Blood- and Urine-Based Liquid Biopsy for Early-Stage Cancer Investigation: Taken Clear Renal Cell Carcinoma as a Model.

Liquid biopsy is a noninvasive technique that can provide valuable information for disease characterization by using biofluids as a source of biomarkers. Proteins found in biofluids can offer a wealth of information for understanding pathological processes. In this study, we used early-stage clear cell renal cell carcinoma (ccRCC) as a model to explore the proteomic relationships among tissue, plasma, and urine. We analyzed samples of tumor tissue, plasma, and urine from a cohort of 27 ccRCC patients with T1-2 stage and 27 matched healthy controls, using liquid chromatography-mass spectrometry (LC-MS) for proteomic analysis. We integrated the differential proteins found in the three types of samples to explore ccRCC-associated molecular changes. Our results showed that both plasma and urine proteomes could reflect functional changes in tumor tissue. In plasma, cytoskeletal proteins and metabolic enzymes were differentially expressed, while in urine, adhesion molecules and defense proteins showed differential levels. The differential proteins found in plasma and urine both reflect the binding and catalytic activity of tumor tissue. Additionally, proteins only changed in biofluids could reflect body immune response changes, with plasma proteins involved in actin cytoskeleton and oxidative stress, and urine proteins involved in granulocyte adhesion and leukocyte extravasation signaling. Plasma and urine proteins could effectively distinguish RCC from control, with good performances (plasma/urine: 92.6%/92.6% specificity, 96.3%/92.6% sensitivity, and an area under the curve of 0.981/0.97). In conclusion, biofluids could not only reflect functional changes in tumor tissue but also reflect changes in the body's immune response. These findings will benefit the understanding of body biomarkers in tumors and the discovery of potential disease biomarkers.

Diagnostic efficacy of [68Ga]Ga-NY104 PET/CT to identify clear cell renal cell carcinoma.

PURPOSE: Most clear cell renal cell carcinoma (ccRCC) overexpresses carbonic anhydrase IX (CAIX). [68Ga]Ga-NY104 is a small-molecule PET agent selectively targeting CAIX. This study aims to assess the efficacy of [68Ga]Ga-NY104 PET/CT to identify ccRCC. MATERIALS AND METHODS: Participants were prospectively recruited in the study (ClinicalTrials.gov: NCT05902377). They were further divided into two groups: group 1, patients with primary renal mass who were scheduled for surgery, group 2, patients with suspected/confirmed metastatic ccRCC. All patients underwent [68Ga]Ga-NY104 PET/CT. RESULTS: A total of 47 patients (mean age, 58.8 years ± 13.5, 34 men) were recruited, including 20 patients in group 1 and 27 patients in group 2. The patient-level sensitivity, specificity, and accuracy of [68Ga]Ga-NY104 PET scan was 62%, 33%, 58% for group 1 and 95%, 100%, 96% for group 2. [68Ga]Ga-NY104 PET identified additional 26 disease regions in 67% (14/21) of patients that were previously unknown. The tumor uptake was correlated with immunohistochemical staining results. CONCLUSIONS: [68Ga]Ga-NY104 PET/CT has a high diagnostic efficacy for patients with metastatic ccRCC, while it might be of limited value in the diagnosis of primary ccRCC.

The association between computed tomography attenuation value of renal angiomyolipoma associated with tuberous sclerosis complex and response to everolimus.

BACKGROUND: The response to everolimus in patients with renal angiomyolipoma associated with tuberous sclerosis complex (TSC-RAML) varies among individuals. This study aims to identify potential factors associated with the response to everolimus. METHOD: We retrospectively examined data encompassing age, gender, tumor size, computed tomography attenuation value (CT value), CT enhancement, and tumor reduction rate in patients with TSC-RAML undergoing everolimus in two previously registered clinical trials. RESULT: A total of 33 participants (29.33 ± 6.63 years old, 20 females) were included. The correlation analysis conducted separately for tumors located in the left and right kidneys revealed significant negative correlations (P < 0.05) between tumor reduction rate and age, as well as tumor size. While significant positive correlations (P < 0.05) were observed between tumor reduction rate and unenhanced CT value as well as CT enhancement. Nonetheless, based on multiple linear regression analysis, unenhanced CT value emerged as the sole-independent predictor of tumor reduction rate among age, gender, tumor size, unenhanced CT value and CT enhancement for both left (coefficient = 0.00319, P < 0.0001) and right kidneys (coefficient = 0.00315, P = 0.0104). Notable reductions were observed in unenhanced CT value (- 3.81 vs - 24.70HU, P < 0.0001) and CT enhancement (48.16 vs 33.56HU, P < 0.0001) following a 3-month administration of everolimus. The decline in both unenhanced CT value and tumor size predominantly occurred within the initial 3 months, subsequently maintaining a relatively stable level throughout the treatment. CONCLUSION: The unenhanced CT value of TSC-RAML showed an independent correlation with the response to everolimus, suggesting its potential as a predictor of everolimus efficacy in patients with TSC-RAML.

