Association between periodontitis and dental caries: a systematic review and meta-analysis.

OBJECTIVES: Recent evidence suggested a link between periodontitis (PD) and dental caries, but the trends and nature of this association remained unclear. The overall aim of this study was to critically assess the correlation of two disorders. METHODS: A comprehensive search was conducted within the PUBMED and EMBASE databases including grey literatures up to July 5th, 2023. The Newcastle-Ottawa scale was used to qualitatively evaluate the risk of bias. RESULTS: Overall, 18 studies were included. In terms of caries risk in PD patients, the prevalence of caries was increased by PD (OR = 1.57, 95%CI:1.20-2.07), both in crown (OR = 1.03, 95%CI:1.01-1.05) and root caries (OR = 2.10, 95%CI:1.03-4.29). Odds of caries were also raised by PD severity (OR moderate = 1.38, 95%CI:1.15-1.66; OR severe = 2.14, 95%CI:1.74-2.64). Besides, patients with PD exhibited a higher mean number of decayed, missing and filled teeth (DMFT) and decayed and filled root teeth (DFR) [weighted mean difference (WMD)DMFT = 0.87, 95%CI: -0.03-1.76; WMDDFR = 1.13, 95%CI: 0.48-1.78]. Likewise, patients with caries had an elevated risk of PD (OR = 1.79, 95%CI:1.36-2.35). However, Streptococcus mutans, one of the main pathogens of caries, was negatively correlated with several main pathogens of periodontitis. CONCLUSIONS: This study indicated a positive correlation between dental caries and periodontitis clinically, while the two disease-associated pathogens were antagonistic. CLINICAL RELEVANCE: Further research, including clinical cohort studies and mechanisms of pathogens interaction is needed on this link for better prevention and treatment of PD and caries. In addition, innovative prevention strategies need to be developed and incorporated in dental practices to prevent these two highly prevalent oral diseases.

Real-world evidence of combined treatment of biologics and exclusive enteral nutrition in patients with ileum-dominant Crohn's disease: A multicenter study.

BACKGROUND & AIMS: Although biologics were prescribed to achieve and maintain clinical remission of active Crohn's disease (CD), almost half of patients experienced a loss of response or intolerance. Here, we investigated the efficacy of combined treatment of biologics and 16-weeks exclusive enteral nutrition (EEN) in moderate-to-severe CD patients with small intestine lesions. METHODS: This was a real-world, multicenter retrospective study, from October 2016 to March 2023, medical records of patients registered at three IBD centers were reviewed for patients with ileal or ileocolonic CD in moderate-to-severe activity. All patients received treatment of biologics with concomitant 16-week EEN (BioEEN) or biologics alone (Bio). The clinical outcomes and endoscopic outcomes were assessed at week 16 and 52. RESULTS: There was no statistically significant difference between Bio (97 patients) and BioEEN group (100 patients) at baseline for demographic and clinical characteristics. Compared to treatment with biologics alone, patients with BioEEN treatment achieved higher rates of clinical response (95.0% vs. 66.0%), clinical remission (87.0% vs. 52.6%), endoscopic response (91.4% vs. 47.4%) including mucosal healing (85.7% vs. 23.7%) at week 16. The superiority of BioEEN sustained in maintenance, with 84.7% (vs. 49.1%) clinical response, 77.8% (vs. 38.6%) clinical remission, 69.2% (vs. 32.6%) endoscopic response and 51.9% (vs. 18.6%) mucosal healing at week 52. CONCLUSIONS: Combined treatment of biologics and 16-week EEN was an efficient therapeutic strategy with affirmative effectiveness for small intestine diseases of active CD.

miR-520f-3p blocks MNNG-induced gastric precancerous lesions via the KLF7/NFκB pathway.

