Concurrent ozone and high temperature exacerbates nasal epithelial barrier damage in allergic rhinitis mice: Insights from the nasal transcriptome and nasal microbiota.

The global ambient temperature has been rising in recent decades and high temperature is usually accompanied by ozone (O3) pollution. Environmental change is an underlying factor for the increased prevalence of respiratory allergic disease. However, the potential mechanisms are complex and remain elusive. This study was performed to reveal toxic effects and molecular mechanisms of O3 or/and high temperature induced allergic rhinitis (AR) deterioration. The results indicated that O3 and high temperature co-exposure exacerbated rhinitis symptoms, destroyed ultrastructure of nasal mucosa and down-regulated the expression of nasal epithelial barrier structural proteins ZO-1 and occludin. Moreover, the levels of total protein and lactate dehydrogenase (LDH) in nasal lavage fluid and the levels of IL-1ß and TNF-α in serum also exhibited a significant upward trend. Transcriptomic analysis revealed that immune and inflammatory signaling pathways such as IL-17 signaling pathway was involved in the combined toxicity of O3 and high temperature. Microbiome examination showed that Prevotella and Elizabethkingia were linked to nasal injury. What's more, spearman correlation analysis revealed correlations among nasal microbiota dysbiosis, inflammation and injury. To sum up, the present study assessed the combined toxicity of O3 and high temperature and found potential mechanisms, which provided important experimental evidence for making preventive intervention strategies and protecting vulnerable populations.

Time to complication after primary pediatric hypospadias repair with transverse preputial island flap urethroplasty.

Background: Hypospadias is one of the most common congenital malformations in men. The transverse preputial island urethroplasty is widely used in China, especially for moderate and severe cases due to its convenient prepuce of the penis. This analysis aims to delineate the time to first complication following transverse preputial island urethroplasty. Methods: We analyzed the clinical data and follow-up results of children who underwent hypospadias repair by transverse preputial island urethroplasty in Beijing Children's Hospital, Capital Medical University from December 2018 to December 2019 retrospectively. Postoperative complications included urethral fistula, urethral diverticulum, urethral stricture, persistent chordee. Univariate analysis of clinical variables and time to complication was performed using Kaplan-Meier survival curve. Results: One hundred and sixty-five patients were identified. During the follow-up period, complications occurred in 101 cases (61.2%). Ninety-four percent of complications occurred within 1 year. Among children who experienced complications, Kaplan-Meier survival analysis showed that age less than 18 months and the severity of hypospadias were statistically significant (P=0.005 and P=0.04, respectively). The time to urethral diverticulum was significantly longer than that of urethral fistula and urethral stricture. Conclusions: More than 90% of complications after the transverse preputial island urethroplasty of hypospadias occurred within 1 year, with those related to proximal hypospadias presenting earlier than those of midshaft/distal hypospadias. Surgeons may consider a more frequent follow-up within the first year after surgery to detect these complications as early as possible.

Elevated temperature as the dominant stressor on the harmful algal bloom-causing dinoflagellate Prorocentrum obtusidens in a future ocean scenario.

Marine dinoflagellates are increasingly affected by ongoing global climate changes. While understanding of their physiological and molecular responses to individual stressors anticipated in the future ocean has improved, their responses to multiple concurrent stressors remain poorly understood. Here, we investigated the individual and combined effects of elevated temperature (26 °C relative to 22 °C), increased pCO2 (1000 µatm relative to 400 µatm), and high nitrogen: phosphorus ratio (180:1 relative to 40:1) on a harmful algal bloom-causing dinoflagellate Prorocentrum obtusidens under short-term (28 days) exposure. Elevated temperature was the most dominant stressor affecting P. obtusidens at physiological and transcriptomic levels. It significantly increased cell growth rate and maximum photosynthetic efficiency (Fv/Fm), but reduced chlorophyll a, particulate organic carbon, particulate organic nitrogen, and particulate organic phosphorus. Elevated temperature also interacted with other stressors to produce synergistic positive effects on cell growth and Fv/Fm. Transcriptomic analysis indicated that elevated temperature promoted energy production by enhancing glycolysis, tricarboxylic acid cycle, and nitrogen and carbon assimilation, which supported rapid cell growth but reduced material storage. Increased pCO2 enhanced the expression of genes involved in ionic acid-base regulation and oxidative stress resistance, whereas a high N:P ratio inhibited photosynthesis, compromising cell viability, although the effect was alleviated by elevated temperature. The combined effect of these multiple stressors resulted in increased energy metabolism and up-regulation of material-synthesis pathways compared to the effect caused by elevated temperature alone. Our results underscore ocean warming as the predominant stressor for dinoflagellates and highlight the complex, synergistic effects of multi-stressors on dinoflagellates.

