Primitive new termites (Blattodea, Termitoidae) in Cretaceous amber from Myanmar.

Mastotermitidae, the first-diverging extant family of termites, has only one relic extant species; however, this family had greater richness during the Mesozoic and Cenozoic eras. Fossil termites from the Cretaceous provide information on the early evolution of termites and the transition between extinct families. Herein, two new Mastotermitidae species found in upper Cretaceous (Cenomanian) Kachin amber are reported. One is a female imago described as Angustitermesreflexusgen. et sp. nov. and assigned to the subfamily Mastotermitinae. The other is Mastotermesreticulatussp. nov., which is described from an isolated forewing. With the comparison especially of the antenna and venation, these new mastotermitids further increase our knowledge of the diversity and morphology of Mastotermitidae during the Mesozoic.

Gut microbiota changes associated with low-carbohydrate diet intervention for obesity.

Low-carbohydrate diets (LCDs) are frequently recommended for alleviating obesity, and the gut microbiota plays key roles in energy metabolism and weight loss. However, there is limited in-human research on how LCD changes gut microbiota. In this before-after study, 43 participants were assigned to the LCD intervention for 4 weeks. The main objective was to investigate the specific changes that occur in the participants' microbiome in response to the LCD. Changes in gut microbiota were analyzed using 16s rRNA sequencing. Body composition was measured using InBody 770. Remarkably, 35 participants (79.07%) lost more than 5% of their body weight; levels of BMI, body fat, and total cholesterol were significantly decreased, indicating the effectiveness of the LCD intervention. The richness of microbiota significantly increased after the intervention. By taking the intersection of ANOVA and linear discriminant analysis effect size (LEfSe) analysis results, we identified three phyla, three classes, four orders, five families, and six genera that were differentially enriched between baseline and week-4 time points. Among the three phyla, relative abundances of Firmicutes and Actinobacteriota decreased significantly, while Bacteroidetes increased significantly. At the genus level, Ruminococcus, Agathobacter, Streptococcus, and Bifidobacterium showed a significant reduction in relative abundances, whereas Parabacteroides and Bacteroides increased steadily. Our results demonstrate that LCD can effectively alleviate obesity and modify certain taxa of gut microbiota, providing potential insights for personalized dietary interventions against obesity.

MRI Radiomics Features of Adenohypophysis Determine the Activation of Hypothalamic-Pituitary-Gonadal Axis in Peri-Puberty Children.

BACKGROUND: The status of the hypothalamic-pituitary-gonadal (HPG) axis is important for assessing the onset of physiological or pathological puberty. The reference standard gonadotropin-releasing hormone (GnRH) stimulation test requires hospital admission and repeated blood samples. A simple noninvasive method would be beneficial. OBJECTIVES: To explore a noninvasive method for evaluating HPG axis activation in children using an MRI radiomics model. STUDY TYPE: Retrospective. POPULATION: Two hundred thirty-nine children (83 male; 3.6-14.6 years) with hypophysial MRI and GnRH stimulation tests, randomly divided a training set (168 children) and a test set (71 children). FIELD STRENGTH/SEQUENCE: 3.0 T, 3D isotropic fast spin echo (CUBE) T1-weighted imaging (T1WI) sequences. ASSESSMENT: Radiomics features were extracted from sagittal 3D CUBE T1WI, and imaging signatures were generated using the least absolute shrinkage and selection operator (LASSO) with 10-fold cross-validation. Diagnostic performance for differential diagnosis of HPG status was compared between a radiomics model and MRI features (adenohypophyseal height [aPH] and volume [aPV]). STATISTICAL TESTS: Receiver operating characteristic (ROC) and decision curve analysis (DCA). A P value <0.05 was considered statistically significant. RESULTS: Eight hundred fifty-one radiomics features were extracted and reduced to 10 by the LASSO method in the training cohort. The radiomics model based on CUBE T1WI showed good performance in assessment of HPG axis activation with an area under the ROC curve (AUC) of 0.81 (95% CI: 0.71, 0.91) in the test set. The AUC of the radiomics model was significantly higher than that of aPH (0.81 vs. 0.65) but there was no significant difference compared to aPV (0.81 vs. 0.78, P = 0.58). In DCA analysis, the radiomics signature showed higher net benefit over the aPV and aPH models. DATA CONCLUSIONS: The MRI radiomics model has potential to assess HPG axis activation status noninvasively, potentially providing valuable information in the diagnosis of patients with pathological puberty onset. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Endothelial-to-mesenchymal transition: New insights into vascular calcification.

