Association of congenital heart disease and neurodevelopmental disorders: an observational and Mendelian randomization study.

BACKGROUND: This study aims to thoroughly study the connection between congenital heart disease (CHD) and neurodevelopmental disorders (NDDs) through observational and Mendelian randomization (MR) designs. METHODS: This observational study uses data from the National Survey of Children's Health (2020-2021). Multivariable logistic regression and propensity score matching (PSM) were performed to analyze the association. PSM was used to minimize bias for covariates such as age, race, gender, maternal age, birth weight, concussion or brain injury, preterm birth, cerebral palsy, Down syndrome, and other inherited conditions. In MR analyses, inverse variance-weighted measures, weighted median, and MR-Egger were employed to calculate causal effects. RESULTS: A total of 85,314 children aged 0-17 were analyzed in this study. In regression analysis, CHD (p = 0.04), the current heart condition (p = 0.03), and the severity of current heart condition (p < 0.05) had a suggestive association with speech or language disorders. The severity of current heart condition (p = 0.08) has a potential statistically significant association with attention deficit hyperactivity disorder(ADHD). In PSM samples, ADHD(p = 0.003), intellectual disability(p = 0.012), and speech or language disorders(p < 0.001) were all significantly associated with CHD. The severity of current heart condition (p < 0.001) also had a significant association with autism. MR analysis did not find causality between genetically proxied congenital cardiac malformations and the risk of NDDs. CONCLUSIONS: Our study shows that children with CHD have an increased risk of developing NDDs. Heart conditions currently and severity of current heart conditions were also significantly associated with these NDDs. In the future, we need to try more methods to clarify the causal relationship between CHD and NDDs.

Evaluating the influence of sarcopenia and myosteatosis on clinical outcomes in gastric cancer patients undergoing immune checkpoint inhibitor.

BACKGROUND: The development and progression of gastric cancer (GC) are closely linked to the nutritional status of patients. Although immunotherapy has been demonstrated to be clinically effective, the relationships of sarcopenia and myosteatosis with the use of immune checkpoint inhibitors (ICIs) in patients with gastric cancer remain to be characterized. AIM: To assess the effects of sarcopenia and myosteatosis on the clinical outcomes of patients with GC undergoing treatment with an ICI. METHODS: We performed a retrospective study of patients who were undergoing immunotherapy for GC. For the evaluation of sarcopenia, the optimal cut-off value for the skeletal muscle index was established using receiver operating characteristic analysis of data obtained from pre-treatment computed tomography images at the L3 vertebral level. Myosteatosis was defined using the mean skeletal muscle density (SMD), with a threshold value of < 41 Hounsfield units (HU) for patients with a body mass index (BMI) < 25 kg/m² and < 33 HU for those with a BMI ≥ 25 kg/m². The log-rank test was used to compare progression-free survival (PFS) and overall survival (OS), and a Cox proportional hazard model was used to identify prognostic factors. Nomograms were developed to predict the PFS and OS of patients on the basis of the results of multivariate analyses. RESULTS: We studied 115 patients who were undergoing ICI therapy for GC, of whom 27.4% had sarcopenia and 29.8% had myosteatosis. Patients with sarcopenia or myosteatosis had significantly shorter PFS and OS than those without these conditions. Furthermore, both sarcopenia and myosteatosis were found to be independent predictors of PFS and OS in patients with GC administering an ICI. The prediction models created for PFS and OS were associated with C-indexes of 0.758 and 0.781, respectively. CONCLUSION: The presence of sarcopenia or myosteatosis is a reliable predictor of the clinical outcomes of patients with GC who are undergoing treatment with an ICI.

Histone Acetylation Enhancing Host Melanization in Response to Parasitism by an Endoparasitoid Wasp.

