Simplified integration of optimal self-management behaviors is associated with improved HbA1c in patients with type 1 diabetes.

PURPOSE: Living with type 1 diabetes requires burdensome and complex daily diabetes self-management behaviors. This study aimed to determine the association between integrated behavior performance and HbA1c, while identifying the behavior with the most significant impact on HbA1c. METHODS: A simple and feasible questionnaire was used to collect diabetes self-management behavior in patients with type 1 diabetes (n = 904). We assessed six dimensions of behavior performance: continuous glucose monitor (CGM) usage, frequent glucose testing, insulin pump usage, carbohydrate counting application, adjustment of insulin doses, and usage of apps for diabetes management. We evaluated the association between these behaviors and HbA1c. RESULTS: In total, 21.3% of patients performed none of the allotted behavior, while 28.5% of patients had a total behavior score of 3 or more. 63.6% of patients with a behavior score ≥ 3 achieved HbA1c goal, contrasting with only 30.4% of patients with a behavior score of 0-1. There was a mean 0.54% ± 0.05% decrease in HbA1c for each 1-unit increase in total behavior score after adjustment for age, family education and diabetes duration. Each behavior was independently correlated with a lower HbA1c level, with CGM having the most significant effect on HbA1c levels. CONCLUSIONS: Six optimal self-management behaviors, especially CGM usage, were associated with improved glycemic control, emphasizing the feasibility of implementing a simplified version of DSMES in the routine clinical care. REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT03610984.

[Annual progress of immunotherapy for tuberculosis in 2023].

As a chronic infectious disease, tuberculosis (TB) is closely related to immune regulation and immune effect. Immunotherapy which can improve the curative effect of tuberculosis and control the spread of tuberculosis, is one of the important means for the comprehensive treatment of tuberculosis. From October 2022 to September 2023, research on the immunotherapy of tuberculosis at home and abroad continues to increase, providing new opportunities for the treatment of multidrug-resistant and extensively drug-resistant tuberculosis. Host-targeted therapy and therapeutic vaccines are new directions for research into TB adjuvant therapy.

[Epidemiological investigation of iron deficiency among preschool children in 10 provinces, autonomous regions, or municipalities in China].

Objective: To understand the current status of anemia, iron deficiency, and iron-deficiency anemia among preschool children in China. Methods: A cross-sectional study was conducted with a multi-stage stratified sampling method to select 150 streets or townships from 10 Chinese provinces, autonomous regions, or municipalities (East: Jiangsu, Zhejiang, Shandong, and Hainan; Central: Henan; West: Chongqing, Shaanxi, Guizhou, and Xinjiang; Northeast: Liaoning). From May 2022 to April 2023, a total of 21 470 children, including community-based children aged 0.5 to<3.0 years receiving child health care and kindergarten-based children aged 3.0 to<7.0 years, were surveyed. They were divided into 3 age groups: infants (0.5 to<1.0 year), toddlers (1.0 to<3.0 years), and preschoolers (3.0 to<7.0 years). Basic information such as sex and date of birth of the children was collected, and peripheral blood samples were obtained for routine blood tests and serum ferritin measurement. The prevalence rates of anemia, iron deficiency, and iron-deficiency anemia were analyzed, and the prevalence rate differences were compared among different ages, sex, urban and rural areas, and regions using the chi-square test. Results: A total of 21 460 valid responses were collected, including 10 780 boys (50.2%). The number of infants, toddlers, and preschoolers were 2 645 (12.3%), 6 244 (29.1%), and 12 571 (58.6%), respectively. The hemoglobin level was (126.7±14.8) g/L, and the serum ferritin level was 32.3 (18.5, 50.1) µg/L. The overall rates of anemia, iron deficiency, and iron-deficiency anemia were 10.4% (2 230/21 460), 28.3% (6 070/21 460), and 3.9% (845/21 460), respectively. The prevalence rate of anemia was higher for boys than for girls (10.9% (1 173/10 780) vs. 9.9% (1 057/10 680), χ2=5.58, P=0.018), with statistically significant differences in the rates for infants, toddlers and preschoolers (18.0% (475/2 645), 10.6% (662/6 244), and 8.7% (1 093/12 571), respectively, χ2=201.81, P<0.01), and the rate was significantly higher for children in rural than that in urban area (11.8% (1 516/12 883) vs. 8.3% (714/8 577), χ2=65.54, P<0.01), with statistically significant differences in the rates by region (χ2=126.60, P<0.01), with the highest rate of 15.8% (343/2 173) for children in Central region, and the lowest rate of 5.3% (108/2 053) in Northeastern region. The prevalence rates of iron deficiency were 33.8% (895/2 645), 32.2% (2 011/6 244), and 25.2% (3 164/12 571) in infants, toddlers, and preschoolers, respectively, and 30.0% (3 229/10 780) in boys vs. 26.6% (2 841/10 680) in girls, 21.7% (1 913/8 821), 40.0% (870/2 173), 27.1% (2 283/8 413), 48.9% (1 004/2 053) in Eastern, Central, Western, and Northeastern regions, respectively, and each between-group showed a significant statistical difference (χ2=147.71, 29.73, 773.02, all P<0.01). The prevalence rate of iron-deficiency anemia showed a significant statistical difference between urban and rural areas, 2.9% (251/8 577) vs. 4.6% (594/12 883) (χ2=38.62, P<0.01), while the difference in iron deficiency prevalence was not significant (χ2=0.51, P=0.476). Conclusions: There has been a notable improvement in iron deficiency and iron-deficiency anemia among preschool children in China, but the situation remains concerning. Particular attention should be paid to the prevention and control of iron deficiency and iron-deficiency anemia, especially among infants and children in the Central, Western, and Northeastern regions of China.

