Associations between rheumatoid arthritis and intestinal flora, with special emphasis on RA pathologic mechanisms to treatment strategies.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that primarily affects the joints. Individuals at risk for RA and people with RA develop intestinal dysbiosis. The changes in intestinal flora composition in preclinical and confirmed RA patients suggest that intestinal flora imbalance may play an important role in the induction and persistence of RA. METHODS: Based on the current research on the interaction between RA and intestinal microbiota, intestinal microbiota metabolites and intestinal barrier changes. This paper systematically summarized the changes in intestinal microbiota in RA patients, the metabolites of intestinal flora, and the influence mechanism of intestinal barrier on RA, and further discussed the influence of drugs for RA on intestinal flora and its mechanism of action. RESULTS: Compared with healthy controls, α diversity analysis of intestinal flora showed no significant difference, ß diversity analysis showed significant differences. The intestinal flora produces bioactive metabolites, such as short-chain fatty acids and aromatic amino acids, which have anti-inflammatory effects. Abnormal intestinal flora leads to impaired barrier function and mucosal immune dysfunction, promoting the development of inflammation. Traditional Chinese medicine (TCM) and chemical drugs can also alleviate RA by regulating intestinal flora, intestinal flora metabolites, and intestinal barrier. Intestinal flora is closely related to the pathogenesis of RA and may become potential biomarkers for the diagnosis and treatment of RA. CONCLUSIONS: Intestinal flora and its metabolites play an important role in the pathogenesis of autoimmune diseases such as RA, and are expected to become a new target for clinical diagnosis and treatment, providing a new idea for targeted treatment of RA.

[Cuiru Keli Improves Postpartum Hypogalactia in Rats Through Secreted Frizzled-Related Protein 2-Wnt/ß-catenin Signaling Pathway]. / 催乳颗粒通过分泌Frizzledç›¸å ³è›‹ç™½2-Wnt/ß-cateninä¿¡å·é€šè·¯æ”¹å–„å¤§é¼ äº§åŽç¼ºä¹³.