Enhanced Quantum Metrology with Non-Phase-Covariant Noise.

The detrimental impact of noise on sensing performance in quantum metrology has been widely recognized by researchers in the field. However, there are no explicit fundamental laws of physics stating that noise invariably weakens quantum metrology. We reveal that phase-covariant noise either degrades or remains neutral to sensing precision, whereas non-phase-covariant noise can potentially enhance parameter estimation, surpassing even the ultimate precision limit achievable in the absence of noise. This implies that a non-Hermitian quantum sensor may outperform its Hermitian counterpart in terms of sensing performance. To illustrate and validate our theory, we present several paradigmatic examples of magnetic field metrology.

Characterization of Ucp1-iCre Knockin Mice Reveals the Recombination Activity in Male Germ Cells.

Ucp1 promoter-driven Cre transgenic mice are useful in the manipulation of gene expression specifically in thermogenic adipose tissues. However, the wildly used Ucp1-Cre line was generated by random insertion into the genome and showed ectopic activity in some tissues beyond adipose tissues. Here we characterized a knockin mouse line Ucp1-iCre generated by targeting IRES-Cre cassette immediately downstream the stop codon of the Ucp1 gene. The Cre insertion had little to no effect on UCP1 protein levels in brown adipose tissue. Ucp1-iCre mice of both genders exhibited normal thermogenesis and cold tolerance. When crossed with Rosa-tdTomato reporter mice, Ucp1-iCre mice showed robust Cre activity in thermogenic adipose tissues. Additionally, limited Cre activity was sparsely present in the hypothalamus (VMH), choroid plexus, kidney, adrenal glands, ovary, and testis in Ucp1-iCre mice, albeit to a much lesser extent and with reduced intensity compared to the conventional Ucp1-Cre line. Single-cell transcriptome analysis revealed UCP1 mRNA expression in male spermatocytes. Moreover, male Ucp1-iCre mice displayed a high frequency of Cre-mediated recombination in the germline, whereas no such effect was observed in female Ucp1-iCre mice. These findings suggest that Ucp1-iCre mice offer promising utility in the context of conditional gene manipulation in thermogenic adipose tissues, while also highlighting the need for caution in mouse mating and genotyping procedures.

Multifaceted paternal exposures before conception and their epigenetic impact on offspring.

As scientific research progresses, there is an increasing understanding of the importance of paternal epigenetics in influencing the health and developmental path of offspring. Prior to conception, the environmental exposures and lifestyle choices of fathers can significantly influence the epigenetic state of sperm, including DNA methylation and histone changes, among other factors. These alterations in epigenetic patterns have the potential for transgenerational transmission potential and may exert profound effects on the biological characteristics of descendants. Paternal epigenetic changes not only affect the regulation of gene expression patterns in offspring but also increase the risk to certain diseases. It is crucial to comprehend the conditions that fathers are exposed to before conception and the potential outcomes of these conditions. This understanding is essential for assessing personal reproductive decisions and anticipating health risks for future generations. This review article systematically summarizes and analyzes current research findings regarding how paternal pre-pregnancy exposures influence offspring as well as elucidates underlying mechanisms, aiming to provide a comprehensive perspective for an enhanced understanding of the impact that paternal factors have on offspring health.

Central precocious puberty should be taken seriously in children with Leydig cell tumors of the testis after surgical treatment: a tertiary center experience.