[High LINC00626 expression promotes esophagogastric junction adenocarcinoma metastasis: the mediating role of the JAK1/STAT3/KHSRP axis].

OBJECTIVE: To investigate the role of JAK1/STAT3/KHSRP axis in mediating the regulatory effect of LINC00626 on progression of esophagogastric junction adenocarcinoma. METHODS: We collected surgical tumor and adjacent tissue specimens from 64 patients with esophagogastric junction adenocarcinoma and examined the expression levels of LINC00626 and KHSRP. qRT-PCR was used to detect the expressions of LINC00626 and KHSRP in 6 esophageal adenocarcinoma cell lines (OE-19, TE-7, Bic-1, Flo-1, SK-GT-4, and BE-3) and a normal esophageal epithelial cell line (HET-1A). OE-19 and TE-7 cell lines with stable LINC00626 knockdown and FLO-1 and SK-GT-4 cells stably overexpressing LINC00626 were constructed by lentiviral transfection, and the changes in proliferation, migration and invasion of the cells were evaluated using Cell Counting Kit-8 (CCK-8) assay and Transwell migration/invasion assay. The expressions of KHSRP and JAK/STAT pathway proteins in the transfected cells were detected with Western blotting. The effects of LINC006266 knockdown and overexpression on subcutaneous tumor formation and lung metastasis of OE-19 and FLO-1 cell xenografts were tested in nude mice. RESULTS: The expression levels of LINC00626 and KHSRP were significantly increased in esophagogastric junction adenocarcinoma tissues and in esophageal adenocarcinoma cells. LINC00626 knockdown obviously inhibited the proliferation, migration and invasion of esophageal adenocarcinoma cells in vitro and decreased their tumor formation and lung metastasis abilities in nude mice, while overexpression of LINC00626 produced the opposite effects. In esophageal adenocarcinoma cells, LINC0626 knockdown significantly decreased and LINC00626 overexpression strongly enhanced the phosphorylation of JAK1 and STAT3. CONCLUSION: High LINC00626 expression promotes esophageal-gastric junction adenocarcinoma metastasis by activating the JAK1/STAT3/KHSRP signal axis.

[Progress in treatment of primary mediastinal large B-cell lymphoma].

Primary mediastinal large B-cell lymphoma (PMBCL) is an aggressive B-cell lymphoma originating from the thymus, which has different clinical and biological characteristics from diffuse large B-cell lymphoma, NOS. PMBCL tends to occur in young women, usually presenting as a large anterior mediastinal mass. Most patients are in stage Ⅰ-Ⅱ at the time of presentation. There is no standard prognostic scoring system for PMBCL. Immunochemotherapy is commonly used in the treatment of PMBCL, but the optimal first-line treatment has not been determined, and the status of radiotherapy is controversial. The value of PET-CT guided therapy needs to be further verified. Relapsed/refractory PMBCL has a poor prognosis, while novel therapies such as PD-1 inhibitors, brentuximab vedotin, and CAR-T can help improve survival in these patients.

