UPK3A+ umbrella cell damage mediated by TLR3-NR2F6 triggers programmed destruction of urothelium in Hunner-type interstitial cystitis/painful bladder syndrome.

Urothelial damage and barrier dysfunction emerge as the foremost mechanisms in Hunner-type interstitial cystitis/bladder pain syndrome (HIC). Although treatments aimed at urothelial regeneration and repair have been employed, their therapeutic effectiveness remains limited due to the inadequate understanding of specific cell types involved in damage and the lack of specific molecular targets within these mechanisms. Therefore, we harnessed single-cell RNA sequencing to elucidate the heterogeneity and developmental trajectory of urothelial cells within HIC bladders. Through reclustering, we identified eight distinct clusters of urothelial cells. There was a significant reduction in UPK3A+ umbrella cells and a simultaneous increase in progenitor-like pluripotent cells (PPCs) within the HIC bladder. Pseudotime analysis of the urothelial cells in the HIC bladder revealed that cells faced challenges in differentiating into UPK3A+ umbrella cells, while PPCs exhibited substantial proliferation to compensate for the loss of UPK3A+ umbrella cells. The urothelium in HIC remains unrepaired, despite the substantial proliferation of PPCs. Thus, we propose that inhibiting the pivotal signaling pathways responsible for the injury to UPK3A+ umbrella cells is paramount for restoring the urothelial barrier and alleviating lower urinary tract symptoms in HIC patients. Subsequently, we identified key molecular pathways (TLR3 and NR2F6) associated with the injury of UPK3A+ umbrella cells in HIC urothelium. Finally, we conducted in vitro and in vivo experiments to confirm the potential of the TLR3-NR2F6 axis as a promising therapeutic target for HIC. These findings hold the potential to inhibit urothelial injury, providing promising clues for early diagnosis and functional bladder self-repair strategies for HIC patients. © 2024 The Pathological Society of Great Britain and Ireland.

Assessment of scintillation and Cherenkov imaging as beam shape verification method in CyberKnife® radiotherapy.

PURPOSE: The goal of this study is to assess the utility of Cherenkov imaging (CI) and scintillation imaging (SI) as high-resolution techniques to measure CyberKnife® beam shape quantitatively at the irradiation surface in quality assurance (QA). METHODS: The EMCCD camera captured scintillation and Cherenkov photons arising from 6 MV x-ray dose deposition produced by the CyberKnife® VSI System. Two imaging methods were done at source to surface distance of 800 cm with the same field size, ranging from 10 to 60 mm using fixed cones and iris collimators. The output sensitivity and constancy were measured using the SI and CI, and benchmarked against an ionization chamber. Line profiles of each beam measured by optical imaging were compared with film measurement. Position shifts were introduced to test the sensitivity of SI and CI to small beam position deviations. To assess reproducibility, the beam measurements were tested three times on 5 consecutive days. RESULTS: Both systems exhibited comparable sensitivity to the ionization chamber in response to fluctuations in CyberKnife® output. The beam profiles in SI matched well with the measured film image, with accuracy in the range of ± 0.20 and ± 0.26 mm standard deviation for the circle and iris field, respectively. The corresponding accuracy measured by CI is in the range of ± 0.25 and ± 0.33 mm, respectively. These are all within the tolerance recommended by the guidelines of CyberKnife® QA. The accuracy measured by SI and CI for 1 mm beam position shift within 0.21 and 0.45 mm tolerance, respectively. Repeatability measurements of the beam have shown a standard deviation within 0.94 mm. CONCLUSIONS: SI and CI techniques are tested to provide a valid way to measure CyberKnife® beam shape in this study. Meanwhile, the systematic comparison of SI and CI also provides evidence for the measurement methods selection appropriately.

Cervical carcinogenesis risk association of HPV33 E6 and E7 genetic variations in Taizhou, Southeast China.

