Pre-operative MRI in evaluating pathologic complete response to neoadjuvant chemotherapy in patients with breast cancer: a study focused on influencing factors of baseline clinical-pathological and imaging features.

Purpose: To investigate what pre-treatment clinical-pathological features and MRI characteristics influence the performance of breast MRI in assessing the pathologic complete response (pCR) of breast cancer patients to Neoadjuvant Chemotherapy (NAC). Methods: A total of 225 patients with pathologically-confirmed breast cancer who underwent pre- and post-NAC breast MRI between January 2020 and April 2023 were retrospectively analyzed. All patients were categorized into radiologic complete response (rCR) and non-rCR groups based on pre-operative MRI. Univariable and multivariable logistic regression were used to identify independent clinicopathological and imaging features associated with imaging-pathological discordance. The performance of pre-operative MRI for predicting pCR to NAC was assessed according to the baseline characteristics of the clinicopathological data and pre-NAC MRI. In addition, the discrepancy between the pre-operative MRI and post-operative pathological findings was further analyzed by a case-control approach. Results: Among 225 patients, 99 (44.0%) achieved pCR after NAC. MRI showed the overall sensitivity of 97.6%, specificity of 58.6%, accuracy of 80.4%, a positive predictive value (PPV) of 75.0%, and a negative predictive value (NPV) of 95.1% in identifying pCR. Of baseline features, presence of ductal carcinoma in situ (DCIS) (OR, 3.975 [95% CI: 1.448-10.908], p = 0.007), luminal B (OR, 5.076 [95% CI: 1.401-18.391], p = 0.013), HER2-enriched subtype (OR, 10.949 [95% CI: 3.262-36.747], p < 0.001), multifocal or multicentric lesions (OR, 2.467 [95% CI: 1.067-5.706], p = 0.035), segmental or regional distribution of NME (OR, 8.514 [95% CI: 1.049-69.098], p = 0.045) and rim enhancement of mass (OR, 4.261 [95% CI: 1.347-13.477], p = 0.014) were significantly associated with the discrepancy between MRI and pathology. Conclusion: Presence of DCIS, luminal B or HER2-enriched subtype, multicentric or multifocal lesions, segmental or regional distribution of NME and rim enhancement of mass may lead to a decrease in diagnostic accuracy of MRI in patients of breast cancer treated with NAC.

[Mechanism of Notoginseng Radix et Rhizoma in regulating PI3K/Akt/mTORC1-mitochondrial energy metabolism to treat chronic renal failure in rats with blood stasis syndrome].

This study observed the effects of Notoginseng Radix et Rhizoma on the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin complex 1(mTORC1) signaling pathway and mitochondrial energy metabolism in the rat model of adriamycin-induced renal fibrosis with blood stasis syndrome to explore the mechanism of Notoginseng Radix et Rhizoma in protecting the kidney. Thirty male rats with adriamycin-induced renal fibrosis were randomized into model, low-, medium-, and high-dose Notoginseng Radix et Rhizoma, and positive control groups(n=6). Six clean SD male rats were selected into the normal group. The normal group and model group were administrated with normal saline, and other groups with corresponding drugs. After 8 weeks of treatment, the renal function, renal pathology, adenosine triphosphate(ATP) levels, Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase activities, and the protein levels of ATP5B, mTORC1, 70 kDa ribosomal protein S6 kinase(P70S6K), P85, Akt, p-Akt, and SH2-containing inositol phosphatase(SHIP2) in the renal tissue were determined. Compared with the normal group, the model group showed elevated levels of blood urea nitrogen(BUN) and serum creatinine(SCr)(P<0.01). Compared with the model group, Notoginseng Radix et Rhizoma and the positive control lowered the levels of BUN and SCr, which were significant in the medium-and high-dose Noto-ginseng Radix et Rhizoma groups and the positive control group(P<0.05). Compared with the model group, Notoginseng Radix et Rhizoma and the positive control alleviated the pathological changes in the renal tissue, such as vacuolar and fibroid changes, glomerulus atrophy, cystic expansion of renal tubules, and massive infiltration of inflammatory cells. Compared with the normal group, the model group showed decreased mitochondrial ATP content and Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase activities in the renal tissue(P<0.05), and medium-and high-dose Notoginseng Radix et Rhizoma and positive control mitigated such decreases(P<0.05). Compared with the model group, medium-and high-dose Notoginseng Radix et Rhizoma and the positive control up-regulated the protein levels of ATP5B and SHIP2 and down-regulated the protein levels of mTORC1, P70S6K, P85, Akt, and p-Akt(P<0.05 or P<0.01 or P<0.001). Notoginseng Radix et Rhizoma may exert an anti-fibrosis effect by inhibiting the activation of the PI3K/Akt/mTORC1 pathway to restore mitochondrial energy metabolism, thus protecting the kidney.