Endoparasitoids are insects that develop within other insects, employing unique strategies to enhance their offspring's survival. They inject polydnavirus and/or venom into their hosts along with eggs, effectively suppressing the host's immune system. Polydnavirus from Braconidae and Ichneumonidae wasps can integrate into the host's genome to express viral genes using the host's transcription systems. However, the ability of parasitoids without polydnavirus to manipulate host gene expression remains unclear. Lysine acetylation (LysAc), a post-translational modification critical for gene regulation, is hypothesized to be used by endoparasitoids lacking polydnavirus. We utilized the Chalcidoidea wasp Tetrastichus brontispae, which lacks polydnavirus, as an idiobiont endoparasitoid model to test this hypothesis, with pupae of the nipa palm hispid beetle Octodonta nipae as the host. Parasitism by T. brontispae resulted in the reduced expression of histone deacetylase Rpd3 and elevated levels of LysAc modification at histones H3.3K9 and H3.3K14 through proteomics and LysAc modification omics. The knockdown of Rpd3 increased the expression level of OnPPAF1 and OnPPO involved in the phenoloxidase cascade, leading to melanization in the host body whereby it resembled a mummified parasitized pupa and ultimately causing pupa death. This study enhances our understanding of how endoparasitoids employ histone acetylation to regulate immunity-related genes, offering valuable insights into their survival strategies.

A Robust Anti-Thermal-Quenching Phosphor Based on Zero-Dimensional Metal Halide Rb3InCl6:xSb3.

High-power phosphor-converted white light-emitting diodes (hp-WLEDs) have been widely involved in modern society as outdoor lighting sources. In these devices, due to the Joule effect, the high applied currents cause high operation temperatures (>500 K). Under these conditions, most phosphors lose their emission, an effect known as thermal quenching (TQ). Here, we introduce a zero-dimensional (0D) metal halide, Rb3InCl6:xSb3+, as a suitable anti-TQ phosphor offering robust anti-TQ behavior up to 500 K. We ascribe this behavior of the metal halide to two factors: (1) a compensation process via thermally activated energy transfer from structural defects to emissive centers and (2) an intrinsic structural rigidity of the isolated octahedra in the 0D structure. The anti-TQ phosphor-based WLEDs can stably work at a current of 2000 mA. The low synthesis cost and nontoxic composition reported here can herald a new generation of anti-TQ phosphors for hp-WLED.

Architecture of symbiotic dinoflagellate photosystem I-light-harvesting supercomplex in Symbiodinium.

Symbiodinium are the photosynthetic endosymbionts for corals and play a vital role in supplying their coral hosts with photosynthetic products, forming the nutritional foundation for high-yield coral reef ecosystems. Here, we determine the cryo-electron microscopy structure of Symbiodinium photosystem I (PSI) supercomplex with a PSI core composed of 13 subunits including 2 previously unidentified subunits, PsaT and PsaU, as well as 13 peridinin-Chl a/c-binding light-harvesting antenna proteins (AcpPCIs). The PSI-AcpPCI supercomplex exhibits distinctive structural features compared to their red lineage counterparts, including extended termini of PsaD/E/I/J/L/M/R and AcpPCI-1/3/5/7/8/11 subunits, conformational changes in the surface loops of PsaA and PsaB subunits, facilitating the association between the PSI core and peripheral antennae. Structural analysis and computational calculation of excitation energy transfer rates unravel specific pigment networks in Symbiodinium PSI-AcpPCI for efficient excitation energy transfer. Overall, this study provides a structural basis for deciphering the mechanisms governing light harvesting and energy transfer in Symbiodinium PSI-AcpPCI supercomplexes adapted to their symbiotic ecosystem, as well as insights into the evolutionary diversity of PSI-LHCI among various photosynthetic organisms.

A conserved protein inhibitor brings under check the activity of RNase E in cyanobacteria.

The bacterial ribonuclease RNase E plays a key role in RNA metabolism. Yet, with a large substrate spectrum and poor substrate specificity, its activity must be well controlled under different conditions. Only a few regulators of RNase E are known, limiting our understanding on posttranscriptional regulatory mechanisms in bacteria. Here we show that, RebA, a protein universally present in cyanobacteria, interacts with RNase E in the cyanobacterium Anabaena PCC 7120. Distinct from those known regulators of RNase E, RebA interacts with the catalytic region of RNase E, and suppresses the cleavage activities of RNase E for all tested substrates. Consistent with the inhibitory function of RebA on RNase E, depletion of RNase E and overproduction of RebA caused formation of elongated cells, whereas the absence of RebA and overproduction of RNase E resulted in a shorter-cell phenotype. We further showed that the morphological changes caused by altered levels of RNase E or RebA are dependent on their physical interaction. The action of RebA represents a new mechanism, potentially conserved in cyanobacteria, for RNase E regulation. Our findings provide insights into the regulation and the function of RNase E, and demonstrate the importance of balanced RNA metabolism in bacteria.