BACKGROUND: Human papillomavirus (HPV) 33 belongs to the Alphapapillomavirus 9 (α-9 HPV) species group, which also contains types 16, 31, 35, 52, 58 and 67. The purpose of this study was to investigate the genetic variations of HPV33 and to explore its carcinogenicity among women in Taizhou, Southeast China. METHODS: Exfoliated cervical cells were collected for HPV genotyping. Only single HPV33 infection cases were selected, and their E6 and E7 genes were sequenced using the ABI 3730xl sequencer and then analysed using MEGA X. RESULTS: From 2014 to 2020, a total of 185 single HPV33-positive specimens were successfully amplified. We obtained 15 distinct HPV33 E6/E7 variants, which were published in GenBank under accession numbers OQ672665-OQ672679. Phylogenetic analysis revealed that all HPV33 E6/E7 variants belonged to lineage A, of which 75.7% belonged to lineage A1. Compared with CIN1, the proportion of sublineage A1 in CIN2/3 was higher, but there was no significant difference (76.5% vs. 80.6%, P > 0.05). Altogether, 20 single nucleotide substitutions were identified, of which 6 were novel substitutions, including T196G (C30G), A447T, G458T (R117L), G531A, A704A, and C740T. In addition, no significant trends were observed between the nucleotide substitutions of HPV33 E6/E7 variants and the risk of cervical lesions. CONCLUSION: This study provides the most comprehensive data on genetic variations, phylogenetics and carcinogenicity of HPV33 E6/E7 variants in Southeast China to date. The data confirmed that cervical lesions among women in Taizhou are attributable to HPV33, which may be due to the high infection rate of sublineage A1 in the population.

The association of dietary intake of riboflavin and thiamine with kidney stone: a cross-sectional survey of NHANES 2007-2018.

BACKGROUND: Kidney stone disease (KSD) is a common condition that affects 10% population in the United States (US). The relationship between thiamine and riboflavin intake and KSD has not been well-studied. We aimed to investigate the prevalence of KSD and the association between dietary thiamine and riboflavin intake with KSD in the US population. METHODS: This large-scale, cross-sectional study included subjects from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. KSD and dietary intake were collected from questionnaires and 24-hour recall interviews. Logistic regression and sensitivity analyses were performed to investigate the association. RESULTS: This study included 26,786 adult participants with a mean age of 50.12 ± 17.61 years old. The prevalence of KSD was 9.62%. After adjusting for all potential covariates, we found that higher riboflavin intake was negatively related to KSD compared with dietary intake of riboflavin < 2 mg/day in the fully-adjusted model (OR = 0.541, 95% CI = 0.368 to 0.795, P = 0.002). After stratifying by gender and age, we found that the impact of riboflavin on KSD still existed in all age subgroups (P < 0.05) but only in males (P = 0.001). No such associations were found between dietary intake of thiamine and KSD in any of the subgroups. CONCLUSIONS: Our study suggested that a high intake of riboflavin is independently inversely associated with kidney stones, especially in male population. No association was found between dietary intake of thiamine and KSD. Further studies are needed to confirm our results and explore the causal relationships.

Genetic variability in the E6 and E7 oncogenes of HPV52 and its prevalence in the Taizhou area, China.

BACKGROUND: Human papillomavirus (HPV) 52 is one of the prevalent oncogenic HPV genotypes in East Asia. Chinese women have the highest susceptibility to the HPV52 type, but research data on HPV52 genetic variability and its carcinogenicity in China is lacking. METHODS: The present study aimed to investigate the genetic variability of HPV52 currently circulating among Chinese women by PCR sequencing the entire E6 and E7 oncogenes. HPV52 sequence alignment, genetic heterogeneity analyses and maximum-likelihood phylogenetic tree construction were performed by BioEdit software and MEGA X software. RESULTS: Between 2016 and 2018, the overall HPV infection rate was 21.3%, of which HPV52 was the most prevalent high-risk type (17.2%) in the Taizhou area, China. A total of 339 single HPV52-positive samples were included in this study. We obtained 27 distinct variation patterns of HPV52 with the accession GenBank numbers ON529577-ON529603. Phylogenetic analysis showed that 96.6% of HPV52 variants belonged to lineage B, which seemed to be uniquely defined by G350T, A379G (K93R) in the E6 gene and C751T, A801G in the E7 gene. Due to the dominance of lineage B in our study population, the results could not be used to assess the association of the HPV52 (sub)lineage with the risk of cervical lesions. In addition, no significant trends were observed between the nucleotide substitutions of HPV52 variants and the risk of cervical carcinogenesis. CONCLUSION: Our data showed that HPV52 variants were strongly biased towards lineage B. These results confirmed that cervical lesions in the Taizhou area are highly attributable to HPV52, which may be due to the high infection rate of lineage B in the population.