ABSTRACT: Central precocious puberty secondary to Leydig cell tumors is rare in children. We retrospectively analyzed the mid- to long-term follow-up data of patients with Leydig cell tumors. The clinical data of 12 consecutive patients who were treated at Beijing Children's Hospital, Capital Medical University (Beijing, China), between January 2016 and October 2023 were retrospectively reviewed. Clinical evaluations, including physical examination, hormone examination, serum tumor marker analysis, abdominal and scrotal ultrasound, chest X-ray, and bone age measurement, were conducted before surgery and at follow-up time points. Surgical approaches were selected according to the individual conditions. Patients with an abnormal hormonal status and suspected of having central precocious puberty were referred to endocrinologists to confirm the diagnosis. Subsequently, gonadotropin-releasing hormone analog therapy was proposed. The mean patient age was 81.3 (range: 40-140) months at the time of the operation. Ten patients had peripheral precocious puberty at admission. All patients had elevated preoperative testosterone levels, whereas tumor marker levels were normal. Testis-sparing surgery was performed in eleven patients, and radical orchiectomy was performed in one patient. The follow-up duration (mean ± standard deviation) was 36.2 ± 25.3 months. Five patients had central precocious puberty, with a mean duration of 3.4 (range: 1-6) months postoperatively. Three patients were receiving gonadotropin-releasing hormone analog therapy, and good suppression of puberty was observed. No risk factors were found for secondary central precocious puberty. There was a high prevalence of central precocious puberty secondary to Leydig cell tumors in our study. Gonadotropin-releasing hormone analog therapy has satisfactory treatment effects. Larger sample sizes and long-term follow-up are needed in future studies.

Clinical best practices in interdisciplinary management of human epidermal growth factor receptor 2 antibody-drug conjugates-induced interstitial lung disease/pneumonitis: An expert consensus in China.

Antibody-drug conjugates (ADCs) have demonstrated effectiveness in treating various cancers, particularly exhibiting specificity in targeting human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Recent advancements in phase 3 clinical trials have broadened current understanding of ADCs, especially trastuzumab deruxtecan, in treating other HER2-expressing malignancies. This expansion of knowledge has led to the US Food and Drug Administration's approval of trastuzumab deruxtecan for HER2-positive and HER2-low breast cancer, HER2-positive gastric cancer, and HER2-mutant nonsmall cell lung cancer. Concurrent with the increasing use of ADCs in oncology, there is growing concern among health care professionals regarding the rise in the incidence of interstitial lung disease or pneumonitis (ILD/p), which is associated with anti-HER2 ADC therapy. Studies on anti-HER2 ADCs have reported varying ILD/p mortality rates. Consequently, it is crucial to establish guidelines for the diagnosis and management of ILD/p in patients receiving anti-HER2 ADC therapy. To this end, a panel of Chinese experts was convened to formulate a strategic approach for the identification and management of ILD/p in patients treated with anti-HER2 ADC therapy. This report presents the expert panel's opinions and recommendations, which are intended to guide the management of ILD/p induced by anti-HER2 ADC therapy in clinical practice.

[Analysis of risk factors for postoperative delirium in elderly patients undergoing spinal surgery].

OBJECTIVE: To investigate the risk factors of postoperative delirium in elderly patients undergoing spine surgery. METHODS: The basic case data of 566 patients who underwent spine surgery under general anesthesia from January 2021 to January 2023 were retrospectively analyzed. There were 296 males and 270 females with an average age of (71.58 ± 4.21) years old. There were 195 cases of cervical spine surgery, 26 cases of thoracic spine surgery and 345 cases of lumbar spine surgery.According to the occurrence of postoperative delirium, the patients were divided into postoperative delirium group(41 patients) and non-delirium group (525 patients). Univariate analysis was used to analyze the possible influencing factors such as gender, age, weight, smoking history, drinking history, surgical site, preoperative anxiety, intraoperative hypotension times, blood loss and so on, and binary Logistic regression was used to analyze the univariate factors with P<0.05. RESULTS: A total of 41 patients developed postoperative delirium. Univariate analysis showed that age (P=0.000), duration of surgery (P=0.039), preoperative anxiety (P=0.001), blood loss (P=0.000), history of opioid use (P=0.003), history of stroke (P=0.005), C-reactive protein (P=0.000), sodium ion(P=0.000) were significantly different between delirium group and non-delirium group. These factors were included in the binary Logistic regression analysis, and the results showed that age [OR=0.729, 95%CI(0.569, 0.932), P=0.012], opioid use [OR=21.500, 95%CI(1.334, 346.508), P=0.031], blood loss [OR=0.932, 95%CI(0.875, 0.993), P=0.029], C-reactive protein [OR=0.657, 95%CI(0.485, 0.890), P=0.007], preoperative anxiety [OR=23.143, 95%CI(1.859, 288.090), P=0.015], and sodium [OR=1.228, 95%CI(1.032, 1.461), P=0.020] were independent risk factors for the development of delirium after spinal surgery in elderly patients. CONCLUSION: Age, opioid use, blood loss, preoperative anxiety, elevated c-reactive protein, and hyponatremia are independent risk factors for the development of postoperative delirium in elderly patients undergoing spinal surgery.