Integrated Metabolome and Transcriptome Analysis of Gibberellins Mediated the Circadian Rhythm of Leaf Elongation by Regulating Lignin Synthesis in Maize.

Plant growth exhibits rhythmic characteristics, and gibberellins (GAs) are involved in regulating cell growth, but it is still unclear how GAs crosstalk with circadian rhythm to regulate cell elongation. The study analyzed growth characteristics of wild-type (WT), zmga3ox and zmga3ox with GA3 seedlings. We integrated metabolomes and transcriptomes to study the interaction between GAs and circadian rhythm in mediating leaf elongation. The rates of leaf growth were higher in WT than zmga3ox, and zmga3ox cell length was shorter when proliferated in darkness than light, and GA3 restored zmga3ox leaf growth. The differentially expressed genes (DEGs) between WT and zmga3ox were mainly enriched in hormone signaling and cell wall synthesis, while DEGs in zmga3ox were restored to WT by GA3. Moreover, the number of circadian DEGs that reached the peak expression in darkness was more than light, and the upregulated circadian DEGs were mainly enriched in cell wall synthesis. The differentially accumulated metabolites (DAMs) were mainly attributed to flavonoids and phenolic acid. Twenty-two DAMs showed rhythmic accumulation, especially enriched in lignin synthesis. The circadian DEGs ZmMYBr41/87 and ZmHB34/70 were identified as regulators of ZmHCT8 and ZmBM1, which were enzymes in lignin synthesis. Furthermore, GAs regulated ZmMYBr41/87 and ZmHB34/70 to modulate lignin biosynthesis for mediating leaf rhythmic growth.

Auxin efflux carrier ZmPIN1a modulates auxin reallocation involved in nitrate-mediated root formation.

BACKGROUND: Auxin plays a crucial role in nitrate (NO3-)-mediated root architecture, and it is still unclear that if NO3- supply modulates auxin reallocation for regulating root formation in maize (Zea mays L.). This study was conducted to investigate the role of auxin efflux carrier ZmPIN1a in the root formation in response to NO3- supply. RESULTS: Low NO3- (LN) promoted primary root (PR) elongation, while repressed the development of lateral root primordia (LRP) and total root length. LN modulated auxin levels and polar transport and regulated the expression of auxin-responsive and -signaling genes in roots. Moreover, LN up-regulated the expression level of ZmPIN1a, and overexpression of ZmPIN1a enhanced IAA efflux and accumulation in PR tip, while repressed IAA accumulation in LRP initiation zone, which consequently induced LN-mediated PR elongation and LR inhibition. The inhibition rate of PR length, LRP density and number of ZmPIN1a-OE plants was higher than that of wild-type plants after auxin transport inhibitor NPA treatment under NN and LN conditions, and the degree of inhibition of root growth in ZmPIN1a-OE plants was more obvious under LN condition. CONCLUSION: These findings suggest that ZmPIN1a was involved in modulating auxin levels and transport to alter NO3--mediated root formation in maize.

Preclinical and pilot clinical evaluation of a small-molecule carbonic anhydrase IX targeting PET tracer in clear cell renal cell carcinoma.