Objective: Based on the secreted frizzled-related protein 2 (SFRP2)-Wnt/ß-catenin signaling pathway, this study explored the effect and mechanism of Cuiru Keli (CRKL) in the treatment of postpartum hypogalactia. Methods: A rat model of postpartum hypogalactia was established by gavaging 2 mL of 1.6 mg/mL bromocriptine mesylate to female rats on the third day after delivery. Female rats with a delivery time difference of less than 48 hours were selected and randomly assigned to 7 groups, including a normal group (without any modeling or medication), a model group, a CRKL low-dose group of model group model rats receiving CRKL at the dose of 3 g/kg, a CRKL medium-dose group of model rats receiving CRKL at the dose of 6 g/kg, a CRKL high-dose group of model rats receiving CRKL at the dose of 9 g/kg, a positive drug group of model rats receiving domperidone at the dose of 3 mg/kg, and a negative control (NC) group of model rats receiving normal saline. Each group contained 6 rats. Except for the normal and model groups, the remaining 5 groups were continuously administered with the respective intervention drugs at the specified doses by gavage once a day for 10 days. Changes in the total litter mass of the offspring in the 7 groups within 10 days were measured, and HE staining was performed to identify pathological changes in the mammary tissue (MT). Six groups of rats (excluding the positive control group) were used to observe the pathological changes of eosinophils in pituitary tissue. ELISA was performed to determine the content of prolactin (PRL) in serum, immunohistochemical staining was used to determine the expression of prolactin receptor (PRLR) in MT, and RT-qPCR was used to determine the mRNA expression of genes related to lactation in MT. Network pharmacology and molecular docking were used to study the therapeutic effect and mechanism of CRKL on postpartum hypogalactia, particularly whether it acted through the SFRP2-Wnt/ß-catenin signaling pathway. The mechanism of CRKL treatment was further validated by detecting mRNA (RT-qPCR) and protein expression (Western blot) of related pathway genes. Cell experiments were conducted using primary culture rat mammary epithelial cells (RMEC) from rat MT. RMEC were divided into four groups, including a normal group (primary culture RMEC, untreated), SFRP2 overexpression group (primary cultured RMEC treated with SFRP2 overexpression vector), SFRP2 overexpression+CRKL group (receiving treatment for SFRP2 overexpression group plus 10% drug-containing serum), and negative control group (primary culture RMEC treated with empty vector). The effect of CRKL on the expression of lactation-related genes FASN, CSN2, and GLUT1 mRNA after SFRP2 overexpression was detected by RT-qPCR. Results: In this study, CRKL was administered at a dose of 3 g/kg in the CRKL low-dose group, 6 g/kg in the medium-dose group, and 9 g/kg in the high-dose group (P<0.05 or P<0.01). Compared with the model group, CRKL at all doses significantly increased the total litter weight gain of the offsprings within 10 days (P<0.05 or P<0.01), and effectively increased lactation (P<0.01), the area of mammary lobules, and the size and filling of acinar cavities. CRKL at all doses also increased the number of eosinophils that secreted PRL in the pituitary gland of the postpartum hypogalactia rat model, and increased the content of PRL in the serum (P<0.05 or P<0.01). CRKL promoted the secretion and expression of PRL in postpartum hypogalactic model rats. In addition, it significantly promoted the expression of genes related to milk fat, milk protein, and lactose synthesis in MT (P<0.05 or P<0.01). Network pharmacology predicted that the Wnt signaling pathway might be a key pathway for CRKL in treating postpartum hypogalactia. The molecular docking results showed that related chemical components in CRKL had good binding ability with CCND1 and SFRP2. Compared with the model group, CRKL at all doses inhibited the expression of SFRP2 gene in vivo (P<0.01) and activated the mRNA and protein expression of CCND1 and c-Myc in the Wnt/ß-catenin signaling pathway in MT (P<0.05 or P<0.01). Cell experiments showed that, compared to the normal group, SFRP2 overexpression reduced the mRNA expression of milk synthesis-related genes FASN, CSN2, and GLUT1 in RMEC (P<0.01). The CCK8 results indicated that 10% of the drug-containing serum was the effective concentration administered to cells (P<0.01). After administering drug-containing serum, the expression of the lactation-related genes FASN, CSN2, and GLUT1 were up-regulated (compared with the SFRP2 overexpression group, P<0.01). Conclusion: CRKL alleviates postpartum hypogalactia through the SFRP2-Wnt/ß-catenin signaling pathway. SFRP2 might be a potential new target for the diagnosis and treatment of postpartum hypogalactia. This reveals a new mechanism of CRKL in treating postpartum hypogalactia and promotes its clinical application.

[Mechanism of Huangqin Qingre Chubi Capsules in improving rheumatoid arthritis based on METTL3-SFRP4/Wnt/ß-catenin pathway].

