Efficacy and safety of Supine Daoyin in the treatment of acute exacerbation of chronic obstructive pulmonary disease: A randomized controlled trial.

AIM: This study aimed to develop and evaluate the efficacy and safety of Supine Daoyin, a TCM PR technique, in hospitalized patients with AECOPD. METHODS: This is a multicenter, prospective, randomized, controlled trial involving AECOPD inpatients recruited from April 2021 to December 2023 in five tertiary hospitals in China. Participants were randomly assigned to 14 days of Supine Daoyin group or control group and evaluated at days 3, 7, and 14 (posttreatment). The primary outcomes were LOS and CCQ and secondary outcomes were 6MWD, 30-STS, BI, Borg CR10, time on mechanical ventilation, SGRQ, mCOPD-PRO, and mESQ-COPD. RESULTS: Out of 369 participants screened, 228 were randomly assigned (Supine Daoyin group: n = 114; control group: n = 114). For primary outcomes, there was no significant between-group difference in LOS (p > 0.05), but for CCQ the Supine Daoyin was superior to control at days 7 (p < 0.01) and 14 (p < 0.01). For secondary outcomes, Supine Daoyin groups showed robust and superior improvements in 6MWD, 30-STS, BI, Borg CR10, SGRQ, mCOPD-PRO, and mESQ-COPD (all p < 0.05), but for time on mechanical ventilation there was no significant difference in two groups (p > 0.05). CONCLUSION: Supine Daoyin, a novel TCM PR technique, demonstrates safety and efficacy for AECOPD inpatients, yielding clinically meaningful improvements in health status, exercise capacity, and quality of life. This study offers a viable PR option for AECOPD patients with severe symptoms and limited mobility.

Tremella aurantialba polysaccharides alleviates ulcerative colitis in mice by improving intestinal barrier via modulating gut microbiota and inhibiting ferroptosis.

We aimed to investigate the effect of a polysaccharide from Tremella aurantialba on ulcerative colitis (UC), which targets ferroptosis in epithelial cells. TA 2-1 (127 kDa) was isolated from T. aurantialba and consisted of Man, Xyl, GlcA, Glc, Fuc and Rha with a molar ratio of 59.2: 23.2: 13.9: 1.6: 1.7: 0.4, exhibited a 1, 3-Man structure with branch chains of T-Xylp, 1,3-Xylp, 1,4-GlcAp, and T-Manp at its O-2 position. TA 2-1 (100 mg/mL) inhibited the cell viability of ferroptosis (19.8 %) in RLS3-induced Caco2 cells and significantly ameliorated symptoms in the colons of mice with dextran sodium sulfate (DSS)-induced UC. TA 2-1 remarkably repaired the intestinal barrier by upregulating claudin-1 and zonula occludens-1 levels. Further analysis found TA 2-1 significantly suppressed lipid peroxidation by regulating ferroptosis-related proteins in UC mice, suggesting that its protective effects are partially mediated by inhibiting ferroptosis. Further analysis of the gut microbiota and fecal microbiota transplantation revealed TA 2-1 might relieve UC symptoms or inhibit ferroptosis by modulating the gut microbiota's composition or metabolites. Results suggest the protective effects of TA 2-1 on the intestinal barrier by inhibiting ferroptosis of epithelial cells, at least by regulating the gut microbiota, highlighting the potential of TA 2-1 in UC treatment.

iPLA2ß loss leads to age-related cognitive decline and neuroinflammation by disrupting neuronal mitophagy.

BACKGROUND: During brain aging, disturbances in neuronal phospholipid metabolism result in impaired cognitive function and dysregulation of neurological processes. Mutations in iPLA2ß are associated with neurodegenerative conditions that significantly impact brain phospholipids. iPLA2ß deficiency exacerbates mitochondrial dysfunction and abnormal mitochondrial accumulation. We hypothesized that iPLA2ß contributes to age-related cognitive decline by disrupting neuronal mitophagy. METHODOLOGY: We used aged wild-type (WT) mice and iPLA2ß-/- mice as natural aging models to assess cognitive performance, iPLA2ß expression in the cortex, levels of chemokines and inflammatory cytokines, and mitochondrial dysfunction, with a specific focus on mitophagy and the mitochondrial phospholipid profile. To further elucidate the role of iPLA2ß, we employed adeno-associated virus (AAV)-mediated iPLA2ß overexpression in aged mice and re-evaluated these parameters. RESULTS: Our findings revealed a significant reduction in iPLA2ß levels in the prefrontal cortex of aged brains. Notably, iPLA2ß-deficient mice exhibited impaired learning and memory. Loss of iPLA2ß in the PFC of aged mice led to increased levels of chemokines and inflammatory cytokines. This damage was associated with altered mitochondrial morphology, reduced ATP levels due to dysregulation of the parkin-independent mitophagy pathway, and changes in the mitochondrial phospholipid profile. AAV-mediated overexpression of iPLA2ß alleviated age-related parkin-independent mitophagy pathway dysregulation in primary neurons and the PFC of aged mice, reduced inflammation, and improved cognitive function. CONCLUSIONS: Our study suggests that age-related iPLA2ß loss in the PFC leads to cognitive decline through the disruption of mitophagy. These findings highlight the potential of targeting iPLA2ß to ameliorate age-related neurocognitive disorders.