[Linderae Radix water extract treats diarrhea-predominant irritable bowel syndrome in rats: a serum metabolomics study].

This study aims to investigate the mechanism of Linderae Radix water extract(LRWE) in the prevention and treatment of diarrhea-predominant irritable bowel syndrome(IBS-D) based on serum metabolomics. Eighteen 2-week-old male SD rats were randomized into control, IBS-D model, and LRWE groups. The rats in other groups except the control group received gavage of senna concentrate combined with restraint stress for the modeling of IBS-D. The rats in the LRWE group were administrated with LRWE(5.4 g·kg~(-1)) by gavage, and those in the control and IBS-D model groups with an equal volume of distilled water for a total of 14 days. The visceral sensitivity was evaluated by the abdominal withdrawal reflex(AWR) score, and the degree of diarrhea was assessed by the fecal water content(FWC). The morphological changes of the colon and the morphology and number of goblet cells were observed by hematoxylin-eosin(HE) and periodic acid-schiff(PAS) staining, respectively. Ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) was used for the screening of the potential biomarkers in the rat serum and their related metabolic pathways. The results showed that LRWE reduced the AWR score, decreased FWC, and alleviated visceral sensitivity and diarrhea symptoms in IBS-D rats. HE and PAS staining showed that LRWE mitigated low-grade intestinal inflammation and increased the number of mature secretory goblet cells in the colonic epithelium of IBS-D rats. A total of 25 potential biomarkers of LRWE in treating IBS-D were screened out in this study, which were mainly involved in riboflavin, tryptophan, glycine, serine and threonine metabolism, glyoxylate and dicarboxylate metabolism, and cysteine and methionine metabolism. The regulatory effects were the most significant on the riboflavin and tryptophan metabolism pathways. LRWE may alleviate the visceral hypersensitivity by promoting energy metabolism and amino acid metabolism, enhancing intestinal barrier function, and improving intestinal immune function in IBS-D rats.

Bidirectional Relationship Between Circadian Rhythm and Frailty.

Coupled with the ageing population, frailty, characterized by high prevalence and difficult treatment, has progressively evolved into a significant public health concern. Frail individuals can often observe serious metabolic disorders and sleep-wake cycle disruption, which may be caused by the decline in physiological reserve and increased vulnerability. Moreover, sleep-wake cycle disruptions and metabolic dysfunctions associated with circadian rhythm disorders are considered to be a central part of the disorder. Previous studies have documented a correlation between frailty and sleep-wake disruptions; nevertheless, the association between circadian rhythm disorders and frailty has not yet been definitively established. Hence, we hypothesize a bidirectional link between circadian rhythm disorders and frailty, with each condition exerting a significant influence on the progression of the other's disease trajectory.

Causal relationship association of cheese intake with gestational hypertension and diabetes result from a Mendelian randomization study.

BACKGROUND: The evidence from observational studies has been inconclusive on the causal relationship between cheese intake and gestational hypertension or diabetes. AIM: To determine whether cheese consumption was causally related to hypertension and diabetes during pregnancy. METHODS: This was a two-sample Mendelian randomized (MR) study. Summary-level genetic data for cheese intake was exposure and corresponding outcome data for gestational hypertension and gestational diabetes were extracted from the IEU OpenGWAS database. MR analysis was conducted using inverse variance weighting. For sensitivity analyses, MR-Egger regression, weighted median, weighted mode, and leave-one-out methods were conducted. A fixed-effect model was used to meta-analyze two sample MR estimates. The traits of gestational hypertension were pregnancy hypertension (123579 individuals) and oedema, proteinuria and hypertensive disorders in pregnancy, childbirth and the puerperium (123579 individuals), and traits of gestational diabetes were gestational diabetes (123579 individuals) and diabetes mellitus in pregnancy (116363 individuals), respectively. RESULTS: Cheese intake per standard deviation increase has causally reduced the risks of gestational hypertension [odds ratio (OR) = 0.60, 95% confidence interval (CI): 0.47-0.76, P < 0.001] and gestational diabetes (OR = 0.41, 95%CI: 0.30-0.55, P < 0.001) in inverse variance weighted analysis. Sensitivity analysis showed no heterogeneity (all P > 0.05) nor horizontal pleiotropy (all P > 0.05) in the relationship between cheese intake and gestational hypertension, but heterogeneity presented (all P < 0.05) in relation to gestational diabetes in the two-sample MR analysis. CONCLUSION: Cheese intake was inversely associated with gestational hypertension and gestational diabetes in MR analysis, suggesting that cheese consumption may be beneficial in preventing hypertension and diabetes during pregnancy.

