Epidemiological analysis reveals a surge in inflammatory bowel disease among children and adolescents: A global, regional, and national perspective from 1990 to 2019 - insights from the China study.

Background: The burden of inflammatory bowel disease (IBD) among children and adolescents is rising globally, with substantial variation in levels and trends of disease in different countries and regions, while data on the burden and trends were sparse in children and adolescents. We aimed to assess the trends and geographical differences in children and adolescents aged zero to 19 in 204 countries and territories over the past 30 years. Methods: Data on IBD among children and adolescents was collected from the Global Burden of Disease (GBD) 2019 database from 1990 to 2019. We used the GBD data and methodologies to describe the change in the burden of IBD among children and adolescents involving prevalence, incidence, disability-adjusted life years (DALYs), and mortality. Results: Globally, the IBD prevalence cases increased between 1990 and 2019. Annual percentage changes (AAPC) = 0.15; 95% confidence interval (CI) = 0.11-0.19, and incidence cases of IBD increased from 20 897.4 (95% CI = 17 008.6-25 520.2 in 1990 to 25 658.6 (95% CI = 21 268.5-31 075.6) in 2019, representing a 22.78% increase, DALYs cases decreased between 1990 and 2019 (AAPC = -3.02; 95% CI = -3.15 to -2.89), and mortality cases of IBD decreased from 2756.5 (95% CI = 1162.6-4484.9) in 1990 to 1208.0 (95% CI = 802.4-1651.4) in 2019, representing a 56.17% decrease. Decomposition analysis showed that IBD prevalence and incidence increased significantly, and a trend exhibited a decrease in underlying age and population-adjusted IBD DALYs and mortality rates. Correlation analysis showed that countries with high health care quality and access (HAQ) had relatively higher IBD age-standardised prevalence rate (ASPR) and age-standardised incidence rate (ASIR), but lower age-standardised DALYs rate (ASDR) and age-standardised mortality rate (ASMR). Conclusions: Global prevalence and incidence rate of IBD among children and adolescents have been increasing from 1990 to 2019, while the DALYs and mortality have been decreasing. Rising prevalence and rising incidence in areas with historically low rates will have crucial health and economic implications.

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OBJECTIVES: To explore the action characteristics of acupuncture manipulations by combining visual and sensor technique, so as to improve the identification and classification accuracy of acupuncture manipulations and to quantificate the classifiations. METHODS: In this paper, the time domain features of acupuncture physical parameters and dynamic gesture features in the video of acupuncture manipulations are combined together to identify and classify acupuncture techniques. The acupuncture needle manipulation processes of 2 acupuncture experts and 3 young acupuncturists were selected as the study objects. The collected data included 4 basic manipulation techniques：lifting-thrusting reinforcing, lifting- thrusting reducing, twisting reinforcing and twisting reducing methods, all of which were performed by right-handed doctors. During acupuncture manipulation, a three-axis attitude sensor was used to acquire finger moving acceleration velocity and needle-rotating angle velocity, followed by analyzing the parameters of hand-moving velocity, amplitude, strength and angle. The mapping relationship among physical parameters and different manipulating methods was formed in time domain. The computer vision technology was employed to extract the spatio-temporal features of the acupuncture manipulation video images, and a hybrid model of three-dimensional convolutional neural network (3D CNN) and long- and short-term memory (LSTM) neural network were used for the recognition and classification of dynamic gestures of hand in acupuncture manipulation videos. Then the time-domain features of physical parameters were combined with the dynamic gestures in the classification process, with the manipulation classification realized. RESULTS: In performing the lift-thrusting reinforcing method, the needle insertion speed was faster and the force was larger, while the needle lifting speed was slower and the force was smaller. And in performing the lift-thrusting reducing method, the needle lifting speed was faster, the force was stronger, and the needle insertion speed was slower and the force was smaller. In the performance of twisting reinforcing, the leftward twisting force was bigger and the rotation amplitude was larger, while in performing the reducing method, the rightward twisting force was larger and the rotation amplitude was larger. When using the mean value of time of acceleration, speed, and amplitude as the basis of discrimination, the accuracy rates of lifting-thrusting reinforcing and reducing were 95.56% and 93.33%, while those of the two twisting manipulations were 95.56% and 91.11%, respectively. Compared with the classification method that only uses the sensor to obtain the manipulation information, the recognition accuracy was significantly improved. CONCLUSIONS: The acupuncture manipulation classification system can achieve quantitative analysis of physical parameters and dynamic recognition of acupuncture techniques, providing a certain foundation for the quantification and inheritance of acupuncture techniques.

