ObjectiveTo investigate the role of DEAD-box helicase 3 X-linked （DDX3X） in immune-mediated liver injury （ILI）， and to clarify its mechanism by regulating endoplasmic reticulum stress （ERS）-dependent apoptotic pathway and its association with the clinical progression of hepatitis B. MethodsMice were given injection of concanavalin A （ConA） via the caudal vein to establish a model of ILI， PBS （control group） and different concentrations of ConA were injected into the tail vein of hepatocyte-specific DDX3X-knockout mice （DDX3X^ΔHep and DDX3X-flox mice （DDX3X^fl/fl）， respectively.. The log-rank survival analysis， measurement of the serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT）， and HE staining of liver tissue were performed to assess liver injury， and qRT-PCR and Western Blot were used to measure the mRNA and protein expression levels of glucose-regulated protein 78 （GRP78）， CCAAT/enhancer-binding protein homologous protein （CHOP）， and DDX3X in liver tissue. Intraperitoneal injection of 4-phenylbutyric acid （4-PBA， 100 mg/kg） was performed to inhibit ERS. Serum samples （n=30） and liver tissue samples （n=6） were collected from healthy controls， chronic hepatitis B （CHB） patients， and hepatitis B virus-associated liver failure （HBV-LF） patients； ELISA was used to measure the serum level of DDX3X， and qRT-PCR/Western Blot was used to analyze the expression of targets in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the control group of mice， the expression of DDX3X in the liver of mice induced by ConA was significantly increased after liver injury （P<0.05）， and hepatocyte-specific DDX3X knockout increased the 72-hour survival rate of mice by 55% （compared with 20% in the DDX3X^fl/fl group）， with significant reductions in the serum levels of ALT and AST （P<0.000 1） and the expression levels of the ERS markers GRP78 and CHOP （P<0.05）. After ERS was inhibited by 4-PBA， there was alleviation of liver injury （with reductions in ALT and AST， P <0.001） and a reduction in DDX3X expression （P<0.01）. The analysis of clinical samples showed that the mRNA and protein expression levels of liver DDX3X in CHB patients and HBV-LF patients were significantly higher than those in healthy controls （all P<0.01）， and there was a significant increase in the serum level of DDX3X in HBV-LF patients （P<0.000 1）. ConclusionDDX3X exacerbates ILI by regulating the ERS-dependent apoptotic pathway （GRP78/CHOP）， and its expression is associated with the progression of hepatitis B. Therefore， it can be used as a potential therapeutic target.

Five compounds were isolated and purified from the water extract of Elaeagnus oxycarpa Schlechtend leaf by multi-dimensional reversed-phase preparative liquid chromatographic system based on the separation and enrichment model. Their structures were identified by spectral analysis such as NMR, MS, UV, IR and by comparison with literature information as 2,4(1H,3H)-pyrimidinedione (1), elaeagnussugarester B (2), elaeagnussugarester A (3), elaeagnussugarester C (4), gallic acid (5). Compounds 2-4 are new compounds, compound 1 was isolated from Elaeagnus oxycarpa Schlechtend for the first time. The antioxidant and anti-tyrosinase activities of these compounds were evaluated by using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical method, the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical method, the potassium ferricyanide reduction method and the colorimetric method with L-tyrosine as substrate. The results showed that compounds 2-5 have good antioxidant activities and inhibitory effect on tyrosinase. Compound 4 exhibited the most strong antioxidant activities, with IC₅₀ = 3.59 ± 0.06 μmol·L^-1 for DPPH free radical scavenging ability, IC₅₀ = 10.04 ± 0.20 μmol·L^-1 for ABTS free radical scavenging ability, and total reduction capacity of compound 4 was better than vitamin C respectively. Compound 3 possessed better inhibitory effect on tyrosinase with IC₅₀ = 0.25 ± 0.06 mmol·L^-1.