Quantitative characterization of breast lesions and normal fibroglandular tissue using compartmentalized diffusion-weighted model: comparison of intravoxel incoherent motion and restriction spectrum imaging.

BACKGROUND: To compare the compartmentalized diffusion-weighted models, intravoxel incoherent motion (IVIM) and restriction spectrum imaging (RSI), in characterizing breast lesions and normal fibroglandular tissue. METHODS: This prospective study enrolled 152 patients with 157 histopathologically verified breast lesions (41 benign and 116 malignant). All patients underwent a full-protocol preoperative breast MRI, including a multi-b-value DWI sequence. The diffusion parameters derived from the mono-exponential model (ADC), IVIM model (Dt, Dp, f), and RSI model (C1, C2, C3, C1C2, F1, F2, F3, F1F2) were quantitatively measured and then compared among malignant lesions, benign lesions and normal fibroglandular tissues using Kruskal-Wallis test. The Mann-Whitney U-test was used for the pairwise comparisons. Diagnostic models were built by logistic regression analysis. The ROC analysis was performed using five-fold cross-validation and the mean AUC values were calculated and compared to evaluate the discriminative ability of each parameter or model. RESULTS: Almost all quantitative diffusion parameters showed significant differences in distinguishing malignant breast lesions from both benign lesions (other than C2) and normal fibroglandular tissue (all parameters) (all P < 0.0167). In terms of the comparisons of benign lesions and normal fibroglandular tissues, the parameters derived from IVIM (Dp, f) and RSI (C1, C2, C1C2, F1, F2, F3) showed significant differences (all P < 0.005). When using individual parameters, RSI-derived parameters-F1, C1C2, and C2 values yielded the highest AUCs for the comparisons of malignant vs. benign, malignant vs. normal tissue and benign vs. normal tissue (AUCs = 0.871, 0.982, and 0.863, respectively). Furthermore, the combined diagnostic model (IVIM + RSI) exhibited the highest diagnostic efficacy for the pairwise discriminations (AUCs = 0.893, 0.991, and 0.928, respectively). CONCLUSIONS: Quantitative parameters derived from the three-compartment RSI model have great promise as imaging indicators for the differential diagnosis of breast lesions compared with the bi-exponential IVIM model. Additionally, the combined model of IVIM and RSI achieves superior diagnostic performance in characterizing breast lesions.

Climate change drove the route shift of the ancient Silk Road in two distinct ways.

Although climate change has convincingly been linked to the evolution of human civilization on different temporal scales, its role in influencing the spatial patterns of ancient civilizations has rarely been investigated. The northward shift of the ancient Silk Road (SR) route from the Tarim Basin (TB) to the Junggar Basin during ∼420-850 CE provides the opportunity to investigate the relationship between climate change and the spatial evolution of human societies. Here, we use a new high-resolution chironomid-based temperature reconstruction from arid China, combined with hydroclimatic and historical datasets, to assess the possible effects of climate fluctuations on the shift of the ancient SR route. We found that a cooling/drying climate in the TB triggered the SR route shift during ∼420-600 CE. However, a warming/wetting climate during ∼600-850 CE did not inhibit this shift, but instead promoted it, because of the favorable climate-induced geopolitical conflicts between the Tubo Kingdom and the Tang Dynasty in the TB. Our findings reveal two distinct ways in which climate change drove the spatial evolution of human civilization, and they demonstrate the flexibility of societal responses to climate change.

Emergency hybrid surgery for transection of pancreas at the head and neck after blunt abdominal trauma: A case report and review of the literature.