Peptic ulcer disease burden, trends, and inequalities in 204 countries and territories, 1990-2019: a population-based study.

Background: Peptic ulcer disease has been a major threat to the world's population, which remains a significant cause of hospitalization worldwide and healthcare resource utilization. Objectives: We aimed to describe the global burden, trends, and inequalities of peptic ulcer disease. Design: An observational study was conducted. Methods: In this secondary analysis of the Global Burden of Disease, Injuries, and Risk Factors Study 2019, we extracted data for age-standardized incidence rates (ASIRs), disability-adjusted life year rates (ASDRs), and mortality rates (ASMRs); then, we stratified by age, level of regionals, and country; subsequently, we calculated estimated annual percentage changes (EAPC) of ASIR, ASDR, ASMR, and quantified cross-country inequalities in peptic ulcer disease mortality. Results: Globally, ASIR showed a continuous downward trend, from 63.84 in 1990 to 44.26 per 100,000 population in 2019, with an annual decrease of 1.42% [EAPC = -1.42 (95% CI: -1.55 to -1.29)]. ASDR showed a continuing downward trend, and the EAPC was -3.47% (-3.58 to -3.37). ASMR showed a persistent decline, declining by nearly half in 2019 compared to 1990 (3.0 versus 7.39 per 100,000 population), with an annual decrease of 2.55% [EAPC = -3.36 (95% CI: -3.47 to -3.25)]. A significant reduction in sociodemographic index (SDI)-related inequality, from an excess of 190.43 disability-adjusted life years (DALY) per 100,000 (95% CI: -190.83 to -190.02) between the poorest and richest countries in 1990 to 62.85 DALY per 100,000 (95% CI -62.81 to -62.35) in 2019. Conclusion: Global peptic ulcer disease morbidity and mortality rates decreased significantly from 1990 to 2019. These health gains were in accordance with a substantial reduction in the magnitude of SDI-related inequalities across countries, which is paired with overall socioeconomic and health improvements observed in the region.

AI-Assisted Ultrasound for the Early Diagnosis of Antibody-Negative Autoimmune Thyroiditis.

The prevalence of antibody-negative chronic autoimmune thyroiditis (SN-CAT) is increasing. The early diagnosis of SN-CAT can effectively prevent its further development. Thyroid ultrasound can diagnose autoimmune thyroiditis and predict hypothyroidism. Primary hypothyroidism with a hypoechoic pattern suggested by thyroid ultrasound and negative thyroid serum antibodies is the main basis for the diagnosis of SN-CAT. However, for early SN-CAT, only hypoechoic thyroid changes and serological antibodies are currently available. This study explored how to achieve an accurate and early diagnosis of SN-CAT and prevent the development of SN-CAT combined with hypothyroidism. The diagnosis of a hypoechoic thyroid by artificial intelligence is expected to be a breakthrough in the accurate diagnosis of SN-CAT.

Reprogramming the Metabolic Network in Kluyveromyces lactis with a Transcriptional Switch for De Novo Lacto-N-biose Synthesis.