Objective To analyze the characteristics of adverse drug reactions （ADR） reported in Sixth People’s Hospital South Campus, Shanghai Jiaotong University from 2021 to 2023, to provide reference for promoting rational clinical drug use. Methods ADR data reported in our hospital were collected retrospectively, including patients’ basic information, drugs causing adverse reactions, types of adverse reactions and outcomes. Descriptive analysis methods were used to summarize and analyze the data. Results A total of 979 cases of ADR were reported in our hospital from 2021 to 2023. The highest proportion of patients with ADR occurred in the age range of 31 to 50, and more male patients （63.5%）. The top five drugs involved with adverse reactions were antibiotics （48.8%）, Chinese medicine injections（19.2%）, vitamins（7.5%）, Chinese traditional medicine（7.2%）, equine tetanus immunoglobulin（6.3%）. Among antibiotics, cefuroxime, ceftazidime and cefotiam were the majority. The organs/systems involved in all ADR were mainly skin and accessories damage （55.4%）. The clinical manifestations were rash, itching, and maculopapular rash. Conclusion From 2021 to 2023, the most common drugs causing adverse drug reactions in our hospital were mainly antibacterial drugs, and the rational clinical use of antibacterial drugs still needs to be concerned.

Objective: To investigate the mechanism of in alleviating colonic mucosal inflammation in ten-eleven translocation (TET) protein 2 gene knockout (TET2-/-) mice with ulcerative colitis (UC) by regulating DNA methyltransferase (DNMT) and DNA hydroxymethylase. Methods: Male specific pathogen-free (SPF) grade C57BL/6J wild-type (WT) mice (n = 8) and TET2-/- mice (n = 20) were used to establish UC models by freely drinking 3% dextran sulfate sodium solution for 7 d. After UC model validation through histopathological examination in two mice from each type, the remaining mice were divided into four groups (n = 6 in each group): WT model (WT + UC), TET2-/- model (TET2-/- + UC), TET2-/- mild moxibustion (TET2-/- + MM), and TET2-/- electroacupuncture (TET2-/- + EA) groups. TET2-/- + MM group received mild moxibustion on Tianshu (ST25) and Qihai (CV6) for 10 min daily for 7 d. The TET2-/- + EA group also applied electroacupuncture (1 mA, 2/100 Hz) at the same acupoints for 10 min daily for 7 d. The disease activity index (DAI) scores of each group of mice were accessed daily. The colon lengths of mice in groups were measured following intervention. The pathological changes in the colon tissues were observed with hematoxylin and eosin (HE) staining. The concentrations of interleukin (IL)-6, C-C motif chemokine 17 (CCL17), and C-X-C motif chemokine ligand 10 (CXCL10) in serum were detected by enzyme-linked immunosorbent assay (ELISA). The expression of DNMT proteins (DNMT1, DNMT3A, and DNMT3B) in the colon tissues was detected by immunohistochemistry. The expression of 5-methylcytosine (5-mC), 5-hydroxymethylcytosine (5-hmC), histone deacetylase 2 (HDAC2), and DNA hydroxymethylase family proteins (TET 1 and TET3) was detected using immunofluorescence, which also determined the co-localization of TET1 and IL-6 protein. Results: Compared with WT + UC group, TET2-/- + UC group exhibited significantly higher DAI scores and shorter colon lengths (P < 0.01). Both mild moxibustion and electroacupuncture significantly decreased DAI scores and ameliorated colon shortening in TET2-/- mice (P < 0.001). Histopathological scores of TET2-/- + UC mice were significantly higher than those of WT + UC group (P < 0.001) and were significantly reduced after both mild moxibustion and electroacupuncture interventions (P < 0.001). Serum levels of IL-6, CCL17, and CXCL10 were significantly elevated in TET2-/- + UC group compared with WT + UC group (P < 0.001). Mild moxibustion significantly reduced IL-6, CCL17, and CXCL10 levels (P < 0.001, P < 0.001, and P < 0.01, respectively), while electroacupuncture also significantly reduced IL-6, CCL17, and CXCL10 levels (P < 0.05, P < 0.01, and P < 0.01, respectively). TET2-/- + UC mice showed increased expression levels of DNMT1, DNMT3A , DNMT3B, and 5-mC (P < 0.05, P < 0.01 and P < 0.001, respectively), with decreased expression levels of TET1, TET3, 5-hmC, and HDAC2 (P < 0.001). Mild moxibustion significantly reduced DNMT1, DNMT3B, and 5-mC levels (P < 0.05, P < 0.01, and P < 0.001, respectively), while increasing expression levels of TET1, TET3, 5-hmC, and HDAC2 (P < 0.001, P < 0.001, P < 0.05, and P < 0.001, respectively). Electroacupuncture significantly decreased 5-mC and DNMT3B levels (P < 0.001 and P < 0.01, respectively) and increased 5-hmC and HDAC2 levels (P < 0.05 and P < 0.001, respectively), but did not significantly affect TET1 and TET3 expression (P > 0.05). Compared with TET2-/- + MM group, TET2-/- + EA group showed significantly higher 5-mC expression (P < 0.001). TET2-/- + UC group exhibited markedly increased IL-6 expression and higher co-localization of TET1 and IL-6 in mucosal epithelium, whereas minimal IL-6 expression was observed in the other groups. Conclusion Mild moxibustion and electroacupuncture significantly ameliorate colonic inflammation exacerbated by TET2 deficiency in UC mice via epigenetic modulation. Distinct mechanisms exist between the two interventions: mild moxibustion regulates both DNMT and hydroxymethylase, whereas electroacupuncture primarily affects DNMT.

