A Rare Case of Benign Recurrent Intrahepatic Cholestasis Initially Diagnosed in Middle-age.

Background: Repeated episodes of jaundice and pruritus are common in a group of autosomal recessive liver diseases known as benign recurrent intrahepatic cholestasis. Benign recurrent intrahepatic cholestasis (BRIC) is divided into two types, type 1 and type 2, and is caused by mutations in the ATP8B1 and ABCB11 genes. Here, we report a rare case of BRIC type 2 mutation. Case presentation: A 45-year-old Chinese man had three frequent episodes of jaundice marked by extensive excoriation and severe pruritis, although he had no prior history of jaundice. Laboratory investigations showed no evidence of liver damage caused by viral, autoimmune, or acquired metabolic etiologies. The CT scan revealed an enlarged gallbladder with numerous punctate high-density shadows, while no wall thickening was observed. Endoscopic ultrasonography showed no evidence of dilation of the intrahepatic and extrahepatic bile duct, as well as the absence of gallstone. Diagnostic evaluation: Immunohistochemical examinations of liver biopsy samples showed cytokeratin-7 positive hepatocytes, suggesting chronic intrahepatic cholestasis. The reticulin fiberstaining demonstrated that the portions of the hepatic plate in the center of the lobule were asymmetrically organized,and somewhat enlarged, with collapsed areas indicating intralobular inflammation. Moreover, there were areas of collapse that indicated the presence of intralobular inflammation. Whole exome sequencing revealed mutations in the ABCB11 gene; c.3084A>G, p.A1028A homozygous mutation (chr2-169789016), and c.2594C>T, p.A865V heterozygous mutation (chr2-169801131). Based on these findings, the final diagnosis of the patient was metabolism-related jaundice. Treatment: Apart from receiving tapering dosage of prednisone to lower bilirubin levels, the patient received no extra care. Conclusion: The comprehensive diagnosis of a middle-aged male patient with BRIC-2, which involved extensive radiological, hematological, and genetic investigations, informed a tailored tapering prednisone regimen, highlighting the importance of personalized medicine in managing atypical presentations of this rare cholestatic disorder.

Erratum: Author correction to "Tumor-microenvironment activated duplex genome-editing nanoprodrug for sensitized near-infrared titania phototherapy" [Acta Pharm Sin B (2022) 4224-4234].

[This corrects the article DOI: 10.1016/j.apsb.2022.06.016.].

Treatment of gouty arthritis with traditional Chinese medicine decoction: Meta-analysis, network pharmacology analysis, and molecular docking.

BACKGROUND: Previous studies have shown that traditional Chinese medicine decoction (TCMD) could ameliorate the clinical symptoms and laboratory indicators of gouty arthritis (GA) patients. However, few investigations have been conducted on the efficacy and safety of TCMD for GA, the underlying mechanism of TCMD for GA, and the relationship between the TCMD active ingredients and GA targets. METHODS: Randomized controlled trials of TCMD for GA were retrieved from Chinese and English databases. Meta-analysis was conducted by Stata 17 software. Potential sources of heterogeneity were identified through subgroup analysis, meta-regression, and heterogeneity test. Publication bias was assessed by Egger's test and funnel plots. The ingredients and targets related to TCMD and GA were obtained from multiple databases, such as TCMSP and DrugBank. The protein-protein interaction network, GO and KEGG analysis was constructed using STRING and DAVID. Molecular docking and visualization of the results were completed by AutoDock and PyMOL software. RESULTS: Eighty-four studies were included, involving 7151 patients and 10 outcome indicators. Meta-analysis showed that, compared to routine treatment, TCMD could better reduce the incidence of adverse events and the level of laboratory indicators including blood uric acid (BUA), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 1ß (IL-1ß), and tumor necrosis factor-α (TNF-α). In the section of network pharmacology, we retrieved 150 active ingredients and 303 target genes from the top 10 herbs in 84 studies, as well as 3082 disease targets and 195 cross targets of the herbs and GA. The top ranked ingredients, intersection targets, and signaling pathways included quercetin, kaempferol, and wogonin; AKT1, TNF, and TP53; as well as IL-17, HIF-1, and PI3K-AKT, etc. Among the 81 molecular docking results, we visualized 10 results with low binding energy, including IL1B and beta-sitosterol, MYC and beta-sitosterol, etc. CONCLUSION: TCMD could be a satisfactory complementary and alternative therapy for GA. However, it should be verified by further studies. Future research could be conducted from the following active ingredients, targets, and signal pathways, such as wogonin, sitosterol, and sitosterol; AKT1, TNF, IL6, and TP53; and IL-17, HIF-1, and PI3K-AKT signaling pathway.