INTRODUCTION: A complete disruption of main pancreatic duct (MPD) presents a significant challenge to the surgeon. Historically, the standard surgical approach for addressing a complete disruption of the MPD involved distal pancreatic resection and pancreaticojejunostomy Roux-en-Y anastomosis. Nevertheless, there have been no reported cases of hybrid surgery being employed for the complete disruption of the MPD. PATIENT CONCERNS: A 63-year-old male patient presented with blunt trauma in the upper abdomen and was transferred to our trauma center 10 hours after injury. Upon arrival at the emergency department, he was conscious, hemodynamically stable, and complained of upper abdominal pain and distention. Physical examination revealed right upper abdominal tenderness and slight abdominal tension. Abdominal contrast-enhanced CT scan revealed a complete transection of pancreatic parenchyma at the junction of the head and neck. DIAGNOSES: Complete transection of pancreatic parenchyma at the junction of the head and neck combined with complete disruption of the MPD, AIS grade IV. INTERVENTIONS: The hybrid surgery was initially utilized for complete MPD disruption, incorporating endoscope-assisted stent placement in the MPD along with primary repair of the pancreatic parenchyma and duct. OUTCOMES: The postoperative period went smoothly, and the patient recovered and was discharged 4 weeks after operation. The MPD stent was removed under endoscope 4 months after operation, and Endoscopic Retrograde Pancreatography examination showed that the MPD was patency and slight MPD stenosis without pancreatic leakage. At the most recent follow-up, the patient had returned to normal life and work without any pancreatic endocrine or exocrine dysfunction. LESSONS: The hybrid surgery, incorporating endoscope-assisted MPD stent placement and primary repair of the pancreatic parenchyma and duct, emerges as a promising alternative for complete MPD disruption in hemodynamically stable patients. The challenge in this hybrid surgery is the precise localization of the distal end of the MPD.

Development of a Thermodynamically Favorable Multi-enzyme Cascade Reaction for Efficient Sustainable Production of ω-Amino Fatty Acids and α,ω-Diamines.

Invited for this issue's cover is the group of Huilei Yu at the East China University of Science and Technology. The image shows a sustainable biosynthesis route to nylon monomers from bio-based substrate α, ω-dicarboxylic acids. The Research Article itself is available at 10.1002/cssc.202301477.

Comparison of continuous-time random walk and fractional order calculus models in characterizing breast lesions using histogram analysis.

OBJECTIVE: To compare the diagnostic performance of different mathematical models for DWI and explore whether parameters reflecting spatial and temporal heterogeneity can demonstrate better diagnostic accuracy than the diffusion coefficient parameter in distinguishing benign and malignant breast lesions, using whole-tumor histogram analysis. METHODS: This retrospective study was approved by the institutional ethics committee and included 104 malignant and 42 benign cases. All patients underwent breast magnetic resonance imaging (MRI) with a 3.0 T MR scanner using the simultaneous multi-slice (SMS) readout-segment ed echo-planar imaging (rs-EPI). Histogram metrics of Mono- apparent diffusion coefficient (ADC), CTRW, and FROC-derived parameters were compared between benign and malignant breast lesions, and the diagnostic performance of each diffusion parameter was evaluated. Statistical analysis was performed using Mann-Whitney U test and receiver operating characteristic (ROC) curve. RESULTS: The DFROC-median exhibited the highest AUC for distinguishing benign and malignant breast lesions (AUC = 0.965). The temporal heterogeneity parameter αCTRW-median generated a statistically higher AUC compared to the spatial heterogeneity parameter ßCTRW-median (AUC = 0.850 and 0.741, respectively; p = 0.047). Finally, the combination of median values of CTRW parameters displayed a slightly higher AUC than that of FROC parameters, with no significant difference however (AUC = 0.971 and 0.965, respectively; p = 0.172). CONCLUSIONS: The diffusion coefficient parameter exhibited superior diagnostic performance in distinguishing breast lesions when compared to the temporal and spatial heterogeneity parameters.

Radiomics analysis based on multiparametric magnetic resonance imaging for differentiating early stage of cervical cancer.