PURPOSE: Clear cell renal cell carcinoma (ccRCC) highly expresses carbonic anhydrase IX (CAIX). The purpose of this study was to evaluate 68Ga-NY104, a small-molecule CAIX-targeting PET agent, in tumor models of ccRCC and patients diagnosed with confirmed, or suspicious, ccRCC. METHODS: The in vivo and ex vivo biodistribution of 68Ga-NY104 was investigated in CAIX-positive OS-RC-2 xenograft-bearing models. The binding of the tracer was further validated using autoradiography for human ccRCC samples. In addition, three patients with confirmed or suspicious ccRCC were studied. RESULTS: NY104 can be labeled with high radiochemical yield and purity. It quickly cleared through kidney with α-half-life of 0.15 h. Discernible uptake is noted in the heart, lung, liver, stomach, and kidney. The OS-RC-2 xenograft demonstrated intense uptake 5 min after injection and gradually increased until 3 h after injection with ID%/g of 29.29 ± 6.82. Significant binding was detected using autoradiography on sections of human ccRCC tumor. In the three patients studied, 68Ga-NY104 was well-tolerated and no adverse events were reported. Substantial accumulation was observed in both primary and metastatic lesions in patient 1 and 2 with SUVmax of 42.3. Uptake in the stomach, pancreas, intestine, and choroid plexus was noted. The lesion in third patient was correctly diagnosed as non-metastatic for negative 68Ga-NY104 uptake. CONCLUSION: 68Ga-NY104 can efficiently and specifically bind to CAIX. Given the pilot nature of our study, future clinical studies are warranted to evaluate 68Ga-NY104 for detection of CAIX-positive lesions in patients with ccRCC. TRIAL REGISTRATION: The clinical evaluation part of this study was retrospectively registered at ClinicalTrial.gov (NCT05728515) as NYPILOT on 6 Feb, 2023.

Fractional flow reserve versus intravascular imaging to guide decision-making for percutaneous coronary intervention in intermediate lesions: A meta-analysis.

BACKGROUND: Both fractional flow reserve (FFR) and intravascular imaging (IVI) have been used to guide the decision-making for percutaneous coronary intervention (PCI) in intermediate coronary stenosis. Nevertheless, studies that directly compared the prognostic significance of these two strategies are scarce. AIMS: The aim of this meta-analyses was to evaluate the impact of FFR versus IVI to guide the decision-making in PCI for intermediate stenosis on clinical outcomes. METHODS: We systematically searched PubMed, Embase, Cochrane, and relevant database from inception date to September 2022 for observational studies and randomized clinical trials (RCTs) which compared FFR and IVI-based decision-making in PCI for intermediate stenosis. The primary outcome was a composite of major adverse cardiac event (MACE). Pooled risk ratios (RR) were calculated using random effects models and heterogeneity were evaluated with the I2 statistic. RESULTS: We identified 5 studies (3 RCTs and 2 observational studies) with 3208 patients. The follow-up duration ranged from 12 to 24 months. Among five studies, four compared FFR with intravascular ultrasound while one compared FFR with optical coherence tomography. There was no statistically difference between FFR and IVI in the incidence of MACE (RR: 1.19; 95% confidence interval: 0.85-1.68; p = 0.31) and its individual components. These results were consistent regardless of various cut-off value of PCI across the studies. Compared with IVI, FFR was associated with a lower PCI rate (37.0% vs. 60.3%; p < 0.001). CONCLUSIONS: The decision to perform PCI for intermediate stenosis guided by FFR or IVI showed a similar clinical outcome. The use of FFR significantly reduced the need for PCI.

Functional nodules in primary aldosteronism: identification of CXCR4 expression with 68Ga-pentixafor PET/CT.

OBJECTIVES: We analyzed the diagnostic efficiency of 68Ga-pentixafor PET/CT for functional nodules in primary aldosteronism (PA). Furthermore, we compared the correlation of CXCR4 expression with aldosterone synthase (CYP11B2) expression and PET/CT uptake in these patients. METHODS: We prospectively assessed 50 patients diagnosed with PA and 10 patients with non-functional adrenal adenoma (NFA). All patients underwent 68Ga-pentixafor PET/CT before adrenalectomy. Immunohistochemistry (IHC) was performed to detect the protein expression of CYP11B2 and the G-protein-coupled receptor CXCR4. RESULTS: CYP11B2 IHC revealed the presence of 43 functional nodules. Subsequently, 40/43 functional nodules could be detected on 68Ga-pentixafor PET/CT, while negative imaging findings were noted for 11/13 non-functional nodules (sensitivity, 93.0%; specificity, 84.6%). The optimum SUVmax cut-off for the identification of functional nodules was 8.95 (AUC 0.914 [0.828-1.000], p < 0.001). Regarding the size of functional nodules, diagnostic efficiency appeared to be much higher for nodules greater than 1 cm in size (sensitivity, up to 97.3%). Moreover, we examined the relationship between CXCR4 and CYP11B2 expression in 56 lesions. All 43 CYP11B2-positive nodules were CXCR4-positive, but one of the 13 CYP11B2-negative nodules (7.7%) showed false-positive staining for CXCR4. Moreover, the consistency between PET/CT uptake and CXCR4 staining results was 92.9% (52/56). CONCLUSIONS: At least 90% of functional nodules show positive uptake on 68Ga-pentixafor PET/CT, and the detection ability is much better for nodules with a diameter ≥ 1 cm. With its high sensitivity and specificity, 68Ga-pentixafor PET/CT can be considered a promising surgical decision-making tool for patients with PA. KEY POINTS: • 68Ga-pentixafor PET/CT could be a useful tool for the identification of functional adrenal nodules in APAs and even IHAs. • The diagnostic efficiency appears to be much higher for nodules ≥ 1 cm in size. • There is high consistency between the results of 68Ga-pentixafor PET/CT imaging and CXCR4 immunohistochemistry.