[Neutrophil-lymphocyte and platelet-lymphocyte ratios for assessing disease activity in patients with rheumatoid arthritis receiving tofacitinib treatment].

OBJECTIVE: To evaluate the value of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for assessing disease activity in patients with rheumatoid arthritis (RA) treated with tofacitinib. METHODS: This retrospective study was conducted among 98 RA patients in active stage treated with tofacitinib in Third Xiangya Hospital and 100 healthy control subjects from the Health Management Center of the hospital from 2019 to 2021. We collected blood samples from all the participants for measurement of erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and other blood parameters 1 month before and 6 months after tofacitinib treatment. We further evaluated PLR and NLR before and after tofacitinib treatment in the RA patients, and analyzed their correlations with RA disease activity. RESULTS: PLR and NLR increased significantly in RA patients as compared with the healthy controls. In the RA patients, PLR and NLR were positively correlated with the levels of hs- CRP, ESR, IL- 6, Disease Activity Score of 28 joints-ESR (DAS28-ESR), anti-cyclic citrullinated peptide (CCP), and rheumatoid factor (RF) before and after tofacitinib treatment. Tofacitinib treatment for 6 months significantly decreased hs-CRP, ESR, IL-6, CCP, RF and DAS28-ESR levels in the RA patients. CONCLUSION: NLR and PLR can be useful biomarkers for assessing disease activity in RA patients treated with tofacitinib.

[Astragalus polysaccharide inhibits IDO1 expression in colon tumor microenvironment to increase intratumoral CD8~+ T cell infiltration].

This study aims to investigate the regulatory effects of Astragalus polysaccharide(APS) and APS combined with 5-fluorouracil(5-FU) on indoleamine-2,3-dioxygenase(IDO1) in the colon tumor microenvironment. Sixty Balb/c mice were randomized into a blank group, a model group, an APS group, an APS + 5-FU group, an APS + low-dose 5-FU group, and a 5-FU group. A tumor model was established by subcutaneous transplantation with CT-26 mouse colon cancer cells in other groups except the blank group. After successful modeling, each group was treated with corresponding drugs for 7 days. The general condition, body weight, and tumor volume of the mice were observed and measured daily during the treatment period. The mice were sacrificed at the end of treatment, and the tumor suppression rate and spleen index of the mice were calculated. Western blot and fluorescence quantitative PCR were employed to determine the protein and mRNA levels, respectively, of IDO1 in the tumor tissue of mice. High performance liquid chromatography was employed to measure the levels of tryptophan(Trp) and kynurenine(Kyn) in the tumor tissue of mice. Hematoxylin-eosin(HE) staining was performed to observe the histological changes of the tumor tissue, and immunohistochemistry to detect the changes of CD4 and CD8 expression in the tumor tissue. Compared with that in the model group, the tumor volume of mice in each treatment group significantly reduced. The body weights of mice in APS + 5-FU group and 5-FU group significantly reduced from day 4 to day 7 of treatment. In addition, the APS + 5-FU group and 5-FU group showed significantly decreased spleen index. The protein and mRNA levels of IDO1 were significantly down-regulated in the APS, APS + 5-FU, and APS + low-dose 5-FU groups. The drug interventions significantly increased the Trp content and decreased the Kyn content. The APS + 5-FU group showed significantly reduced infiltration of CD4~+ T lymphocytes and increased infiltration of CD8~+ T lymphocytes. APS inhibited the expression of IDO1 in the colon tumor microenvironment to increase CD8~+ T lymphocyte infiltration, and the combination of APS with 5-FU demonstrated better effect.