Studying the regulatory mechanism of gastric disease progression to gastric cancer (GC) is essential. miR-520f expression is down-regulated in GC and inhibits the proliferation of gastric cancer cells, suggesting that it is associated with the development of GC, but whether it plays a role in the gastric precancerous lesion (GPL) is unclear. This study aimed to investigate the effect of miR-520f-3p in the N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced GPL model and to elucidate the role of its downstream target gene Kruppel-like factor 7 (KLF7) in it. The experimental results showed that miR-520f-3p expression was down-regulated in the MNNG-induced GES-1 cell model, and overexpression of miR-520f-3p reversed the effects of MNNG on cell migration, invasion and epithelial-mesenchymal transition (EMT) -related protein expression. Meanwhile, overexpression of KLF7 attenuated the effect of miR-520f-3p on GPL. In a mouse GPL model, it was observed that MNNG elicited inflammation and EMT processes in mouse gastric tissues through the KLF7/ Nuclear Factor Kappa B (NFκB) pathway, and silencing KLF7 alleviated MNNG-induced gastric epithelial cell injury and gastric atrophy symptoms. These results provide a new perspective for understanding the development of GPL, and the development of new therapies targeting miR-520f-3p and KLF7 may provide new ideas for the prevention and treatment of gastric cancer.

Risk of Tuberculosis and Hepatitis B Reactivation in Patients With Crohn's Disease on Ustekinumab: A Nationwide Real-World Study.

BACKGROUND: Ustekinumab (UST) was approved in China for moderate-to-severe Crohn's disease (CD) in 2020. The prevalence rates of tuberculosis and hepatitis B virus (HBV) infection are high in China, and no guideline clearly states that tuberculosis chemoprophylaxis or prophylactic anti-HBV therapy should be prescribed before UST administration. This study aimed to assess the risk of tuberculosis and HBV reactivation in CD patients with latent tuberculosis infection (LTBI) and previous HBV infection receiving UST. METHODS: A multicenter retrospective cohort study was carried out at 68 hospitals in China to assess 721 adult CD cases administered UST between May 1, 2020, and December 31, 2021. CD and concurrent LTBI or HBV carrier were included. Hepatitis B serology, T-SPOT.TB, and tuberculin skin tests were performed at baseline. The primary outcome was tuberculosis or HBV reactivation. RESULTS: Patients with CD-concomitant LTBI or who were HBV carriers receiving UST therapy were retrospectively enrolled from 15 hospitals in China. A total of 53 CD with LTBI patients and 17 CD with HBV carrier patients receiving UST were included. Treatment and follow-up durations were 50 ± 20 weeks and 50 ± 15 weeks in the LTBI and HBV carrier groups, respectively. A total of 25 CD patients with LTBI underwent chemoprophylaxis and 28 did not. A total of 11 HBV carriers had antiviral prophylaxis and 6 did not. No patient experienced tuberculosis or HBV reactivation or liver dysfunction during follow-up. CONCLUSIONS: UST was safe for treatment of CD because no patient developed tuberculosis, persistent hepatitis, or acute liver failure during therapy, whether with a prophylactic regimen or not, based on our sample size and limited follow-up time.

Multilevel Gradient-Ordered Silicon Anode with Unprecedented Sodium Storage.

While cost-effective sodium-ion batteries (SIBs) with crystalline silicon anodes promise high theoretical capacities, they perform poorly because silicon stores sodium ineffectively (capacity <40 mAh g-1 ). To address this issue, herein an atomic-order structural-design tactic is adopted for obtaining unique multilevel gradient-ordered silicon (MGO-Si) by simple electrochemical reconstruction. In situ-formed short-range-, medium-range-, and long-range-ordered structures construct a stable MGO-Si, which contributes to favorable Na-Si interaction and fast ion diffusion channels. These characteristics afford a high reversible capacity (352.7 mAh g-1 at 50 mA g-1 ) and stable cycling performance (95.2% capacity retention after 4000 cycles), exhibiting record values among those reported for pure silicon electrodes. Sodium storage of MGO-Si involves an adsorption-intercalation mechanism, and a stepwise construction strategy of gradient-ordered structure further improves the specific capacity (339.5 mAh g-1 at 100 mA g-1 ). Reconstructed Si/C composites show a high reversible capacity of 449.5 mAh g-1 , significantly better than most carbonaceous anodes. The universality of this design principle is demonstrated for other inert or low-capacity materials (micro-Si, SiO2 , SiC, graphite, and TiO2 ), boosting their capacities by 1.5-6 times that of pristine materials, thereby providing new solutions to facilitate sodium storage capability for better-performing battery designs.