Efficacy and safety of Duhuo-Jisheng decoction in rheumatoid arthritis: A systematic review and meta-analysis of 42 randomized controlled trials.

BACKGROUND: Duhuo-Jisheng decoction (DJD) is a Chinese herb formula. Previous studies have reported that the clinical symptoms and laboratory indicators of rheumatoid arthritis (RA) patients could be improved by DJD. However, the existing evidence was not robust enough and controversial. METHODS: Randomized controlled trials of DJD for RA were retrieved from Chinese and English databases from their inception to April 16, 2023. Meta-analysis was performed by Stata 17 software. We used subgroup analysis, meta-regression, and sensitivity analysis to identify potential sources of heterogeneity. The subgroup analysis and meta-regression were conducted from 6 aspects, including age, course of disease, course of treatment, interventions used in the experimental or control group, and random sequence generation. Galbraith plot was used to find studies with possible heterogeneity. Publication bias was assessed by Egger's test and funnel plots when the number of relevant studies was greater than or equal to 10. RESULTS: Forty-two studies were included, involving 3635 patients and 19 outcome indicators. Meta-analysis showed that, compared with the routine disease-modifying antirheumatic drugs (rDMARDs), DJD could better improve the level of laboratory indicators, main symptoms and signs, and questionnaire scores of RA patients. The laboratory indicators included rheumatoid factor, T lymphocyte subpopulation (including CD4+, CD8+, and CD4+/CD8+), and inflammatory biomarkers (including erythrocyte sedimentation rate, C-reactive protein, tumor necrosis factor-α, interleukin 6, interleukin 1ß, and interleukin 1). The main symptoms and signs included the duration of morning stiffness, the number of joint tenderness, the number of swollen joints, and the grip strength of both hands. The questionnaire included visual analogue scale, health assessment questionnaire, and disease activity score in 28 joints. In addition, the adverse events of DJD treatment were significantly lower than those of rDMARDs. However, the results of a few subgroup analyses differed from the overall results. Furthermore, the publication bias assessment showed that, out of 11 evaluated results, 4 had publication bias. CONCLUSION: DJD could be a satisfactory complementary and alternative therapy for RA. However, due to a small number of subgroup analysis results being different from the overall results, it should be verified by further studies.

Clinical efficacy evaluation and potential mechanism prediction on Guizhi-Shaoyao-Zhimu decoction in the treatment of gouty arthritis based on meta-analysis, network pharmacology analysis, and molecular docking.