Mapping the functional B-cell epitopes of Shigella invasion plasmid antigen D (IpaD).

Shigella bacteria utilize the type III secretion system (T3SS) to invade host cells and establish local infection. Invasion plasmid antigen D (IpaD), a component of Shigella T3SS, has garnered extensive interest as a vaccine target, primarily due to its pivotal role in the Shigella invasion, immunogenic property, and a high degree of conservation across Shigella species and serotypes. Currently, we are developing an epitope- and structure-based multivalent vaccine against shigellosis and require functional epitope antigens of key Shigella virulence determinants including IpaD. However, individual IpaD B-cell epitopes, their contributions to the overall immunogenicity, and functional activities attributing to bacteria invasion have not been fully characterized. In this study, we predicted continuous B-cell epitopes in silico and fused each epitope to a carrier protein. Then, we immunized mice intramuscularly with each epitope fusion protein, examined the IpaD-specific antibody responses, and measured antibodies from each epitope fusion for the activity against Shigella invasion in vitro. Data showed that all epitope fusion proteins induced similar levels of anti-IpaD IgG antibodies in mice, and differences were noted for antibody inhibition activity against Shigella invasion. IpaD epitope 1 (SPGGNDGNSV), IpaD epitope 2 (LGGNGEVVLDNA), and IpaD epitope 5 (SPNNTNGSSTET) induced antibodies significantly better in inhibiting invasion from Shigella flexneri 2a, and epitopes 1 and 5 elicited antibodies more effectively at preventing invasion of Shigella sonnei. These results suggest that IpaD epitopes 1 and 5 can be the IpaD representative antigens for epitope-based polyvalent protein construction and protein-based cross-protective Shigella vaccine development.IMPORTANCEShigella is a leading cause of diarrhea in children younger than 5 years in developing countries (children's diarrhea) and continues to be a major threat to public health. No licensed vaccines are currently available against the heterogeneous Shigella species and serotype strains. Aiming to develop a cross-protective multivalent vaccine against shigellosis and dysentery, we applied novel multiepitope fusion antigen (MEFA) technology to construct a broadly immunogenic polyvalent protein antigen, by presenting functional epitopes of multiple Shigella virulence determinants on a backbone protein. The functional IpaD epitopes identified from this study will essentially allow us to construct an optimal polyvalent Shigella immunogen, leading to the development of a cross-protective vaccine against shigellosis (and dysentery) and the improvement of global health. In addition, identifying functional epitopes from heterogeneous virulence determinants and using them as antigenic representatives for the development of cross-protective multivalent vaccines can be applied generally in vaccine development.

The early predictive value of maternal serum PAPP-A concentration at 11-14 weeks of pregnancy for preeclampsia.

INTRODUCTION: To determine the expression and clinical significance of maternal serum pregnancy-associated plasma protein A (PAPP-A) in pregnant women with different degrees of preeclampsia at 11-14 weeks of gestation. MATERIAL AND METHODS: The clinical data of 65 pregnant women with preeclampsia admitted to our hospital from January 2020 to October 2022 were retrospectively analysed. Another 45 normal pregnant women who came to our hospital for prenatal examination and delivery during the same period were selected as the healthy control group. The serum contents of PAPP-A, a-fetoprotein (AFP) and free estriol (uE3) in each group were compared. The correlation between PAPP-A and AFP as well as uE3 was analysed by Pearson analysis. The clinical value of serological indexes in diagnosing preeclampsia was analysed using ROC curve. RESULTS: The levels of PAPP-A and uE3 in pregnant women in the preeclampsia group were lower, while the contents of AFP were higher than these in the healthy control group ( p < 0.01). The pregnant women with severe preeclampsia had lower levels of PAPP-A and uE3 with higher levels of AFP compared to these with mild preeclampsia ( p < 0.001). Pearson correlation analysis showed that serum PAPP-A was negatively correlated with AFP ( r = -0.246, p < 0.05) and positively correlated with uE3 ( r = 0.398, p < 0.01) in preeclampsia patients. ROC curve analysis demonstrated that the area under the curve (AUC) of PAPP-A, AFP and uE3 to assist in the diagnosis of preeclampsia was 0.740, 0.738 and 0.806, respectively. The AUC of the combination of PAPP-A, AFP and uE3 to assist in the diagnosis was 0.912, with a sensitivity of 90.38% and a specificity of 80.33%. The clinical assisted diagnostic value of combined detection was high. CONCLUSIONS: The serum level of PAPP-A in pregnant women with preeclampsia in the early pregnancy was significantly lower and related to the severity of the disease. The combination of routine detection for AFP and uE3 had a good predictive value for preeclampsia, which was helpful to take relevant interventions to reduce the incidence of preeclampsia as early as possible, and had a positive impact on protecting maternal and infant health.