A bibliometric analysis of top-cited journal articles in interstitial cystitis and bladder pain syndrome.

INTRODUCTION AND HYPOTHESIS: To identify and compare the top-cited articles from all indexed journals and urology-nephrology and obstetrics-gynecology journals in the Institute for Scientific Information Web of Science's Citation Index Expanded on interstitial cystitis and bladder pain syndrome (IC/BPS). METHODS: Cross-sectional bibliometric analysis of top-cited articles in Web of ScienceTM (WoS) from 1900-2022. The articles were retrieved by the MeSH terms from NCBI. The characteristics of top 100 cited articles from all indexed journals and specialized journals were evaluated. RESULTS: A total of 5547 articles were collected from 1115 journals, in which 3225 articles were from 141 urological and gynecological specialized journals. The USA and the UK were the top two origins for articles on interstitial cystitis. The articles from non-specialized journals were more frequently cited than those from specialized journals (median [IQR], 221.5 [189.8-313.5] vs 131.0 [126.0-142.8], P < 0.0001). The citation number per year showed similar results (median [IQR], 239.9 [194.5-311.8] vs 132.0 [126.7-140.5], P < 0.0001). There were many more open-access articles in non-specialized than specialized journals (P = 0.0018). CONCLUSIONS: The current study initially queried the articles published on WoS on IC/BPS by the number of citations to identify the differences between two journal categories. The characteristics and trends of research were analyzed by citations to provide insights into the current research status and future direction.

Association of cervical carcinogenesis risk with HPV16 E6 and E7 variants in the Taizhou area, China.

BACKGROUND: Human papillomavirus (HPV) type 16 accounts for a larger share of cervical cancer and has been a major health problem worldwide for decades. The progression of initial infection to cervical cancer has been linked to viral sequence properties; however, the role of HPV16 variants in the risk of cervical carcinogenesis, especially with longitudinal follow-up, is not fully understood in China. METHODS: We aimed to investigate the genetic variability of HPV16 E6 and E7 oncogenes in isolates from cervical exfoliated cells. Between December 2012 and December 2014, a total of 310 single HPV16-positive samples were selected from women living in the Taizhou area, China. Sequences of all E6 and E7 oncogenes were analysed by PCR-sequencing assay. Detailed sequence comparison, genetic heterogeneity analyses and maximum-likelihood phylogenetic tree construction were performed with BioEdit Sequence Alignment Editor and MEGA X software. Data for cytology tests and histological diagnoses were obtained from our Taizhou Area Study with longitudinal follow-up for at least 5 years. The relationship between HPV16 variants and cervical carcinogenesis risk was analysed by the chi-square test or Fisher's exact test. RESULTS: In this study, we obtained 64 distinct variation patterns with the accession GenBank numbers MT681266-MT681329. Phylogenetic analysis revealed that 98.3% of HPV16 variants belong to lineage A, in which the A4 (Asian) sublineage was dominant (64.8%), followed by A2 (12.1%), A1 (11.4%), and A3 (10.0%). The A4 (Asian) sublineage had a higher risk of CIN2+ than the A1-3 (European) sublineages (OR = 2.69, 95% CI = 1.04-6.97, P < 0.05). Furthermore, nucleotide variation in HPV16 E6 T178G is associated with the development of cervical cancer. CONCLUSION: These data could provide novel insights into the role of HPV16 variants in cervical carcinogenesis risk in China.

Efficacy and safety comparison of pharmacotherapies for interstitial cystitis and bladder pain syndrome: a systematic review and Bayesian network meta-analysis.