With the continuous progress of atherosclerosis research, the significant pathological change of it--vascular calcification (VC), gains increasing attention. In recent years, numerous studies have demonstrated that it is an independent predictor of death risk of cardiovascular disease, and it has a strong correlation with poor clinical prognosis. As the world's population continues to age, the occurrence of VC is expected to reach its highest point in the near future. Therefore, it is essential to investigate ways to prevent or even reverse this process for clinical purposes. Endothelial-to-mesenchymal transition (EndMT) describes the progressive differentiation of endothelial cells into mesenchymal stem cells (MSCs) under various stimuli and acquisition of pluripotent cell characteristics. More and more studies show that EndMT plays a vital role in various cardiovascular diseases, including atherosclerosis, vascular calcification and heart valvular disease. EndMT is also involved in the formation and progression of VC. This review vividly describes the history, characteristics of EndMT and how it affects the endothelial cell process, then focuses on the relationship between vascular endothelium, EndMT, amino acid metabolism, and vascular calcification. Finally, it overviews the signal pathway of EndMT and drugs targeting EndMT, hoping to provide new ideas and a theoretical basis for studying potential therapeutic targets of VC.

Loganin reduces diabetic kidney injury by inhibiting the activation of NLRP3 inflammasome-mediated pyroptosis.

Diabetic kidney disease (DKD) is an essential cause of end-stage renal disease. The ongoing inflammatory response in the proximal tubule promotes the progression of DKD. Timely and effective blockade of the inflammatory process to protect the kidney during DKD progression is a proven strategy. The purpose of this study was to investigate the protective effect of loganin on diabetic nephropathy in vivo and in vitro and whether this effect was related to the inhibition of pyroptosis. The results indicated that loganin reduced fasting blood glucose, blood urea nitrogen and serum creatinine concentrations, and alleviated renal pathological changes in DKD mice. In parallel, loganin downregulated the expression of pyroptosis related proteins in the renal tubules of DKD mice and decreased serum levels of interleukin-1beta (IL-1ß) and interleukin-18 (IL-18). Furthermore, in vitro experiments showed that loganin attenuated high glucose-induced HK-2 cell injury by reducing the expression of pyroptosis-related proteins, and cytokine levels were also decreased. These fundings were also confirmed in the polyphyllin VI (PPVI) -induced HK-2 cell pyroptosis model. Loganin reduces high glucose induced HK-2 cells pyroptosis by inhibiting reactive oxygen species (ROS) production and NOD-like receptor protein 3 (NLRP3) inflammasome activation. In conclusion, the inhibition of pyroptosis via inhibition of the NLRP3/Caspase-1/Gasdermin D (GSDMD) pathway might be an essential mechanism for loganin treatment of DKD.

Chrysophanol alleviates acute lung injury caused by Klebsiella pneumoniae infection by inhibiting pro-inflammatory cytokine production.

Acute lung injury (ALI) caused by acute bacterial infection remains a common life-threatening lung disease. An increased inflammatory response is the basis for the occurrence and development of ALI. Most antibiotics can only reduce the bacterial load but do not protect from lung damage because of an excessive immune response. Chrysophanol (chrysophanic acid, Chr), as a natural anthraquinone extracted from Rheum palmatum L., has various biological functions, including anti-inflammatory, anti-cancer activities, and ameliorative effects on cardiovascular diseases. Considering these properties, we investigated the effect of Chr in Klebsiella pneumoniae (KP)-induced ALI mice and its potential mechanism. Our results showed that Chr had protective effects against KP-infected mice, including increased survival rate, decreased bacterial burden, reduced recruitment of immune cells, and reduced reactive oxygen species level of lung macrophages. Chr reduced the expression of inflammatory cytokines by inhibiting the toll-like receptor 4/nuclear factor kappa-B (TLR4/NF-κB) signaling pathway and inflammasome activation and strengthening autophagy. Overactivation of the TLR4/NF-κB signaling pathway by the activator Neoseptin 3 led to Chr losing control of inflammatory cytokines in cells, resulting in increased cell death. Similarly, overactivation of the c-Jun N-terminal kinase signaling pathway using the activator anisomycin resulted in Chr losing its inhibitory effect on NOD-like receptor thermal protein domain associated protein 3 (NFRP3) inflammasome activation, and cell viability was reduced. In addition, autophagy was blocked by siBeclin1, so Chr could not reduce inflammatory factors, and cell viability was markedly inhibited. Collectively, this work unravels the molecular mechanism underpinning Chr-alleviated ALI via inhibiting pro-inflammatory cytokines. Thus, Chr is a potential therapeutic agent for KP-induced ALI.