Upregulation of the protein kinase Lyn is associated with renal injury in type 2 diabetes patients.

BACKGROUND: The role of inflammation in the pathogenesis of type 2 diabetes mellitus (T2DM) is well established. Lyn, a member of the nonreceptor protein tyrosine kinase Src family, has been reported to modulate inflammatory signaling pathways. METHODS: Lyn expression was assessed in kidney biopsies of 11 patients with diabetic kidney disease (DKD) and in kidney tissues of streptozotocin (STZ)-induced DKD mice. 102 recruited T2DM patients were divided into three groups: normoalbuminuria, microalbuminuria and macroalbuminuria. Twenty-one healthy volunteers were recruited as a control group. Clinical data, blood and urine samples of all individuals were collected for analysis. RESULTS: Lyn expression was augmented in the kidneys of DKD patients and STZ-induced diabetic mice. Compared with control and normoalbuminuria groups, both mRNA and protein expression of Lyn in peripheral blood mononuclear cells (PBMCs) in the macroalbuminuria group were significantly increased (p < .05). Elevated Lyn levels were independently related to urine albumin/urine creatinine ratio and were positively associated with key inflammatory factors, namely interleukin-1ß, monocyte chemoattractant protein-1, and tumor necrosis factor-α. Additionally, Lyn exhibited a noteworthy connection with renal tubular injury indicators, specifically urinary neutrophil gelatinase-associated lipocalin and urinary retinol binding protein. ROC curve analysis showed that Lyn could predict albuminuria in diabetic patients with an area under the curve of 0.844 (95% CI: 0.764-0.924). CONCLUSION: Lyn levels in PBMCs exhibited a positive correlation with the severity of albuminuria, renal tubular damage, and inflammatory responses. Hence, Lyn may be a compelling candidate for predicting albuminuria levels in diabetes.

Serum metabolomics analysis of biomarkers and metabolic pathways in patients with colorectal cancer associated with spleen-deficiency and qi-stagnation syndrome or damp-heat syndrome: a prospective cohort study.

Objective: To profile the serum metabolites and metabolic pathways in colorectal cancer (CRC) patients associated with spleen-deficiency and qi-stagnation syndrome (SDQSS) or damp-heat syndrome (DHS). Methods: From May 2020 to January 2021, CRC patients diagnosed with traditional Chinese medicine (TCM) syndromes of SDQSS or DHS were enrolled. The clinicopathological data of the SDQSS and DHS groups were compared. The serum samples were analyzed by liquid chromatography-mass spectrometry (LC-MS). The variable importance in the projection >1, fold change ≥3 or ≤0.333, and P value ≤0.05 were used to identify differential metabolites between the two groups. Furthermore, areas under the receiver operating characteristic (ROC) curve > 0.9 were applied to select biomarkers with good predictive performance. The enrichment metabolic pathways were searched through the database of Kyoto Encyclopedia of Genes and Genomes. Results: 60 CRC patients were included (30 SDQSS and 30 DHS). The level of alanine aminotransferase was marginally significantly higher in the DHS group than the SDQSS group (P = 0.051). The other baseline clinicopathological characteristics were all comparable between the two groups. 23 differential serum metabolites were identified, among which 16 were significantly up-regulated and 7 were significantly down-regulated in the SDQSS group compared with the DHS group. ROC curve analysis showed that (S)-3-methyl-2-oxopentanoic acid, neocembrene, 1-aminocyclopropanecarboxylic acid, 3-methyl-3-hydroxypentanedioate, and nicotine were symbolic differential metabolites with higher predictive power. The top five enrichment signalling pathways were valine, leucine and isoleucine biosynthesis; lysosome; nicotine addiction; fructose and mannose metabolism; and pertussis. Conclusion: Our study identifies the differential metabolites and characteristic metabolic pathways among CRC patients with SDQSS or DHS, offering the possibility of accurate and objective syndrome differentiation and TCM treatment for CRC patients.