Objective: To investigate the performance of multiparametric magnetic resonance imaging (MRI)-based radiomics models in differentiating early stage of cervical cancer (Stage I-IIa vs. IIb-IV). Methods: One hundred patients with cervical cancer who underwent preoperative MRI between June 2020 and March 2022 were retrospectively enrolled. Training (n = 70) and testing cohorts (n = 30) were assigned by stratified random sampling. The clinical and pathological features, including age, histological subtypes, tumor grades, and node status, were compared between the two cohorts by t-test or chi-square test. Radiomics features were extracted from each volume of interest (VOI) on T2-weighted images (T2WI) and apparent diffusion coefficient (ADC) maps. The data balance of the training cohort was resampled by synthesizing minority oversampling techniques. Subsequently, the adiomics signatures were constructed by the least absolute shrinkage and selection operator algorithm and minimum-redundancy maximum-relevance with 10-fold cross-validation. Logistic regression was applied to predict the cervical cancer stages (low [I-IIa]) and (high [IIb-IV] FIGO stages). The receiver operating characteristic curve (area under the curve [AUC]) and decision curve analysis were used to assess the performance of the radiomics model. Results: The characteristics of age, histological subtypes, tumor grades, and node status were not significantly different between the low [I-IIa] and high [IIb-IV] FIGO stages (p > 0.05 for both the training and test cohorts). Three models based on T2WI, ADC maps, and the combined were developed based on six radiomics features from T2WI and three radiomics features from ADC maps, with AUCs of 0.855 (95% confidence interval [CI], 0.777-0.934) and 0.823 (95% CI, 0.727-0.919), 0.861 (95% CI, 0.785-0.936) and 0.81 (95% CI, 0.701-0.918), 0.934 (95% CI, 0.884-0.984) and 0.902 (95% CI, 0.832-0.972) in the training and test cohorts. Conclusion: The radiomics models combined T2W and ADC maps had good predictive performance in differentiating the early stage from locally advanced cervical cancer.

Transformation process and phytotoxicity of sulfamethoxazole and N4-acetyl-sulfamethoxazole in rice.

Sulfonamide antibiotics, extensively used in human and veterinary therapy, accumulate in agroecosystem soils through livestock manure and sewage irrigation. However, the interaction between sulfonamides and rice plants remains unclear. This study investigated the transformation behavior and toxicity of sulfamethoxazole (SMX) and its main metabolite, N4-acetyl-sulfamethoxazole (NASMX) in rice. SMX and NASMX were rapidly taken up by roots and translocated acropetally. NASMX showed higher accumulating capacity, with NASMX concentrations up to 20.36 ± 1.98 µg/g (roots) and 5.62 ± 1.17 µg/g (shoots), and with SMX concentrations up to 15.97 ± 2.53 µg/g (roots) and 3.22 ± 0.789 µg/g (shoots). A total of 18 intermediate transformation products of SMX were identified by nontarget screening using Orbitrap-HRMS, revealing pathways such as deamination, hydroxylation, acetylation, formylation, and glycosylation. Notably, NASMX transformed back into SMX in rice, a novel finding. Transcriptomic analysis highlights the involvements of cytochrome P450 (CYP450), acetyltransferase (ACEs) and glycosyltransferases (GTs) in these biotransformation pathways. Moreover, exposure to SMX and NASMX disrupts TCA cycle, amino acid, linoleic acid, nucleotide metabolism, and phenylpropanoid biosynthesis pathways of rice, with NASMX exerting a stronger impact on metabolic networks. These findings elucidate the sulfonamides' metabolism, phytotoxicity mechanisms, and contribute to assessing food safety and human exposure risk amid antibiotic pollution.

Development of a Thermodynamically Favorable Multi-enzyme Cascade Reaction for Efficient Sustainable Production of ω-Amino Fatty Acids and α,ω-Diamines.