An education-based telehealth group improves the management and clinical outcomes of patients with inflammatory bowel disease in China (THEIM study).

BACKGROUND: Although poor medication adherence has a negative impact on disease prognosis in patients with inflammatory bowel disease (IBD), finding proven solutions remains a challenge. In this study, we developed a telehealth management model based on education and patient-centered medical care (PCEB) using the social media platform WeChat. OBJECTIVE: To investigate the effect of PCEB on adherence and clinical outcomes. METHODS: In this retrospective cohort, 543 IBD patients (274 in the PCEB group and 269 in the routine group) at the IBD center of Renmin Hospital (Wuhan University, Wuhan, China) were enrolled between January 2020 and September 2022. The routine group received routine follow-up and management, while for PCEB patients, a comprehensive IBD education program and PCEB were conducted. Medication adherence and clinical outcomes were also evaluated. RESULTS: There were no differences between the PCEB and routine groups in terms of patient demographics and clinical characteristics, including disease classification, duration, biological treatment, and educational background at baseline. Compared with routine treatment, PCEB greatly improved patient medication adherence, as assessed by compliance with oral medication, enteral nutrition, biological infusion, and scheduled endoscopic assessment. Clinical and endoscopic remission in patients with PCEB increased during short-term (month 4) and long-term (month 12) follow-ups, along with a decrease in relapse rates for CD (13.3% vs. 31.8%) and UC (19.8% vs. 37.2%). CONCLUSION: The telehealth model applied to the PCEB group improved medication adherence and clinical outcomes in patients with IBD. This is a new and powerful solution for the long-term management of this chronic and progressive disease.

Efficacy of Ustekinumab Optimization by 2 Initial Intravenous Doses in Adult Patients With Severe Crohn's Disease.

BACKGROUND: Although increasing studies have reported that dose escalation can improve treatment response to ustekinumab in patients with Crohn's disease (CD), their strategies mainly focus on maintenance regimen. Evidence of ustekinumab dose escalation in induction regimen, particularly in severe CD, remains limited. This study evaluated the efficacy and safety of intravenous ustekinumab with 2 initial doses in patients with severely active CD. METHODS: A retrospective observational study of 99 adult patients with severe CD treated with ustekinumab from 3 IBD centers included 48 patients with standard and 51 with optimized induction treatment. Clinical outcomes, inflammatory biomarkers including fecal calprotectin (FC) normalization, and endoscopic outcomes were evaluated at weeks 16 and 48. Adverse events and treatment decisions after initial induction were also collected. RESULTS: Compared with the standard group, 2 initial intravenous injections of ustekinumab achieved higher clinical response (92.2%, 47 of 51, P = .656), clinical remission (88.2%, 45 of 51, P = .221), endoscopic response (75.8%, 25 of 33, P = .125), and FC normalization (70.6%, 36 of 51, P = .138) at week 16. The mucosal healing rate at week 16 (63.6%, P = .022) was statistically higher in the optimization group. At week 48, patients with optimized treatment achieved higher clinical response (80.4%, 41 of 51, P = .003), clinical remission (70.6%, 36 of 51, P = .007), FC normalization (66.7%, 34 of 51, P = .031), endoscopic response (72.7%, 24 of 33, P = .006), and mucosal healing (57.6%, 19 of 33, P = .004). At the last follow-up, 82.4% of optimally treated patients adhered to continued treatment with ustekinumab (P < .001). CONCLUSIONS: Optimization of ustekinumab by 2 initial intravenous inductions is more effective than standard therapy for adult patients with severe CD.