Lacto-N-biose (LNB) is a member of the human milk oligosaccharide (HMO) family and is synthesized via an enzymatic reaction in vitro with N-acetylglucosamine (GlcNAc) and cofactors. In this study, LNB was synthesized using a cell factory for the first time. First, three modules were constructed in Kluyveromyces lactis for producing LNB from lactose and GlcNAc without the addition of cofactors. Second, a de novo pathway was constructed in K. lactis for producing LNB from lactose without adding GlcNAc. Finally, a transcriptional switch was introduced into K. lactis to reprogram its metabolic network for improving the flux from GlcNAc-6-P to GlcNAc in the de novo pathway. Subsequently, a final LNB yield of 10.41 g/L, similar to the salvage pathway yield, was achieved through the de novo pathway. The engineered K. lactis provides a promising technology platform for the industrial scale production of LNB.

A novel surgical technique for cervical laminoplasty in patients with multilevel cervical spondylotic myelopathy: A case report and literature review.

Cervical laminoplasty is a posterior-based surgical decompression technique for the treatment of multilevel cervical spondylotic myelopathy (CSM) that may improve the preservation of cervical mobility, spinal canal structure, and natural lordosis. Although this procedure is considered to be comparatively safe, with fewer complications than those seen with laminectomy, several postoperative problems have been noted, including axial neck pain, C5 nerve palsy, and failed resolution of radiculopathy. Hence, various modifications have been made to improve the safety and effectiveness of this technique. Here, we report the case of a 74-year-old man with multilevel CSM who underwent posterior cervical laminoplasty in the C3-C7 segments using a novel surgical technique, termed alternating-side cervical laminoplasty. Preoperative and postoperative assessments, including visual analog scale, modified Japanese Orthopaedic Association, neck disability index scores, and imaging data, were collected and analyzed. The results of a 5-year follow-up indicated that the patient recovered well, with no development of axial neck pain. This is the first report of this modified open-door laminoplasty, which we propose may be a better surgical option for preventing postoperative axial neck pain in patients with multilevel CSM. Additionally, opening the laminae on the alternating sides during laminoplasty could provide a flexible approach to complete decompression on different radiculopathy sides.

Acupuncture for Crohn's disease: a protocol for systematic review and meta-analysis.

INTRODUCTION: Crohn's disease (CD) is a chronic inflammatory bowel disease that seriously affects the quality of life. While conventional medicines are of limitations, acupuncture has been shown to be a promising therapy. While no systematic review related has been published, the present study aimed to evaluate the efficacy and safety of acupuncture for CD. METHODS AND ANALYSIS: PubMed, the Cochrane Central Register of Controlled Trials and Chinese electronic databases, including China National Knowledge Infrastructure, Wan Fang database, VIP, SinoMed and the Chinese Clinical Trial Registry, will be searched from the establishment of the database until 31 December 2022. Randomised controlled trials evaluating the efficacy and safety of acupuncture/electroacupuncture on patients with CD, controlled by conventional therapies, were included. Outcomes include induction of clinical remission and response, maintenance of remission, and the incidence of adverse events. All articles will be screened and extracted by two reviewers independently. The risk of bias will be evaluated using the revised Cochrane Risk of Bias 2 tool. A fixed effect model or a random effects model will be used based on the assessment of heterogeneity. A subgroup analysis and sensitivity analysis will be carried out if necessary. Publication bias will be analysed, and the strength of the body of evidence for primary outcomes will be graded. ETHICS AND DISSEMINATION: There is no necessity for this study to acquire ethical approval, and this review will be disseminated in a peer-reviewed journal or conference presentation. TRIAL REGISTRATION NUMBER: CRD42022356967.

Effects of material nano-topography on the angiogenesis of type H vessels: Size dependence, cell heterogeneity and intercellular communication.

