients with suspected PCa. The diagnostic benefits of the cutoff value for clinical decision making were also evaluated. Results: According to ROC curve analysis, the most appropriate SUVmax cutoff value for discriminating csPCa from BPD was 5.30 (sensitivity, 85.85%; specificity, 86.21%; area under the curve [AUC], 0.893). The cutoff achieved a sensitivity of 83.33%, a specificity of 81.25%, a positive predictive value (PPV) of 92.11%, a negative predictive value (NPV) of 65.00%, and an accuracy of 82.76% in the prospective validation cohort. Metastases were used as an indicator to reduce false negative results in patients with SUVmax ≤ 5.30. In patients without metastases, an SUVmax value of 5.30 was also the best cutoff to diagnose localized csPCa (sensitivity, 80.43%; specificity, 86.21%; AUC, 0.852). The cutoff discriminated localized csPCa from BPD with a sensitivity of 76.19%, a specificity of 81.25%, a PPV of 84.21%, an NPV of 72.22%, and an accuracy of 78.38% in the prospective validation cohort. The cutoff, combined with metastases, achieved an accuracy of 89.12% in all patients, increasing accuracy by 8.29% and reducing equivocal results compared with manual reading. There was a strong correlation between SUVmax and PSMA expression (rs = 0.831, P < 0.001) and a moderate correlation between SUVmax and GS (rs = 0.509, P < 0.001). The PSMA expression and SUVmax values of patients with csPCa were significantly higher than those of patients with BPD (P < 0.001). Conclusion: We established and prospectively validated the best SUVmax cutoff value (5.30) for discriminating csPCa from BPD with high accuracy in patients with suspected PCa. 5.30 is an effective cutoff to discriminate csPCa patients with or without metastases. The cutoff may provide a potential tool for the precise identification of csPCa by 68Ga-PSMA PET/CT, ensuring high accuracy and reducing equivocal results.

Combination of the endoscopic septonasal flap technique and bioabsorbable steroid-eluting stents for repair of congenital choanal atresia in neonates and infants: a retrospective study.

BACKGROUND: Multiple surgical approaches have been proposed to repair the congenital choanal atresia. However, there remains no general consensus about the optimal surgical technique. This study aimed to describe and evaluate outcomes of the endoscopic septonasal flap technique combined with bioabsorbable steroid-eluting stents for repair of congenital choanal atresia in neonates and infants. METHODS: Clinical data of 37 neonates and infants with congenital choanal atresia who received nasal endoscopic surgery with the flap technique between January 2018 and July 2020 were analyzed retrospectively. All patients underwent the ultra­low­dose paranasal sinus computed tomography imaging preoperatively to confirm diagnosis and plan the surgery. In these patients, the mirrored L-shaped flap technique was performed for bilateral atresia and the cross-over L-shaped flap technique was performed for unilateral atresia. A total of 22 patients had silicone stents postoperatively and 15 patients had bioabsorbable steroid-eluting stents postoperatively. Silicone stents were removed at one month postoperatively under secondary general anesthesia, while no anesthesia was needed to remove the bioabsorbable steroid-eluting stents. Postoperative follow-up ranged from 10 months to 3 years. RESULTS: The septonasal flap technique was performed in all patients. Compared with the silicone stents group, the average operative duration and the hospital length of stay in the bioabsorbable steroid-eluting stents group were decreased [(97.46 ± 15.37) min vs (83.49 ± 19.16) min t = 13.733, P < 0.001] [(12.8 ± 3.22) d vs (7.67 ± 3.91) d t = 15.082, P < 0.001], the average number of procedures was reduced [(2.04 ± 0.64) vs (1.00 ± 0.001), t = 82.689, P < 0.001], the differences were statistically significant. There were no reports of postoperative restenosis and complications in the bioabsorbable steroid-eluting stents group, and follow-up endoscopic examinations showed patency and stable nasal passages in all cases. CONCLUSIONS: The endoscopic septonasal flap technique can effectively expose and expand the choanal bony structure for repair of congenital choanal atresia in neonates and infants. The combined use of this technique along with bioabsorbable steroid-eluting stents can help prevent the need for revision procedures and also against stent-related injuries.

Case reports of robot-assisted laparoscopic radical nephrectomy and inferior vena cava tumor thrombectomy: A retrospective analysis.