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans ; Nasal Cavity/surgery* ; Nasal Surgical Procedures ; China ; Consensus ; Sinusitis/surgery* ; Dermal Fillers

Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.

In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

OBJECTIVES: To explore the mechanism of Lacticaseibacillus paracasei E6 for improving vinorelbine-induced immunosuppression in zebrafish. METHODS: The intestinal colonization of L. paracasei E6 labeled by fluorescein isothiocyanate (FITC) in zebrafish was observed under fluorescence microscope. In a zebrafish model of vinorelbine-induced immunosuppression, the immunomodulatory activity of L. paracasei E6 was assessed by analyzing macrophage and neutrophil counts in the caudal hematopoietic tissue (CHT), the number of T-lymphocyte, and the expressions of interleukin-12 (IL-12) and interferon-γ (IFN-γ). The contents of short-chain fatty acids (SCFAs) in L. paracasei E6 fermentation supernatant and the metabolites of L. paracasei E6 in zebrafish were detected by LC-MS/MS-based targeted metabolomics. The immunomodulatory effects of the SCFAs including sodium acetate, sodium propionate and sodium butyrate were evaluated in the zebrafish model of immunosuppression. RESULTS: After inoculation, green fluorescence of FITC-labeled L. paracasei E6 was clearly observed in the intestinal ball, midgut and posterior gut regions of zebrafish. In the immunocompromised zebrafish model, L. paracasei E6 significantly alleviated the reduction of macrophage and neutrophil counts in the CHT, increased the fluorescence intensity of T-lymphocytes, and promoted the expressions of IL-12 and IFN-γ. Compared with MRS medium, L. paracasei E6 fermentation supernatant showed significantly higher levels of acetic acid, propionic acid and butyric acid, which were also detected in immunocompromised zebrafish following treatment with L. paracasei E6. Treatment of the zebrafish model with sodium acetate and sodium propionate significantly increased macrophage and neutrophil counts in the CHT and effectively inhibited vinorelbine-induced reduction of thymus T cells. CONCLUSIONS L. paracasei E6 can improve vinorelbine-induced immunosuppression in zebrafish through its SCFA metabolites acetic acid and propionic acid.
Animals ; Zebrafish/immunology* ; Acetic Acid/metabolism* ; Propionates/metabolism* ; Fatty Acids, Volatile/metabolism*