The effect and mechanism of Huangqin Qingre Chubi Capsules(HQC) on rheumatoid arthritis(RA) were studied.Seventy male SPF rats were randomly divided into normal group, model group, low-(0. 18 g·kg~(-1)), middle-(0. 36 g·kg~(-1)), and high-(0. 72 g·kg~(-1)) dose groups of HQC, methotrexate group(MTX, 0. 75 mg·kg~(-1)), and negative control group(NC group, model +saline). Adjuvant arthritis fibroblast-like synoviocytes(AA-FLS) were divided into normal group, model group, low-, middle-, and high-dose groups of HQC, and negative control group. RT-qPCR and Western blot were used to detect the m RNA and protein expressions of METTL3, SFRP4, ß-catenin, CCND1, c-Myc, MMP3, and fibronectin. The protein expression of MMP3 and ß-catenin was detected by immunofluorescence. The gene expression level of METTL3 on AA-FLS was knocked down to further examine the expression of each gene. ELISA measured the levels of IL-1ß, IL-6, and IL-8. The results showed that compared with the normal group, rats in the model group found redness and swelling in their limbs and significantly increased joint swelling. Compared with the model group, the joint swelling degree of each treatment group significantly decreased(P<0. 05). The paw retraction threshold and body weight mass index both significantly increased(P<0. 05). METTL3 was highly expressed on AA and negatively correlated with the expression of SFRP4. After treatment, the m RNA and protein expression of METTL3, ß-catenin, CCND1, c-Myc, fibronectin, and MMP3 were significantly decreased on AA-FLS(P< 0. 05). Compared with the model group, knocking down METTL3 resulted in reduced m RNA and protein expression of ß-catenin, CCND1, c-Myc, fibronectin, and MMP3(P< 0. 05). At the same time, the m RNA and protein expressions of ß-catenin, CCND1, c-Myc, fibronectin, and MMP3 in the HQC+METTL3 knockdown group were significantly lower than those in the METTL3 knockdown group(P<0. 05). HQC could reduce the levels of IL-1ß, IL-6, and IL-8 to varying degrees(P<0. 05). The results indicate that HQC has a significant improvement effect on arthritis in AA rats. The expression of METTL3 is significantly increased in synovial tissue and AA-FLS of AA rats, which may be a potential target for the diagnosis and treatment of RA. HQC improves RA through the METTL3-SFRP4/Wnt/ß-catenin signaling pathway and has significant antiinflammatory and anti-rheumatic effects.

Wnt5a: A promising therapeutic target for inflammation, especially rheumatoid arthritis.

BACKGROUND: Wnt5a is a member of the Wnt protein family, which acts on classical or multiple non-classical Wnt signaling pathways by binding to different receptors. The expression regulation and signal transduction of Wnt5a is closely related to the inflammatory response. Abnormal activation of Wnt5a signaling is an important part of inflammation and rheumatoid arthritis (RA). OBJECTIVES: This paper mainly focuses on Wnt5a protein and its mediated signaling pathway, summarizes the latest research progress of Wnt5a in the pathological process of inflammation and RA, and looks forward to the main directions of Wnt5a in RA research, aiming to provide a theoretical basis for the prevention and treatment of RA diseases by targeting Wnt5a. RESULTS: Wnt5a is highly expressed in activated blood vessels, histocytes and synoviocytes in inflammatory diseases such as sepsis, sepsis, atherosclerosis and rheumatoid arthritis. It mediates the production of pro-inflammatory cytokines and chemokines, regulates the migration and recruitment of various immune effector cells, and thus participates in the inflammatory response. Wnt5a plays a pathological role in synovial inflammation and bone destruction of RA, and may be an important clinical therapeutic target for RA. CONCLUSION: Wnt5a is involved in the pathological process of inflammation and interacts with inflammatory factors. Wnt5a may be a new target for regulating the progression of RA disease and intervening therapy because of its multi-modal effects on the etiology of RA, especially as a regulator of osteoclast activity and inflammation.

An Analysis of Infection Prevention and Control Practices in Designated Hospitals that Treat COVID-19: A Systematic Review and Meta-Analysis.

Objective: The present investigation aims to conduct a comprehensive examination of the infection prevention and control efforts in hospitals of Xinjiang Production and Construction Corps designated for COVID-19 treatment. Methods: By searching the Cochrane Library, PubMed, Embase, Chinese Academic Journal, Full Text Database, Chinese Biomedical Literature Database (CBM), VIP Chinese Scientific, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Wanfang Database (CECDB), and using Review Manager 5.2 software, the quality assessment, data extraction, and meta-analysis were carried out for the included literature. Results: Between both the experimental and the control groups, there was a statistically significant difference in the level of public awareness of COVID-19 prevention and control [OR = 1.61, 95% confidence interval (CI) (1.31, 1.99), P < .00001, I2 = 32%, Z = 4]; public concern about COVID-19 prevention and control [OR = 1.56, 95% CI (1.28, 1.90), P < .0001, I2 = 0%, Z = 4.35]; public anxiety on COVID-19 prevention and control [OR = 1.67, 95% CI (1.37, 2.03), P < .00001, I2 = 32%, Z = 5.13]. Conclusion: Chinese prophylaxis and controlling measures for COVID-19 are mainly to protect vulnerable populations, cut off transmission routes, and control the source of infection. Therefore, we must also do our best to prevent and control novel coronavirus pneumonia to protect our health and reduce the burden on our country.