[Incidence of postoperative complications in Chinese patients with gastric or colorectal cancer based on a national, multicenter, prospective, cohort study].

Objective: To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications. Methods: This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression. Results: The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion: Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.

Cone Beam Computed Tomography in observing the presence and location of canalis sinuosus.

OBJECTIVE: Cone Beam Computed Tomography (CBCT) was used to observe and describe the distribution of canalis sinuosus (CS) in the Chinese population and the location of CS in the maxillary alveolar bone, so as to help oral surgeons evaluate the intraoperative risk and prognosis before maxillary surgery and reduce the complications caused by the injury of this structure in anterior surgery. PATIENTS AND METHODS: CBCT images of 600 patients admitted from 2021 to 2022 were collected to observe the anatomical structure of CS in the maxillary region. The following parameters were recorded: age, sex, number of CS, left and right distribution of CS, CS diameter, and location. Statistical analysis was performed on all of the collected data. RESULTS: The discovery rate of CS in this study was 59.75%, and it is commonly found in the lateral incisor area (64.82%). No significant difference can be found in the presence and number of CS in different gender and age groups (p>0.05). CONCLUSIONS: The use of high-resolution CBCT before implantation is of irreplaceable significance in the diagnosis and analysis of CS, which is conducive to reducing implantation complications and failure rate. The incidence of CS was independent of age or sex, while the location of CS was statistically significant.

[Evaluation of brain age changes in patients with liver cirrhosis and hepatic encephalopathy with deep learning models based on structural magnetic resonance imaging].

Objective: To investigate the brain aging in patients with cirrhosis and hepatic encephalopathy(HE), constructed a prediction model of brain age based on deep learning and T1 high-resolution MRI, and try to reveal the specific regions where cirrhosis and HE accelerating brain aging. Methods: A cross-sectional study. A brain age prediction model based on the 3D full convolutional neural network was constructed through T1 high-resolution MRI data from 3 609 healthy individuals across eight global public datasets. The mean absolute error (MAE) between actual age and predicted brain age, Pearson correlation coefficient (r) and determination coefficient (R2) were calculated to evaluate the accuracy of the model's predictions. A test set (n=555) from the Human Connectome Project was used to assess the accuracy of the model. A total of 136 patients with cirrhosis were recruited from Tianjin First Central Hospital as the case group (79 patients with cirrhosis without HE and 57 patients with cirrhosis with HE), and 70 healthy individuals were recruited from the society as the healthy control group during the same period. Brain-predicted age difference (Brain-PAD), digital connection-A (NCT-A) and digital-symbol test (DST) scores of all subjects were calculated for all subjects to assess brain aging and cognitive function in the healthy control group, the cirrhosis without HE group, and the cirrhosis with HE group. The network occlusion sensitivity analysis method was employed to assess the importance of each brain region in predicting brain age. Results: As for the prediction model, in the training set, MAE=2.85, r=0.98, R2=0.96. In the test set, MAE=4.45, r=0.96, R2=0.92. In the local data set of the healthy control group, MAE=3.77, r=0.85, R2=0.73. The time of NCT-A in both cirrhosis groups was longer than healthy control group, while the DST scores were lower than healthy control group, and the differences were statistically significant (both P<0.001); the Brain-PAD of healthy control group was (0.8±4.5) years, the Brain-PAD of no-HE group was (6.9±8.1) years, and the HE group was (10.2±7.7) years. The differences between the three groups were statistically significant (P<0.001), and the differences between any two groups were statistically significant (all P<0.05). The importance ratio of visual network in predicting brain age increased in cirrhosis patients, and the HE group was higher than no-HE group. Conclusions: In patients with cirrhosis, the cognitive function is reduced, brain aging is accelerated, and these changes are more obvious in patients with HE. The importance differences of each brain network in predicting brain aging provide a new direction for identifying the specific regions where cirrhosis and HE accelerate brain aging.

[Clinicopathological and molecular genetic characteristics of ELOC mutated renal cell carcinoma].