Long-term effects of childhood trauma subtypes on adult brain function.

INTRODUCTION: Childhood trauma is prevalent in our society, whereas little is known about why and how different forms of early traumatic experiences exert long-term effects on differential brain function in adulthood. PURPOSE: This study aimed to scale experience-specific neural correlates of distinct subtypes of childhood trauma. METHODS: We used resting-state functional magnetic resonance imaging data from 216 adults with different degrees of childhood trauma. Graph analysis was combined with the Childhood Trauma Questionnaire to inspect the impact of distinct subtypes of childhood trauma on the brain. RESULTS: We found that childhood trauma experiences have a detrimental effect on depression and anxiety behavior. On one hand, childhood neglect scores were positively associated with network transmission efficiency of regions involved in cognitive and executive functions, such as temporal lobe, insular cortex, and parahippocampal gyrus. On the other hand, childhood abuse scores were tightly linked to functional reorganizations of regions mediated by immature ego defense system and damaged emotion representation. Specifically, the abuse scores were positively associated with network transmission efficiency of the visual, auditory, linguistic, and motor cortex. Isolated communications in temporal cortex and supplementary motor cortex were related to emotional and physical abuse scores. CONCLUSIONS: Our data showed the differential associations of abusive and neglectful experiences with brain function in adulthood. These experience-specific associations could underpin potentially differential risks of specific forms of psychiatric sequelae in adulthood. More attentions to maltreated children and timely psychological treatment are needed to reduce the incidence of psychosis.

Jiedu Tongluo Baoshen formula enhances renal tubular epithelial cell autophagy to prevent renal fibrosis by activating SIRT1/LKB1/AMPK pathway.

Renal fibrosis, an important pathological change in the development of diabetic kidney disease (DKD), urgently needs new treatment methods clinically. The Jiedu Tongluo Baoshen (JTBF) formula was created based on the theory of toxic damage to the kidney collaterals, and a variety of active ingredients in JTBF have inhibitory effects on epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM). In this study, the Ultra Performance Liquid Chromatography (UPLC) was employed to analyze the effective ingredients in the JTBF formula. After screening in the PubChem database, we identified 94 active compounds of JTBF and predicted the SIRT1 pathway as potential targets through network pharmacology. In addition, in the high fat diet (HFD)+Streptozocin (STZ)-induced DKD rat model and high glucose (HG)-induced NRK-52E cell model, JTBF treatment activates the phosphorylation of LKB1 and AMPK and enhances the autophagy activity of NRK-52E cells, thereby reducing the accumulation of EMT and ECM. These results have been confirmed in vivo and in vitro experiments. JTBF enhances the autophagy activity of renal tubular epithelial cells and inhibits the progression of DKD renal fibrosis by activating the SIRT1/LKB1/AMPK signal pathway. This study provides new insights into the molecular mechanism of JTBF to prevent and treat DKD renal fibrosis.

Contribution of Chinese herbal medicine in the treatment of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis of randomized controlled trials.