Half-life of serum alpha-fetoprotein in prepubertal testicular yolk sac tumors: an index significantly associated with prognosis.

PURPOSE: To evaluate the association between serum alpha-fetoprotein (AFP) half-life (HL) and prognosis in prepubertal children with elevated AFP values 3 to 4 weeks after surgery for testicular yolk sac tumors (YST). METHODS: Prepubertal patients with testicular YST treated with radical orchiectomy between January 2016 and December 2022 were retrospectively reviewed. Negative outcomes were defined as relapse, metastasis or death. Univariate and multivariate logistic regression analyses were conducted to select risk factors for negative outcomes. RESULTS: A total of 42 patients were eventually enrolled into the study. Patients were divided into non-negative and negative outcomes groups, consisting of 35 and 7 patients, respectively. Thirty-five patients were stage I, two cases were stage II, and five cases were stage IV, according to the Children's Oncology Group staging system. The overall survival (OS) rate was 100%. Average AFP values significantly decreased after resection (P < 0.001). A significant positive correlation was shown between pre- and postoperative AFP values (r = 0.60, P < 0.001). Long AFP HL was considered as an independent risk factor for negative outcomes in YST patients underwent radical orchiectomy (P = 0.04). The cut-off value for AFP HL was 5.78 days, regardless of age division. CONCLUSION: Testicular YST is a relatively rare disease in children with an OS of 100%, and salvage chemotherapy is effective even in grade IV patients. The postoperative AFP HL was significantly associated with prognosis in prepubertal patients with testicular YST. The cut-off value for AFP HL is 5.78 days regardless of the effect of physiological AFP elevation.

Does bilateral Wilms' tumor involving the collecting system in children have a worse prognosis?

BACKGROUND: The literature on nephron-sparing surgery (NSS) in children with bilateral Wilms' tumors (BWT) involving the collection system is mostly comprised of case reports. The present study aimed to summarize the clinical characteristics, treatments, and prognosis of children with BWT involving the collecting system admitted to our pediatric surgery center compared with those whose tumors did not involve the collecting system. A secondary aim was to discuss how to preserve more kidney parenchyma and prevent long-term renal failure under the premise of preventing tumor recurrence. METHODS: Patients with BWT admitted to our pediatric surgery center between January 2008 and June 2022 were reviewed. All included patients were grouped according to the relationship between the tumor and collecting system according to the intraoperative findings. Group I included children with tumor infiltrating the collecting system, group II included children with tumor growing into the collecting system, and group III included children whose tumor did not involve the collecting system. The clinical features, treatments and prognosis of the patients were analyzed. RESULTS: Seventy patients were enrolled, including 20 patients with 25 sides of tumors infiltrating the collecting system in group I,10 patients with 13 sides of tumors growing into the collecting system in group II, and 40 patients in group III. There was no significant difference in patients age and gender between group I and group II. In total, 20 patients in group I and 9 patients in group II had partial response (PR) after neoadjuvant chemotherapy. In group I, 22 of 25 sides of tumors underwent NSS; in group II, 11 of 13 sides of tumors underwent NSS. During an average follow-up of 47 months, in group I, 6/20 patients relapsed and 2/20 patients died; in group II, 3/10 patients relapsed and 1/10 patient died. There was no significant difference in 4-year overall survival (OS) rate among groups I, II and III (86.36% vs. 85.71%vs. 91.40%, P = 0.902). CONCLUSIONS: To preserve renal parenchyma, NSS is feasible for children with BWT involving the collecting system. There was no significant difference in postoperative long-term OS between patients with BWT involving the collecting system and not involving the collecting system.

[Spatio-temporal Differentiation of County Carbon Budget and Territorial Space Optimization Zoning Strategy in Gansu Province from the Perspective of Carbon Neutrality].