Type H vessel, a vascular subtype in bone, is a critical regulator of osteogenesis, but how material properties affect this organ-specific vessel remains unknown. Here, titania nanotubes were fabricated on bone implant surface to investigate the effects of nano-topography on type H vessels. In vivo, surface nanotubes with 20-100 nm diameters promoted the angiogenesis of type H vessels and bone regeneration in mouse femurs to different extents, with the best effects induced by 70 nm diameter. In vitro, bone-specific endothelial cells (BECs) and artery endothelial cells (AECs) presented significantly different behaviors on the same material. Nanotubes with 20 nm small diameters significantly improved the adhesion, proliferation, type H differentiation of BECs and their paracrine function to regulate pre-osteoblasts (POBs), possibly via binding integrin ß1 on the cell membrane, but these effects weakened when tube diameter increased, which conflicted with the results in vivo. Further study suggested that the better in vivo effects by larger diameters of 70-100 nm might be exerted indirectly through remodeling the regulation from POBs to BECs, highlighting the underappreciated indirect bio-effects of materials via intercellular communication. These suggest that nanoscale material topography makes significant impact on the angiogenesis of type H vessels, directly via binding integrins on the cell membrane of BECs and indirectly via modulating the regulation from osteoblastic cells to BECs, both in a size-dependent manner. Cells of the same type but from different tissues may show different responses to the same material, thus material properties should be tailored to the specific cell population. In research on material-tissue interactions, conclusions from in vitro experiments exposing a single type of cell to material might deviate from the truth in vivo, because materials may indirectly influence the targeted cells through modulating intercellular communication. These provide new insights into material-tissue interactions.

Meta-Analysis of Simultaneous versus Staged Decompression of Stenotic Regions in Patients with Tandem Spinal Stenosis.

BACKGROUND: Tandem spinal stenosis (TSS) refers to simultaneous spinal canal stenosis of noncontiguous regions. There is no consensus in the surgical strategies for patients with symptomatic TSS because of the confusing clinical manifestations. This meta-analysis aimed to compare the outcomes of 1-stage and 2-stage decompression of all stenotic regions (cervical and lumbar/thoracic segments) in patients with TSS. METHODS: A systematic review was conducted, and a comprehensive literature search with the Japanese Orthopedic Association score, was carried out using MEDLINE, Web of Science, and PubMed databases from inception to September 13, 2022. Observational studies reporting the outcomes after 1-stage or 2-stage decompression of all symptomatic regions were included. Possible heterogeneity among studies was assessed by the Higgins I2 test, and heterogeneity was statistically investigated using the Q statistic. RESULTS: Thirteen retrospective observational studies were included in this meta-analysis. Meta-analysis showed that there was no significant difference in the Japanese Orthopedic Association score improvement in patients with TSS involving either the cervical-thoracic or cervical-lumbar segments. Regarding the surgical parameters and complications, 1-stage decompression showed comparable operation time, blood loss, and major complications to 2-stage decompression in patients with cervical and lumbar TSS. In patients with cervical and thoracic TSS, 1-stage decompression had significant advantages compared with 2-stage decompression in operation time, blood loss, and major complications. CONCLUSIONS: For patients with cervical and lumbar TSS, 2-stage decompression showed slight advantages in clinical outcome without exposing patients to unnecessary surgical risks. For patients with cervical and thoracic TSS, 1-stage decompression showed comparable clinical outcome, although with better operative parameters and lower complication rate than in simultaneous decompression.

Long noncoding RNAs in head and neck squamous cell carcinoma: biological functions and mechanisms.

Head and neck squamous cell carcinoma (HNSCC) is the primary malignant tumor of the oral cavity, larynx, nasopharynx, esophagus and tongue. Although several novel therapeutic methods for HNSCC have been developed, the final therapeutic effect on the patient is still not satisfactory. Thus, it is imperative that scientists identify novel distinguishable markers with specific molecular characteristics that can be used in therapeutic and prognostic evaluation. Previous reports have shown that long noncoding RNAs (lncRNAs) are important regulators of gene expression in many cancers, including head and neck squamous cell carcinomas. Translational studies of lncRNAs in HNSCC are urgently required before their application as a treatment can be realized. We aimed to address the most relevant findings on lncRNAs as biomarkers or treatment targets in head and neck squamous cell carcinoma and to summarize their discovered pathways and mechanisms of action to reveal the possible future applications of these novel biomarkers in clinical translational research.