Coronavirus disease 2019 (COVID-19) has become a global epidemic, and there is no specific treatment for anti-COVID-19 drugs. However, treatment of COVID-19 using Chinese herbal medicine (CHM) has been widely practiced in China. PubMed, Embase, Cochrane Library, CNKI, Wanfang and VIP databases were searched to evaluate the efficacy and safety of CHM in the treatment of COVID-19. Twenty-six studies were included in this meta-analysis. The included cases were all patients diagnosed with COVID-19 according to the "New Coronary Virus Pneumonia Diagnosis and Treatment Program," with a total of 2,407 cases. Patients were treated with CHM, including 36 prescriptions, and 105 flavors of CHM were included. The results of the meta-analysis showed that the CHM group improved in lung CT, clinical cure rate, clinical symptom score and time to negative for viral nucleic acid. However, this study still has many limitations due to the limited number of included studies. Therefore, high-quality RCT studies are needed to provide more reliable evidence for CHM treatment of COVID-19. In conclusion, CHM may significantly improve the clinical manifestations and laboratory indicators of patients with COVID-19. In addition, no serious adverse reactions were found after CHM treatment. Therefore, CHM may be used as a potential candidate for COVID-19. HIGHLIGHTS: COVID-19 has become a global epidemic, and there is no specific treatment for anti-COVID-19 drugs. CHM has made a new breakthrough in the treatment of COVID-19. CHM may relieve lung CT images of COVID-19 patients. CHM may improve clinical symptoms of COVID-19 patients. CHM may inhibit the expression of inflammatory factors in patients with COVID-19.

Differentiation of lower limb vasculitis from physiological uptake on FDG PET/CT imaging.

PURPOSES: To analyze the difference of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) uptake between vasculitis and non-vasculitic patients in PET/CT imaging and the factors related to vascular uptake in non-vasculitic patients. To investigate the feasibility of identifying vasculitis of the lower limb and physiological uptake with delayed imaging. PROCEDURES: Among 244 patients who underwent PET/CT examination, imaging features of patients with or without vasculitis were retrospectively analyzed. The factors related to FDG uptake in the lower limb vessels of non-vasculitic patients were analyzed. Another 44 patients with suspected systemic vasculitis in PET/CT were prospectively studied to analyze the efficacy of delayed imaging on differentiating vascular uptake in lower limbs. RESULTS: In PET/CT imaging of patients with vasculitis, involvement of trunk vessels showed segmental or diffuse FDG distribution. Lower limb vascular involvement showed reticular uptake accompanied by nodular or patchy changes. In non-vasculitic patients, vascular uptake mainly showed linear uptake in lower limb vessels and there was no significant difference in uptake degree compared with vasculitis patients. Body weight and interval time were the independent influence factors of vascular uptake in lower limbs of non-vasculitic patients. In delayed imaging, lower limb vasculitis all showed reticular uptake and physiological uptake all showed a linear pattern. ROC analysis showed the change rate of SUVmax (≥ 20%) between early and delayed imaging could delineate physiological vascular uptake with a sensitivity of 100% and specificity of 81.0%. CONCLUSIONS: When PET/CT is used for the diagnosis and classification of vasculitis, the physiological uptake of lower limb vessels may mislead the diagnosis. PET/CT imaging features or delayed imaging improved diagnostic efficacy.

The effects of Ophiocordyceps sinensis combined with ACEI/ARB on diabetic kidney disease: A systematic review and meta-analysis.