Patient-Reported Outcomes of Postoperative NSCLC Patients with or without Staged Chinese Herb Medicine Therapy during Adjuvant Chemotherapy (NALLC 2): A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: To investigate whether the combination of chemotherapy with staged Chinese herbal medicine (CHM) therapy could enhance health-related quality of life (QoL) in non-small-cell lung cancer (NSCLC) patients and prolong the time before deterioration of lung cancer symptoms, in comparison to chemotherapy alone. METHODS: A prospective, double-blind, randomized, controlled trial was conducted from December 14, 2017 to August 28, 2020. A total of 180 patients with stage I B-IIIA NSCLC from 5 hospitals in Shanghai were randomly divided into chemotherapy combined with CHM (chemo+CHM) group (120 cases) or chemotherapy combined with placebo (chemo+placebo) group (60 cases) using stratified blocking randomization. The European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life-Core 30 Scale (QLQ-C30) was used to evaluate the patient-reported outcomes (PROs) during postoperative adjuvant chemotherapy in patients with early-stage NSCLC. Adverse events (AEs) were assessed in the safety analysis. RESULTS: Out of the total 180 patients, 173 patients (116 in the chemo+CHM group and 57 in the chemo+placebo group) were included in the PRO analyses. The initial mean QLQ-C30 Global Health Status (GHS)/QoL scores at baseline were 57.16 ± 1.64 and 57.67 ± 2.25 for the two respective groups (P>0.05). Compared with baseline, the chemo+CHM group had an improvement in EORTC QLQ-C30 GHS/QoL score at week 18 [least squares mean (LSM) change 17.83, 95% confidence interval (CI) 14.29 to 21.38]. Conversely, the chemo+placebo group had a decrease in the score (LSM change -13.67, 95% CI -22.70 to -4.63). A significant between-group difference in the LSM GHS/QoL score was observed, amounting to 31.63 points (95% CI 25.61 to 37.64, P<0.001). The similar trends were observed in physical functioning, fatigue and appetite loss. At week 18, patients in the chemo+CHM group had a higher proportion of improvement or stabilization in GHS/QoL functional and symptom scores compared to chemo+placebo group (P<0.001). The median time to deterioration was longer in the chemo+CHM group for GHS/QoL score [hazard ratio (HR)=0.33, 95% CI 0.23 to 0.48, P<0.0010], physical functioning (HR=0.43, 95% CI 0.25 to 0.75, P=0.0005), fatigue (HR=0.47, 95% CI 0.30 to 0.72, P<0.0001) and appetite loss (HR=0.65, 95% CI 0.42 to 1.00, P=0.0215). The incidence of AEs was lower in the chemo+CHM group than in the chemo+placebo group (9.83% vs. 15.79%, P=0.52). CONCLUSION: The staged CHM therapy could help improve the PROs of postoperative patients with early-stage NSCLC during adjuvant chemotherapy, which is worthy of further clinical research. (Registry No. NCT03372694).

Hydrogen sulfide inhibits skeletal muscle ageing by up-regulating autophagy through promoting deubiquitination of adenosine 5'-monophosphate (AMP)-activated protein kinase α1 via ubiquitin specific peptidase 5.