Objective: To investigate the clinicopathological features, molecular genetic features, differential diagnosis and prognosis of ELOC mutated renal cell carcinoma. Methods: From January 2015 to June 2022, 11 cases of renal cell carcinoma with clear-cell morphology, expression of CAⅨ and CK7 and no 3p deletion were collected. Two cases of ELOC mutant renal cell carcinoma were diagnosed using whole exome sequencing (WES). The clinical features, morphology, immunophenotype, FISH and WES results were analyzed. The relevant literature was reviewed. Results: The two patients were both male, aged 29 and 51 years, respectively. They were both found to have a renal mass by physical examination. The maximum diameters of the tumors were 3.5 cm and 2.0 cm, respectively. At the low magnification, the tumors were well-defined. The tumor cells showed a pushing border and were separated by thick fibrous bands, forming nodules. The tumor cells were arranged in a variety of patterns, including tubular, papillary, solid nest or alveolar. At high magnification, the tumor cells were large, with well-defined cell borders and clear cytoplasm or fine eosinophilic granules. CAⅨ was diffusely box-like positive in both cases. Case 1 was partially and moderately positive for CK7, strongly positive for CD10, diffusely and moderately positive for P504S, and weakly positive for 34ßE12. In case 2, CK7 and CD10 were both partially, moderately positive and P504s were diffusely positive, but 34ßE12 was negative. FISH results showed that both cases had no 3p deletion. ELOC c.235T>A (p.Y79N) mutation was identified using WES in case 1, while ELOC c.236_237inv (p.Y79C) mutation was identified in case 2. Conclusions: As a new clinical entity, ELOC mutated renal cell carcinoma may be underdiagnosed due to its overlap with clear cell renal cell carcinoma in morphology and immunophenotype. The diagnosis of renal cell carcinoma with ELOC mutation should be confirmed by morphology, immunohistochemistry, FISH and gene mutation detection. However, more additional cases are needed to explain its biological behavior and prognosis.

Reconstructing visual illusory experiences from human brain activity.

Visual illusions provide valuable insights into the brain's interpretation of the world given sensory inputs. However, the precise manner in which brain activity translates into illusory experiences remains largely unknown. Here, we leverage a brain decoding technique combined with deep neural network (DNN) representations to reconstruct illusory percepts as images from brain activity. The reconstruction model was trained on natural images to establish a link between brain activity and perceptual features and then tested on two types of illusions: illusory lines and neon color spreading. Reconstructions revealed lines and colors consistent with illusory experiences, which varied across the source visual cortical areas. This framework offers a way to materialize subjective experiences, shedding light on the brain's internal representations of the world.

Integrative analysis reveals the recurrent genetic etiologies in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is increasingly recognized as a chronic, progressive and fatal lung disease with an unknown etiology. Current studies focus on revealing the genetic factors in the risk of IPF, making the integrative analysis of genetic variations and transcriptomic alterations of substantial value. AIM: This study aimed to improve the understanding of the molecular basis of IPF through an integrative analysis of whole-exome sequencing (WES), bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) data. METHODS: WES is a powerful tool for studying the genetic basis of IPF, allowing for the identification of genetic variants that may be associated with the development of the disease. RNA-seq data provide a comprehensive view of the transcriptional changes in IPF patients, while scRNA-seq data offer a more granule view of cell-type-specific alterations. RESULTS: In this study, we identified a comprehensive mutational landscape of recurrent genomic and transcriptomic variations, including single-nucleotide polymorphisms, CNVs and differentially expressed genes, in IPF populations, which may play a significant role in the development and progression of IPF. CONCLUSIONS: Our study provided valuable insights into the genetic and transcriptomic variations associated with IPF, revealing changes in gene expression that may contribute to disease development and progression. These findings highlight the importance of an integrative approach to understanding the molecular mechanisms underlying IPF and may pave the way for identifying potential therapeutic targets.

Radiomic Analysis Based on Gd-EOB-DTPA Enhanced MRI for the Preoperative Prediction of Ki-67 Expression in Hepatocellular Carcinoma.