Long noncoding RNA LINC01194 enhances the malignancy of laryngeal squamous cell carcinoma by sponging miR-655 to increase SOX18 expression.

Long noncoding RNAs (lncRNAs) have undergone a comprehensive study for their involvements in tumor treatments. The purpose of our study was to explore the biological effects and regulatory mechanisms of lncRNA LINC01194 (LINC01194) in laryngeal squamous cell carcinoma (LSCC). The levels of LINC01194 in 105 LSCC patients were detected by RT-qPCR. The diagnostic and prognostic value of LINC01194 in LSCC patients were statistically analyzed. The potential functions of LINC01194 in proliferation, apoptosis, and metastasis of LSCC cells were evaluated. The interaction among LINC01194, miR-655 and SOX18 was explored by bioinformatics analysis, luciferase reporter assays and biotinylated RNA pull-down. We found that the expression levels of LINC01194 were highly expressed in LSCC, which was negatively correlated with the clinical outcome of LSCC patients. The area under the ROC curve for LINC01194 was up to 0.8388. Functional assays indicated that LINC01194 knockdown distinctly inhibited LSCC cells proliferation, induced apoptosis, and also attenuated LSCC cells migration and invasion in vitro. Furthermore, we elucidated that LINC01194 promoted SOX18 expression in LSCC cells via functioning as a molecular sponge for miR-655. Overall, based on our findings, LINC01194 served as a tumor promoter and potentially represents a novel prognostic indicator and therapeutic target in LSCC.

Flos lonicerae flavonoids attenuate experimental ulcerative colitis in rats via suppression of NF-κB signaling pathway.

This study sought to isolate active Flos lonicerae flavonoids and evaluate their anti-oxidative and anti-inflammatory effects as well as investigate the molecular mechanistic action of these flavonoids in the rat model of ulcerative colitis (UC). Total flavonoids and three flavonoids (hyperoside, lonicerin, and luteolin) were isolated from honeysuckle and purified via column purification. Rat model of UC was established via 2,4,6-trinitrobenzene sulfonic acid (TNBS) intoxication. The anti-oxidative and anti-inflammatory effects of the three flavonoids against TNBS-induced UC were evaluated by measuring appropriate biomarkers via assay kit. The effects of hyperoside, lonicerin, and luteolin on the regulation of nuclear factor-kappa B (NF-κB) pathway were investigated using Western blot (WB) and real-time polymerase chain reaction (RT-PCR) while their protective effects on UC were also elucidated. Pretreatment with flavonoids (hyperoside, lonicerin, and luteolin at 25-100 mg/kg) and sulfasalazine (SSZ, positive control at 100 mg/kg) substantially attenuated TBNS-induced UC. Also, the flavonoids significantly reduced the levels of respective serum oxidative and proinflammatory markers such as superoxide dismutase (SOD), myeloperoxidase (MPO), malondialdehyde (MDA), prostaglandins E2 (PGE2), tumor necrosis factor-alpha (TNF-α), interleukin-beta (IL-ß), and C-reactive protein (CRP). In addition, the flavonoids remarkably inhibited the expression of NF-κB signaling pathway. F. lonicerae flavonoids (hyperoside, lonicerin, and luteolin) demonstrated potent anti-UC activities in TBNS-induced UC rat model via anti-oxidative and anti-inflammatory effects through the inhibition of NF-κB signaling pathway.

Acupuncture for refractory gastro-oesophageal reflux disease: a systematic review and meta-analysis protocol.