Early Predictors of Infected Pancreatic Necrosis in Severe Acute Pancreatitis: Implications of Neutrophil to Lymphocyte Ratio, Blood Procalcitonin Concentration, and Modified CT Severity Index.

BACKGROUND: Infected pancreatic necrosis (IPN) accounts for 30% mortality in severe acute pancreatitis (SAP). Early prediction of IPN occurrence is critical for prophylactic measures to be taken. This study aimed to evaluate the predicting value for IPN of combined markers at early stages of SAP. METHODS: The clinical records of 324 SAP patients admitted within 48 h after disease onset were retrospectively analyzed. As potential predictors, the neutrophil to lymphocyte ratio (NLR), blood procalcitonin (PCT) concentration on the 1st, 4th, and 7th day post admission, as well as modified computerized tomography severity index (MCTSI) on the 5-7th day post admission, were extracted. Correlations between these features with IPN were analyzed using logistic regression, and predictive values were estimated using the receiver operating characteristic curve analyses. RESULTS: NLR, PCT, body mass index, and MCTSI were significantly higher in the IPN group (p < 0.001) compared to the control, among which NLR, PCT, and MCTSI were identified as independent predictors for IPN in logistic regression model. Combination of these parameters yielded significant predicting values with an area under curve of 0.92, sensitivity of 97.2%, and specificity of 77.2% in receiver operating characteristic curve analysis. CONCLUSION: Combination of NLR, PCT, MCTSI might facilitate the prediction of IPN occurrence in SAP patients.

Metagenomic analysis insights into the influence of 3,4-dimethylpyrazole phosphate application on nitrous oxide mitigation efficiency across different climate zones in Eastern China.

Excessive nitrogen (N) fertilization in agroecological systems increases nitrous oxide (N2O) emissions. 3,4-dimethylpyrazole phosphate (DMPP) is used to mitigate N2O losses. The influence of DMPP efficiency on N2O mitigation was clearly affected by spatiotemporal heterogeneity. Using field and incubation experiments combined with metagenomic sequencing, we aimed to investigate DMPP efficiency and the underlying microbial mechanisms in dark-brown (Siping, SP), fluvo-aquic (Cangzhou, CZ; Xinxiang, XX), and red soil (Wenzhou, WZ) from diverse climatic zones. In the field experiments, the DMPP efficiency in N2O mitigation ranged from 51.6% to 89.9%, in the order of XX, CZ, SP, and WZ. The DMPP efficiency in the incubation experiments ranged from 58.3% to 93.9%, and the order of efficiency from the highest to lowest was the same as that of the field experiments. Soil organic matter, total N, pH, texture, and taxonomic and functional α-diversity were important soil environment and microbial factors for DMPP efficiency. DMPP significantly enriched ammonia-oxidizing archaea (AOA) and nitrite-oxidizing bacteria (NOB), which promoted N-cycling with low N2O emissions. Random forest (RF) and regression analyses found that an AOA (Nitrosocosmicus) and NOB (Nitrospina) demonstrated important and positive correlation with DMPP efficiency. Moreover, genes associated with carbohydrate metabolism were important for DMPP efficiency and could influenced N-cycling and DMPP metabolism. The similar DMPP efficiency indicated that the variation in DMPP efficiency was significantly due to soil physicochemical and microbial variations. In conclusion, filling the knowledge gap regarding the response of DMPP efficiency to abiotic and biotic factors could be beneficial in DMPP applications, and in adapting more efficient strategies to improve DMPP efficiency and mitigate N2O emissions in multiple regions.

Ascites Volume Quantification via Abdominal CT: A Novel Approach to Predict Severity in Acute Pancreatitis.