INTRODUCTION AND HYPOTHESIS: The objective was to compare the clinical efficacy and safety of pharmacological interventions for interstitial cystitis and bladder pain syndrome (IC/BPS) with direct and indirect evidence from randomized trials. METHODS: We searched PubMed, the Cochrane library, and EMBASE for randomized controlled trials (RCTs) that assessed the pharmacological therapies for IC/BPS. Primary efficacy outcomes included ICSI (O'Leary Sant Interstitial Cystitis Symptom Index), ICPI (O'Leary Sant Interstitial Cystitis Problem Index), 24-h micturition frequency, visual analog scale (VAS), and Likert score for pain. Safety outcomes are total adverse events (AEs, intravesical instillation, and others), gastrointestinal symptoms, headache, pain, and urinary symptoms. A systematic review and Bayesian network meta-analysis were performed. RESULTS: A total of 23 RCTs with 1,871 participants were identified. The ICSI was significantly reduced in the amitriptyline group (MD = -4.9, 95% CI: -9.0 to -0.76), the cyclosporine A group (MD = -7.9, 95% CI: -13.0 to -3.0) and the certolizumab pegol group (MD = -3.6, 95% CI:-6.5 to -0.63) compared with placebo group. Moreover, for ICPI, cyclosporine A showed superior benefit compared to placebo (MD = -7.6, 95% CI: -13 to -2.3). VAS score improved significantly in cyclosporine A group than pentosan polysulfate sodium (MD = 3.09, 95% CI: 0.13 to 6.07). None of the agents revealed a significant alleviation of 24-h micturition frequency. In terms of safety outcomes, the incidence rate on urinary symptoms for botulinum toxin A was the only variate higher than chondroitin sulfate (MD = -2.02, 95% CI: -4.99 to 0.66) and placebo (MD = -1.60, 95% CI:-3.83 to 0.17). No significant difference was found among the other treatments. CONCLUSIONS: Cyclosporine A might be superior to other pharmacological treatments in efficacy. Amitriptyline and certolizumab pegol were capable of lowering the ICSI as well.

Metabolic syndrome in women with and without interstitial cystitis/bladder pain syndrome.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to compare the frequency of metabolic syndrome (MetS) in patients with and without interstitial cystitis/bladder pain syndrome (IC/BPS). METHODS: This case-control study evaluated the indicators of MetS in 287 females with IC/BPS and in 287 females without IC/BPS in West China Hospital between January 2010 and January 2020. Then, the number of voids per day, frequency of night urination, O'Leary-Sant Interstitial Cystitis Symptom/Problem Index, and visual analog scale were examined in the two groups. RESULTS: Based on both the National Cholesterol Education Program Adult Treatment Panel III recommendations and the International Diabetes Federation criteria, the distribution of MetS was statistically higher in patients with IC/BPS than in the control group, with 34.8% vs 17.8% (P < 0.0001) and 34.2% vs 20.9% (P = 0.0005), respectively. Regarding symptom scores, the IC/BPS group demonstrated significantly higher scores than the control group in all aspects (P < 0.0001). More patients with anxiety (P < 0.0001), insomnia (P < 0.0001), hypertension (P = 0.0001), and diabetes mellitus (P = 0.017) were observed in the IC/BPS group. Moreover, the findings indicated that patients with IC/BPS had a higher BMI (P = 0.0001) and larger waist circumference (P = 0.0001). Blood tests presented a significantly higher level of fasting glycemia, serum cystatin-C, and triglycerides in patients with IC/BPS. Furthermore, higher ORs for the occurrence of MetS among cases were observed, although this was not statistically significant. CONCLUSIONS: MetS frequency was relatively high in patients with IC/BPS. Further research is needed to understand the common pathophysiologic mechanism of IC/BPS and MetS.

Is absorbable suture superior to permanent suture for uterosacral ligament suspension?

AIMS: The aims of this study were to compare surgical results and suture-related complications after uterosacral ligament suspension (USLS) with absorbable suture (AS) vs permanent suture (PS). METHODS: We systematically searched PubMed, Embase, clinicalTrial.gov, and Cochrane Library Central Register of Controlled Trials for articles that compared AS with PS for USLS. The primary outcomes were surgical success rate and suture-related complications (suture exposure/erosion and suture removal). Review Manager 5.3 (Cochrane Collaboration, Oxford, UK) was applied to conduct all analyses. RESULTS: Four articles involving 647 patients were eventually included. Our findings demonstrated that AS had a similar surgical success rates in comparison with PS (RR = 1.00; 95% CI, 0.94-1.06) and that no significant differences in anatomic failure rates were noted between two groups (RR = 1.10; 95% CI, 0.65-1.86). Subgroup analyses in anatomic failure revealed no statistical differences in apical prolapse ≥1/2 TVL (RR = 0.92; 95% CI, 0.48-1.75), recurrent prolapse beyond the hymen (RR = 1.18; 95% CI, 0.68-2.04), as well as in recurrent anterior, posterior or apical prolapse (P = .14, P = .08, P = .09, respectively). However, AS group indicated a lower risk in suture exposure/erosion (RR = 0.31; 95% CI, 0.15-0.63) and lower suture removal rate (RR = 0.35; 95% CI, 0.18-0.67). CONCLUSIONS: Due to similar surgical results, less suture exposure/erosion and less suture removal, the current data supported that AS is as effective as PS, but with a better safety profile.