BACKGROUND: Hydrogen sulfide (H2S), the third gasotransmitter discovered, regulates a variety of physiological functions. Whether H2S alleviates skeletal muscle ageing by regulating autophagy has not been reported. METHODS: Mice were administered 150 mg/kg/day of D-galactose ( D-gal), and C2C12 myotubes were cultured in 20 g/L D-gal to induce ageing. Sodium hydrosulfide (NaHS) was employed as an exogenous donor in the treatment group. The intracellular concentration of H2S was quantified by the 7-azido-4-methylcoumarin fluorescence probe. The proteins involved in the ubiquitin-mediated degradation of AMPKα1 were detected by liquid chromatography tandem mass spectrometry (LC-MS/MS) and co-immunoprecipitation (Co-IP). S-sulfhydration of USP5 was tested by a biotin-switch assay. Associated proteins were analysed by western blot. RESULTS: NaHS was found to effectively restore the H2S content in both ageing gastrocnemius (+91.89%, P < 0.001) and C2C12 myotubes (+27.55%, P < 0.001). In comparison to the D-gal group, NaHS was observed to increase the mean cross-sectional area of muscle fibres (+44.91%, P < 0.001), to decrease the collagen volume fraction of gastrocnemius (-81.32%, P = 0.001) and to reduce the ß-galactosidase-positive area of C2C12 myotubes (-28.74%, P < 0.001). NaHS was also found to reverse the expression of muscle atrophy F box protein (MAFbx), muscle-specific RING finger protein 1 (MuRF1), Cyclin D1 and p21 in the ageing gastrocnemius tissue (MAFbx: -31.73%, P = 0.008; MuRF1: -32.37%, P = 0.003; Cyclin D1: +45.34%, P = 0.010; p21: -25.53%, P = 0.022) and C2C12 myotubes (MAFbx: -16.38%, P < 0.001; MuRF1: -16.45%, P = 0.003; Cyclin D1: +40.23%, P < 0.001; p21: -35.85%, P = 0.026). The AMPKα1-ULK1 pathway was activated and autophagy was up-regulated in NaHS-treated gastrocnemius tissue (p-AMPKα1: +61.61%, P = 0.018; AMPKα1: +30.64%, P = 0.010; p-ULK1/ULK1: +85.87%, P = 0.005; p62: -29.07%, P < 0.001; Beclin1: +24.75%, P = 0.007; light chain 3 II/I [LC3 II/I]: +55.78%, P = 0.004) and C2C12 myotubes (p-AMPKα1: +77.49%, P = 0.018; AMPKα1: +26.18%, P = 0.022; p-ULK1/ULK1: +38.34%, P = 0.012; p62: -9.02%, P = 0.014; Beclin1: +13.36%, P < 0.001; LC3 II/I: +79.38%, P = 0.017; autophagy flux: +24.88%, P = 0.034) compared with the D-gal group. The effects of NaHS on autophagy were comparable to those of acadesine and LYN-1604, and chloroquine could reverse its effects on ageing. LC-MS/MS and Co-IP experiments demonstrated that USP5 is a deubiquitinating enzyme of AMPKα1. Following the knockdown of USP5, the activation of AMPKα1 was decreased (p-AMPKα1: -42.10%, P < 0.001; AMPKα1: -43.93%, P < 0.001), autophagy was inhibited (p-ULK1/ULK1: -27.51, P = 0.001; p62: +36.00, P < 0.001; Beclin1: -22.15%, P < 0.001) and NaHS lost its ability to up-regulate autophagy. NaHS was observed to restore the expression (gastrocnemius: +62.17%, P < 0.001; C2C12 myotubes: +37.51%, P = 0.003) and S-sulfhydration (+53.07%, P = 0.009) of USP5 and reduce the ubiquitination of AMPKα1. CONCLUSIONS: H2S promotes the deubiquitination of AMPKα1 by increasing the expression and S-sulfhydration of USP5, thereby up-regulating autophagy and alleviating skeletal muscle ageing.

Pre-diagnostic plasma advanced glycation end-products and soluble receptor for advanced glycation end-products and mortality in colorectal cancer patients.

Advanced glycation end-products (AGEs), formed endogenously or obtained exogenously from diet, may contribute to chronic inflammation, intracellular signaling alterations, and pathogenesis of several chronic diseases including colorectal cancer (CRC). However, the role of AGEs in CRC survival is less known. The associations of pre-diagnostic circulating AGEs and their soluble receptor (sRAGE) with CRC-specific and overall mortality were estimated using multivariable-adjusted Cox proportional hazards regression among 1369 CRC cases in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Concentrations of major plasma AGEs, Nε-[carboxy-methyl]lysine (CML), Nε-[carboxy-ethyl]lysine (CEL) and Nδ-[5-hydro-5-methyl-4-imidazolon-2-yl]-ornithine (MG-H1), were measured using ultra-performance liquid chromatography mass-spectrometry. sRAGE was assessed by enzyme-linked immunosorbent assay. Over a mean follow-up period of 96 months, 693 deaths occurred of which 541 were due to CRC. Individual and combined AGEs were not statistically significantly associated with CRC-specific or overall mortality. However, there was a possible interaction by sex for CEL (Pinteraction = .05). Participants with higher sRAGE had a higher risk of dying from CRC (HRQ5vs.Q1 = 1.67, 95% CI: 1.21-2.30, Ptrend = .02) or any cause (HRQ5vs.Q1 = 1.38, 95% CI: 1.05-1.83, Ptrend = .09). These associations tended to be stronger among cases with diabetes (Pinteraction = .03) and pre-diabetes (Pinteraction <.01) before CRC diagnosis. Pre-diagnostic AGEs were not associated with CRC-specific and overall mortality in individuals with CRC. However, a positive association was observed for sRAGE. Our findings may stimulate further research on the role of AGEs and sRAGE in survival among cancer patients with special emphasis on potential effect modifications by sex and diabetes.

Impact of radish seeds (Semen Raphani) on the absorption and transportation of ginsenosides in the Caco-2 cell model: a UPLC-ESI-MS analysis.

This study examined the impact of Semen raphani on the absorption of ginsenosides from Panax ginseng C.A. Meyer (ginseng) using a Caco-2 cell model and Ultra-High-Performance Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry (UPLC-ESI-MS). Six primary ginsenosides (Rg1, Re, Rb1, Rb2, Rc, Rd) were quantified. Results showed that Semen Raphani increased the efflux rate of ginsenosides, particularly at higher concentrations, suggesting it inhibits their absorption. The research elucidates the intestinal absorption process of ginsenosides and the antagonistic mechanism of Semen Raphani against ginseng.