This study used an optimization strategy in severe adult Crohn's disease with 2 initial intravenous doses of ustekinumab. This new strategy proved to be effective and safe.

Application of bilingual simulated patients in the medical history collection for international medical students in China.

BACKGROUND: In all international medical student (IMS) programs in China, language barriers between IMSs and Chinese patients greatly reduced the learning in clinical practice and brought great challenges to IMSs in their transition from preclinical to clinical practice. This study aimed to investigate the role of bilingual simulated patients (B-SPs) in IMSs learning of medical history collection in China. METHODS: 48 IMSs of grade 4 between October 2020 to Jan 2021 were enrolled in this study. During the training of medical history collection, students were randomly arranged into two groups trained with either B-SPs (B-SP group) or English-speaking SP (E-SP group). All SPs in Objective Structured Clinical Exam station (OSCE) were trained in the Affiliated Hospital of Wuhan University. Clinical skills in medical history collection were assessed by instructors during pre-clinical, post-clinical OSCE and clinical rotations. RESULTS: The scores of IMSs in each group were analyzed in terms of medical history collection including the ability to effectively consult for information and key communication skills related to patient care. Our results indicated that IMS in B-SP group obtained similar scores in preclinical training for history collection (67.3 ± 8.46 vs 67.69 ± 8.86, P < 0.05) compared to E-SP group, while obtaining significantly higher score improvements between pre- and post-OSCE (17.22 (95% CI 12.74 to 21.70) vs 10.84 (95% CI 3.53 to 18.15), P = 0.0007). CONCLUSION: B-SPs are more conducive to doctor-patient communication and actually improve IMSs learning in medical history collection in China.

Influence of the casing layer on the specific volatile compounds and microorganisms by Agaricus bisporus.

One of the major variables affecting yield of the mushroom Agaricus bisporus is the casing layer, which directly affects the productivity and mass. Here, volatile organic compounds were extracted by headspace solid-phase microextraction and high-throughput sequencing was used to analyze the microbial community diversity. The relationship between mushroom yield at different cropping stages and the contents of volatile organic compounds and microorganisms in three different casing layers: peat, peat + soil and soil were systematically evaluated. The result shows that Benzaldehyde and (E)-2-octenal which stimulate yield, obviously increased as mushrooms grew, while 3-octanone, which inhibits yield, decreased over time in all three casing layers. However, there was not a strong correlation between the concentration of volatile compounds and yield. In addition, more than 3,000 bacterial operational taxonomic units (OTUs) by performing high throughput sequencing of the microbes were obtained in the three casing layers. Interestingly, the microbial community compositions were very similar between the three casing layers at a later cropping stage, but the community richness varied significantly in different casing layers and at different cropping stages. At the phylum level, the communities had similar structures but were quantitively very different, and this was even more obvious at the genus level. Principal component analysis revealed significant alterations in microbial community structure in different casing layers. Sphingomonas, Dongia and Achromobacter were the dominant genera at cropping stage 1, and the stage 3 were abundant in Saccharibacteria_norank, Pseudomonas, Flavobacterium and Brevundimonas, which was positively correlated with yield, while the abundance of Pseudomonas at stage 1 and Lactococcus and Bacillus at stage 3 was negatively correlated with yield. These results provide a guide for the development and agricultural application of microbial agents for yield improvement in the production of A. bisporus.

Evidence-based guideline for the prevention and management of perioperative infection.

