Objective. To determine whether and how longitudinal acupuncture modulates the impaired default mode network (DMN) in chronic migraine (CM) patients without aura. Methods. Resting-state functional magnetic resonance imaging (fMRI) data from 14 CM patients treated with longitudinal pre- and postacupuncture treatment (PPAT) and data of 18 age- and gender-matched healthy controls (HCs) were analyzed using independent component analysis (ICA) and seed-based correlation analysis (SCA) to investigate connectivity within the DMN. Correlation analyses were performed to identify associations between changes in functional connectivity (FC) and in clinical pain based on PPAT observations. The monthly mean visual analog scale (VAS) scores, monthly mean headache attacks, monthly headache days, monthly amount of acute headache medications, and immediate VAS scores were assessed for evaluation of pain. Results. The decreased FC within the DMN found in the left superior prefrontal gyrus (L_SPFG) and left precuneus (L_PRECUN) of CM patients was returned to the healthy control level after acupuncture treatments. Furthermore, the diminished pairwise FC strengths in some regions of interest (ROIs) within the DMN were also increased, mainly distributed between the right temporal lobe (R_TPL) and left anterior cingulate cortex, between the R_TPL and bilateral superior medial gyrus, and between the R_TPL and right precuneus. Increased z-scores within the DMN (L_SPFG and L_PRECUN) were associated with reduced immediate VAS scores, and increases in z-scores of the L_PRECUN were negatively correlated with reductions in the monthly amount of acute headache medications. However, no association existed between the increased DMN connectivity and reduced monthly mean VAS scores, monthly mean headache attacks, and monthly headache days. Conclusion. Altered DMN connectivity and its normalization postacupuncture can be employed to monitor CM and its modulating effects. The DMN is useful for understanding the therapeutic mechanisms of acupuncture in CM.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) worldwide. Renin-angiotensin-aldosterone system (RAAS) inhibitors and sodiumglucose co-transporter 2 (SGLT2) inhibitors have shown efficacy in reducing the risk of ESRD. However, patients vary in their response to RAAS blockades, and the pharmacodynamic responses to SGLT2 inhibitors decline with increasing severity of renal impairment. Thus, effective therapy for DKD is yet unmet. Transforming growth factor-β1 (TGF-β1), expressed by nearly all kidney cell types and infiltrating leukocytes and macrophages, is a pleiotropic cytokine involved in angiogenesis, immunomodulation, and extracellular matrix (ECM) formation. An overactive TGF-β1 signaling pathway has been implicated as a critical profibrotic factor in the progression of chronic kidney disease in human DKD. In animal studies, TGF-β1 neutralizing antibodies and TGF-β1 signaling inhibitors were effective in ameliorating renal fibrosis in DKD. Conversely, a clinical study of TGF-β1 neutralizing antibodies failed to demonstrate renal efficacy in DKD. However, overexpression of latent TGF-β1 led to anti-inflammatory and anti-fibrosis effects in non-DKD. This evidence implied that complete blocking of TGF-β1 signaling abolished its multiple physiological functions, which are highly associated with undesirable adverse events. Ideal strategies for DKD therapy would be either specific and selective inhibition of the profibrotic-related TGF-β1 pathway or blocking conversion of latent TGF-β1 to active TGF-β1.

SS affects the oral microbiota and SS patients carry a different and less diverse microorganism community compared with healthy subjects. Prednisone acetas is an influence on the oral microbiome. This study provides a basic data on the oral flora in SS patients.