Enhancement and suppression of nonsequential double ionization by spatially inhomogeneous fields.

Using the three-dimensional classical ensemble approach, we theoretically investigate the nonsequential double ionization of argon atoms in an intense laser field enhanced by bowtie-nanotip. We observe an anomalous decrease in the double ionization yield as the laser intensity increases, along with a significant gap in the low momentum of photoelectrons. According to our theoretical analysis, the finite range of the induced field by the nanostructure is the fundamental cause of the decline in double ionization yield. Driven by the enhanced inhomogeneous field, energetic electrons can escape from the finite range of nanotips without returning. This reduces the possibility of re-scattering on the nucleus and imprints the finite size effect into the double ionization yield and momentum distribution of photoelectrons in the form of yield decline and a gap in the photoelectron-momentum distribution.

Analysis of the aging-related biomarker in a nonhuman primate model using multilayer omics.

BACKGROUND: Aging is a prominent risk factor for diverse diseases; therefore, an in-depth understanding of its physiological mechanisms is required. Nonhuman primates, which share the closest genetic relationship with humans, serve as an ideal model for exploring the complex aging process. However, the potential of the nonhuman primate animal model in the screening of human aging markers is still not fully exploited. Multiomics analysis of nonhuman primate peripheral blood offers a promising approach to evaluate new therapies and biomarkers. This study explores aging-related biomarker through multilayer omics, including transcriptomics (mRNA, lncRNA, and circRNA) and proteomics (serum and serum-derived exosomes) in rhesus monkeys (Macaca mulatta). RESULTS: Our findings reveal that, unlike mRNAs and circRNAs, highly expressed lncRNAs are abundant during the key aging period and are associated with cancer pathways. Comparative analysis highlighted exosomal proteins contain more types of proteins than serum proteins, indicating that serum-derived exosomes primarily regulate aging through metabolic pathways. Finally, eight candidate aging biomarkers were identified, which may serve as blood-based indicators for detecting age-related brain changes. CONCLUSIONS: Our results provide a comprehensive understanding of nonhuman primate blood transcriptomes and proteomes, offering novel insights into the aging mechanisms for preventing or treating age-related diseases.

miR-153 promotes neural differentiation by activating the cell adhesion/Ca2+ signaling pathway and targeting ion channel activity in HT-22 cells by bioinformatic analysis.

MicroRNAs have been studied extensively in neurodegenerative diseases. In a previous study, miR-153 promoted neural differentiation and projection formation in mouse hippocampal HT-22 cells. However, the pathways and molecular mechanism underlying miR-153-induced neural differentiation remain unclear. To explore the molecular mechanism of miR-153 on neural differentiation, we performed RNA sequencing on miR-153-overexpressed HT-22 cells. Based on RNA sequencing, differentially expressed genes (DEGs) and pathways in miR-153-overexpressed cells were identified. The Database for Annotation, Visualization and Integrated Discovery and Gene Set Enrichment Analysis were used to perform functional annotation and enrichment analysis of DEGs. Targetscan predicted the targets of miR-153. The Search Tool for the Retrieval of Interacting Genes and Cytoscape, were used to construct protein-protein interaction networks and identify hub genes. Q-PCR was used to detect mRNA expression of the identified genes. The expression profiles of the identified genes were compared between embryonic days 9.5 (E9.5) and E11.5 in the embryotic mouse brain of the GDS3442 dataset. Cell Counting Kit-8 assay was used to determine cell proliferation and cellular susceptibility to amyloid ß-protein (Aß) toxicity in miR-153-overexpressed cells. The results indicated that miR-153 increased cell adhesion/Ca2+ (Cdh5, Nrcam, and P2rx4) and Bdnf/Ntrk2 neurotrophic signaling pathway, and decreased ion channel activity (Kcnc3, Kcna4, Clcn5, and Scn5a). The changes in the expression of the identified genes in miR-153-overexpressed cells were consistent with the expression profile of GDS3442 during neural differentiation. In addition, miR-153 overexpression decreased cellular susceptibility to Aß toxicity in HT-22 cells. In conclusion, miR-153 overexpression may promote neural differentiation by inducing cell adhesion and the Bdnf/Ntrk2 pathway, and regulating electrophysiological maturity by targeting ion channels. MiR-153 may play an important role in neural differentiation; the findings provide a useful therapeutic direction for neurodegenerative diseases.

Unveiling the regulatory mechanism of poly-γ-glutamic acid on soil characteristics under drought stress through integrated metagenomics and metabolomics analysis.