BACKGROUND: We have updated the guideline for preventing and managing perioperative infection in China, given the global issues with antimicrobial resistance and the need to optimize antimicrobial usage and improve hospital infection control levels. METHODS: We conducted a comprehensive evaluation of the evidence for prevention and management of perioperative infection, based on the concepts of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The strength of recommendations was graded and voted using the Delphi method and the nominal group technique. Revisions were made to the guidelines in response to feedback from the experts. RESULTS: There were 17 questions prepared, for which 37 recommendations were made. According to the GRADE system, we evaluated the body of evidence for each clinical question. Based on the meta-analysis results, recommendations were graded using the Delphi method to generate useful information. CONCLUSIONS: This guideline provides evidence to perioperative antimicrobial prophylaxis that increased the rational use of prophylactic antimicrobial use, with substantial improvement in the risk-benefit trade-off.

The effects of Saccharomyces boulardii on rat colonic hypermotility induced by repeated water avoidance stress and the potential mechanism.

Background: Saccharomyces boulardii (Sb) has been reported to have the potential to regulate gut motility. The aim of this experiment was to explore the possible function of Sb in gut hypermotility elicited by repeated water avoidance stress (WAS). Methods: Adult male Wistar rats (N = 24) were divided into one of the following three groups: control (C), NS (normal saline) + WAS group (N), and Sb + WAS group (S). A diarrhea-predominant irritable bowel syndrome (IBS-D) model in rats was induced using the WAS method. Gut motility was evaluated by stool pellet expulsion per hour. The contractile activity of the colonic muscle strips was measured using an RM6240 multichannel physiological signal instrument. qRT-PCR and immunohistochemistry were used to assess Toll-like receptor 4 (TLR4) expression in colon tissue. ELISA was used to measure the level of cytokines in the serum and colonic tissue. Also, the microbiota composition was determined using high-throughput 16S rRNA sequencing. Result: The results showed that oral Sb decreased the WAS-induced increased defecation and colonic hypermotility in vivo. Furthermore, Sb also decreased the contractile amplitude of colonic circular muscle (CM) and longitudinal muscle (LM) strips in a dose-dependent manner in vitro. Repeated WAS increased TLR4 expression, but Sb reversed it. Sb also reduced interleukin-6 (IL-6), IL-1ß, and interferon-γ (IFN-γ) levels in serum and colonic tissue, while increasing IL-10 levels in colonic tissue. Meanwhile, the rats from the NS + WAS group had decreased microbiota diversity and had lower relative abundances of Patescibacteria, Epsilonbacteraeota, Cyanobacteria, and Turicibacter compared with controls. The rats in the Sb + WAS group showed a tendency to increase the relative abundance of Blautia when compared to control rats and had lower relative abundances of Acidobacteria and Anaerostipes compared with the NS + WAS group. Conclusion: Our findings demonstrated that Sb improved colonic hypermotility in rats, reversed the high-expression of TLR4 in the colon caused by repeated WAS, modulated cytokines in the colon and serum, and altered the gut microbiota, indicating that Sb may be useful for IBS-D.

Recent Progress in the Preparation Technologies for Micro Metal Coils.

The recent development of micro-fabrication technologies has provided new methods for researchers to design and fabricate micro metal coils, which will allow the coils to be smaller, lighter, and have higher performance than traditional coils. As functional components of electromagnetic equipment, micro metal coils are widely used in micro-transformers, solenoid valves, relays, electromagnetic energy collection systems, and flexible wearable devices. Due to the high integration of components and the requirements of miniaturization, the preparation of micro metal coils has received increasing levels of attention. This paper discusses the typical structural types of micro metal coils, which are mainly divided into planar coils and three-dimensional coils, and the characteristics of the different structures of coils. The specific preparation materials are also summarized, which provides a reference for the preparation process of micro metal coils, including the macro-fabrication method, MEMS (Micro-Electro-Mechanical System) processing technology, the printing process, and other manufacturing technologies. Finally, perspectives on the remaining challenges and open opportunities are provided to help with future research, the development of the Internet of Things (IoTs), and engineering applications.