RATIONALE AND OBJECTIVES: To develop and validate a random forest model based on radiomic features in Gd-EOB-DTPA enhanced MRI for predicting the Ki-67 expression in solitary HCC. MATERIALS AND METHODS: This retrospective study analyzed 258 patients with solitary HCC. Significant clinicoradiological factors were identified through univariate and multivariate analyses for distinguishing HCC with high (>20%) and low (≤20%) Ki-67 expression. Radiomic features were extracted at Gd-EOB-DTPA enhanced MRI. The recursive feature elimination (RFE) strategy was employed to screen robust radiomic features, and the Random Forest (RF) algorithm was utilized to rank radiomic features and construct prediction models. The AUC, accuracy, precision, recall, and f1-score were used to evaluate the performance of RF models. RESULTS: Multivariate analysis identified serum AFP level, tumor size, growth type, and peritumoral enhancement as independent predictors for HCC with high Ki-67 expression. The clinicoradiological-radiomic model that incorporated the clinicoradiological predictors and the top ten radiomic features outperformed the clinicoradiological model in the training set (AUCs 0.876 vs. 0.780; p < 0.001), though the test set did not have a statistical significance (AUCs 0.809 vs. 0.723; p = 0.123). The addition of clinicoradiological predictors did not yield a significant improvement in the performance of radiomic features in both sets (training, p = 0.692; test, p = 0.229). Decision curve analysis further confirmed the clinical utility of the RF models. CONCLUSION: The RF models based on radiomic features of Gd-EOB-DTPA enhanced MRI achieved satisfactory performance in preoperatively predicting Ki-67 expression in HCC.

[Mechanism of piRNA in bisphenol A-promoted invasion and migration of prostate cancer cells].

Objective: To investigate the regulatory mechanisms of piwi-interacting RNA (piRNA) in bisphenol A (BPA)-induced prostate cancer cell invasion and migration. Methods: The Cancer Genome Atlas (TCGA) data was used to analyze and screen for piRNAs with significantly increased expression in prostate cancer tissues. PC-3 cells were treated with different concentrations of BPA for 12, 24, and 48 h, respectively, and the 20% inhibitory concentration (IC20) was measured using a CCK-8 assay. The expression levels of piRNAs before and after BPA treatment were determined by reverse transcription-quantitative PCR. Target genes regulated by BPA and associated with prostate cancer were screened in the Comparative Toxicogenomics Database (CTD). Dual-luciferase reporter gene assay was performed to verify the relationship between piRNA and target genes, and the expression change of the piRNA target gene was detected by Western blotting. Cell migration and invasion assays were used to determine the effects of piRNA on the malignant phenotype of prostate cancer cells. Results: After treatment of PC-3 cells with 160 µmol/L BPA, the expression of piR-sno48 was most significantly increased (P<0.05). Transfection of piR-sno48 antagomir resulted in decreased expression of endogenous piR-sno48 and a significant increase in the expression of its target gene GSTP1 (P<0.05). However, the expression of GSTP1 did not change significantly in BPA-treated PC-3 cells after transfection with piR-sno48 antagomir (P>0.05). The dual-luciferase reporter gene confirmed that piR-sno48 inhibited the expression of GSTP1 by forming an inversely complementary sequence with the 3'-UTR of GSTP1. The Transwell assay results showed that treatment with BPA significantly increased the invasion and migration ability of prostate cancer cells (P<0.01), whereas piR-sno48 antagonists significantly inhibited the effects above (P<0.01). Conclusion: BPA promotes the invasion and migration of prostate cancer cells by upregulating the expression of piR-sno48 and suppressing the expression of GSTP1. Interfering with the expression of endogenous piR-sno48 may inhibit the malignant phenotype of prostate cancer cells caused by BPA.

The J-shape Association between Total Bilirubin and Stroke in Older Patients with Obstructive Sleep Apnea Syndrome: A Multicenter Study.

OBJECTIVES: To explore the relationship between total bilirubin (TBil) and stroke risk in older patients with obstructive sleep apnea syndrome (OSAS). METHODS: A total of 1,007 patients with OSAS without stroke history aged ≥ 60 years and with complete serum TBil records were enrolled in this study. The median follow-up was 42 months. Participants were divided into four groups based on the quartile of the baseline serum TBil concentration. Multivariate Cox proportional hazards analysis and restricted cubic spline (RCS) were used to investigate the association of TBil with the incidence of new-onset stroke. RESULTS: The PRIMARY part: the third quantile TBil level group had the lowest prevalence of stroke among the four groups. The RCS functions depicted a J-type curve relationship between TBil (3.3-33.3 µmol/L) and stroke (nonlinear P < 0.05). When the TBil level was in the range of 3.3 to 11.5 µmol/L, the possible protective influence of bilirubin against stroke in patients with OSAS enhanced with an increasing TBil level. However, when the TBil level exceeded 11.5 µmol/L and gradually increased, the effect of TBil on stroke risk became more and more pronounced. The SECONDARY part: for every 1 µmol/L increase in TBil levels in the range of 11.5 to 33.3 µmol/L, the risk of stroke in patients with OSAS increased by 16.2% (P < 0.001). In addition, there was a higher risk in women with OSAS (hazard ratio (HR)=1.292, 95% confidence interval (95%CI): 1.093-1.528; P = 0.003). Moreover, an increased TBil level alone was significantly associated with stroke in subjects aged < 75 years (HR: 1.190, 95%CI: 1.069-1.324), patients with mild-to-moderate OSAS (HR: 1.215, 95%CI: 1.083-1.364), and individuals without atrial fibrillation (AF) (HR: 1.179, 95%CI: 1.083-1.285) within a TBil level in the range of 11.5 to 33.3 µmol/L. CONCLUSIONS: Both lower and higher bilirubin levels may increase the risk of stroke in older persons with OSAS, and there was a J-type dose-response relationship. The risk of stroke was lowest when the TBil level was approximately 11.5 µmol/L.