It is of utmost importance to understand the characteristics and regulatory mechanisms of soil in order to optimize soil management and enhance crop yield. Poly-γ-glutamic acid (γ-PGA), a stress-resistant amino acid polymer, plays a crucial role in plant drought stress resistance. However, little is known about the effects of γ-PGA on soil characteristics during drought treatments. In this study, the effects of different forms of γ-PGA on soil texture and basic physical and chemical properties under short-term drought conditions were investigated. Furthermore, the impact of γ-PGA on the microbial community and metabolic function of maize was analyzed. Under drought conditions, the introduction of γ-PGA into the soil resulted in notable improvements in the mechanical composition ratio and infiltration capacity of the soil. Concurrently, this led to a reduction in soil bulk density and improved soil organic matter content and fertility. Additionally, metagenomic analysis revealed that under drought conditions, the incorporation of γ-PGA into the soil enhanced the soil microbiota structure. This shift led to the predominance of bacteria that are crucial for carbon, nitrogen, and phosphorus cycles in the soil. Metabolomics analysis revealed that under drought treatment, γ-PGA affected soil metabolic patterns, with a particular focus on alterations in amino acid and vitamin metabolism pathways. Correlation analysis between the soil metagenome and metabolites showed that microorganisms played a significant role in metabolite accumulation. These results demonstrated that γ-PGA could improve soil characteristics under drought conditions and play an important role in soil microorganisms and microbial metabolism, providing further insights into the changes in soil characteristics under drought conditions.

Nitric Oxide Ameliorates the Effects of Hypoxia in Mice by Regulating Oxygen Transport by Hemoglobin.

Xiaoying Zhou, Wenting Su, Quanwei Bao, Yu Cui, Xiaoxu Li, Yidong Yang, Chengzhong Yang, Chengyuan Wang, Li Jiao, Dewei Chen, and Jian Huang. Nitric oxide ameliorates the effects of hypoxia in mice by regulating oxygen transport by hemoglobin. High Alt Med Biol. 25:174-185, 2024.-Hypoxia is a common pathological and physiological phenomenon in ischemia, cancer, and strenuous exercise. Nitric oxide (NO) acts as an endothelium-derived relaxing factor in hypoxic vasodilation and serves as an allosteric regulator of hemoglobin (Hb). However, the ultimate effects of NO on the hematological system in vivo remain unknown, especially in extreme environmental hypoxia. Whether NO regulation of the structure of Hb improves oxygen transport remains unclear. Hence, we examined whether NO altered the oxygen affinity of Hb (Hb-O2 affinity) to protect extremely hypoxic mice. Mice were exposed to severe hypoxia with various concentrations of NO, and the survival time, exercise capacity, and other physical indexes were recorded. The survival time was prolonged in the 5 ppm NO (6.09 ± 1.29 minutes) and 10 ppm NO (6.39 ± 1.58 minutes) groups compared with the 0 ppm group (4.98 ± 1.23 minutes). Hypoxia of the brain was relieved, and the exercise exhaustion time was prolonged when mice inhaled 20 ppm NO (24.70 ± 6.87 minutes vs. 20.23 ± 6.51 minutes). In addition, the differences in arterial oxygen saturation (SO2%) (49.64 ± 7.29% vs. 42.90 ± 4.30%) and arteriovenous SO2% difference (25.14 ± 8.95% vs. 18.10 ± 6.90%) obviously increased. In ex vivo experiments, the oxygen equilibrium curve (OEC) left shifted as P50 decreased from 43.77 ± 2.49 mmHg (0 ppm NO) to 40.97 ± 1.40 mmHg (100 ppm NO) and 38.36 ± 2.78 mmHg (200 ppm NO). Furthermore, the Bohr effect of Hb was enhanced by the introduction of 200 ppm NO (-0.72 ± 0.062 vs.-0.65 ± 0.051), possibly allowing Hb to more easily offload oxygen in tissue at lower pH. The crystal structure reveals a greater distance between Asp94ß-His146ß in nitrosyl -Hb(NO-Hb), NO-HbßCSO93, and S-NitrosoHb(SNO-Hb) compared to tense Hb(T-Hb, 3.7 Å, 4.3 Å, and 5.8 Å respectively, versus 3.5 Å for T-Hb). Moreover, hydrogen bonds were less likely to form, representing a key limitation of relaxed Hb (R-Hb). Upon NO interaction with Hb, hydrogen bonds and salt bridges were less favored, facilitating relaxation. We speculated that NO ameliorated the effects of hypoxia in mice by promoting erythrocyte oxygen loading in the lung and offloading in tissues.

Hypoxia-Induced Myocardial Hypertrophy Companies with Apoptosis Enhancement and p38-MAPK Pathway Activation.