BACKGROUND: Ophiocordyceps sinensis (OS), a medicinal fungus, has been made into OS preparations, which are frequently used as adjunctive therapy for patients with Diabetic Kidney Disease (DKD) in China. It is necessary to assess the efficacy and safety of OS preparations in the adjunctive treatment of DKD by conducting a systematic review and meta-analysis. OBJECTIVE: Ophiocordyceps sinensis preparations were evaluated for their efficacy and safety as adjunctive therapy to conventional drugs (angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs)) for DKD. METHODS: We searched seven electronic literature databases for randomized controlled trials (RCTs) comparing ACEI/ARB and OS combined with ACEI/ARB from inception up to March 2022. Two reviewers extracted data and assessed the risk of bias independently. Evidence certainty was rated using the GRADE system. Standardized mean difference (SMD) or mean difference (MD) was pooled with random effects models and was reported with corresponding 95% confidence intervals (CIs). Meta-analysis, sensitivity analysis and Egger's test were performed using R software (version 14.2) (PROSPERO registration no. CRD42021248634). RESULTS: Thirty eight RCTs involving 3167 patients met the inclusion criteria. No trials were reported with outcomes about kidney disease progression and cardiovascular events. In meta-analysis, compared with the control group of ACEI/ARB alone, OS combined with ACEI/ARB can achieve better effects in the treatment of DKD on reducing serum creatinine (Scr) [MDScr =-11.48 95% CI [-15.78, -7.18], p < 0.01], blood urea nitrogen (BUN) [MDBUN= -1.00, 95% CI [-1.44, -0.55], p < 0.01], ß2-microglobulin (ß2-MG) [SMDß2-MG= -1.32, 95% CI [-2.27, -0.37], p < 0.01], cystatin C (CysC) [MDCysC=-0.64, 95% CI [-0.83, -0.45], p < 0.01], 24-h urine proteinuria (24hUP) [SMD24hUP= -1.99, 95% CI [-2.68; -1.31], p < 0.01], urine microalbumin (UALB) [MDUALB= -37.41, 95% CI [-44.76, -30.06], p < 0.01] and decreasing urinary albumin excretion rate (UAER) [MDUAER= -24.11, 95% CI [-30.54, -17.68], p < 0.01] and albumin creatinine ratio (ACR) [SMDACR = 1.01, 95% CI [-1.73, -0.29], p < 0.01]. The OS adjuvant treatment also improved outcomes of blood pressure, blood glucose, blood lipid, inflammation and oxidative stress. No significant change in fasting blood glucose (FPG), glycated hemoglobin (HbA1c), malondialdehyde (MDA), and transforming growth factor beta 1 (TGF-ß1) was detected. Yet, no significant difference was found about the adverse events between the two groups. CONCLUSIONS: Ophiocordyceps sinensis preparation combined with ACEI/ARB has beneficial influence on renal function, decrease proteinuria, dyslipidemia, and even oxidative stress and inflammation in DKD patients. However, there is no trial that evaluated outcomes of kidney disease progression and cardiovascular events. Future study should move beyond surrogate endpoints to actual cardiovascular or renal outcome benefits with an aim to explore effects of OS preparation in the long-term.

Long-term mortality and patency after drug-coated balloon angioplasty in the hemodialysis circuit: A systematic review and meta-analysis of randomized controlled trials.

PURPOSE: To compare all-cause mortality and primary patency with drug-coated balloon angioplasty (DCBA) compared with plain balloon angioplasty (PBA) in people with hemodialysis-related stenosis. MATERIALS AND METHODS: PubMed, Embase, and Cochrane Library databases were searched from November 1966 to February 2021 to identify randomized controlled trials (RCTs) that assessed the use of DCBA versus PBA for stenosis in hemodialysis circuits. Data extracted from the articles were integrated to determine all-cause mortality, target lesion primary patency (TLPP), circuit access primary patency (CAPP), 30-day adverse events, and technical success for the two approaches. We performed meta-analysis on these results using a fixed-effects model to evaluate odds ratios (ORs) and 95% confidence intervals (CIs) where I2 < 50% in a test for heterogeneity, or a random-effect model if otherwise. Sensitivity and subgroup analyses were also performed. RESULTS: Sixteen RCTs of 1672 individuals were included in our meta-analysis, of which 839 individuals received DCBA and 833 received PBA. The pooled outcome showed no statistical difference between DCBA and PBA in all-cause mortality at 6 months (OR = 1.29, 95% CI = 0.72-2.32, p = 0.39, I2 = 4%), 12 months (OR = 1.02, 95% CI = 0.68-1.53, p = 0.91, I2 = 0%), and 24 months (OR = 1.50, 95% CI = 0.87-2.57, p = 0.15, I2 = 0%), 30-day adverse events (OR = 1.09, 95% CI = 0.30-3.98, p = 0.90, I2 = 66%), and technical success (OR = 0.18, 95% CI = 0.02-1.92, p = 0.16, I2 = 65%). The DCBA had significantly better outcomes versus PBA in TLPP at 6 months (OR = 2.37, 95% CI = 1.84-3.04, p < 0.001, I2 = 44%) and 12 months (OR = 1.77, 95% CI = 1.22-2.56, p = 0.002, I2 = 56%), and CAPP at 6 months (OR = 2.07, 95% CI = 1.21-3.54, p = 0.008, I2 = 67%) and 12 months (OR = 1.66, 95% CI = 1.29-2.15, p < 0.001, I2 = 0%). CONCLUSION: In hemodialysis circuit stenosis, DCBA appears to have similar safety but greater efficacy than PBA.