BACKGROUND Acute pancreatitis, a sudden inflammation of the pancreas, can result in severe complications. The presence and volume of ascites, an abnormal accumulation of fluid in the abdomen, has been linked to disease severity. Our study investigates ascites volume, quantified via abdominal CT scans, as a potential predictive tool for disease severity. MATERIAL AND METHODS In this retrospective analysis, patients diagnosed with acute pancreatitis were evaluated. Patients were categorized into groups with and without ascites, with comparisons made regarding clinical characteristics. We further compared the mean ascitic volume against various outcome parameters in patients with ascites. Ascites volume and other predictive systems were assessed through receiver operating characteristic (ROC) curves, with the area under the ROC curve (AUC) for different predictive systems being analyzed. RESULTS The ascites group had higher severity scores and related serological indexes (P<0.05 for all). Among patients with ascites, a significant correlation was observed between ascites volume and outcome parameters (P<0.05 for all). The area under the ROC curve for predicting severe acute pancreatitis was 0.896, with 93% sensitivity and 79% specificity. Ascites volume yielded the highest diagnostic odds ratio (53.1; 95% confidence interval: 13.2,199.6). CONCLUSIONS Early-stage acute pancreatitis patients with ascites are indicative of severe illness and poor prognosis. An increase in ascites volume correlates with adverse clinical outcomes, thus highlighting the significance of ascites volume as a prognostic marker. This underscores the importance of abdominal CT in measuring ascites volume to predict disease severity.

Organic amendments alter microbiota assembly to stimulate soil metabolism for improving soil quality in wheat-maize rotation system.

Straw retention (SR) and organic fertilizer (OF) application contribute to improve soil quality, but it is unclear how the soil microbial assemblage under organic amendments mediate soil biochemical metabolism pathways to perform it. This study collected soil samples from wheat field under different application of fertilizer (chemical fertilizer, as control; SR, and OF) in North China Plain, and systematically investigated the interlinkages among microbe assemblages, metabolites, and physicochemical properties. Results showed that the soil organic carbon (SOC) and permanganate oxidizable organic carbon (LOC) in soil samples followed the trend as OF > SR > control, and the activity of C-acquiring enzymes presented significantly positive correlation with SOC and LOC. In organic amendments, bacteria and fungi community were respectively dominated by deterministic and stochastic processes, while OF exerted more selective pressure on soil microbe. Compared with SR, OF had greater potential to boost the microbial community robustness through increasing the natural connectivity and stimulating fungal taxa activities in inter-kingdom microbial networks. Altogether 67 soil metabolites were significantly affected by organic amendments, most of them belonged to benzenoids (Ben), lipids and lipid-like molecules (LL), and organic acids and derivatives (OA). These metabolites were mainly derived from lipid and amino acid metabolism pathways. A list of keystone genera such as stachybotrys and phytohabitans were identified as important to soil metabolites, SOC, and C-acquiring enzyme activity. Structural equation modeling showed that soil quality properties were closely associated with LL, OA, and PP drove by microbial community assembly and keystone genera. Overall, these findings suggested that straw and organic fertilizer might drive keystone genera dominated by determinism to mediate soil lipid and amino acid metabolism for improving soil quality, which provided new insights into understanding the microbial-mediated biological process in amending soil quality.

Lonicerae flos polysaccharides improve nonalcoholic fatty liver disease by activating the adenosine 5'-monophosphate-activated protein kinase pathway and reshaping gut microbiota.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver cirrhosis and cancer. Lonicerae flos polysaccharides (LPs) have been shown to be effective in treating metabolic diseases; however, the therapeutic effects and underlying molecular mechanisms of LPs in NAFLD remain unclear. PURPOSE: The objective of this study was to investigate the morphological characterization of Lonicerae flos polysaccharides (LPs) and the mechanism of LPs in relieving NAFLD. METHODS: The morphology of LPs was observed using atomic force microscopy (AFM), X-ray diffraction (XRD), thermal weight (TG), and thermal weight derivative (DTG); NAFLD mice were treated with LPs at the same time as they were induced with a Western diet, and then the indexes related to glycolipid metabolism, fibrosis, inflammation, and autophagy in the serum and liver of the mice were detected. RESULTS: The atomic force microscope analysis results indicated that the LPs displayed sugar-chain aggregates, exhibited an amorphous structure, and were relatively stable in thermal cracking at 150 °C. It was also found that LPs exerted therapeutic effects in NAFLD. The LPs prevented high-fat and -cholesterol diet-induced NAFLD progression by regulating glucose metabolism dysregulation, insulin resistance, lipid accumulation, inflammation, fibrosis, and autophagy. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) inhibitor compound C abrogated LP-induced hepatoprotection in mice with NAFLD. The LPs further treated NAFLD by reshaping the structure of the gut microbiota, in which Desulfovibrio bacteria plays a key roles. CONCLUSION: Lonicerae flos polysaccharides exert protective effects against NAFLD in mice by improving the structure of the intestinal flora and activating the AMPK signaling pathway. © 2023 Society of Chemical Industry.