Li, Xiaoxu, Zhijun Pu, Gang Xu, Yidong Yang, Yu Cui, Xiaoying Zhou, Chenyuan Wang, Zhifeng Zhong, Simin Zhou, Jun Yin, Fabo Shan, Chengzhong Yang, Li Jiao, Dewei Chen, and Jian Huang. Hypoxia-induced myocardial hypertrophy companies with apoptosis enhancement and p38-MAPK pathway activation. High Alt Med Biol. 25:186-196, 2024. Background: Right ventricular function and remodeling are closely associated with symptom severity and patient survival in hypoxic pulmonary hypertension. However, the detailed molecular mechanisms underlying hypoxia-induced myocardial hypertrophy remain unclear. Methods: In Sprague-Dawley rats, hemodynamics were assessed under both normoxia and hypobaric hypoxia at intervals of 7 (H7), 14 (H14), and 28 (H28) days. Morphological changes in myocardial tissue were examined using hematoxylin and eosin (HE) staining, while myocardial hypertrophy was evaluated with wheat germ agglutinin (WGA) staining. Apoptosis was determined through TUNEL assays. To further understand the mechanism of myocardial hypertrophy, RNA sequencing was conducted, with findings validated via Western blot analysis. Results: The study demonstrated increased hypoxic pulmonary hypertension and improved right ventricular diastolic and systolic function in the rat models. Significant elevations in pulmonary arterial systolic pressure (PASP), mean pulmonary arterial pressure (mPAP), right ventricular mean pressure (RVMP), and the absolute value of +dp/dtmax were observed in the H14 and H28 groups compared with controls. In addition, right ventricular systolic pressure (RVSP), -dp/dtmax, and the mean dp/dt during isovolumetric relaxation period were notably higher in the H28 group. Heart rate increased in the H14 group, whereas the time constant of right ventricular isovolumic relaxation (tau) was reduced in both H14 and H28 groups. Both the right heart hypertrophy index and the heart weight/body weight ratio (HW/BW) were elevated in the H14 and H28 groups. Myocardial cell cross-sectional area also increased, as shown by HE and WGA staining. Western blot results revealed upregulated HIF-1α levels and enhanced HIF-2α expression in the H7 group. In addition, phosphorylation of p38 and c-fos was augmented in the H28 group. The H28 group showed elevated levels of Cytochrome C (Cyto C), whereas the H14 and H28 groups exhibited increased levels of Cleaved Caspase-3 and the Bax/Bcl-2 ratio. TUNEL analysis revealed a rise in apoptosis with the extension of hypoxia duration in the right ventricle. Conclusions: The study established a link between apoptosis and p38-MAPK pathway activation in hypoxia-induced myocardial hypertrophy, suggesting their significant roles in this pathological process.

Artemdubosides A-G, seven unusual polyacetylenes from Artemisia dubia var. subdigitata and their antihepatoma activity.

Artemdubosides A-E (1-5), the first examples of natural polyacetylenes substituted by 6'-O-crotonyl ß-glucopyranoside, and artemdubosides F-G (6-7) that were two unusual polyacetylenes featuring a 6'-O-acetyl ß-glucopyranoside moiety, were isolated from Artemisia dubia var. subdigitata. Their structures were elucidated based on the spectral data including HRESIMS, UV, IR, 1D and 2D NMR, and ECD calculations. Antihepatoma assay suggested that compound 1 exhibited activity against HepG2, Huh7, and SK-Hep-1 cells with inhibitory ratios of 77.1%, 90.8%, and 73.1% at 200.0 µM, respectively.

Dissecting the mechanism of atlastin-mediated homotypic membrane fusion at the single-molecule level.

Homotypic membrane fusion of the endoplasmic reticulum (ER) is mediated by dynamin-like GTPase atlastin (ATL). This fundamental process relies on GTP-dependent domain rearrangements in the N-terminal region of ATL (ATLcyto), including the GTPase domain and three-helix bundle (3HB). However, its conformational dynamics during the GTPase cycle remain elusive. Here, we combine single-molecule FRET imaging and molecular dynamics simulations to address this conundrum. Different from the prevailing model, ATLcyto can form a loose crossover dimer upon GTP binding, which is tightened by GTP hydrolysis for membrane fusion. Furthermore, the α-helical motif between the 3HB and transmembrane domain, which is embedded in the surface of the lipid bilayer and self-associates in the crossover dimer, is required for ATL function. To recycle the proteins, Pi release, which disassembles the dimer, activates frequent relative movements between the GTPase domain and 3HB, and subsequent GDP dissociation alters the conformational preference of the ATLcyto monomer for entering the next reaction cycle. Finally, we found that two disease-causing mutations affect human ATL1 activity by destabilizing GTP binding-induced loose crossover dimer formation and the membrane-embedded helix, respectively. These results provide insights into ATL-mediated homotypic membrane fusion and the pathological mechanisms of related disease.

Interface fluid syndrome caused by the corneal perforation injury after small incision lenticule extraction: a case report.