Under the background of comprehensively practicing the overall system concept of the "living community" in the new era, incorporating the carbon neutral development goal into the territorial spatial planning and construction and establishing the territorial spatial pattern and optimization strategy in line with the actual development of Gansu Province are of great significance for promoting the comprehensive green low-carbon transformation and high-quality development of regional economy and society. Taking counties in Gansu Province as an example, based on the perspective of carbon neutrality research, the land use carbon budget of 87 counties in Gansu Province in 2010, 2015, and 2021 was calculated and analyzed. GIS spatial analysis and social network analysis were used to further explore their spatial differentiation characteristics and the overall characteristics of the carbon emission spatial correlation network. At last, combined with the main function zoning, the low-carbon oriented land space optimization zoning was carried out, and differentiated low-carbon development strategies were proposed. The results were as follows： ① Carbon emissions in Gansu Province showed an upward trend, but the increase rate decreased, showing a spatial distribution of "high in the central and eastern part of the country, low in the southwest." Construction land was the main carbon source. The carbon uptake showed a spatial distribution of "high in the south and low in the north, high in the west and low in the east." Woodlands were the main carbon sinks. The net carbon emissions showed an increasing trend, and approximately 58.62% of the counties in the province were in a carbon imbalance situation. ② In 2021, the spatial network of county carbon emissions was closely related, showing a "core-edge" pattern. The Chenguan District and Qilihe District were in the core position of the network and received more correlation relationships in the network. The network contacts in Longzhong area were frequent, followed by the contacts in Longdongnan area. ③ Based on carbon emissions, carbon sequestration, and ecological carrying capacity coefficients and using the results of spatial correlation of social networks as role positions, the province was divided into four carbon-neutral sub-districts. At the same time, superimposed analysis of the main function zoning, the county area of the province was reconstructed into seven territorial space zones, and the differentiated regional low-carbon optimization development strategy was proposed for each zone.

Insulin receptor isoform B is required for efficient proinsulin processing in pancreatic ß cells.

The insulin receptor (INSR, IR) has two isoforms, IRA and IRB, through alternative splicing. However, their distinct functions in vivo remain unclear. Here we generated ß cell-specific IRB knockout (KO) mice (ßIRBKO). The KO mice displayed worsened hyperinsulinemia and hyperproinsulinemia in diet-induced obesity due to impaired proinsulin processing in ß cells. Mechanistically, loss of IRB suppresses eukaryotic translation initiation factor 4G1 (eIF4G1) by stabilizing the transcriptional receptor sterol-regulatory element binding protein 1 (SREBP1). Moreover, excessive autocrine proinsulin in ßIRBKO mice enhances the activity of extracellular signal-regulated kinase (ERK) through the remaining IRA to further stabilize nuclear SREBP1, forming a feedback loop. Collectively, our study paves the way to dissecting the isoform-specific function of IR in vivo and highlights the important roles of IRB in insulin processing and protecting ß cells from lipotoxicity in obesity.

Dietary fructose regulates hepatic manganese homeostasis in female mice.

Arginase, an enzyme dependent on manganese (Mn), plays a crucial role in the production of urea and processing of ammonia in the liver. Previous studies have shown that overconsumption of fructose disrupts Mn homeostasis in the liver of male mice. However, the potential sex-specific differences in the impact of fructose on hepatic Mn homeostasis remain uncertain. In this study, we provide evidence that heightened fructose intake disrupts liver Mn homeostasis in female mice. Elevated fructose exposure led to a reduction in liver Mn levels, resulting in decreased arginase and manganese superoxide dismutase (Mn-SOD) activity in the liver of female mice. The underlying mechanism involves the upregulation of carbohydrate-responsive element binding protein (ChREBP) expression and the Mn exporting gene Slc30a10 in the liver in response to fructose consumption. In summary, our findings support the involvement of fructose in liver Mn metabolism via the ChREBP/Slc30a10 pathway in female mice, and indicate that there is no disparity in the impact of fructose on hepatic Mn homeostasis between sexes.

Application of citric acid can enhance the accuracy for 13C-urea breath tests in the diagnosis of Helicobacter pylori infection in Chinese patients.