Enhanced Adsorption of Cd on Iron-Organic Associations Formed by Laccase-Mediated Modification: Implications for the Immobilization of Cadmium in Paddy Soil.

The objectives of this study were to evaluate the cadmium adsorption capacity of iron-organic associations (Fe-OM) formed by laccase-mediated modification and assess the effect of Fe-OM on the immobilization of cadmium in paddy soil. Leaf organic matter (OM) was extracted from Changshan grapefruit leaves, and then dissolved organic matter (Lac-OM) and precipitated organic matter (Lac-P) were obtained by laccase catalytic modification. Different Fe-OM associations were obtained by co-precipitation of Fe with OM, Lac-OM, and Lac-P, respectively, and the adsorption kinetics, adsorption edge, and isothermal adsorption experiments of Cd on Fe-OM were carried out. Based on the in situ generation of Fe-OM, passivation experiments on Cd-contaminated soils with a high geological background were carried out. All types of Fe-OM have a better Cd adsorption capacity than ferrihydrite (FH). The theoretical maximum adsorption capacity of the OM-FH, Lac-OM-FH, and Lac-P-FH were 2.2, 2.53, and 2.98 times higher than that of FH, respectively. The adsorption of Cd on Fe-OM is mainly chemisorption, and the -OH moieties on the Fe-OM surface form an inner-sphere complex with the Cd ions. Lac-OM-FH showed a higher Cd adsorption capacity than OM-FH, which is related to the formation of more oxygen-containing groups in the organic matter modified by laccase. The immobilization effect of Lac-OM-FH on active Cd in soil was also higher than that of OM-FH. The Lac-OM-FH formed by laccase-mediated modification has better Cd adsorption performance, which can effectively inactivate the activity of Cd in paddy soil.

Ferroptosis and its role in skeletal muscle diseases.

Ferroptosis is characterized by the accumulation of iron and lipid peroxidation products, which regulates physiological and pathological processes in numerous organs and tissues. A growing body of research suggests that ferroptosis is a key causative factor in a variety of skeletal muscle diseases, including sarcopenia, rhabdomyolysis, rhabdomyosarcoma, and exhaustive exercise-induced fatigue. However, the relationship between ferroptosis and various skeletal muscle diseases has not been investigated systematically. This review's objective is to provide a comprehensive summary of the mechanisms and signaling factors that regulate ferroptosis, including lipid peroxidation, iron/heme, amino acid metabolism, and autophagy. In addition, we tease out the role of ferroptosis in the progression of different skeletal muscle diseases and ferroptosis as a potential target for the treatment of multiple skeletal muscle diseases. This review can provide valuable reference for the research on the pathogenesis of skeletal muscle diseases, as well as for clinical prevention and treatment.

Regulation of amino acid metabolism in Aphis gossypii parasitized by Binodoxys communis.

The vast majority of parasitoids are capable of precise and meticulous regulation of nutrition and metabolism within the host. An important building block of life, amino acids are critical to the development of parasitoids. To date, research on how parasitoids regulate host amino acid metabolism remains limited. In this study, Aphis gossypii and its dominant parasitoid Binodoxys communis were used as a study system to explore how parasitism may change the regulation of amino acids in A. gossypii with UHPLC-MS/MS and RT-qPCR techniques. Here, for the first 8 h of parasitism the abundance of almost all amino acids in cotton aphids increased, and after 16 h most of the amino acids decreased. An amino acid of parasitic syndrome, the content of Tyr increased gradually after being parasitized. The expression of genes related to amino acid metabolism increased significantly in early stages of parasitism and then significantly decreased gradually. At the same time, the abundance of Buchnera, a cotton aphid specific symbiont increased significantly. Our comprehensive analyses reveal impacts of B. communis on the amino acid regulatory network in cotton aphid from three aspects: amino acid metabolism, gene expression, and bacterial symbionts. Therefore, this research provides an important theoretical basis for parasitoid nutritional regulation in host, which is highly significant as it may inform the artificial reproduction of parasitoids and the biological control of insect pests.