INTRODUCTION: Refractory gastro-oesophageal reflux disease (rGORD) is a common disease, affecting patients' quality of life. Since conventional medicines have limitations, like low effective rates and adverse events, acupuncture may be a promising therapy for rGORD. While no related systematic review has been published, the present study is designed to evaluate the efficacy and safety of acupuncture for rGORD. METHODS AND ANALYSIS: PubMed, the Cochrane Central Register of Controlled Trials and Chinese electronic databases, including China National Knowledge Infrastructure, Wan Fang database, VIP, SinoMed and the Chinese Clinical Trial Registry, will be searched from establishment of the database to 31 August 2019. There will be no limitations on language, and all articles will be screened and collected by two reviewers independently. RevMan V.5.3.5 software will be used for meta-analysis, and the conduction of study will refer to the Cochrane Handbook for Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol guidelines. The efficacy and safety of acupuncture for rGORD will be evaluated based on outcomes, including global symptom improvement, oesophageal sphincter function test measured by high-resolution manometry, quality of life, recurrence rate and adverse events. ETHICS AND DISSEMINATION: There is no necessity for this study to acquire an ethical approval, and this review will be disseminated in a peer-reviewed journal or conference presentation. TRIAL REGISTRATION NUMBER: CRD42018111912.

Stepwise detection and evaluation reveal miR-10b and miR-222 as a remarkable prognostic pair for glioblastoma.

Despite the existence of many clinical and molecular factors reported that contribute to survival in glioblastoma, prevailing studies fell into partial or local feature selection for survival analysis. We proposed a feature selection strategy including not only joint covariate detection but also its evaluations, and performed it on miRNA expression profiles with glioblastoma. MiR-10b and miR-222 were selected as the most significant two-dimensional feature. Crucially, we integrated in vitro experiments on GBM cells and in vivo studies on a mouse model of human glioma to elucidate the synergistic effects between miR-10b and miR-222. Inhibition of miR-10b and miR-222 strongly suppress GBM cells growth, invasion, and induce apoptosis by co-targeting PTEN and leading to activation of p53 ultimately. We also demonstrated that miR-10b and miR-222 co-target BIM to induce apoptosis independent of p53 status. The results define mir-10b and mir-222 important roles in gliomagenesis and provided a reliable survival analysis strategy.

Establishment of knockout adult sea urchins by using a CRISPR-Cas9 system.

Sea urchins are used as a model organism for research on developmental biology and gene regulatory networks during early development. Gene knockdown by microinjection of morpholino antisense oligonucleotide (MASO) has been used to analyze gene function in early sea urchin embryos. However, as the effect of MASO is not long lasting, it is impossible to perturb genes expressed during late development by MASO. Recent advances in genome editing technologies have enabled gene modification in various organisms. We previously reported genome editing in the sea urchin Hemicentrotus pulcherrimus using zinc-finger nuclease (ZFN) and transcription activator-like effector nuclease (TALEN); however, the efficiencies of these technologies were not satisfactory. Here, we applied clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated nuclease 9 (Cas9) technology to knock out the Pks1 gene in H. pulcherrimus. When sgRNAs targeting Pks1, which is required for the biosynthesis of larval pigment, were microinjected into fertilized eggs with SpCas9 mRNA, high-efficiency mutagenesis was achieved within 24 hr post fertilization and SpCas9/sgRNA-injected pluteus larvae had an albino phenotype. One of the sgRNAs yielded 100% mutagenesis efficiency, and no off-target effect was detected. In addition, the albino phenotype was maintained in juvenile sea urchins after metamorphosis, and the knockout sea urchins survived for at least one year and grew to albino adult sea urchins. These findings suggest that knockout adult sea urchins were successfully established and the CRISPR-Cas9 system is a feasible method for analyzing gene functions from late developmental to adult stage.

Long noncoding RNA LINC-PINT regulates laryngeal carcinoma cell stemness and chemoresistance through miR-425-5p/PTCH1/SHH axis.