Aliphatic ω-amino fatty acids (ω-AFAs) and α,ω-diamines (α,ω-DMs) are essential monomers for the production of nylons. Development of a sustainable biosynthesis route for ω-AFAs and α,ω-DMs is crucial in addressing the challenges posed by climate change. Herein, we constructed an unprecedented thermodynamically favorable multi-enzyme cascade (TherFavMEC) for the efficient sustainable biosynthesis of ω-AFAs and α,ω-DMs from cheap α,ω-dicarboxylic acids (α,ω-DAs). This TherFavMEC was developed by incorporating bioretrosynthesis analysis tools, reaction Gibbs free energy calculations, thermodynamic equilibrium shift strategies and cofactor (NADPH&ATP) regeneration systems. The molar yield of 6-aminohexanoic acid (6-ACA) from adipic acid (AA) was 92.3 %, while the molar yield from 6-ACA to 1,6-hexanediamine (1,6-HMD) was 96.1 %, which were significantly higher than those of previously reported routes. Furthermore, the biosynthesis of ω-AFAs and α,ω-DMs from 20.0 mM α,ω-DAs (C6-C9) was also performed, giving 11.2 mM 1,6-HMD (56.0 % yield), 14.8 mM 1,7-heptanediamine (74.0 % yield), 17.4 mM 1,8-octanediamine (87.0 % yield), and 19.7 mM 1,9-nonanediamine (98.5 % yield), respectively. The titers of 1,9-nonanediamine, 1,8-octanediamine, 1,7-heptanediamine and 1,6-HMD were improved by 328-fold, 1740-fold, 87-fold and 3.8-fold compared to previous work. Therefore, this work holds great potential for the bioproduction of ω-AFAs and α,ω-DMs.

Platelet-rich gel versus external tissue expansion technique in treating scalp defects: A retrospective study.

Reconstruction of scalp defects is a complicated and challenging procedure for reconstructive surgeons. This retrospective observational study assessed the effectiveness of using platelet-rich gel (PRG) versus the external tissue expansion technique (TET) in reconstructing scalp defects. The clinical data of 24 patients with scalp defects treated with PRG or external TET were collected from September 2018 to March 2022. Data on the wound characteristics, wound healing time, cost of treatment, visual analog scale, and observed wound healing status were collected. The mean wound healing times in the PRG and TET groups were 25.00 ± 5.77 and 13.58 ± 9.68 days, respectively (P < .05). The PRG group was significantly more cost-effective than the TET group (P < .05). TET treatment significantly increased patients' postoperative pain, which decreased over time (P < .05), while PRG treatment caused no significant change in pain (P > .05). The 2 groups showed no tissue depression or color change after wound healing at follow-up, but the hair growth in the TET group was significantly better than that in the PRG group (P < .05). Compared with TET treatment of scalp defects, PRG is not only simple and painless but also has a low treatment cost and, more importantly, does not involve the risk of surgery and anesthesia. However, using TET to treat scalp defects requires the careful selection of appropriate cases.

Epidemiology of asthma exacerbation in children before and after the COVID-19 pandemic: a retrospective study in Chengdu, China.

PURPOSE: To examine the numbers and characteristics of children affected by asthma exacerbation in Chengdu, China, before and after the COVID-19 pandemic to inform efforts to manage childhood asthma in the post epidemic era. METHODS: Data were retrospectively collected from children admitted for asthma exacerbation to Chengdu Women and Children's Central Hospital between January 2017 and December 2022. Rates of hospitalization, ages of the affected children, comorbidities and infections, and relationships between hospitalization and seasonal or environmental factors were examined before and after the epidemic. RESULTS: Fewer children were hospitalized for asthma exacerbation, yet more hospitalized children had severe exacerbation after the epidemic than before. Rates of hospitalization varied considerably with time of year, and the timing of peak hospitalizations differed before and after the epidemic. Only before the epidemic, rates of hospitalization for asthma exacerbation were positively correlated with humidity. Infants made up a smaller proportion of hospitalized children after the epidemic than before, with preschool children accounting for most hospitalizations after the epidemic. The proportion of children hospitalized for asthma exacerbation who also had pneumonia was significantly smaller after the epidemic than before. Conversely, the proportion of children hospitalized for asthma exacerbation who also had allergic diseases was significantly greater after the epidemic than before. CONCLUSION: The epidemiology of asthma exacerbation in children changed after the epidemic. Future efforts to manage the condition in the paediatric population should focus on severe asthma exacerbation, prevention and management of allergic diseases, and the influence of meteorological and environmental factors.

Role of combined clinical-radiomics model based on contrast-enhanced MRI in predicting the malignancy of breast non-mass enhancements without an additional diffusion-weighted imaging sequence.