Saikosaponin A mitigates the progression of Parkinson's disease via attenuating microglial neuroinflammation through TLR4/MyD88/NF-κB pathway.

OBJECTIVE: Neuroinflammation caused by excessive microglial cell activation and the subsequent death of dopaminergic neurons plays a role in the pathogenesis of Parkinson's disease (PD). Saikosaponin A (Ssa), a triterpene saponin derived from Radix Bupleuri, has anti-inflammatory and antioxidant functions. This research aimed to investigate whether Ssa has a therapeutic effect on PD. MATERIALS AND METHODS: BV2 microglia- and SH-SY5Y cells were treated with a neurotoxin N-methyl-4- phenylpyridinium (MPP+) and Ssa. Cell viability, apoptosis, inflammatory reactions, and expression levels of oxidative stress mediators were assessed. A PD rat model was created by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), followed by the Ssa treatment. Hematoxylin-eosin (H&E) staining, Nissl staining, and immunohistochemistry were used to detect neuronal apoptosis and microglial activation. Open-field test (OFT) was performed to evaluate the locomotion of the rats. The underlying mechanism of Ssa effect in PD was explored using network pharmacology analysis and verified experimentally. RESULTS: Ssa dampened neuronal apoptosis and had anti-inflammatory and anti-oxidative stress proprieties in MPP+-treated SH-SY5Y cells and BV2 microglia. As shown in in-vivo experiments, Ssa reduced MPTP-mediated neuronal apoptosis and motor dysfunction and lowered the expression of inflammatory factors and oxidative stressors in the substantia nigra (SN) of the PD rat. Additionally, Ssa inactivated the TLR4/MyD88/NF-κB pathway. CONCLUSIONS: This study provides the first evidence that Ssa prevents dopaminergic neurodegeneration caused by microglia activation by modulating the TLR4/MyD88/NF-κB axis.

[Prickle planar cell polarity protein 1 involved in the pathogenesis of skeletal class â ¢ malocclusion].

Objective: To explore the mechanisms of prickle planar cell polarity protein 1 (PRICKLE1) involved in the occurrence of skeletal Class Ⅲ malocclusion. Methods: After extracting the genomic DNA of all family members of the skeletal Class Ⅲ malocclusion pedigree with maxillary hypoplasia collected in the Department of Orthodontics at the Affiliated Stomatological Hospital of Nanjing Medical University in October 2021, whole exome sequencing and Sanger sequencing were performed to screen pathogenic genes/mutation sites and validate the mutations. Jaw tissue was collected during the operation of orthognathic patients who were treated in the Department of Oral and Maxillofacial Surgery at the same hospital from October 2021 to December 2022. Following the extraction of human jaw bone marrow mesenchymal stem cells and transfection with overexpressing lentivirus (lentiviruses overexpressing the gene of interest served as the wild group, lentiviruses overexpressing mutation site served as the mutant group) and knockdown lentivirus (divided into knockdown group 1 and 2, with transfection interference negative lentiviruses as the control group). Various assays including real-time fluorescence quantitative PCR (RT-qPCR), Western blotting, proliferation and Transwell assays, alkaline phosphatase staining and alizarin red staining were performed. Construction of zebrafish animal model, morpholino oligonucleotide (MO) were injected to knock down the expression of prickle1a and prickle1b in zebrafish (co-knocking group), and the control group was injected with standardized MO as a reference. Transcriptome sequencing, enrichment analysis and co-expression analysis were performed on the zebrafish craniofacial tissues of the two groups. Results: Two patients of this family carried this mutation PRICKLE1 c.113C>T. The transfection experiments showed that compared with the wild group (relative expression of PRICKLE1 was 21.97±0.60), the relative expression of mutant group (5.05±0.05) was significantly reduced (P<0.05), and cell proliferation and migration ability significantly enhanced (P<0.05), and osteogenic differentiation ability was significantly reduced (P<0.05). Compared with the control group, the proliferation and migration ability of cells in the two knockdown groups were significantly enhanced (P<0.05), and the osteogenic differentiation ability was significantly reduced (P<0.05). Zebrafish model experiments showed the width of the ethmoid plate was significantly reduced in the co-knocking group (282.50±61.77, t=5.29, P<0.001) compared with the control group (338.80±24.92). Transcriptome data and enrichment analysis showed that the differentially expressed genes were significantly enriched in the mitogen-activated protein kinase (MAPK) signaling pathway after the simultaneous knockdown of prickle1a and prickle1b in zebrafish. Conclusions: PRICKLE1 c.113C>T mutation might suppress the osteoblastic differentiation ability of jaw bone marrow mesenchymal stem cells by downregulating the MAPK signaling pathway, thereby involving the development of skeletal Class Ⅲ malocclusion.