BACKGROUND: To report a case of interface fluid syndrome (IFS) following traumatic corneal perforation repair after small incision lenticule extraction (SMILE). CASE PRESENTATION: A 23-year-old woman, with a past history of SMILE, was struck in the left eye with a barbecue prod and subsequently underwent corneal perforation repair at local hospital. Primary wound repaired with a single 10 - 0 nylon suture at the area of leakage. After the surgery, her best corrected visual acuity (BCVA) was 20/30. Four days later, she presented at our hospital with blurred vision, and interface fluid syndrome (IFS) was diagnosed. Intraoperative optical coherence tomography (iOCT) was used to guide the resuturing of the corneal perforation in the left eye, followed by anterior chamber gas injection. At the first postoperative month, the BCVA was 20/25. The corneal cap adhered closely to the stroma, the surface became smooth. CONCLUSIONS: This case illustrates that any corneal perforation following lamellar surgery, including SMILE, may lead to IFS. It is crucial to consider the depth of corneal perforation, and intraoperative optical coherence tomography (iOCT) plays a unique role in the repair procedure.

Clinical Observation on the Modified Huangan Lipi Decoction Combined with Acupuncture at Sifeng Points in the Treatment of Children with Tic Disorders / 广州中医药大学学报

Objective To observe the clinical efficacy of the modified Huangan Lipi Decoction(mainly composed of Sclerotium Poriae Pararadicis,Paeoniae Radix Alba,Atractylodis Macrocephalae Rhizoma,Polygalae Radix,Acori Tatarinowii Rhizoma,and Curcumae Radix)combined with acupuncture at Sifeng(EX-UE10)points in the treatment of children with tic disorders(TD).Methods Seventy cases of TD children with spleen deficiency and liver hyperactivity syndrome were randomly divided into the treatment group and the control group,with 35 cases in each group.The control group was treated with conventional western medicine of Tiapride Hydrochloride Tablets,while the treatment group was treated with the combination of the modified Huangan Lipi Decoction and acupuncture at Sifeng points.Both groups were treated for 8 weeks.The changes of the Yale Global Tic Severity Scale(YGTSS)item scores of tic muscle group,tic frequency,tic intensity,complexity and interference degree as well as their total scores in the two groups were observed before and after treatment.Moreover,the clinical efficacy and safety in the two groups were evaluated.Results(1)After 8 weeks of treatment,the total effective rate of the treatment group was 88.57%(31/35),and that of the control group was 68.57%(24/35).The intergroup comparison showed that the total effective rate(tested by chi-square test)and the overall therapeutic efficacy(tested by rank-sum test)of the treatment group were significantly superior to those of the control group,and the differences were statistically significant(P＜0.05).(2)After treatment,the YGTSS item scores of tic muscle group,tic frequency,tic intensity,complexity and interference degree as well as their total scores in the two groups were significantly lower than those before treatment(P＜0.01),and the effect on lowering the above scores of the treatment group was significantly superior to that of the control group,the differences being all statistically significant(P＜0.01).(3)During the treatment,the incidence of adverse reactions in the treatment group was 2.86%(1/35)and that in the control group was 8.57%(3/35).The intergroup comparison showed that the incidence of adverse reactions in the treatment group tended to be lower than that of the control group,but the difference was not statistically significant(P＞0.05).Conclusion Modified Huangan Lipi Decoction combined with acupuncture at Sifeng points exert certain effect in the treatment of TD children with spleen deficiency and liver hyperactivity syndrome,and its efficacy is superior to that of the western medicine Tiapride Hydrochloride Tablets.

Factors influencing allogeneic platelet concentrate in chronic refractory wounds / 中国组织工程研究

BACKGROUND:Clinical application of autologous platelet-rich plasma is limited by the condition of patients and by the quantity and activity of platelets.Transfusable platelet component blood platelet concentrates,collected and prepared by blood collection and supply agencies,are widely available,can be standardized and are effective in the clinic. OBJECTIVE:To review the factors influencing the preparation of platelet concentrate by the buffy-coat method for the treatment of chronic refractory wounds. METHODS:A computer search of the PubMed,CNKI,and WanFang databases for platelet-related articles from January 2000 to April 2023 was conducted using the Chinese and English search terms"allogeneic platelets(concentrate),buffy-coat method,skin ulcer,refractory wounds".The titles and abstracts were screened,and the full text was reviewed,resulting in the inclusion of 51 articles that met the subject criteria. RESULTS AND CONCLUSION:(1)Platelet concentrates supplied by blood collection and supply agencies are effective in the treatment of diabetic foot wounds,pressure sores,lower limb venous ulcers and other chronic refractory wounds:reducing the size of the ulcer and shortening the wound healing time,especially in the first two weeks,with significant healing-promoting effects.(2)The storage conditions of the raw material used to prepare platelet concentrates(whole blood overnight/buffy-coat overnight,shaking/resting(time)),centrifugation conditions(centrifugation parameters,canning method)and the structure of the blood bag can affect the concentration of platelet concentrates,indirectly affecting the efficacy of allogeneic platelet concentrates.(3)There are also some problems with studies of allogeneic platelet concentrates for the treatment of chronic refractory wounds,such as the sample size of the available evidence is small,the results lack the optimal preparation parameters,optimal dose and treatment regimen for platelet concentrates to promote healing of different wounds are unknown,so more randomized multicenter clinical studies are needed.