Background: In our previous study, we developed a combined diagnostic model based on time-intensity curve (TIC) types and radiomics signature on contrast-enhanced magnetic resonance imaging (CE-MRI) for non-mass enhancement (NME). The model had a high diagnostic ability for differentiation without the additional diffusion-weighted imaging (DWI) sequence. In this study, we aimed to compare the diagnostic performance of the combined clinical-radiomics model based on CE-MRI and DWI in discriminating Breast Imaging-Reporting and Data System (BI-RADS) 4 NME breast lesions, ductal carcinoma in situ (DCIS), and invasive carcinoma. Methods: This retrospective study enrolled 364 NME lesions (343 patients). Of these, 183 malignant and 84 benign breast lesions classified as BI-RADS 4 NMEs by the initial diagnosis were reclassified based on the combined clinical-radiomics model and DWI, respectively. The nomogram score (NS) values for malignancy risk derived from the combined clinical-radiomics model and the minimal apparent diffusion coefficient (ADC) values from DWI were calculated and compared. The percentage of false positives were estimated in comparison with the original classification. Receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic value of the NS and minimal ADC values in distinguishing benign and malignant lesions, DCIS, and invasive breast carcinoma. An ablation experiment was used to test the value of the additional DWI sequence. Results: The diagnostic value of the NS values [area under curve (AUC) =0.843; 95% CI: 0.789-0.896] for discriminating the 267 NME breast lesions categorized as BI-RADS 4 was significantly higher than the minimal ADC values (AUC =0.662; 95% CI: 0.590-0.735). The NS values showed higher sensitivity, specificity, and accuracy compared with the minimal ADC values (sensitivity: 80.3% vs. 65.6%; specificity: 79.8% vs. 65.5%; accuracy: 80.1% vs. 65.5%). The NS values and minimal ADC values did not achieve high diagnostic accuracy in discriminating between DCIS and invasive cancer. However, the diagnostic performance of the combined NS-ADC model (AUC =0.731; 95% CI: 0.655-0.806) was higher than that of the NS values alone (P=0.008) and comparable to that of the minimal ADC values (P=0.440). Conclusions: The combined clinical-radiomics model based on CE-MRI could improve the diagnostic performance in discriminating the BI-RADS 4 NME lesions without an additional DWI sequence. However, DWI may improve the diagnostic performance in discriminating DCIS from invasive cancer.

Bacterial Colonization in the Airways and Intestines of Twin and Singleton Preterm Neonates: A Single-Center Study.

Limited studies have investigated the microbial colonization of the airways and intestines in preterm neonates. We studied the composition of intestinal and airway bacterial colonies in several preterm twin pairs and singletons to explore the dominant bacteria, assess their variability, and predict their phenotypic and metabolic functions. In this descriptive study, we collected sputum and fetal stool specimens from 10 twin pairs (20 cases) and 20 singleton preterm neonates. These specimens were analyzed using 16S rRNA deep sequencing to study the alpha and beta diversities and community structures of airway and intestinal bacteria and predict their metabolic functions. Specimens from twins and singleton neonates had distinct aggregations of intestinal and airway bacteria but showed similarities and high microbial diversities during initial colonization. The top five phyla were Proteobacteria, Firmicutes, Actinobacteriota, Bacteroidota, and Cyanobacteria. The top ten genera were Streptococcus, Acinetobacter, Ralstonia, Staphylococcus, Comamonas, Enterococcus, Stenotrophomonas, Dechlorosoma, Sphingopyxis, and Rothia. Potentially pathogenic and highly stress-tolerant Gram-negative bacteria were predominant in the intestinal flora. A considerable proportion of colonies recovered from the airway and intestines of preterm neonates were functional bacteria. The richness of the intestinal and airway flora was not significantly different between twins and singletons, and the flora clustered together. Both intestinal and airway bacteria of twins and singletons were similar. The species involved in initial colonization were similar but different in proportions; therefore, changes in microbial structure and richness may not be attributed to these species.

Voriconazole-Induced Hepatotoxicity in a Patient with Pulmonary Aspergillosis: A Case Report.