Functional, noncoding RNA of about 200 nucleotides in length are known as long noncoding RNA (lncRNA). Advances in -omics have revolutionized the information with respect to the coding and noncoding regions of the genome. Several studies have illustrated the role of lncRNA in cell growth and cancer. Profiling and bioinformatic studies of laryngeal cancer has identified LINC-PINT as one of the lncRNA. However, the functional aspects of the deregulation have not been studied in laryngeal tumors. In this study, LINC-PINT expression in normal and tumor tissues were studied. Using a bioinformatic approach, microRNA (miRNA) targets of LINC-PINT and gene targets of the miRNA were determined. The impact of LINC-PINT on cell proliferation and chemoresistance was determined. Further through a set of silencing and re-expression studies phenotype rescue was studied. LINC-PINT expression was downregulated in laryngeal tumors. LINC-PINT targeted miR-425-5p by three sites. miR-425-5p also targeted PTCH1 a protein of the Hedgehog pathway. Downregulation of LINC-PINT was associated with increased cancer stemness and chemoresistance to cisplatin. Our results indicate a probable role of LINC-PINT in the pathology of laryngeal tumors. LINC-PINT re-expression in laryngeal tumors may be explored for reversion of cancer cell stemness and also for rescue of drug resistance phenotype.

LncRNA NORAD promotes thyroid carcinoma progression through targeting miR-202-5p.

Long noncoding RNAs (lncRNAs) have been shown to have several functional roles in tumor biology, and they are deregulated in many types of cancer. The role of a novel lncRNA, NORAD, in papillary thyroid carcinoma (PTC) is still unknown. In this study, we demonstrated that NORAD expression was upregulated in PTC cell lines and samples. Ectopic expression of NORAD promoted PTC cell growth, invasion and migration. Overexpression of NORAD promotes epithelial-to-mesenchymal transition (EMT) progression in the PTC cell. Furthermore, overexpression of NORAD suppressed miR-202-5p expression in PTC cells. The data suggested that miR-202-5p expression was downregulated in PTC cell lines and samples and was negatively correlated with NORAD expression in PTC tissues. Overexpression of miR-202-5p suppressed PTC cell growth, invasion and migration. In addition, we demonstrated that elevated expression of NORAD promoted PTC cell growth, invasion and migration by inhibiting miR-202-5p expression. These results suggested that the lncRNA NORAD acts as an oncogene in PTC progression, partly by regulating miR-202-5p expression.

Markov Clustering Analysis-Based Validation for Traditional Chinese Medicine Syndrome Patterns of Poststroke Cognitive Impairment.

Objectives: Poststroke cognitive impairment (PSCI) has constituted a heavy public health burden worldwide. Traditional Chinese Medicine (TCM) has been widely used in treating PSCI. This study aimed at validating the TCM syndrome patterns of PSCI by using data mining methods. The findings will shed light on the TCM pathogenesis theory of PSCI, and thus provide translation for optimization of syndrome-targeted treatment strategies of PSCI. Design: This is a registry study-based participant survey conducted in 14 medical centers in eastern China. Mutual information and Markov clustering analysis (MCL) were carried out to achieve syndrome patterns validation of PSCI. Results: Based on MCL, six syndrome patterns were extracted: heart and spleen qi deficiency, liver and kidney yin deficiency, phlegm-turbidity internal obstruction and spleen deficiency, blood stagnation, kidney yang deficiency, and hyperactivity of heart-liver fire (heat). Conclusions: Combination of qi deficiency, yin deficiency, phlegm turbidity, blood stasis, yang deficiency, and fire (heat) may play a key role in PSCI pathogenesis. Treatment strategies by TCM herbal prescriptions should thus be targeted to regulating qi, nourishing yin, resolving turbidity, activating blood, warming yang, clearing fire (heat), regulating kidney, regulating spleen, regulating liver, and regulating heart. Further studies are needed to verify the current findings.