Factors influencing success of external cephalic version: analysis of 118 cases / 中华围产医学杂志

Objective:To investigate the factors influencing the success of external cephalic version.Methods:Pregnant women who underwent an external cephalic version due to breech or transverse presentation by the same operator in the Third Affiliated Hospital of Zhengzhou University from July 2015 to July 2021 were selected as the study objects. Univariate analysis and logistic regression analysis were used to explore the clinical factors influencing the success of the external cephalic version. The receiver operating characteristic (ROC) curve was used to analyze the best cut-off value of gestational week and amniotic fluid index at the time of operation and to evaluate the predictive value of the influencing factors on the success of the external cephalic version.Results:(1) A total of 118 cases finally entered this study. Among the 118 cases,77 cases (65.3%) succeeded in the external cephalic version, among which the success rate was 49.1% (27/55) for primipara and 79.4% (50/63) for multipara. The vaginal delivery rate was 56.8% (67/118). (2) Complications occurred in 19 (16.1%) of the 118 cases. The main complications were abnormal fetal heart rate (13 cases, 11.0%), umbilical cord presentation, and fetal position reversion (two cases and 1.7% in each), and the serious complications were intrauterine fetal death and placental abruption (one case and 0.8% in each).The complication rate of patients with successful external cephalic version was 7.8% (6/77), which was lower than that of those who failed the external cephalic version [31.7%(13/41)] ( χ 2=11.33, P=0.001). (3) Multivariate analysis showed that gestational week at surgery before 38, amniotic fluid index >11.10 cm, and multipara were the factors affecting the success of the external cephalic version [ OR(95% CI)=0.561(0.351-0.897), 1.173(1.018-1.351) and 4.201(1.547-11.404), all P<0.05]. (4) The area under the ROC curve of the combination of the gestational week at surgery, amniotic fluid index, and parity was 0.744 (95% CI: 0.640-0.848, P<0.001), and the Youden index was 0.518, with a sensitivity of 70.0% and a specificity of 81.8%. Conclusion:Gestational weeks, amniotic fluid index, and multipara are related to the success of the external cephalic version, and the combination of the three has certain predictive power for the success of the surgery.

Impact of lithocholic acid on the osteogenic and adipogenic differentiation balance of bone marrow mesenchymal stem cells / 中国修复重建外科杂志

OBJECTIVE@#To Investigate the effects of lithocholic acid (LCA) on the balance between osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs).@*METHODS@#Twelve 10-week-old SPF C57BL/6J female mice were randomly divided into an experimental group (undergoing bilateral ovariectomy) and a control group (only removing the same volume of adipose tissue around the ovaries), with 6 mice in each group. The body mass was measured every week after operation. After 4 weeks post-surgery, the weight of mouse uterus was measured, femur specimens of the mice were taken for micro-CT scanning and three-dimensional reconstruction to analyze changes in bone mass. Tibia specimens were taken for HE staining to calculate the number and area of bone marrow adipocytes in the marrow cavity area. ELISA was used to detect the expression of bone turnover markers in the serum. Liver samples were subjected to real-time fluorescence quantitative PCR (RT-qPCR) to detect the expression of key genes related to bile acid metabolism, including cyp7a1, cyp7b1, cyp8b1, and cyp27a1. BMSCs were isolated by centrifugation from 2 C57BL/6J female mice (10-week-old). The third-generation cells were exposed to 0, 1, 10, and 100 μmol/L LCA, following which cell viability was evaluated using the cell counting kit 8 assay. Subsequently, alkaline phosphatase (ALP) staining and oil red O staining were conducted after 7 days of osteogenic and adipogenic induction. RT-qPCR was employed to analyze the expressions of osteogenic-related genes, namely ALP, Runt-related transcription factor 2 (Runx2), and osteocalcin (OCN), as well as adipogenic-related genes including Adiponectin (Adipoq), fatty acid binding protein 4 (FABP4), and peroxisome proliferator-activated receptor γ (PPARγ).@*RESULTS@#Compared with the control group, the body mass of the mice in the experimental group increased, the uterus atrophied, the bone mass decreased, the bone marrow fat expanded, and the bone metabolism showed a high bone turnover state. RT-qPCR showed that the expressions of cyp7a1, cyp8b1, and cyp27a1, which were related to the key enzymes of bile acid metabolism in the liver, decreased significantly ( P<0.05), while the expression of cyp7b1 had no significant difference ( P>0.05). Intervention with LCA at concentrations of 1, 10, and 100 μmol/L did not demonstrate any apparent toxic effects on BMSCs. Furthermore, LCA inhibited the expressions of osteogenic-related genes (ALP, Runx2, and OCN) in a dose-dependent manner, resulting in a reduction in ALP staining positive area. Concurrently, LCA promoted the expressions of adipogenic-related genes (Adipoq, FABP4, and PPARγ), and an increase in oil red O staining positive area.@*CONCLUSION@#After menopause, the metabolism of bile acids is altered, and secondary bile acid LCA interferes with the balance of osteogenic and adipogenic differentiation of BMSCs, thereby affecting bone remodelling.