RAB26 contributes to the progression of non-small cell lung cancer after being transcriptionally activated by SMAD3.

Non-small cell lung cancer (NSCLC) accounts for 85% of all cases of lung cancer, which constitutes the leading cause of cancer mortality. RAB26, a member of Rab GTPase superfamily, has been suggested to play a role in the tumorigenesis of NSCLC. The present work aimed to explore whether and how RAB26 contributed to the progression of NSCLC. NSCLC cell line A549 was transfection with short hairpin RNA (shRNA) or overexpression (Ov) vector to knockdown RAB26 or overexpress SMAD3, respectively. Then the malignant processes of A549 cells including proliferation, migration, invasion and apoptosis were evaluated by CCK-8, colony formation, wound-healing, transwell and TUNEL assays, respectively. Expression of proteins involved in these processes was measured by western blot. A549 xenograft mice model was established to confirm the effect of RAB26 silence on NSCLC progression in vivo. The relationship between RAB26 and SMAD3 was analyzed by bioinformatics and then verified by dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays. We found that silence of RAB26 inhibited the proliferation, migration and invasion but promoted apoptosis of A549 cells. In vivo studies revealed that the tumor growth of A549 xenograft was markedly suppressed upon RAB26 silence. Moreover, it was confirmed that SMAD3 bound to the promoter of RAB26 and enhance its expression. Finally, we observed that overexpression of SMAD3 significantly blocked the inhibitory effect of RAB26 silence on NSCLC progression. Collectively, RAB26 may contribute to the progression of NSCLC after being transcriptionally activated by SMAD3.

Effect of phosphodiesterase-4 inhibitor rolipram on colonic hypermotility in water avoidance stress rat model.

BACKGROUND: Phosphodiesterase (PDE) inhibition has been reported to play a role in regulating gut motility, but the evidence is insufficient, and the mechanism remains unknown. The aim of this study was to investigate the possible role of phosphodiesterase-4 (PDE4) inhibitor rolipram in water avoidance stress-induced colonic hypermotility. METHODS: A rat model of irritable bowel syndrome (IBS) with diarrhea (IBS-D) was established by water avoidance stress (WAS). Intestinal motility was assessed by fecal pellets expulsion per hour. The cyclic adenosine monophosphate (cAMP) and nitric oxide (NO) level in colon tissue were detected using ELISA assay and the Griess test, respectively. Western blotting was performed to assess the protein level of PDE, PKA/p-CREB, and neuronal nitric oxide synthase (nNOS) in the colon. To determine the role of rolipram in gut motility, the rats of the WAS + Rolipram and Rolipram group were injected with rolipram intraperitoneally. The colonic contractile activity was recorded with a RM6240 multichannel physiological signal system. KEY RESULTS: WAS-induced gastrointestinal hypermotility and increased defecation in rats. After repeated stress, protein levels of PDE4 in the colon were promoted while PKA/p-CREB and nNOS were highly decreased. cAMP content in colon tissue did not change significantly. However, NO content decreased after WAS, and rolipram partly enhanced NO in WAS-exposed rats. In addition, intraperitoneal injection of rolipram partly inhibited the colonic motility in vivo. Meanwhile, we observed rolipram inhibited the contraction of colonic smooth muscle strips, and this inhibitory effect was abolished by Nω-Nitro-L-arginine (L-NNA), a nitric oxide synthase (NOS) inhibitor, tetrodotoxin (TTX), a blocker of neuronal voltage-dependent Na+ channels, Rp-Adenosine 3',5'-cyclic monophosphorothioate triethylammonium salt hydrate (Rp-cAMPS), an antagonist of cAMP. CONCLUSIONS AND INFERENCES: Rolipram could relieve stress-induced gastrointestinal hypermotility. This effect may be partly through the cAMP-PKA-p-CREB pathway and NO pathway.

Realizing the Multi-electron Reaction in the Na3V2(PO4)3 Cathode via Reversible Insertion of Dihydrogen Phosphate Anions.