Primary seminal vesicle adenocarcinoma with a history of seminal vesicle cyst: A case report and review of literature.

BACKGROUND: Primary seminal vesicle adenocarcinoma is a rare malignancy that is difficult to diagnose. CASE SUMMARY: A 54-year-old man with an 18-year history of a seminal vesicle cyst presented with worsening hematospermia that had persisted for one month. Dynamic contrast-enhanced computed tomography and pelvic magnetic resonance imaging indicated a mass with a cystic-solid component. Robot-assisted seminal vesicle tumor resection was performed, and primary seminal vesicle adenocarcinoma was confirmed pathologically. The patient received pelvic radiotherapy for six weeks, and to date, no evidence of recurrence has been found. CONCLUSION: Seminal vesicle cysts should be monitored long-term. Seminal vesicle adenocarcinoma presents with non-specific symptoms and can be diagnosed by immunohistochemistry.

Multimodality US versus Thyroid Imaging Reporting and Data System Criteria in Recommending Fine-Needle Aspiration of Thyroid Nodules.

Background Current guidelines recommend the use of conventional US for risk stratification and management of thyroid nodules. However, fine-needle aspiration (FNA) is often recommended in benign nodules. Purpose To compare the diagnostic performance of multimodality US (including conventional US, strain elastography, and contrast-enhanced US [CEUS]) with the American College of Radiology Thyroid Imaging Reporting and Data System (TI-RADS) in the recommendation of FNA for thyroid nodules to reduce unnecessary biopsies. Materials and Methods In this prospective study, 445 consecutive participants with thyroid nodules from nine tertiary referral hospitals were recruited between October 2020 and May 2021. With univariable and multivariable logistic regression, the prediction models incorporating sonographic features, evaluated with interobserver agreement, were constructed and internally validated with bootstrap resampling technique. In addition, discrimination, calibration, and decision curve analysis were performed. Results A total of 434 thyroid nodules confirmed at pathologic analysis (259 malignant thyroid nodules) in 434 participants (mean age, 45 years ± 12 [SD]; 307 female participants) were included. Four multivariable models incorporated participant age, nodule features at US (proportion of cystic components, echogenicity, margin, shape, punctate echogenic foci), elastography features (stiffness), and CEUS features (blood volume). In recommending FNA in thyroid nodules, the highest area under the receiver operating characteristic curve (AUC) was 0.85 (95% CI: 0.81, 0.89) for the multimodality US model, and the lowest AUC was 0.63 (95% CI: 0.59, 0.68) for TI-RADS (P < .001). At the 50% risk threshold, 31% (95% CI: 26, 38) of FNA procedures could be avoided with multimodality US compared with 15% (95% CI: 12, 19) with TI-RADS (P < .001). Conclusion Multimodality US had better performance in recommending FNA to avoid unnecessary biopsies than the TI-RADS. Clinical trial registration no. NCT04574258 © RSNA, 2023 Supplemental material is available for this article.

Lyn attenuates sepsis-associated acute kidney injury by inhibition of phospho-STAT3 and apoptosis.

Sepsis-associated acute kidney injury (SA-AKI) is a life-threatening condition associated with high mortality and morbidity. However, the underlying pathogenesis of SA-AKI is still unclear. Lyn belongs to Src family kinases (SFKs), which exert numerous biological functions including modulation in receptor-mediated intracellular signaling and intercellular communication. Previous studies demonstrated that Lyn gene deletion obviously aggravates LPS-induced lung inflammation, but the role and possible mechanism of Lyn in SA-AKI have not been reported yet. Here, we found that Lyn protected against renal tubular injury in cecal ligation and puncture (CLP) induced AKI mouse model by inhibition of signal transducer and activator of transcription 3 (STAT3) phosphorylation and cell apoptosis. Moreover, Lyn agonist MLR-1023 pretreatment improved renal function, inhibited STAT3 phosphorylation and decreased cell apoptosis. Thus, Lyn appears to play a crucial role in orchestrating STAT3-mediated inflammation and cell apoptosis in SA-AKI. Hence, Lyn kinase may be a promising therapeutic target for SA-AKI.