Combination of intratumoural micellar paclitaxel with radiofrequency ablation: efficacy and toxicity in rodents.

OBJECTIVES: To determine whether radiofrequency ablation (RFA) is more effective when combined with intratumoural injection (IT) than with intravenous injection (IV) of micelles. MATERIALS AND METHODS: Balb/c mice bearing 4T1 breast cancer were used. The tumour drug accumulation and biodistribution in major organs were evaluated at different time points after IT, IV, IT+RFA and IV+RFA. Periablational drug penetration was evaluated by quantitative analysis and pathologic staining after different treatments. For long-term outcomes, mice bearing tumours were randomised into six groups (n = 7/group): the control, IV, IT, RFA alone, IV+RFA and IT+RFA groups. The end-point survival was estimated for the different treatment groups. RESULTS: In vivo, intratumoural drug accumulation was always much higher for IT than for IV within 48 h (p < 0.001). The IT+RFA group (3084.7 ± 985.5 µm) exhibited greater and deeper drug penetration than the IV+RFA group (686.3 ± 83.7 µm, p < 0.001). Quantitatively, the intratumoural drug accumulation in the IT+RFA group increased approximately 4.0-fold compared with that in the IV+RFA group (p < 0.001). In addition, compared with the IT treatment, the IT+RFA treatment further reduced the drug deposition in the main organs. Survival was longer in the IT+RFA group than in the IV+RFA (p = 0.033) and RF alone (p = 0.003) groups. CONCLUSION: The use of IT+RFA achieved much deeper and greater intratumoural drug penetration and accumulation, resulting in better efficacy, and decreased the systemic toxicity of nanoparticle-delivered chemotherapy. KEY POINTS: • Association of IT+RFA achieved much deeper and greater intratumoural drug penetration than of IV+RFA, leading to better therapeutic efficacy. • Compared with IV or IT chemotherapy alone, the combination with RFA decreased toxicity, especially in the IT+RFA group.

Association between Healthy Eating Index-2015 and prostate enlargement: A cross-sectional study of the National and Nutrition Examination Survey 2001-2008.

Background: Benign prostate hyperplasia (BPH) occurs in elder men globally with high prevalence. Human diet and lifestyle aroused great attention in the prevalence of BPH. Prostate enlargement (PE) is a major symptom of BPH. Objectives: To elaborate the effect of total diet quality for adults from the United States, we investigated the association between Health Eating Index (HEI)-2015 and the risk of PE in adults from the National Health and Nutrition Examination Survey (NHANES). Methods: This cross-sectional study was conducted based on NHANES 2001-2008. Participants who reported a PE history were included. We conducted a logistic regression analysis to investigate the association between HEI-2015 and PE. Results: A total of 4,866 male participants aged 40 and above were enrolled. Compared with Q1 of HEI-2015, no significant differences were found in adjusted models. Higher vegetables intake (Odds ratio [OR] = 1.073; 95% confidence interval [95%CI] 1.015 to 1.134, P = 0.02) and higher total dairy intake (OR = 1.034; 95%CI 1.009 to 1.061, P = 0.01) were significantly related with higher risk of PE. Conclusions: There was no significant difference between HEI-2015 and PE after full adjustment. Total vegetables and dairy product might be associated with higher risk of PE and needed further validation.

Enhanced Cherenkov imaging for real-time beam visualization by applying a novel carbon quantum dot sheeting in radiotherapy.