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Background: Chronic migraine (CM) is a common and disabling neurological disorder that affects 1-2% of the global population. The aim of the present study was to identify the functional characteristics of the CM brain using static functional connectivity (s-FC), static functional network connectivity (s-FNC), and dynamic functional network connectivity (d-FNC) analyses. Methods: In the present study, 17 CM patients and 20 sex-and age-matched healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. We utilized independent component (IC) analysis to identify 13 ICs. These 13 ICs were then classified into the following 6 resting-state networks (RSNs): the default mode network (DMN), executive control network (ECN), dorsal attention network, auditory network (AN), visual network (VN), and cerebellum network. Subsequently, s-FC, s-FNC, and d-FNC analyses of 13 ICs were employed for between-group comparisons. Three temporal metrics (fraction of time spent, mean dwell time, and number of transitions), which were derived from the state-transition vector, were calculated for group comparisons. In addition, correlation analyses were performed between these dynamic metrics and clinical characteristics [mean visual analog scale (VAS) scores, days with headache per month, days with migraine pain feature per month, and disease duration]. Results: In the comparison of s-FC of 13 ICs within RSNs between the CM and HC groups, increased connectivity was observed in the left angular gyrus (Angular_L) of the ECN (IC 2) and the right superior parietal gyrus (Parietal_Sup_R) of the AN (IC 5), and reduced connectivity was found in the left superior frontal gyrus (Frontal_Sup_2_L) of the AN (IC 5) and DMN (IC 19), the right calcarine sulcus (Calcarine_ R) of the VN (IC 7), and the left precuneus (Precuneus_L) of the DMN (IC 17) in CM patients. In the comparison of the d-FNC of 13 IC pairs within RSNs between the two groups, the CM group exhibited significantly decreased connections between the DMN (IC 11) and AN (IC 5), and increased connections between the ECN (IC 2, IC 4) and DMN (IC 19), ECN (IC 4) and AN (IC 5), and ECN (IC 4) and VN (IC 13) in state 1. However, no significant differences in s-FNC were observed between the two groups during the s-FNC analysis. Between-group comparisons of three dynamic metrics between the CM and HC groups showed a longer fraction of time spent and mean dwell time in state 2 for CM patients. Furthermore, from the correlation analyses between these metrics and clinical characteristics, we observed a significant positive correlation between the number of transitions and mean VAS scores. Conclusions: Our findings suggest that functional features of the CM brain may fluctuate over time instead of remaining static, and provide further evidence that migraine chronification may be related to abnormal pattern connectivity between sensory and cognitive brain networks.

Diffuse midline glioma, H3 K27M-mutant (H3 K27Mmt DMG), is a rare and highly aggressive tumor that is more common in children than in adults. Few studies have compared the differences between pediatric and adult patients with this rare tumor. We here report our retrospective study of 94 adult and 70 pediatric cases of diffuse midline glioma. Surgical tumor samples were analyzed by routine histopathology and immunohistochemistry for H3 K27M, IDH1 R132H, ATRX, p53, OLIG2, glial fibrillary acidic protein, and Ki-67; Sanger sequencing for hot mutation spots in genes including H3F3A, HIST1H3B, IDH1, IDH2, TERT, and BRAF; and methylation-specific polymerase chain reaction for O 6 -methylguanine DNA methyltransferase promoter methylation. The most frequent anatomic locations in adult and pediatric patients were the thalamus and brainstem, respectively. Molecular profiling revealed higher frequencies of ATRX loss and H3.3 mutation in adult than in pediatric H3 K27M-mt DMGs. TERT promoter mutations and O 6methylguanine DNA methyltransferase promoter methylation were not detected in pediatric patients but were present in a few adult patients. During the follow-up period, 93/122 patients (70.1%) died from the disease, with a median survival time of 10.5 months (range: 1 to 104 mo). Kaplan-Meier analyses demonstrated that the prognosis was better for adult patients than the pediatric cohort (P = 0.0003). Multivariate analyses indicated that patient age, primary tumor size, status of ATRX expression, and Ki-67 index were independent prognosticators. The present study showed that there were differences between adult and pediatric H3 K27M-mt DMGs in terms of the anatomic location of tumor, molecular changes, and prognosis.

The serum lipid profile and clinical outcomes of cancer patients are commonly correlated in a wide range of carcinomas. However, few studies have investigated the serum lipid profile of patients with thyroid cancer (TC). The present study therefore aimed to analyze the lipid profiles of patients with TC. The serum proteomes of 31 participants with stage I-IV TC were screened using Orbitrap Q Exactive Plus. Analytical data collected between November 1, 2013 and November 11, 2018 from the laboratory information system included the total cholesterol (CHO), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), lipoprotein (a) and apolipoprotein B (ApoB) levels that were used to validate the screening results. A total of 3875 outpatients were enrolled in this study. A number of 17 differentially expressed proteins were identified. An Ingenuity pathway analysis identified activation of the liver X receptor/retinoid X receptor (LXR/RXR) activation, which is a crucial pathway involved in lipid metabolism. The results demonstrated that the total CHO levels were significantly different between patients with TC and control groups, both in men and women. In women, the levels of TG, HDL-C, Apo A1 and LDL-C/HDL-C were significantly different between patients with TC and control groups (all P<0.05). Higher concentrations of TG and LDL-C/HDL-C were observed in the cancer group compared with the control group. However, lower levels of Apo A1 and HDL-C were observed in women from the cancer group compared with the control group. The results from the present study revealed the presence of a disordered lipid profile in patients with TC. The molecular mechanism underlying the association between lipid metabolism and cancer requires further investigation and may be used to develop novel diagnostic biomarkers and therapeutic targets in human cancers.

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