Dual-ion battery (DIB) is an up-and-coming technology for the energy storage field. However, most of the current cathodes are still focused on the graphite hosts, which deliver a limited specific capacity. In this work, we demonstrated for the first time that H2PO4- can be used as the charge carrier for Na3V2(PO4)3 under an aqueous electrolyte, which enabled the V3+/V4+ and V4+/V5+ multielectron reactions in the Na3V2(PO4)3 electrode. The fabricated aqueous DIB delivers a high average voltage of ∼0.75 V (vs Ag/AgCl) and a high capacity of 280.7 mA h g-1. Moreover, the formed V5+-based novel cathode exhibits a capacity of 170.2 mA h g-1 in an organic sodium-ion battery. This study may open a new direction for fabricating high-voltage electrodes through the design of DIBs.

Unraveling Anionic Redox for Sodium Layered Oxide Cathodes: Breakthroughs and Perspectives.

Sodium-ion batteries (SIBs) as the next generation of sustainable energy technologies have received widespread investigations for large-scale energy storage systems (EESs) and smart grids due to the huge natural abundance and low cost of sodium. Although the great efforts are made in exploring layered transition metal oxide cathode for SIBs, their performances have reached the bottleneck for further practical application. Nowadays, anionic redox in layered transition metal oxides has emerged as a new paradigm to increase the energy density of rechargeable batteries. Based on this point, in this review, the development history of anionic redox reaction is attempted to systematically summarize and provide an in-depth discussion on the anionic redox mechanism. Particularly, the major challenges of anionic redox and the corresponding available strategies toward triggering and stabilizing anionic redox are proposed. Subsequently, several types of sodium layered oxide cathodes are classified and comparatively discussed according to Na-rich or Na-deficient materials. A large amount of progressive characterization techniques of anionic oxygen redox is also summarized. Finally, an overview of the existing prospective and the future development directions of sodium layered transition oxide with anionic redox reaction are analyzed and suggested.

An Effective Treatment of Perimenopausal Syndrome by Combining Two Traditional Prescriptions of Chinese Botanical Drugs.

Ethnopharmacological relevance: Two types of traditional Chinese formulas of botanical drugs are prescribed for treating perimenopausal syndrome (PMS), a disorder in middle-aged women during their transition to menopause. One is for treating PMS as kidney deficiency (KD) due to senescence and declining reproductive functions, and the other is for treating it as liver qi stagnation (LQS) in association with stress and anxiety. Despite the time-tested prescriptions, an objective attestation to the effectiveness of the traditional Chinese treatment of PMS is still to be established and the associated molecular mechanism is still to be investigated. Materials and methods: A model for PMS was generated from perimenopausal rats with chronic restraint stress (CRS). The effectiveness of traditional Chinese formulas of botanical drugs and a combination of two of the formulas was evaluated based on 1H NMR plasma metabolomic, as well as behavioral and physiological, indicators. To investigate whether the formulas contained ligands that could compensate for the declining level of estrogen, the primary cause of PMS, the ligand-based NMR technique of saturation transfer difference (STD) was employed to detect possible interacting molecules to estrogen receptors in the decoction. Results: Each prescription of the classical Chinese formula moderately attenuated the metabolomic state of the disease model. The best treatment strategy however was to combine two traditional Chinese formulas, each for a different etiology, to adjust the metabolomic state of the disease model to that of rats at a much younger age. In addition, this attenuation of the metabolomics of the disease model was by neither upregulating the estrogen level nor supplementing an estrogenic compound. Conclusion: Treatment of PMS with a traditional Chinese formula of botanical drugs targeting one of the two causes separately could ameliorate the disorder moderately. However, the best outcome was to treat the two causes simultaneously with a decoction that combined ingredients from two traditional prescriptions. The data also implicated a new paradigm for phytotherapy of PMS as the prescribed decoctions contained no interacting compound to modulate the activity of estrogen receptors, in contrast to the treatment strategy of hormone replacement therapy.