BACKGROUND: Guizhi-Shaoyao-Zhimu decoction (GSZD) is a Chinese herb formula. Previous studies have reported that the clinical symptoms and laboratory indicators of gouty arthritis patients could be improved by GSZD. However, no previous study has evaluated and analyzed its efficacy, safety, underlying mechanisms, and the relationship between related ingredients of herbs and targets of gouty arthritis. METHODS: Randomized controlled trials of GSZD for gouty arthritis were retrieved from various databases. Meta-analysis was performed by Stata 17 software. Galbraith plot was used to find studies with possible heterogeneity. Publication bias was assessed by Egger test and funnel plot. The related ingredients of herbs and the targets of herbs and gouty arthritis were obtained from several databases, such as TCMSP, HERB, and DrugBank. The protein-protein interaction network was conducted by the STRING platform. DAVID database was used to perform GO and KEGG analysis. Molecular docking and visualization of docking results were carried out by AutoDock and PyMOL software. RESULTS: Twenty studies with 1633 patients were included. Meta-analysis indicated that GSZD could better improve the clinical efficiency and visual analogue scale score, and reduce the level of blood uric acid and inflammatory biomarkers (including C-reactive protein, erythrocyte sedimentation rate, interleukin 6, interleukin 8, and tumor necrosis factor-α) than conventional treatment. In addition, we retrieved 157 active compounds, 517 herb target genes, 3082 disease targets, and 295 intersection targets of herb and disease. The results of network pharmacology analysis showed that the core related ingredients included quercetin, kaempferol, sitosterol, luteolin, catechin, etc. The core intersection targets contained AKT1, TNF-α, TP53, IL6, etc. And the critical signaling pathways included IL-17, HIF-1, TNF, PI3K-Akt, etc. Among the 56 molecular docking results, only 8 results had binding energy values greater than -5.0 kcal/mol. CONCLUSION: GSZD could be a satisfactory complementary and alternative therapy for treating gouty arthritis. However, it should be verified by further studies. Future research on gouty arthritis could be conducted from the active components including beta-sitosterol and sitosterol, the targets including TNF-1, IL1B, and ESR1, and the signaling pathways including IL-17 and HIF-1.

Accurate delivery of pristimerin and paclitaxel by folic acid-linked nano-micelles for enhancing chemosensitivity in cancer therapy.

Chemoresistance remains a huge challenge for effective treatment of non-small cell lung cancer (NSCLC). Previous studies have shown Chinese herbal extracts possess great potential in ameliorating tumor chemoresistance, however, the efficacy is clinically limited mainly because of the poor tumor-targeting and in vivo stability. The construction of nano-delivery systems for herbal extracts has been shown to improve drug targeting, enhance therapeutic efficacy and reduce toxic and side effects. In this study, a folic acid (FA)-modified nano-herb micelle was developed for codelivery of pristimerin (PRI) and paclitaxel (PTX) to enhance chemosensitivity of NSCLC, in which PRI could synergistically enhance PTX-induced growth inhibition of A549 cancer cell. PTX was firstly grafted with the FA-linked polyethylene glycol (PEG) and then encapsulated with PRI to construct the PRI@FA-PEG-PTX (P@FPP) nano-micelles (NMs), which exhibited improved tumor-targeting and in vivo stability. This active-targeting P@FPP NMs displayed excellent tumor-targeting characteristics without obvious toxicity. Moreover, inhibition of tumor growth and metastasis induced by P@FPP NMs were significantly enhanced compared with the combined effects of the two drugs (PRI in combination of PTX), which associated with epithelial mesenchymal transition inhibition to some extent. Overall, this active-targeting NMs provides a versatile nano-herb strategy for improving tumor-targeting of Chinese herbal extracts, which may help in the promotion of enhancing chemosensitivity of NSCLC in clinical applications.

Tumor-microenvironment activated duplex genome-editing nanoprodrug for sensitized near-infrared titania phototherapy.

Near-infrared (NIR)-light-triggered nanomedicine, including photodynamic therapy (PDT) and photothermal therapy (PTT), is growing an attractive approach for cancer therapy due to its high spatiotemporal controllability and minimal invasion, but the tumor eradication is limited by the intrinsic anti-stress response of tumor cells. Herein, we fabricate a tumor-microenvironment responsive CRISPR nanoplatform based on oxygen-deficient titania (TiO2-x ) for mild NIR-phototherapy. In tumor microenvironment, the overexpressed hyaluronidase (HAase) and glutathione (GSH) can readily destroy hyaluronic acid (HA) and disulfide bond and releases the Cas9/sgRNA from TiO2-x to target the stress alleviating regulators, i.e., nuclear factor E2-related factor 2 (NRF2) and heat shock protein 90α (HSP90α), thereby reducing the stress tolerance of tumor cells. Under subsequent NIR light illumination, the TiO2-x demonstrates a higher anticancer effect both in vitro and in vivo. This strategy not only provides a promising modality to kills cancer cells in a minimal side-effects manner by interrupting anti-stress pathways but also proposes a general approach to achieve controllable gene editing in tumor region without unwanted genetic mutation in normal environments.