Voriconazole is the therapy of choice for aspergillosis. However, hepatotoxicity is the most common reason for the discontinuation of voriconazole. In contrast, posaconazole is well tolerated, with a low incidence of hepatotoxicity. In most cases, hepatotoxicity is associated with high voriconazole trough concentration influenced mainly by cytochrome P450 (CYP) 2C19 gene polymorphism. Compared with normal metabolizers, intermediate and poor metabolizers generally have higher voriconazole trough concentrations with an increased risk of hepatotoxicity. Here, we describe changes in hepatotoxicity throughout azole therapy in a patient with pulmonary aspergillosis (PA). Nevertheless, the patient with the normal metabolism genotype of CYP2C19 developed severe hepatotoxicity caused by voriconazole but tolerated posaconazole well, with a lack of direct cross-hepatotoxicity between the both. Interestingly, the patient had a high risk of hepatotoxicity at a low voriconazole trough concentration. Fortunately, elevated liver enzymes declined to the baselines with posaconazole treatment.

Effectiveness of sublingual immunotherapy with house dust mite drops in asthmatic children at different ages.

Background: Respiratory allergies in children, such as asthma and rhinitis, are becoming progressively common every year. Recent studies found that pediatric patients with asthma receiving regular medication and specific immunotherapy (SIT) had improved therapeutic outcomes in a wide age range. However, there are few studies that have examined the effectiveness of SIT treatment in children with allergic asthma at different ages in terms of the degree of asthma control, improvements in lung function, and changes in exhaled nitric oxide (FeNO). Method: A total of 200 asthmatic pediatric patients who had been receiving regular treatment for at least a year were split into the observation and the control groups, which depended on whether sublingual immunotherapy was added based on conventional treatment medicines. The children who were divided by an age cut-off of 6 years old in these two groups were compared before and after therapy based on the exhaled levels of FeNO, pulmonary function, visual analog scale, medication scores, daytime and nighttime ratings of asthma symptom, and rhinitis symptom scores. Results: Before treatment, there was no significant difference between the observation group and the control group in various indicators of the patients under 6 years old; and in the older children (6-16 years old) group, the scores of FVC, FEV1, and FEF25 in the observation group were significantly lower than those in the control group (P < 0.05). The FEF75, FEF50, FEF25, and MMEF75/MMEF25 indexes in the observation group were significantly higher than those in the control group after treatment (P < 0.05), but there was no statistical significance in other indexes (P > 0.05). The scores of ACT, FEF75, FEF50, MMEF72/MMEF25, and FeNO in the observation group were all higher than those in the control group after treatment (P < 0.05), and the differences in other indexes were not statistically significant (P > 0.05). Between the young-age group and the elder group, there was no significant difference in all indexes in the observation group before and after treatment (P > 0.05). Conclusion: Children with asthma of all ages can considerably benefit from sublingual immunotherapy. Specifically, younger patients showed greater tendency on the improvement of small airway resistance, whereas school-age children with asthma significantly improved their small airway resistance as well as their asthma control and inflammation alleviation.

Changes in the liver of Tinca tinca under successive domestication using an integrated multi-omics approach.

Domestication is the process of modifying the phenotype of a population through anthropic selection from human perspectives. Successive generations of domestication have influenced the physiological characteristics of tench Tinca tinca. In current study, we investigated gene and protein expression alterations in the liver of fifth-generation (F5). A total of 420 genes were found to be upregulated and 351 genes were downregulated, while 410 proteins were upregulated and 279 proteins were downregulated in domesticated T. tinca (DT). The integrated analysis of omics data revealed a total of 55 genes/proteins exhibiting consistent upregulation and 12 genes/proteins displaying consistent downregulation in DT. The upregulated genes/proteins in DT, such as SSR1, DERLIN2, OS9, DNAJB11, and HYOU1, exhibit enrichment in the protein processing in the endoplasmic reticulum pathway. Additionally, upregulated genes/proteins such as IL2RB, F13B, and IRF3 are associated with immune response. Conversely, downregulated genes/proteins in DT, including HSD11B1, CYP24A1, and COMT, play roles in hormone metabolism. These findings indicate that domestication can have a substantial impact on the physiological modifications related to protein processing, immune response, and hormone metabolism in DT. These adaptations potentially enhance their ability to thrive in artificial aquaculture environments, leading to improved growth and development. The exploration of genetic changes in DT will not only improve aquaculture practices but also provide significant insights into the broader process of domestication and its effects on physiological functions.

Histogram analysis of multi-model high-resolution diffusion-weighted MRI in breast cancer: correlations with molecular prognostic factors and subtypes.