Identification of Prognostic Factors Related to Super Enhancer-Regulated ceRNA Network in Metastatic Lung Adenocarcinoma.

INTRODUCTION: The regulatory mechanisms of super enhancers (SEs) and ceRNA networks in LUAD progression are not well understood. We aimed to discover the prognostic-related ceRNA network regulated by SEs in metastatic LUAD. METHODS: RNA-seq data were extracted from The Cancer Genome Atlas (TCGA) database. Differentially expressed (DE) RNAs were identified by edgeR. CeRNA network was predicted and visualized using starBase and Cytoscape. H3K27ac ChIP-seq data were derived from the Gene Expression Omnibus (GEO) database, and used for SE identification. Kaplan-Meier curve and multivariate Cox model were applied for prognostic analysis. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) network were performed for functional analysis. SEs of AC074117.1 were verified by ChIP-qPCR in A549 and H1299 cells. MTT assay was performed to analyze cell proliferation. Luciferase activity assay was carried out to validate the target targeting relationships of ceRNA network. RESULTS: A total of 2355 DEmRNA, 483 DElncRNA and 155 DEmiRNA were identified between metastatic LUAD and adjacent normal tissues. CeRNA network consisting of 7 DElncRNAs, 18 DEmiRNAs and 15 DEmRNAs was constructed. Among the seven DElncRNAs in ceRNA network, only AC074117.1 was regulated by SEs. SE-regulated prognostic ceRNA sub-network consisting of FKBP3, E2F2, AC074117.1 and hsa-let-7c-5p was screened and verified. The overlapping co-expressed mRNAs of FKBP3, E2F2, AC074117.1 and hsa-let-7c-5p were mainly related to cell division and Fanconi anemia pathway. Genes in the ceRNA sub-network were correlated with DNA mismatch repair markers. Functional experiments proved that AC074117.1 was highly expressed in LUAD cells. AC074117.1 silencing notably inhibited proliferation of A549 and H1299 cells. Luciferase activity assay confirmed the direct relationship in AC074117.1-hsa-let-7c-5p-FKBP3/E2F2 network. CONCLUSION: A novel prognostic ceRNA sub-network regulated by SEs was identified in metastatic LUAD. This study provided potential therapeutic targets and prognostic markers for further study of metastatic LUAD.

Boosting Sodium Storage Performance of Hard Carbon Anodes by Pore Architecture Engineering.

Hard carbon (HC) displays great potential for high-performance sodium-ion batteries (SIBs) due to its cost-effective, simple fabrication and most likely to be commercialized. However, the complicated microstructures of HC lead to difficulties in deeply understanding the structure-performance correlation. Particularly, evaluation of influence of pore structure on Na storage performances is still causing disputes and rational strategies of designing pore architecture of HC are still necessary. In this work, the skillful and controllable phase-inversion method is applied to construct porous HC with abundantly interconnected and permeable tunnel-like pores, which can promote ionic diffusion and improve electrode-electrolyte interfacial affinity. Structure-performance investigation reveals that porous HC with cross-coupled macropore architecture can boost Na storage performances comprehensively. Compared to pristine HC with negligible pores, well-regulated porous HC anodes show an obvious enhancement on initial Coulombic efficiency (ICE) of 68.3% (only 51.5% for pristine HC), reversible capacity of 332.7 mAh g-1 at 0.05 A g-1, rate performance with 67.4% capacity retention at 2 A g-1 (46.5% for pristine HC), and cycling stability with 95% capacity maintained for 90 cycles (86.4% for pristine HC). Additionally, the ICE can be optimized up to 76% by using sodium carboxymethyl cellulose as a binder. This work provides an important view of optimizing Na storage performances of HC anodes by pore engineering, which can be broadened into other electrode materials.