Efficacy of keverprazan for duodenal ulcer: A phase II randomized, double-blind, parallel-controlled trial.

BACKGROUND AND AIM: Considering the limitation of varying acid suppression of proton pump inhibitors, this study was aimed to assess the efficacy, safety, and dose-effect relationship of keverprazan, a novel potassium-competitive acid blocker, in the treatment of duodenal ulcer (DU) compared with lansoprazole. METHODS: A randomized, double-blind, double-dummy, multicenter, low-dose, high-dose, and positive-drug parallel-controlled study was conducted to verify the non-inferiority of keverprazan (20 or 30 mg) to lansoprazole of 30 mg once daily for 4 to 6 weeks and dose-effect relationship of keverprazan in the treatment of patients with active DU confirmed by endoscopy. RESULTS: Of the 180 subjects randomized, including 55 cases in the keverprazan_20 mg group, 61 cases in the keverprazan_30 mg group, and 64 cases in the lansoprazole_30 mg group, 168 subjects (93.33%) completed the study. The proportions of healed DU subjects in the keverprazan_20 mg, keverprazan_30 mg, and lansoprazole_30 mg groups were respectively 87.27%, 90.16%, and 79.69% at week 4 (P = 0.4595) and were respectively 96.36%, 98.36%, and 92.19% at week 6 (P = 0.2577). The incidence of adverse events in the keverprazan_20 mg group was lower than that in the lansoprazole_30 mg (P = 0.0285) and keverprazan_30 mg groups (P = 0.0398). CONCLUSIONS: Keverprazan was effective and non-inferior to lansoprazole in healing DU. Based on the comparable efficacy and safety data, keverprazan of 20 mg once daily is recommended for the follow-up study of acid-related disorders. (Trial registration number: ChiCTR2100043455.).

Baicalin confers hepatoprotective effect against alcohol-associated liver disease by upregulating microRNA-205.

Recently, baicalin refers to flavonoid compound extracted from Scutellaria baicalensis Georgi has been indicated to hold promising therapeutic effects in alcohol-associated liver disease (ALD). However, knowledge of the molecular mechanisms for its hepatoprotective effect is still very limited. Evidence exists suggesting potential association between miR-205 and baicalin's function. Bioinformatic analysis and dual luciferase reporter assay were conducted to determine the binding affinity between miR-205 and importinα5. Our findings revealed that baicalin could alleviate ALD by raising the expression of miR-205. Additionally, miR-205 repressed NF-κB signaling pathway activation by binding to importinα5 to relieve ALD. Baicalin inhibited importinα5-mediated NF-κB signaling pathway to protect the liver against alcohol-induced injury, inflammation, oxidative stress and hepatocyte apoptosis. Taken conjointly, baicalin confers hepatoprotective effect against ALD through miR-205-mediated importinα5 inhibition via the NF-κB signaling pathway, highlighting a promising therapeutic target for ALD treatment with the help of traditional Chinese medicine.

Species composition and overall diversity are significantly correlated between the tongue coating and gastric fluid microbiomes in gastritis patients.