BACKGROUND: Cherenkov imaging can be used to visualize the placement of the beam directly on the patient's surface tissue and evaluate the accuracy of treatment planning. However, Cherenkov emission intensity is lower than ambient light. At present, time gating is the only way to realize Cherenkov imaging with ambient light. PURPOSE: This study proposes preparing a novel carbon quantum dot (cQD) sheeting to adjust the wavelength of Cherenkov emission to obtain the optimal wavelength meeting the sensitive detection region of the camera, meanwhile the total optical signal is also increased. By combining a specific filter, this approach might help in using lower-cost camera systems without intensifier-coupled to accomplish in vivo monitoring of the surface beam profile on patients with ambient light. METHODS: The cQD sheetings were prepared by spin coating and UV curing with different concentrations. All experiments were performed on the Varian VitalBeam system and optical emission was captured using an electron multiplying charge-coupled device (EMCCD) camera. To quantify the optical characteristics and certify the improvement of light intensity as well as signal-to-noise ratio (SNR) of cQD sheeting, the first part of the study was carried out on solid water with 6 and 10 MV photon beams. The second part was carried out on an anthropomorphic phantom to explore the applicability of sheeting when using different radiotherapy materials and the imaging effect of sheeting with the impact of ambient light sources. Additionally, thanks to the narrow emission spectrum of the cQD, a band-pass filter was tested to reduce the effect from environmental lights. RESULTS: The experimental results show that the optical intensity collected with sheeting has an excellent linear relationship (R2  > 0.99) with the dose for 6 and 10 MV photons. The full-width half maximum (FWHM) in x and y axis matched with the measured EBT film image, with accuracy in the range of ±1.2 and ±2.7 mm standard deviation, respectively. CQD sheeting can significantly improve the light intensity and SNR of optical images. Using 0.1 mg/ml sheeting as an example, the signal intensity is increased by 209%, and the SNR is increased by 147.71% at 6 MV photons. The imaging on the anthropomorphic phantom verified that cQD sheeting could be applied to different radiotherapy materials. The average optical intensity increased by about 69.25%, 63.72%, and 61.78%, respectively, after adding cQD sheeting to bolus, mask sample and the combination of bolus and mask. Corresponding SNR is improved by about 62.78%, 56.77%, and 68.80%, respectively. Through the sheeting, optical images with SNR > 5 can be obtained in the presence of ambient light and it can be improved through combining with a band-pass filter. When red ambient lights are on, the SNR is increased by about 98.85% after adding a specific filter. CONCLUSION: Through a combination of cQD sheeting and corresponding filter, light intensity and SNR of optical images can be increased significantly, and it shed new light on the promotion of the clinical application of optical imaging to visualize the beam in radiotherapy.

Familial 5.29 Mb deletion in chromosome Xq22.1-q22.3 with a normal phenotype: a rare pedigree and literature review.

BACKGROUND: Xq22.1-q22.3 deletion is a rare chromosome aberration. The purpose of this study was to identify the correlation between the phenotype and genotype of chromosome Xq22.1-q22.3 deletions. METHODS: Chromosome aberrations were identified by copy number variation sequencing (CNV-seq) technology and karyotype analysis. Furthermore, we reviewed patients with Xq22.1-q22.3 deletions or a deletion partially overlapping this region to highlight the rare condition and analyse the genotype-phenotype correlations. RESULTS: We described a female foetus who is the "proband" of a Chinese pedigree and carries a heterozygous 5.29 Mb deletion (GRCh37: chrX: 100,460,000-105,740,000) in chromosome Xq22.1-q22.3, which may affect 98 genes from DRP2 to NAP1L4P2. This deletion encompasses 7 known morbid genes: TIMM8A, BTK, GLA, HNRNPH2, GPRASP2, PLP1, and SERPINA7. In addition, the parents have a normal phenotype and are of normal intelligence. The paternal genotype is normal. The mother carries the same deletion in the X chromosome. These results indicate that the foetus inherited this CNV from her mother. Moreover, two more healthy female family members were identified to carry the same CNV deletion through pedigree analysis according to the next-generation sequencing (NGS) results. To our knowledge, this family is the first pedigree to have the largest reported deletion of Xq22.1-q22.3 but to have a normal phenotype with normal intelligence. CONCLUSIONS: Our findings further improve the understanding of the genotype-phenotype correlations of chromosome Xq22.1-q22.3 deletions.This report may provide novel information for prenatal diagnosis and genetic counselling for patients who carry similar chromosome abnormalities.