Qizhi Kebitong Formula Ameliorates Streptozocin-Induced Diabetic Osteoporosis through Regulating the PI3K/Akt/NF-κB Pathway.

Background: Diabetic osteoporosis (DOP) is a progressive osteoblast dysfunction induced by high glucose, which has negative impacts on bone homeostasis. Qizhi Kebitong formula (QKF) is a traditional Chinese medicine (TCM) formula for treating DOP. However, its role in the protection of DOP has not been clarified yet. Here, we aimed to explore the potential mechanisms of QKF on DOP development via in vivo experiment. Methods: Network pharmacology was used to detect the key targets and signaling pathways of QKF on DOP. The effects of QKF on DOP were examined by the phenotypic characteristics, micro-CT, and hematoxylin-eosin (H&E) staining. The predicted targets and pathways were validated by a streptozocin- (STZ-) induced mouse model. Subsequently, the levels of the selected genes and proteins were analyzed using qRT-PCR and Western blot. Finally, AutoDock and PyMOL were used for molecular docking. Results: In this study, 90 active compounds and 2970 related disease targets have been found through network pharmacology. And QKF could improve the microstructures of femur bone mass, reduce inflammatory cell infiltration, and downregulate the levels of TNF-α, IKBKB, IL-6, and IL-1ß. Moreover, the underlying effect of PI3K/Akt/NF-κB pathways was also recommended in the treatment. Conclusion: Altogether, our findings suggested that QKF could markedly alleviate osteoblast dysfunction by modulating the key targets and PI3K/Akt/NF-κB signaling pathway.

Purple sweet potato delphinidin-3-rutin represses glioma proliferation by inducing miR-20b-5p/Atg7-dependent cytostatic autophagy.

Glioma is the most common primary malignant intracranial tumor. Owing to highly aggressive invasiveness and metastatic properties, the prognosis of this disease remains poor even with surgery, radiotherapy, and chemotherapy. Rutin is a glycoside natural flavonoid that modulates microglia inflammatory profile and improves anti-glioma activity. Here, a glycoside flavonoid was extracted and named purple sweet potato delphinidin-3-rutin (PSPD3R). In an experiment using the subcutaneous xenograft model of human glioblastoma (GBM) and alamar blue assay, we found that PSPD3R suppressed the glioma proliferation both in vitro and in vivo. Flow cytometry assay and transmission electron microscopy observation revealed that PSPD3R stimulated glioma cell autophagy and apoptosis. High-throughput microRNA (miRNA) sequencing showed that PSPD3R substantially affected the miRNA expression of U251 cells. Acridine orange staining and immunoblotting indicated that PSPD3R regulated autophagy via Akt/Creb/miR-20b-5p in glioma cells. Luciferase reporter assays showed that autophagy-related gene 7 (Atg7) mRNA was the target gene of miR-20b-5p. The downregulation of miR-20b-5p inhibited glioma proliferation in vivo. In summary, PSPD3R regulated autophagy in glioma via the Akt/Creb/miR-20b-5p/Atg7 axis. This work unraveled the molecular mechanism of PSPD3R-induced autophagy in glioma and revealed its potential as a therapeutic agent for glioma treatment.

Multislice Spiral Computer Tomography Findings of Simple Congenital Middle Ear Malformations.