BACKGROUND: In traditional Chinese medicine, it is believed that the "tongue coating is produced by fumigation of stomach gas", and that tongue coating can reflect the health status of humans, especially stomach health. Therefore, studying the relationship between the microbiome of the tongue coating and the gastric fluid is of great significance for understanding the biological basis of tongue diagnosis. METHODS: This paper detected the microbiomes of the tongue coating and the gastric fluid in 35 gastritis patients using metagenomic sequencing technology, systematically constructed the microbial atlas of tongue coating and gastric juice, and first described the similar characteristics between the two sites. RESULTS: There was a significant correlation between tongue coating and gastric juice in terms of microbial species composition and overall diversity. In terms of species composition, it was found that the two sites were dominated by five phyla, namely, Actinobacteria, Bacteroidetes, Firmicutes, Fusobacteria and Proteobacteria, and that most of the gastric microbial species could be detected from the patient's own tongue coating. In terms of overall diversity, a significant correlation was found between the alpha diversity of the tongue coating microbiome and the gastric juice microbiome. Furthermore, in terms of abundance, 4 classes, 2 orders, 4 families, 18 genera and 46 species were found to significantly correlate between the tongue coating and the gastric fluid. CONCLUSIONS: The results provide microbiome-based scientific evidence for tongue diagnosis, and offer a new perspective for understanding the biological basis of tongue diagnosis.

Controlled CRISPR-Cas9 Ribonucleoprotein Delivery for Sensitized Photothermal Therapy.

Manipulation of CRISPR delivery for stimuli-responsive gene editing is crucial for cancer therapeutics through maximizing efficacy and minimizing side-effects. However, realizing controlled gene editing for synergistic combination therapy remains a key challenge. Here, a near-infrared (NIR) light-triggered thermo-responsive copper sulfide (CuS) multifunctional nanotherapeutic platform is constructed to achieve controlled release of CRISPR-Cas9 ribonucleoprotein (RNP) and doxorubicin for tumor synergistic combination therapy involving in gene therapy, mild-photothermal therapy (PTT), and chemotherapy. The semiconductor CuS serves as a "photothermal converter" and can stably convert NIR light (808 nm) into local thermal effect to provide photothermal stimulation. The double-strand formed between CuS nanoparticle-linked DNA fragments and single-guide RNA is employed as a controlled element in response to photothermal stimulation for controlled gene editing and drug release. Hsp90α, one subunit of heat shock protein 90 (Hsp90), is targeted by Cas9 RNP to reduce tumor heat tolerance for enhanced mild-PTT effects (≈43 °C). Significant synergistic therapy efficacy can be observed by twice NIR light irradiation both in vitro and in vivo, compared to PTT alone. Overall, this exogenously controlled method provides a versatile strategy for controlled gene editing and drug release with potentially synergistic combination therapy.

Production of gold/silver doped carbon nanocomposites for effective photothermal therapy of colon cancer.

Surgery followed by adjuvant chemotherapy is a reliable therapy for colon cancer, but is associated with side effects and risks. Recent advancements in nanobioengineering in the form of targeted nanoparticles, cubosomes, liposomes, nanosheets, nanorods, quantum dots have generated substantial advancements in theranostics of colon cancer decreasing the cytotoxic drugs' side effects. We describe a facile mechanism of preparation of hybrid nanocomposite encompassing Au and Ag. Preparation of hybrid nanocomposite is one step process which may be easily escalated. The nanocomposite was characterized using transmission eleactron microscopy, energy dispersive X-Ray spectroscopy, X-ray photoelectron spectroscopy, Fourier transform infra-red spectroscopy, UV-Vis spectroscopy, photoluminescence and cytotoxic studies. In-vivo studies were carried out in Balb/c mice. Photothermal heating experiments in HeLa cells were promising and the characterization studies clearly indicated the formation of hybrid nanocomposite. In-vivo experiments confirmed the efficacy of treatment, along with involvement of epigenetic regulation, which may be helpful in translation from research to clinical applications.

Tongue coating microbiome as a potential biomarker for gastritis including precancerous cascade.