A rare case report of multifocal para-aortic and para-vesical paragangliomas.

Background: Paragangliomas (PGLs) are uncommon tumors of uncertain malignant potential. Multifocal paragangliomas are scarcely reported in the literature. Case summary: A 25-year-old male patient was reported for the first time with multifocal para-aortic and para-vesical PGLs. The diagnosis was identified by blood catecholamine tests and enhanced CT scan and MIBG scintigraphy. A resection surgery was performed for treatment and the immunochemistry test of the tumors presented the features of PGL. Conclusion: A case of multifocal para-aortic and para-vesical PGLs confirmed by the catecholamine test, enhanced CT, and MIBG scintigraphy is presented. The cooperation of experienced surgeons, anesthesiologists, and endocrinologists was critical in treatment.

HLA-G 3'UTR polymorphism diplotypes and soluble HLA-G plasma levels impact cervical cancer susceptibility and prognosis.

Background: Human leukocyte antigen G (HLA-G) is an immune checkpoint molecule with relevance in several cancers. The aim of this study was to evaluate the potential role of soluble HLA-G (sHLA-G), its genetic polymorphisms and its haplotype structure in the susceptibility and prognosis of primary cervical cancer in a Chinese Han population. Methods: We investigated sHLA-G plasma levels and 3' untranslated region (3'UTR) polymorphisms through ELISA and direct DNA sequencing, respectively, in cervical cancer patients (120 cases) and healthy control women (96 cases). The data were analyzed for associations using PowerMarker, Haploview, and GraphPad Prism. Results: In this study, 8 polymorphic sites, 16 haplotypes and 23 diplotypes in the HLA-G 3'UTR were identified in our study population. We observed that each pair of 8 polymorphic sites exhibited linkage disequilibrium. The heterozygote CT genotype at position +3422 (rs17875408) was more common in cervical cancer patients than in healthy women (OR=5.285, P<0.05). Haplotypes UTR-1, UTR-3, and UTR-7 accounted for more than 85% of both groups, but no significant difference was found. The frequency of the UTR-1/UTR-3 diplotype in patients was significantly higher than that in controls (P<0.05). In addition, we further observed that HLA-G 3'UTR polymorphisms may influence the sHLA-G plasma level in patients' peripheral blood, especially 14 bp Ins/Del (rs371194629) and +3142 C/G (rs1063320). A receiver operating characteristic (ROC) curve analysis showed that the sHLA-G level had good diagnostic performance in differentiating patients with cervical cancer from healthy women (AUC>0.7). Among patients, mean sHLA-G levels increased with increasing FIGO stages but were not related to the overall survival time. Conclusions: The results of the present study enhance our understanding of how HLA-G 3'UTR polymorphisms can influence the peripheral sHLA-G plasma level and play a key role in cervical carcinogenesis. This study further confirmed that sHLA-G may represent a novel plasma biomarker for the prognosis and potential therapeutic target of cervical cancer.

YAP/Smad3 promotes pathological extracellular matrix microenviroment-induced bladder smooth muscle proliferation in bladder fibrosis progression.

Fibrosis is a chronic inflammation process with excess extracellular matrix (ECM) deposition that cannot be reversed. Patients suffer from bladder dysfunction caused by bladder fibrosis. Moreover, the interactive mechanisms between ECM and bladder fibrosis are still obscure. Hence, we assessed the pivotal effect of Yes-associated protein (YAP) on the proliferation of bladder smooth muscle in fibrosis process. We identified that stiff ECM increased the expression and translocation of YAP in the nucleus of human bladder smooth muscle cell (hBdSMC). Sequencings and proteomics revealed that YAP bound to Smad3 and promoted the proliferation of hBdSMC via MAPK/ERK signaling pathway in stiff ECM. Moreover, CUT and TAG sequencing and dual-luciferase assays demonstrated that Smad3 inhibited the transcription of JUN. The YAP inhibitor CA3 was used in a partial bladder outlet obstruction (pBOO) rat model. The results showed that CA3 attenuated bladder smooth muscle proliferation. Collectively, YAP binding with Smad3 in the nucleus inhibited the transcription of JUN, and promoted the proliferation of bladder smooth muscle through the MAPK/ERK signaling pathway. The current study identified a novel mechanism of mechanical force induced bladder fibrosis that provided insights in YAP-associated organ fibrosis.