[Intrauterine Device Totally Embedded in the Bladder Wall:Report of One Case].

Intrauterine device(IUD)migrating to the bladder is rare,especially the migration far away from the uterus into the bladder wall.Due to no obvious clinical symptom in the early stage and being far away from the uterus,the IUD totally embedded in the bladder wall is prone to misdiagnosis and delay in treatment.We reported one case of such migration,aiming to improve the clinical management of the IUD totally embedded in the bladder wall.

High-throughput screening of circRNAs reveals novel mechanisms of tuberous sclerosis complex-related renal angiomyolipoma.

OBJECTIVE: Tuberous sclerosis complex (TSC) is a rare autosomal dominant disease characterized by lesions throughout the body. Our previous study showed the abnormal up-regulation of miRNAs plays an important part in the pathogenesis of TSC-related renal angiomyolipoma (TSC-RAML). circRNAs were known as important regulators of miRNA, but little is known about the circRNAs in TSC-RAMLs. METHODS: Microarray chips and RNA sequencing were used to identify the circRNAs and mRNAs that were differently expressed between the TSC-RAML and normal kidney tissue. A competitive endogenous RNA (ceRNA) regulatory network was constructed to reveal the regulation of miRNAs and mRNAs by the circRNAs. The biological functions of circRNA and mRNA were analyzed by pathway analysis. Microenvironmental cell types were estimated with the MCP-counter package. RESULTS: We identified 491 differentially expressed circRNAs (DECs) and 212 differentially expressed genes (DEGs), and 6 DECs were further confirmed by q-PCR. A ceRNA regulatory network which included 6 DECs, 5 miRNAs, and 63 mRNAs was established. Lipid biosynthetic process was significantly up-regulated in TSC-RAML, and the humoral immune response and the leukocyte chemotaxis pathway were found to be down-regulated. Fibroblasts are enriched in TSC-RAML, and the up-regulation of circRNA_000799 and circRNA_025332 may be significantly correlated to the infiltration of the fibroblasts. CONCLUSION: circRNAs may regulate the lipid metabolism of TSC-RAML by regulation of the miRNAs. Fibroblasts are enriched in TSC-RAMLs, and the population of fibroblast may be related to the alteration of circRNAs of TSC-RAML. Lipid metabolism in fibroblasts is a potential treatment target for TSC-RAML.

Correlation Between Severity of Illness and Levels of Free Triiodothyronine, Interleukin-6, and Interleukin-10 in Patients with Acute Pancreatitis.

BACKGROUND Acute pancreatitis (AP) is a common acute abdominal disease. Rapid evaluation of the severity is important for AP prognosis and treatment. Free triiodothyronine (fT3) level is associated with the prognosis of AP patients. This study aimed to investigate the fT3 level in patients with acute pancreatitis; early warning signs of inflammation, including interleukin-6 (IL-6) and interleukin-10 (IL-10); and the correlation of fT3 level with illness severity. MATERIAL AND METHODS Enrolled AP patients (N=312) were divided into an SAP group (N=92) and a non-SAP group (N=220) according to the Revision of Atlanta classification. Blood or tissue samples and baseline clinical characteristics were recorded. The t test and chi-square test were used to evaluate differences between the 2 groups. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curves were used to investigate protective factors. One-way repeated measures analysis of variance was used to evaluate the prognosis of SAP patients. RESULTS In our study, compared with APACHII score (AUC 0.829 [95% CIs 0.769-0.889]) and Ranson score (AUC 0.629 [95% CIs 0.542-0.715]), our predictive model (AUC 0.918 [95% CIs 0.875-0.961]) showed better prognostic performance in predicting poor patient outcomes. In the SAP group, changes in fT3 level were significantly associated with prognosis (P<0.05). CONCLUSIONS The predictive model can improve the diagnostic accuracy and prediction of the severity of disease. FT3 level could be used as an independent risk factor to predict the mortality of SAP patients.