The development of gastritis is associated with an increased risk of gastric cancer. Current invasive gastritis diagnostic methods are not suitable for monitoring progress. In this work based on 78 gastritis patients and 50 healthy individuals, we observed that the variation of tongue-coating microbiota was associated with the occurrence and development of gastritis. Twenty-one microbial species were identified for differentiating tongue-coating microbiomes of gastritis and healthy individuals. Pathways such as microbial metabolism in diverse environments, biosynthesis of antibiotics and bacterial chemotaxis were up-regulated in gastritis patients. The abundance of Campylobacter concisus was found associated with the gastric precancerous cascade. Furthermore, Campylobacter concisus could be detected in tongue coating and gastric fluid in a validation cohort containing 38 gastritis patients. These observations provided biological evidence of tongue diagnosis in traditional Chinese medicine, and indicated that tongue-coating microbiome could be a potential non-invasive biomarker, which might be suitable for long-term monitoring of gastritis.

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.

Validating traditional Chinese syndrome features in varied stages of chronic gastritis malignant transformation: study protocol for a cross-sectional study.

INTRODUCTION: The transition from chronic non-atrophic gastritis (CNAG) to chronic atrophic gastritis (CAG) and gastric carcinoma (GC) is regarded as a representative disease model of gastric mucosa malignant transformation led by uncontrolled inflammation. Traditional Chinese medicine (TCM) syndrome-targeted therapies have been applied in treating chronic gastritis (CG) malignant transformation in China with satisfying efficacy. This study aims to validate TCM syndrome features in each stage of CG malignant transformation. The findings may shed light on the TCM hypothesis of CG malignant transformation, and thus optimise syndrome-targeted treatment strategies of CNAG, CAG and GC, respectively. METHODS AND ANALYSIS: The present study is a cross-sectional study conducted in China. A total of 2000 eligible patients, including 500 CNAG cases, 1000 CAG cases and 500 GC cases, will be recruited from four TCM hospitals. Primary outcome measures include the prevalence of TCM syndrome patterns in varied stages of CG malignant transformation. Secondary outcome measures include prevalence and severity of all the presenting signs and symptoms collected by using TCM four diagnostic methods. Descriptive analysis, comparative analysis and correlation analysis of all the measurement data will be performed by biostatisticians. Unsupervised data mining analyses, including exploratory factor analysis, association rule analysis, hierarchical clustering analysis, complex system entropy clustering analysis, and so on, will also be performed by data scientists respectively for in-depth analyses of TCM syndrome-related indicators. ETHICS AND DISSEMINATION: The protocol has been approved by the Ethical Review Board of Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine (No ECPJ-BDY-2014-02). All the study outcomes will be disseminated through national conference reports and in the meantime published on peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03314038; Pre-results.

VFFDT: A New Software for Preparing AMBER Force Field Parameters for Metal-Containing Molecular Systems.

Force fields are fundamental to molecular dynamics simulations. However, the incompleteness of force field parameters has been a long-standing problem, especially for metal-related systems. In our previous work, we adopted the Seminario method based on the Hessian matrix to systematically derive the zinc-related force field parameters for AMBER. In this work, in order to further simplify the whole protocol, we have implemented a user-friendly Visual Force Field Derivation Toolkit (VFFDT) to derive the force field parameters via simply clicking on the bond or angle in the 3D viewer, and we have further extended our previous program to support the Hessian matrix output from a variety of quantum mechanics (QM) packages, including Gaussian 03/09, ORCA 3.0, QChem, GAMESS-US, and MOPAC 2009/2012. In this toolkit, a universal VFFDT XYZ file format containing the raw Hessian matrix is available for all of the QM packages, and an instant force field parametrization protocol based on a semiempirical quantum mechanics (SQM) method is introduced. The new function that can automatically obtain the relevant parameters for zinc, copper, iron, etc., which can be exported in AMBER Frcmod format, has been added. Furthermore, our VFFDT program can read and write files in AMBER Prepc, AMBER Frcmod, and AMBER Mol2 format and can also be used to customize, view, copy, and paste the force field parameters in the context of the 3D viewer, which provides utilities complementary to ANTECHAMBER, MCPB, and MCPB.py in the AmberTools.