[Mechanism of Huangjing Qianshi Decoction in treatment of prediabetic mice based on transcriptome sequencing].

Based on transcriptome sequencing technology, the mouse model of prediabetes treated with Huangjing Qianshi Decoction was sequenced to explore the possible mechanism of treating prediabetes. First of all, transcriptome sequencing was performed on the normal BKS-DB mouse group, the prediabetic model group, and the Huangjing Qianshi Decoction treatment group(treatment group) to obtain differentially expressed genes in the skeletal muscle samples of mice. The serum biochemical indexes were detected in each group to screen out the core genes of Huangjing Qianshi Decoction in prediabetes. Gene Ontology(GO) database and Kyoto Encyclopedia of Genes and Genomes(KEGG) database were used to conduct signaling pathway enrichment analysis of differentially expressed genes, and real-time quantitative polymerase chain reaction(RT-qPCR) was used to verify them. The results showed that the levels of fasting blood glucose(FBG), fasting insulin(FINS), insulin resistance index(HOMA-IR), total cholesterol(TC), triglycerides(TG), and low-density lipoprotein cholesterol(LDL-C) in the mouse model were significantly decreased after treatment with Huangjing Qianshi Decoction. In the results of differential gene screening, there were 1 666 differentially expressed genes in the model group as compared with the normal group, and there were 971 differentially expressed genes in the treatment group as compared with the model group. Among them, interleukin-6(IL-6) and NR3C2 genes, which were closely related to the regulation of insulin resis-tance function, were significantly up-regulated between the model group and the normal group, and vascular endothelial growth factor A(VEGFA) genes were significantly down-regulated between the model group and the normal group. However, the expression results of IL-6, NR3C2, and VEGFA genes were adverse between the treatment group and the model group. GO functional enrichment analysis found that the biological process annotation mainly focused on cell synthesis, cycle, and metabolism; cell component annotation mainly focused on organelles and internal components; and molecular function annotation mainly focused on binding molecular functions. KEGG pathway enrichment analysis found that it involved the protein tyrosine kinase 6(PTK6) pathway, CD28-dependent phosphoinositide 3-kinase/protein kinase B(PI3K/AKT) pathway, p53 pathway, etc. Therefore, Huangjing Qianshi Decoction can improve the state of prediabetes, and the mechanism may be related to cell cycle and apoptosis, PI3K/AKT pathway, p53 pathway, and other biological pathways regulated by IL-6, NR3C2, and VEGFA.

Granulomatous prostatitis after bacille Calmette-Guérin instillation resembles prostate carcinoma: A case report and review of the literature.

BACKGROUND: Bacille Calmette-Guérin (BCG) instillation is recommended in patients with non-muscle-invasive bladder cancer who have intermediate-risk and high-risk tumors. However, granulomatous prostatitis is a rare complication induced by BCG instillation, which can easily be misdiagnosed as prostate cancer. Here, we report a case of granulomatous prostatitis that resembled prostate cancer. CASE SUMMARY: A 64-year-old Chinese man with bladder cancer received BCG instillation. Three days later, he stopped BCG instillation and received anti-infective therapy due to the urinary tract infection. Three months after BCG restart, he had rising total prostate-specific antigen (PSA) (9.14 ng/mL) and decreasing free PSA/total PSA (0.09). T2-weighted images of magnetic resonance imaging (MRI) showed a 28 mm × 20 mm diffuse low signal abnormality in the right peripheral zone, which was markedly hyperintense on high b-value diffusion-weighted MRI and hypointense on apparent diffusion coefficient map images. Considering Prostate Imaging Reporting and Data System score of 5 and possibility of prostate cancer, a prostate biopsy was conducted. Histopathology showed typical features of granulomatous prostatitis. The nucleic acid test for tuberculosis was positive. He was finally diagnosed with BCG-induced granulomatous prostatitis. Thereafter, he stopped BCG instillation and received anti-tuberculosis treatment. During 10 mo follow-up, he had no evidence of tumor recurrence or symptoms of tuberculosis. CONCLUSION: Temporarily elevated PSA and high followed by low signal abnormality on diffusion-weighted MRI are important indicators of BCG-induced granulomatous prostatitis.