[Initial experience of 640-slice CT coronary angiography in pacemaker patients].

OBJECTIVE: To investigate the feasibility and image quality of coronary artery angiography with 640-slice CT system in the pacemaker patients. METHODS: ECG-triggered 640-slice CT coronary angiography was performed in 16 pacemaker patients. Image quality of the fifteen coronary segments and metal-related artifact originating from pacemaker were assessed by two experienced radiologists in consensus. Image quality was assessed using a 4-point grading scale. ECG trigger information was recorded. RESULTS: The rate of available diagnostic images was 99.07% (Grade 1 in 83.64%, Grade 2 in 15.42%, Grade 3 in 0.47% and Grade 4 in 0.47% of patients, respectively). Image quality and the effect of streak artifact were similar between the high heart rate group and low heart rate group (P > 0.05) and between normal pacing group and arrhythmia group (P > 0.05). In coronary MSCT angiography, streak artifact of the pacemaker can render segments of the coronary artery uninterpretable, especially on S1, S2, S3, S4 and S8 segments of the coronary artery. Small shifts in the reconstruction window resulted in significance reduction of streak artifact (χ(2) = 151.818, P < 0.01). CONCLUSIONS: 640-slice gated CT coronary angiography could provide excellent image quality for patients with pacemaker. The streak artifact induced by pacemaker on some segments of the coronary artery could be improved by small shifts in the reconstruction window.

[Application value of FS-3D-FISP sequence in the diagnosis of ankle cartilage injury].

OBJECTIVE: To compare several sequences of MRI and arthroscopy for detecting the ankle articular cartilage lesions and to evaluate the clinical outcome of special sequence of FS-3D-FISP. METHODS: Forty patients (41 ankles) with iterative ankle pain who were scheduled for arthroscopy underwent MR scanning, including FS-3D-FISP, FSE T2WI and FSE PDWI sequences. The results of each sequence were then compared with the arthroscopic findings. RESULTS: Using arthroscopic results as the standard of reference, the FS-3D-FISP images had the higher sensitivity (92.86%) than the other two sequences. The FS-3D-FISP sequence was well consistent with the result of arthroscopy. Kappa value (0.7590) was higher than the other two sequences (P < 0.01). CONCLUSION: As a favorable scanning sequence, FS-3D-FISP imaging can show the early-stage pathological changes of articular cartilage and it has an excellent correlation with the arthroscopic findings. A 3-D reconstruction is helpful to determine the location and the degree of lesion and obtain a more accurate classification to guide clinical decisions.

Comparison of neoadjuvant chemotherapy followed by surgery vs. surgery alone for locally advanced gastric cancer: a meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#The neoadjuvant chemotherapy is increasingly used in advanced gastric cancer, but the effects on safety and survival are still controversial. The objective of this meta-analysis was to compare the overall survival and short-term surgical outcomes between neoadjuvant chemotherapy followed by surgery (NACS) and surgery alone (SA) for locally advanced gastric cancer.@*METHODS@#Databases (PubMed, Embase, Web of Science, Cochrane Library, and Google Scholar) were explored for relative studies from January 2000 to January 2021. The quality of randomized controlled trials and cohort studies was evaluated using the modified Jadad scoring system and the Newcastle-Ottawa scale, respectively. The Review Manager software (version 5.3) was used to perform this meta-analysis. The overall survival was evaluated as the primary outcome, while perioperative indicators and post-operative complications were evaluated as the secondary outcomes.@*RESULTS@#Twenty studies, including 1420 NACS cases and 1942 SA cases, were enrolled. The results showed that there were no significant differences in overall survival (P = 0.240), harvested lymph nodes (P = 0.200), total complications (P = 0.080), and 30-day post-operative mortality (P = 0.490) between the NACS and SA groups. However, the NACS group was associated with a longer operation time (P < 0.0001), a higher R0 resection rate (P = 0.003), less reoperation (P = 0.030), and less anastomotic leakage (P = 0.007) compared with SA group.@*CONCLUSIONS@#Compared with SA, NACS was considered safe and feasible for improved R0 resection rate as well as decreased reoperation and anastomotic leakage. While unbenefited overall survival indicated a less important effect of NACS on long-term oncological outcomes.