Exploratory Factor Analysis for Validating Traditional Chinese Syndrome Patterns of Chronic Atrophic Gastritis.

Background. Traditional Chinese medicine (TCM) has long been used to treat chronic atrophic gastritis (CAG). The aim of the present study was to evaluate the TCM syndrome characteristics of CAG and its core pathogenesis so as to promote optimization of treatment strategies. Methods. This study was based on a participant survey conducted in 4 hospitals in China. Patients diagnosed with CAG were recruited by simple random sampling. Exploratory factor analysis (EFA) was conducted on syndrome extraction. Results. Common factors extracted were assigned to six syndrome patterns: qi deficiency, qi stagnation, blood stasis, phlegm turbidity, heat, and yang deficiency. Distribution frequency of all syndrome patterns showed that qi deficiency, qi stagnation, blood stasis, phlegm turbidity, and heat excess were higher (76.7%-84.2%) compared with yang deficiency (42.5%). Distribution of main syndrome patterns showed that frequencies of qi deficiency, qi stagnation, phlegm turbidity, heat, and yang deficiency were higher (15.8%-20.8%) compared with blood stasis (8.3%). Conclusions. The core pathogenesis of CAG is combination of qi deficiency, qi stagnation, blood stasis, phlegm turbidity, heat, and yang deficiency. Therefore, treatment strategy of herbal prescriptions for CAG should include herbs that regulate qi, activate blood, resolve turbidity, clear heat, remove toxin, and warm yang.

Pancake π-π Bonding Goes Double: Unexpected 4e/All-Sites Bonding in Boron- and Nitrogen-Doped Phenalenyls.

Chemical bonding interactions are the main driving force for the formation of molecules and materials from atoms. The two-electron/multicenter pancake π-π bonding found in phenalenyl (PLY, 1) radical π-dimers is intriguing due to its unconventional nature of covalent bonding for molecular aggregations and its propensity to induce unique optical, electronic, and magnetic properties. By using high-level quantum chemistry calculations, we show that the B- or N-doped PLYs (2 and 4), usually considered closed-shell and therefore trifling, can be rendered open-shell singlet by proper edge substitutions (3 and 5). The resulting two unpaired valence electrons on each molecular unit contribute to the formation of a genuine pancake-shaped 4e/all-sites double π-π bonding upon intermolecular π-dimerization, in contrast to the 2e/half-sites single π-π bonding in the parent PLY π-dimers. The unusual double π-π bonding motif discovered in these PLY analogues may broaden the landscape of, and find new applications for, intermolecular covalent bonding interactions.

Retrograde gastric electrical stimulation suppresses calorie intake in obese subjects.

OBJECTIVE: The effect of acute retrograde gastric electrical stimulation (RGES) on food intake, gastric accommodation, and gastric emptying in obese patients was investigated. METHODS: Simple obesity patients underwent RGES or sham stimulation. The maximum food intake volume was determined and the total calorie of consumed food was calculated. Gastric emptying was determined by (99m) -diethylenetriaminepentaacetic acid scintigraphy. RESULTS: Sixteen obese patients were studied, with a median BMI of 32.1 (IQR, 31.2, 33.8) kg/m(2) . The median gastric emptying time was 106.1 (IQR, 81.8, 122.4) min with sham stimulation and 113.0 (IQR, 83.7, 124.8) min with RGES (P = 0.352). The mean maximum satiety food intake was 580 (IQR, 510, 725) mL with sham stimulation and 490 (IQR, 385, 590) mL with RGES (P = 0.003). No statistically significant difference was noted between sham stimulation and RGES in the 1 and 2-h food retention rate. The total calories of maximum satiety food intake with sham stimulation were 985.2 (IQR, 842.5, 1063.1) kcal and 759.9 (IQR, 547.9, 784.9) kcal with RGES (P = 0.007). CONCLUSIONS: Acute RGES reduces calorie intake by decreasing gastric accommodation in obese subjects.