Background: Simple congenital middle ear malformations (SCMEMs) are a group of congenital ear malformations. The study aims to analyze the multi-slice spiral computer tomography (MSCT) manifestations of normal ears and SCMEM ears. Objectives: This study aimed to investigate the MSCT manifestations of normal ears and SCMEM ears and to evaluate the relationship between the SCMEM and the tympanic segment of the FNC pathway. Methods: This was a retrospective case-control study. Patients who were diagnosed with SCMEM were included in the SCMEM group. Patients with vertigo, pulsatile tinnitus, or other symptoms were included in the control group. MSCT examination and image processing of the ossicular chain, facial nerve canal, and related structures were performed and compared between the two groups. Results: There were 94 cases in the SCMEM group (125 ears) and 97 cases in the control group (190 ears). Sixty-three cases (67.0%) were unilateral malformations (36 right ears and 27 left ears). MSCT showed congenital stapes malformation in 107 ears (85.6%) and incus long process malformation in 84 ears (67.2%). Among these, simple stapes malformations were found in 41 ears (32.8%), simple incus malformation in 18 ears (14.4%), and stapes malformation complicated with incus malformation in 66 ears (52.8%). The distance between the facial nerve and lateral semicircular canal (FNC-LSC) in the SCMEM group was 1.30 ± 0.64 mm compared to 0.79 ± 0.11 mm in the control group (P < 0.001), and the distance between facial nerve canal and oval window (FNC-OW) was 0.67 ± 0.53 mm in the SCMEM group and 1.13 ± 0.18 mm in the control group (P < 0.001). Conclusion: SCMEM occurred mainly in ossicular chain abnormalities. MSCT clearly showed the slight structural changes in the middle ear and provided an accurate basis for preoperative diagnosis.

Role of Collagen in Vascular Calcification.

ABSTRACT: Vascular calcification is a pathological process characterized by ectopic calcification of the vascular wall. Medial calcifications are most often associated with kidney disease, diabetes, hypertension, and advanced age. Intimal calcifications are associated with atherosclerosis. Collagen can regulate mineralization by binding to apatite minerals and promoting their deposition, binding to collagen receptors to initiate signal transduction, and inducing cell transdifferentiation. In the process of vascular calcification, type I collagen is not only the scaffold for mineral deposition but also a signal entity, guiding the distribution, aggregation, and nucleation of vesicles and promoting the transformation of vascular smooth muscle cells into osteochondral-like cells. In recent years, collagen has been shown to affect vascular calcification through collagen disc-domain receptors, matrix vesicles, and transdifferentiation of vascular smooth muscle cells.

Comparative effectiveness and safety among different tip-design hemodialysis long-term catheters: A meta-analysis.

PURPOSE: The aim of this meta-analysis is to compare effectiveness and safety among different tip-design long-term hemodialysis (HD) catheters. MATERIALS AND METHODS: PubMed, Embase, and Cochrane Library databases were searched until 8 December 2021 to identify randomized controlled trials (RCTs) and cohort studies comparing step-tip, split-tip, or symmetrical-tip design catheters in patients undergoing HD will be included. The Cochrane Risk of Bias tool and the Newcastle-Ottawa Scale were used to evaluate the quality of RCTs and cohort studies. Data extracted from the articles were integrated to determine mean effective blood pump velocity (Qb), blood recirculation rates, secondary patency, catheter-related infection, catheter-related blood stream infection (CRBSI), thrombosis rates, and all-cause mortality for the three tip-designs. We performed meta-analysis on dichotomous outcomes using a random-effects model to evaluate risk ratios (RRs) and 95% confidence intervals (Cls). The effect sizes of continuous outcomes were reported as the mean difference (MD). Sensitivity and subgroup analyses were also performed. The study was registered in the PROSPERO (CRD42021297069). RESULTS: Six RCTs and 11 cohort studies of 2617 individuals were included in our meta-analysis, of which 1088 individuals inserted split-tip catheters, 897 individuals inserted step-tip catheters and 650 received symmetrical-tip design catheters. Sym-tip performed better in mean Qb (MD = 43.85, 95% Cl = 18.13-69.56, p = 0.0008) than step-tip. Split-tip had better outcomes vs step-tip in blood recirculation (RR = 3.44, 95% Cl = 2.49-4.39, p < 0.00001). Sym-tip had significantly better outcomes compared with step-tip (RR = 0.28, 95%Cl = 0.09-0.81, Z = 2.34, p = 0.02) and split-tip (RR = 0.19, 95% Cl = 0.09-0.43, p < 0.0001) in thrombotic events. No significant difference was found in secondary patency, infection rates, CRBSI, and all-cause mortality among the three tip-designs. CONCLUSION: The sym-tip of tunneled cuffed catheters performed better mean Qb, lower thrombotic events, and lower blood recirculation when blood line reversed, which may have an advantage over other two catheter-tips.