Objective: To investigate the correlations between quantitative diffusion parameters and prognostic factors and molecular subtypes of breast cancer, based on a single fast high-resolution diffusion-weighted imaging (DWI) sequence with mono-exponential (Mono), intravoxel incoherent motion (IVIM), diffusion kurtosis imaging (DKI) models. Materials and Methods: A total of 143 patients with histopathologically verified breast cancer were included in this retrospective study. The multi-model DWI-derived parameters were quantitatively measured, including Mono-ADC, IVIM-D, IVIM-D*, IVIM-f, DKI-Dapp, and DKI-Kapp. In addition, the morphologic characteristics of the lesions (shape, margin, and internal signal characteristics) were visually assessed on DWI images. Next, Kolmogorov-Smirnov test, Mann-Whitney U test, Spearman's rank correlation, logistic regression, receiver operating characteristic (ROC) curve, and Chi-squared test were utilized for statistical evaluations. Results: The histogram metrics of Mono-ADC, IVIM-D, DKI-Dapp, and DKI-Kapp were significantly different between estrogen receptor (ER)-positive vs. ER-negative groups, progesterone receptor (PR)-positive vs. PR-negative groups, Luminal vs. non-Luminal subtypes, and human epidermal receptor factor-2 (HER2)-positive vs. non-HER2-positive subtypes. The histogram metrics of Mono-ADC, DKI-Dapp, and DKI-Kapp were also significantly different between triple-negative (TN) vs. non-TN subtypes. The ROC analysis revealed that the area under the curve considerably improved when the three diffusion models were combined compared with every single model, except for distinguishing lymph node metastasis (LNM) status. For the morphologic characteristics of the tumor, the margin showed substantial differences between ER-positive and ER-negative groups. Conclusions: Quantitative multi-model analysis of DWI showed improved diagnostic performance for determining the prognostic factors and molecular subtypes of breast lesions. The morphologic characteristics obtained from high-resolution DWI can be identifying ER statuses of breast cancer.

Primary angiosarcoma of the breast: Two case reports and brief review of the literature.

Angiosarcoma is a rare but very aggressive tumor. It occurs in all organs of the body, and approximately 8% of all angiosarcomas arise in the breast. We reported 2 cases of primary breast angiosarcomas in young women. The 2 patients showed similar clinical features, but were quite different in dynamic contrast-enhanced MR imaging. The 2 patients were treated with mastectomy and axillary sentinel lymph node dissection and confirmed by post-operative pathological test. We suggested that dynamic contrast-enhanced MR imaging was the most helpful imaging tool in the diagnosis and pre-operative evaluation of the breast angiosarcoma.

A pilot study exploring the association of bronchial bacterial microbiota and recurrent wheezing in infants with atopy.

Background: Differences in bronchial microbiota composition have been found to be associated with asthma; however, it is still unclear whether these findings can be applied to recurrent wheezing in infants especially with aeroallergen sensitization. Objectives: To determine the pathogenesis of atopic wheezing in infants and to identify diagnostic biomarkers, we analyzed the bronchial bacterial microbiota of infants with recurrent wheezing and with or without atopic diseases using a systems biology approach. Methods: Bacterial communities in bronchoalveolar lavage samples from 15 atopic wheezing infants, 15 non-atopic wheezing infants, and 18 foreign body aspiration control infants were characterized using 16S rRNA gene sequencing. The bacterial composition and community-level functions inferred from between-group differences from sequence profiles were analyzed. Results: Both α- and ß-diversity differed significantly between the groups. Compared to non-atopic wheezing infants, atopic wheezing infants showed a significantly higher abundance in two phyla (Deinococcota and unidentified bacteria) and one genus (Haemophilus) and a significantly lower abundance in one phylum (Actinobacteria). The random forest predictive model of 10 genera based on OTU-based features suggested that airway microbiota has diagnostic value for distinguishing atopic wheezing infants from non-atopic wheezing infants. PICRUSt2 based on KEGG hierarchy (level 3) revealed that atopic wheezing-associated differences in predicted bacterial functions included cytoskeleton proteins, glutamatergic synapses, and porphyrin and chlorophyll metabolism pathways. Conclusion: The differential candidate biomarkers identified by microbiome analysis in our work may have reference value for the diagnosis of wheezing in infants with atopy. To confirm that, airway microbiome combined with metabolomics analysis should be further investigated in the future.