Previous published data have confirmed that the addition of a citric acid meal improves the accuracy of the 13C-urea breath test (13C-UBT). However, some studies have suggested that a citric acid test meal may not be necessary. Thus, the aim of this study was to evaluate the combination of a 13C-UBT with a citric acid meal for the diagnosis of Helicobacter pylori (Hp) infection in a Chinese population, particularly for patients with results in the gray zone. In this paired self-controlled study, all subjects had previously undergone 13C-UBTs without citric acid meals and were randomly divided into two groups based on different doses of citric acid (a low-dose citric acid group and a high-dose citric acid group, comprising meals with 0.68 g and 3.84 g citric acid powder, respectively). Positive rapid urease test (CLO) test and histology results were considered the 'gold standard'. The mean delta over baseline (DOB) value, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were compared between the two groups, particularly for patients with results in the gray zone. In total, 285 patients were tested. Of these patients, 189 were included in the low-dose citric acid group, and 96 were included in the high-dose citric acid group. Among patients with a positive 13C-UBT result without citric acid [delta over baseline (DOB) value ≥ 4‰, n = 174] and a negative 13C-UBT result without citric acid (DOB value < 4‰, n = 111), 8.0% (14/174) were false positive, and 0.9% (1/111) was false negative as determined by gold standard. Of 14 patients with false positive, 78.6% (11/14) false positive were in the gray zone of 4-10‰. However, there were no false positive 13C-UBT results with citric acid in the the gray zone of 4-10‰. In the comparison of the commercial 13C-UBT with the 13C-UBT in the low-dose citric acid group, the sensitivity, specificity, PPV, NPV and accuracy at 15 min were as follows: 99.1% vs. 99.1%, 97.5% vs. 88.9%, 98.2% vs. 92.2%, 98.8% vs. 98.6% and 98.4% vs. 94.7%, respectively. In the the gray zone of 4.0-10.0‰, the comparison of the commercial 13C-UBT with the 13C-UBT in the low-dose citric acid group, the sensitivity, specificity, PPV, and accuracy at 15 min were as follows: 94.4% vs. 100.0%, 100.0% vs. 0%, 100.0% vs. 75.0% and 95.8% vs. 75.0%, respectively. No significant difference was observed between the 15-min and 30-min measurement intervals in the low- and high-dose citric acid groups, including patients with results in the gray zone. The low-dose citric acid test, with an optimal measurement interval of 15 min, was highly accurate in the diagnosis of Hp infection in the Chinese population, especially for individuals with results in the gray zone.

Qualitative and quantitative assessment of non-clear cell renal cell carcinoma using contrast-enhanced ultrasound.

BACKGROUND: Non-clear cell renal cell carcinoma (nccRCC) represents a rare form of renal cell carcinoma (RCC) in the clinic. It is now understood that contrast-enhanced ultrasound (CEUS) exhibits diverse manifestations and can be prone to misdiagnosis. Therefore, summarizing the distinctive features of contrast-enhanced ultrasonography is essential for differentiation from ccRCC. OBJECTIVE: This study aims to evaluate the diagnostic efficacy of qualitative and quantitative CEUS in diagnosing nccRCC to enhance our understanding of this condition. METHODS: We conducted a retrospective analysis of 21 patients with confirmed nccRCC following surgery and assessed the characteristic conventional ultrasound and CEUS imaging features. The paired Wilcoxon signed-rank sum test was employed to compare differences in CEUS time-intensity curve (TIC) parameters between the lesions and the normal renal cortex. RESULTS: Routine ultrasound revealed the following primary characteristics in the 21 nccRCC cases: hypoechoic appearance (10/21, 47.6%), absence of liquefaction (18/21, 66.7%), regular shape (19/21, 90.5%), clear boundaries (21/21, 100%), and absence of calcification (17/21, 81%). Color Doppler flow imaging (CDFI) indicated a low blood flow signal (only 1 case of grade III). Qualitative CEUS analysis demonstrated that nccRCC predominantly exhibited slow progression (76.1%), fast washout (57%), uniformity (61.9%), low enhancement (71.5%), and ring enhancement (61.9%). Quantitative CEUS analysis revealed that parameters such as PE, WiAUC, mTTI, WiR, WiPI, WoAUC, WiWoAUC, and WOR in the lesions were significantly lower than those in the normal renal cortex (Z=-3.980, -3.563, -2.427, -3.389, -3.980, -3.493, -3.528, -2.763, P < 0.001, < 0.001, = 0.015, = 0.001, < 0.001, < 0.001, < 0.001, = 0.006). However, there were no significant differences in RT, TTP, FT, or QOF (all P > 0.05). CONCLUSION: nccRCC exhibits distinctive CEUS characteristics, including slow progression, fast washout, low homogeneity enhancement, and ring enhancement, which can aid in distinguishing nccRCC from ccRCC.