ABSTRACT: Renal cell carcinoma is one common type of urologic cancers. It has tendencies to invade into the inferior vena cava (IVC) and usually requires an open surgery procedure. High rates of operative complications and mortality are usually associated with an open surgery procedure. The recently emerged robot-assisted laparoscopic radical nephrectomy (RAL-RN) and IVC tumor thrombectomy have shown to reduce operative related complications in patients with renal cell carcinoma.This case series study aimed to summarize technical utilization, perioperative outcomes, and efficacies of RAL-RN and IVC tumor thrombectomy in our hospital. A retrospective analysis was performed on clinical data from 20 patients who underwent RAL-RN and IVC tumor thrombectomy from January 2017 to December 2019 in our department.Patients had a median age of 59 years (interquartile range [IQR], 46-68). Four patients had renal neoplasm on left side and 16 on right side. Nineteen patients underwent RAL-RN (level 0: n = 2) or RAL-RN with IVC thrombectomy (n = 17) (level I: n = 3; level II: n = 12; and level III: n = 3) and 1 patient was converted into an open surgery. The median operative time was 328 minutes (IQR, 221-453). The estimated median blood loss was 500 mL (IQR, 200-1200). The median size of removed renal carcinoma was 67 cm2 (IQR, 40-91); the length of IVC tumor thrombus was 5 cm (IQR, 3-7). The postsurgery hospital length of stay was 6 days (IQR, 5-7). The complications included intestinal obstruction (n = 1), lymphatic fistula (n = 1), heart failure (n = 1), and low hemoglobin level (n = 1). The outcomes for patients after 16 months (IQR, 11-21) follow-up were tumor-free (n = 10), tumor progression (n = 4), loss of contact (n = 1), and death (n = 5).We concluded that RAL-RN and IVC thrombectomy renders good safety profiles including minimal invasiveness, low estimated median blood loss, short hospitalization, low morbidity, and quick renal function recovery. The long-term efficacy needs a further investigation.

PHLDA3 exerts an antitumor function in prostate cancer by down-regulating Wnt/ß-catenin pathway via inhibition of Akt.

Pleckstrin homology-like domain family A, member 3 (PHLDA3) is a novel tumor-related protein that mediates carcinogenesis of multiple cancers. However, the relevance of PHLDA3 in prostate cancer has not been explored. The purpose of this work was to illustrate the possible roles and mechanisms of PHLDA3 in prostate cancer. Our data showed strikingly lower abundance of PHLDA3 in prostate cancer, and that low levels of PHLDA3 in prostate cancer patients was associated with reduced survival. PHLDA3 was also weakly expressed in prostate cancer cells, and demethylation treatment dramatically up-regulated the expression level of PHLDA3. Up-regulation of PHLDA3 restrained proliferation, induced G1 cell cycle arrest, suppressed epithelial-mesenchymal transition of prostate cancer cells. In addition, up-regulation of PHLDA3 increased the sensitivity of prostate cancer cells to docetaxel In-depth research into the mechanism elucidated that PHLDA3 overexpression decreased the phosphorylation of Akt and suppressed the activation of Wnt/ß-catenin signaling. Overexpression of constitutively active Akt strikingly abolished PHLDA3-mediated inactivation of Wnt/ß-catenin pathway. A xenograft assay revealed that prostate cancer cells with PHLDA3 overexpression displayed reduced tumorigenicity in vivo. Collectively, these data document that PHLDA3 exerts an outstanding cancer-inhibiting role in prostate cancer by down-regulating Wnt/ß-catenin pathway via the inhibition of Akt. This work highlights PHLDA3 as a novel anticancer target for prostate cancer.

The first competing risk survival nomogram in patients with papillary renal cell carcinoma.

There is still a lack of competing risk analysis of patients with papillary renal cell carcinoma (pRCC) following surgery. We performed the cumulative incidence function (CIF) to estimate the absolute risks of cancer-specific mortality (CSM) and other-cause mortality (OCM) of pRCC over time, and constructed a nomogram predicting the probability of 2-, 3- and 5-year CSM based on competing risk regression. A total of 5993 pRCC patients who underwent nephrectomy between 2010 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The 2-, 3-, 5-year CSM rates were 3.2%, 4.4% and 6.5%, respectively, and that of OCM were 3.2%, 5.0% and 9.3%, respectively. The estimates of 5-year cumulative mortality were most pronounced among patients aged > 75 years in OCM (17.0%). On multivariable analyses, age, tumor grade, T stage, N stage, and with or without bone, liver and lung metastases were identified as independent predictors of CSM following surgery and were integrated to generate the nomogram. The nomogram achieved a satisfactory discrimination with the AUCt of 0.730 at 5-year, and the calibration curves presented impressive agreements. Taken together, age-related OCM is a significant portion of all-cause mortality in elderly patients and our nomogram can be used for decision-making and patient counselling.