Metabolic pathway analysis of hyperuricaemia patients with hyperlipidaemia based on high-throughput mass spectrometry: a case‒control study.

BACKGROUND: Both hyperuricaemia and hyperlipidaemia are common metabolic diseases that are closely related to each other, and both are independent risk factors for the development of a variety of diseases. HUA combined with hyperlipidaemia increases the risk of nonalcoholic fatty liver disease and coronary heart disease. This study aimed to investigate the relationship between HUA and hyperlipidaemia and study the metabolic pathway changes in patients with HUA associated with hyperlipidaemia using metabolomics. METHODS: This was a case‒control study. The prevalence of hyperlipidaemia in HUA patients in the physical examination population of Tianjin Union Medical Centre in 2018 was investigated. Metabolomics analysis was performed on 308 HUA patients and 100 normal controls using Orbitrap mass spectrometry. A further metabolomics study of 30 asymptomatic HUA patients, 30 HUA patients with hyperlipidaemia, and 30 age-and sex-matched healthy controls was conducted. Differential metabolites were obtained from the three groups by orthogonal partial least-squares discrimination analysis, and relevant metabolic pathways changes were analysed using MetaboAnalyst 5.0 software. RESULTS: The prevalence of hyperlipidaemia in HUA patients was 69.3%. Metabolomic analysis found that compared with the control group, 33 differential metabolites, including arachidonic acid, alanine, aspartate, phenylalanine and tyrosine, were identified in asymptomatic HUA patients. Pathway analysis showed that these changes were mainly related to 3 metabolic pathways, including the alanine, aspartate and glutamate metabolism pathway. Thirty-eight differential metabolites, including linoleic acid, serine, glutamate, and tyrosine, were identified in HUA patients with hyperlipidaemia. Pathway analysis showed that they were mainly related to 7 metabolic pathways, including the linoleic acid metabolism pathway, phenylalanine, tyrosine and tryptophan biosynthesis pathway, and glycine, serine and threonine metabolism pathway. CONCLUSIONS: Compared to the general population, the HUA population had a higher incidence of hyperlipidaemia. HUA can cause hyperlipidaemia. by affecting the metabolic pathways of linoleic acid metabolism and alanine, aspartate and glutamate metabolism. Fatty liver is closely associated with changes in the biosynthesis pathway of pahenylalanine, tyrosine, and tryptophan in HUA patients with hyperlipidaemia. Changes in the glycine, serine and threonine metabolism pathway in HUA patients with hyperlipidaemia may lead to chronic kidney disease.

Analysis of serum lipid parameters predicting lipid metabolic disorders in TSC-AML patients with treatment of mTOR inhibitors.

WHAT IS KNOWN AND OBJECTIVE: Patients with tuberous sclerosis complex (TSC) demonstrate disrupted lipid homeostasis before and during treatment with mammalian target of rapamycin (mTOR) inhibitor. However, few previous reports focused on if the serum lipid status at baseline would influence lipid metabolic side-effects of mTOR inhibitors for TSC associated renal angiomyolipomas (TSC-AML). The present study was designed to evaluate the predictive function of serum lipid status at baseline for hyperlipidaemia by mTOR inhibitor treatment in TSC-AML patients. METHODS: The clinical data of TSC-AML patients who took mTOR inhibitors in Department of Urology of Peking Union Medical College Hospital (PUMCH) from 1 January 2014 to 1 January 2021, were retrospectively analysed. The record of lipid parameters at baseline and the highest levels of total cholesterol (TC) and triglyceride (TG) after treatment at least ≥3 months were collected. The correlation of serum lipid parameters at baseline with incidence of hyperlipidaemia during mTOR inhibitor treatment was analysed. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the ability of the serum lipid parameters in predicting hyperlipidaemia. RESULTS AND DISCUSSION: 19 patients experienced hyperlipidaemia and 13 patients still had normal TC and TG levels during mTOR inhibitor treatment. The levels of high-density lipoprotein cholesterol (HDL-C) (0.98 ± 0.30 mmol/L vs. 1.23 ± 0.31 mmol/L, p = 0.030), low-density lipoprotein cholesterol (LDL-C) (2.47 ± 0.69 mmol/L vs. 1.95 ± 0.53 mmol/L, p = 0.029) and apolipoprotein B (ApoB) (0.82 ± 0.21 g/L vs. 0.65 ± 0.16 g/L, p = 0.019) are higher in the patients who experienced hyperlipidaemia during mTOR inhibition therapy. TC, TG, LDL-C, ApoB and high-sensitivity C-reactive protein (hsCRP) at baseline had positive correlation with TC after treatment; ApoB at baseline had positive correlation, while HDL-C and free fat acid (FFA) at baseline had negative correlation with TG after treatment. Therefore, ApoB concentration at baseline has statistically significant correlation with both TC (p < 0.001) and TG (p = 0.012) levels after mTOR inhibitor treatment. ROC curve and AUC revealed that ApoB with a cut-off value of 0.640g/L may be the best parameter for predicting hyperlipidaemia during mTOR inhibitor treatment in TSC-AML patients. The incidence rates of hyperlipidaemia were 27.3% and 76.2% among the patients with ApoB level ≤0.640 g/L and >0.640 g/L respectively. WHAT IS NEW AND CONCLUSION: Some baseline serum lipid parameters could be used for predicting incidence of hyperlipidaemia during mTOR inhibition therapy in TSC-AML patients, and ApoB with 0.640 g/L as a cut-off value may be a potentially optimal indicator, which could help for diagnosis and treatment decision-making.