Hierarchical and Complex System Entropy Clustering Analysis Based Validation for Traditional Chinese Medicine Syndrome Patterns of Chronic Atrophic Gastritis.

Objectives: Chronic atrophic gastritis (CAG) is the precancerous stage of gastric carcinoma. Traditional Chinese Medicine (TCM) has been widely used in treating CAG. This study aimed to reveal core pathogenesis of CAG by validating the TCM syndrome patterns and provide evidence for optimization of treatment strategies. Design: This is a cross-sectional study conducted in 4 hospitals in China. Hierarchical clustering analysis (HCA) and complex system entropy clustering analysis (CSECA) were performed, respectively, to achieve syndrome pattern validation. Results: Based on HCA, 15 common factors were assigned to 6 syndrome patterns: liver depression and spleen deficiency and blood stasis in the stomach collateral, internal harassment of phlegm-heat and blood stasis in the stomach collateral, phlegm-turbidity internal obstruction, spleen yang deficiency, internal harassment of phlegm-heat and spleen deficiency, and spleen qi deficiency. By CSECA, 22 common factors were assigned to 7 syndrome patterns: qi deficiency, qi stagnation, blood stasis, phlegm turbidity, heat, yang deficiency, and yin deficiency. Conclusions: Combination of qi deficiency, qi stagnation, blood stasis, phlegm turbidity, heat, yang deficiency, and yin deficiency may play a crucial role in CAG pathogenesis. In accord with this, treatment strategies by TCM herbal prescriptions should be targeted to regulating qi, activating blood, resolving turbidity, clearing heat, removing toxin, nourishing yin, and warming yang. Further explorations are needed to verify and expand the current conclusions.

Decorin-Modified Umbilical Cord Mesenchymal Stem Cells (MSCs) Attenuate Radiation-Induced Lung Injuries via Regulating Inflammation, Fibrotic Factors, and Immune Responses.

PURPOSE: To evaluate the therapeutic effects of decorin (DCN)-modified mesenchymal stem cells (MSCs) on radiation-induced lung injuries (RILIs) and to clarify the underlying mechanisms. METHODS AND MATERIALS: Umbilical cord-derived mesenchymal stem cells (MSCs) were modified with Ad(E1-).DCN to generate DCN-expressing MSCs (DCN-modified MSCs [MSCs.DCN]). In an experimental mouse model of RILI, MSCs.DCN and MSCs.Null [MSCs modified with Ad(E1-).Null] were intravenously engrafted at 6 hours or 28 days after irradiation. The therapeutic effects on lung inflammation and fibrosis were evaluated by histopathologic analysis at 28 days and 3 months after irradiation. Inflammatory cytokines and chemokines were analyzed in both sera and lung tissues, and subtypes of T lymphocytes including regulatory T cells (Tregs) were analyzed in the peripheral blood and spleen. RESULTS: Both MSC treatments could alleviate histopathologic injuries by reducing lymphocyte infiltration, decreasing apoptosis, increasing proliferation of epithelial cells, and inhibiting fibrosis in the later phase. However, treatment with MSCs.DCN resulted in much more impressive therapeutic effects. Moreover, we discovered that MSC treatment reduced the expression of chemokines and inflammatory cytokines and increased the expression of anti-inflammatory cytokines in both the peripheral blood and local pulmonary tissues. An important finding was that MSCs.DCN were much more effective in inducing interferon-γ expression, inhibiting collagen type III α1 expression in pulmonary tissues, and decreasing the proportion of Tregs. Furthermore, our data suggested that treatment during the acute phase (6 hours) after irradiation evoked much stronger responses both in attenuating inflammation and in inhibiting fibrosis than in the later phase (28 days). CONCLUSIONS: MSCs.DCN could attenuate acute inflammation after irradiation and significantly inhibit later fibrosis. Likewise, DCN enhanced the functions of MSCs by targeting profibrotic factors and Tregs.