Source apportionment and ozone formation mechanism of VOCs considering photochemical loss in Guangzhou, China.

Understanding the sources and impact of volatile organic compounds (VOCs) on ozone formation is challenging when the traditional method does not account for their photochemical loss. In this study, online monitoring of 56 VOCs was carried out in summer and autumn during high ozone pollution episodes. The photochemical age method was used to evaluate the atmospheric chemical loss of VOCs and to analyze the effects on characteristics, sources, and ozone formation of VOC components. The initial concentrations during daytime were 5.12 ppbv and 4.49 ppbv higher than the observed concentrations in the summer and autumn, respectively. The positive matrix factorization (PMF) model identified 5 major emission sources. However, the omission of the chemical loss of VOCs led to underestimating the contributions of sources associated with highly reactive VOC components, such as those produced by biogenic emissions and solvent usage. Conversely it resulted in overestimating the contributions from VOC components with lower chemical activity such as liquefied petroleum gas (LPG) usage, vehicle emissions, and gasoline evaporation. Furthermore, the estimation of ozone formation may be underestimated when the atmospheric photochemical loss is not taken into account. The ozone formation potential (OFP) method and propylene-equivalent concentration method both underestimated ozone formation by 53.24 ppbv and 47.25 ppbc, respectively, in the summer, and by 40.34 ppbv and 26.37 ppbc, respectively, in the autumn. The determination of the ozone formation regime based on VOC chemical loss was more acceptable. In the summer, the ozone formation regime changed from the VOC-limited regime to the VOC-NOx transition regime, while in the autumn, the ozone formation regime changed from the strong VOC-limited regime to the weak VOC-limited regime. To obtain more thorough and precise conclusions, further monitoring and analysis studies will be conducted in the near future on a wider variety of VOC species such as oxygenated VOCs (OVOCs).

[Efficacy of decitabine combined with low dose chemotherapy on children with acute myeloid leukemia].

Objective: To evaluate the efficacy of decitabine combined with low dose chemotherapy (LDC) in the treatment of high-risk, refractory and relapsed pediatric acute myeloid leukemia (AML). Methods: Clinical data of 19 AML children treated with decitabine combined with LDC in the Department of Hematology, Children's Hospital of Soochow University from April 2017 to November 2019 were analyzed retrospectively. The therapeutic response, adverse effects and survival status were analyzed,and the outcomes of patients were followed up. Results: Among 19 AML cases, there were 10 males and 9 females. Five cases were high-risk AML, 7 cases were refractory AML, and 7 cases were relapsed AML. After one course of decitabine+LDC treatment, 15 cases achieved complete remission, 3 cases got partial remission, and only 1 case didn't get remission. All patients received allogeneic hematopoietic stem cell transplantation as consolidation therapy. The follow-up time of all cases was 46 (37, 58) months, 14 children had survived. The cumulative three-year overall survival rate was (79±9) %, events free survival rates was (68±11) %, and recurrence free survival rate was (81±10) %. The most common adverse effects related to the induction treatment were cytopenia (19 cases) and infection (16 cases).There were no treatment-related death during the therapy. Conclusion: Decitabine combined with LDC is a safe and effective option for high-risk, refractory and relapsed AML children, which provides an opportunity for HSCT.