Analysis of renal lesions in Chinese tuberous sclerosis complex patients with different types of TSC gene mutations.

We sought to explore the relationship between renal lesion features and genetic mutations in tuberous sclerosis complex (TSC) patients. TSC patients with renal lesions were subjected to TSC1/2 gene next-generation sequencing (NGS). TSC1/2 mutation types and imaging examinations were screened for combined analysis of genetic and clinical features. Seventy-three probands among TSC patients with renal lesions were included. Twenty affected relatives were also included. In total, 93 patients were included. Eighty patients (86.0%) had bilateral renal angiomyolipomas (AMLs), and one had epithelioid AML. Two patients had polycystic kidney disease, one had renal cell carcinoma, and one had Wilms tumor. Among the 73 probands, four had TSC1 mutations, 53 had TSC2 mutations, and 16 had no mutations identified (NMI). There was no statistically significant difference between TSC1 mutation, TSC2 mutation and NMI group (P= 0.309), or between familial and sporadic groups (P= 0.775) when considering AML size. There was no statistically significant difference between pathogenic/likely pathogenic and benign/likely benign/NMI groups (P= 0.363) or among patients with different mutation types of TSC2 (P= 0.906). The relationship between the conditions of TSC gene mutations and the severity of renal lesions still needs more analysis. Patients with NMI, particularly those with familial disease, need more attention because the pathogenesis remains unknown.

[A novel mouse allergy tested model and its application for traditional Chinese medicine injections's allergy evaluation].

When the drug induces the organism to produce a type Ⅰ allergic reaction, the combination of IgE and mast cells results in the degranulation of the mast cells. Release of vasoactive substances, increase in vascular permeability, and exudation of intravascular substances outside the blood vessels. Based on this pathophysiological mechanism, a mouse model that can objectively and quantitatively assess the allergic response to the injection has been established. ICR mice were sensitised by intraperitoneal injection of different doses of OVA once every two days for three times. 14 days after the last sensitization, a combination OVA solution of 4 times the sensitizing dose and Evans blue were injected intravenously into mice for the challenge. Compared with the normal group, OVA 0.625/2.5, 1.25/5, 2.5/10, 5/20 mg·kg~(-1) sensitized and challenged can induce allergic reactions mainly manifested by blue staining of the auricle in mice. Direct injection of OVA intravenously did not cause an auricular blue colouration reaction in mice. The passive cutaneous anaphylaxis reaction in mice was conducted with the aforementioned OVA-sensitized mouse serum, and there were obvious blue spots on the mouse's back. In addition, the content of anti-OVA-IgE in 5 mg·kg~(-1) OVA-sensitized mice was significantly increased. Ears and lungs of mice sensitized to OVA showed evident exudation inflammation. Significantly elevated inflammatory factors(VEGF and IL-10) were also detected in the serum of OVA-sensitized mice. The equivalent dose of OVA caused obvious allergic reactions in both guinea pigs and mice. Compared with nude mice, ICR and BALB/c mice are more sensitive to OVA sensitization. Injections of selected TCMI did not induce type Ⅰ allergic reactions in mice and guinea pigs, but there was a risk of inducing pseu-doallergic reactions in mice. The model is problematic and may well reflect the sensitization effect of allergens. It obtains the benefits of simple operation, accuracy, low cost, easy extension, and high repeatability. It is suitable for predicting and researching for IgE-dependent type Ⅰ allergic reactions.