Inhibiting miR-129-5p alleviates inflammation and modulates autophagy by targeting ATG14 in fungal keratitis.

To investigate the role of miR-129-5p in inflammation and autophagy in fungal keratitis, we established a keratitis mouse model infected with Fusarium solani (F. solani) and conducted experiments on corneal stromal cells infected with F. solani. The expression of miR-129-5p was detected via quantitative real-time polymerase chain reaction (PCR). The miR-129-5p antagomir was used to transfect cells and mice to study the regulatory role of miR-129-5p in autophagy and inflammation after fungal infection. The expression of Beclin1 and LC3B and colocalization of LC3B with lysosomes were detected via Western blotting and immunofluorescence. CCK-8 was used to determine the viability of corneal stromal cells. The expression of IL-1ß were detected by ELISA. Bioinformatics software was used to predict the potential targets of miR-129-5p, which were verified by a luciferase reporter gene assay. RT-PCR showed that miR-129-5p expression in mouse corneas was significantly increased after infection with F. solani. Subconjunctival injection of the miR-129-5p antagomir significantly enhanced the proteins Beclin-1 and LC3B. At the same time, inhibiting miR-129-5p expression could reduce the inflammatory response in FK and significantly increase the viability of corneal stromal cells infected with F. solan. Moreover, the dual luciferase reporter assay indicated that Atg14 was a direct target of miR-129-5p. Our study shows that miR-129-5p is a novel small molecule that regulates autophagy by targeting Atg14, indicating that it may be a proinflammatory and therapeutic target for fungal keratitis.

Protective effect inhibiting the expression of miR-181a on the diabetic corneal nerve in a mouse model.

To investigate the protective effect of inhibiting miR-181a on diabetic corneal nerve in mice, we chose male C57BL/6 mice with streptozotocin (STZ) -induced diabetes as animal models. The expression of miR-181a in trigeminal ganglion tissue (TG) of diabetic mice was detected by real-time PCR. In vitro, we cultured mouse trigeminal ganglion neurons and measured the neuronal axon growth when treated under miR-181a antagomir and negative conditions (NTC). Immunofluorescence showed a significant increase in neuronal axon length in trigeminal ganglion cells treated with miR-181a antagomir. In animal models, we performed epithelial scraping and subconjunctival injection of the miR-181a antagomir and miRNA antagomir NTC to observe the corneal nerve repair by corneal nerve staining. miR-181a antagomir subconjunctival injection significantly increased the corneal epithelium healing of diabetic mice compared with that of the NTC group. Meanwhile, corneal nerve staining showed that the repair of corneal nerve endings was significantly promoted. As the targets of the 181a, ATG5 and BCL-2 were previously identified. The results of Western blot showed that the expression of autophagy associated protein ATG5 and LC3B-II and the expression of anti-apoptotic protein Bcl-2 were decreased in the high-glucose cell culture environment and the diabetic TG tissue. The expression of ATG5, LC3B-II and Bcl-2 were significantly increased after miR-181a antagomir treatment compared with negative control group. This study showed that inhibition of miR-181a expression in diabetic mice could increase ATG5-mediated autophagic activation, BCL-2-mediated inhibition of apoptosis, and promote the growth of trigeminal sensory neurons and the regeneration of corneal nerve fibers. It has a protective effect on diabetic corneal neuropathy.

Primary central nervous system lymphoma in China: a single-center retrospective analysis of 167 cases.

Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin's lymphoma and a limited number of cases have been reported from China. This study aimed to investigate the clinicopathological features of newly diagnosed PCNSLs from a single center in eastern China and to identify the potential prognostic factors for overall survival (OS) and progression-free survival (PFS). All consecutive patients with histopathologically diagnosed PCNSLs at our center between January 2003 and October 2017 were recruited. Demographic and clinicopathological data were collected and reviewed retrospectively. The potential risk factors for OS and PFS were identified using the log-rank test and Cox regression analysis. A total of 167 immunocompetent cases were enrolled. The median age was 58 years (range 17-96 years), and the male:female ratio was 3:2. Headache (n = 65; 39%) and cerebral hemisphere (n = 96; 57%) were the most common presenting complaint and location, respectively. Out of 167 cases, 150 cases were diffuse large B cell lymphomas. With a median follow-up of 25 months (range 1-152 ), the median OS and PFS were 37 months (95% CI, 25-49) and 17 months (95% CI, 13-20), respectively. Residual tumor after operation, chemotherapy without HD-MTX and palliative treatment was revealed as independent prognostic markers. Moreover, ECOG > 3, multifocal lesions, and palliative treatment were revealed as unfavorable independent prognostic markers for PFS. In conclusion, Chinese patients with PCNSL have distinct characteristics. Further studies are warranted to confirm the prognostic value of these factors and to optimize treatments for these patients.

Short-term early exposure to thirdhand cigarette smoke increases lung cancer incidence in mice.

Exposure to thirdhand smoke (THS) is a recently described health concern that arises in many indoor environments. However, the carcinogenic potential of THS, a critical consideration in risk assessment, remains untested. Here we investigated the effects of short-term early exposure to THS on lung carcinogenesis in A/J mice. Forty weeks after THS exposure from 4 to 7 weeks of age, the mice had increased incidence of lung adenocarcinoma, tumor size and, multiplicity, compared with controls. In vitro studies using cultured human lung cancer cells showed that THS exposure induced DNA double-strand breaks and increased cell proliferation and colony formation. RNA sequencing analysis revealed that THS exposure induced endoplasmic reticulum stress and activated p53 signaling. Activation of the p53 pathway was confirmed by an increase in its targets p21 and BAX. These data indicate that early exposure to THS is associated with increased lung cancer risk.

Clinical analysis of intracranial germinoma's craniospinal irradiation using helical tomotherapy.

OBJECTIVE: To evaluate the short-term clinical outcomes of intracranial germinoma patients treated with craniospinal irradiation (CSI) using helical tomotherapy (HT) system in our center. METHODS: Twenty-three patients who were treated with CSI in our center from January 2008 to July 2012 were collected, with an average age of 20. All of the patients' CSI used the HT system. The total doses were 27-36 Gy/15-20 F (1.5-2 Gy per fraction), and total local doses were 46-60 Gy/30-50 F (5 fractions per week). All female patients for CSI were treated with left-right parallel-opposed field irradiation to protect their ovarian functions. Median follow-up time was 30.9 months (range, 5-67 months). The SPSS19.0 software was used, and the overall survival (OS) was calculated using the Kaplan-Meier method. RESULTS: Among 17 patients with assessable tumors, 9 cases (52.9%) were CR, 7 cases (41.2%) were PR, and 1 case (5.9%) was SD. Hematological toxicity was the severest side-effect occurred in the procedure of CSI. The level 1-4 acute leukopenia were 8.7%, 30.4%, 34.8% and 21.7% and the level 1-4 acute thrombopenia were 8.7%, 30.4%, 21.7% and 8.7%, respectively. CONCLUSIONS: For primary intracranial germinomas, HT can be used to implement CSI for simplifying radiotherapy procedures, improving radiotherapy accuracy, enhancing protection of peripheral organs at risk (ORA) and guaranteeing therapeutic effects. With the acceptable acute and long-term toxicity, CSI using HT in intracranial germinoma patients can be a safe and alternative mode.

Association between 23 drugs and inflammatory bowel disease: a two-sample Mendelian randomization study.

Background: Inflammatory bowel disease (IBD) is a group of diseases characterized by chronic and recurrent inflammation of the gastrointestinal tract. The etiology of IBD remains multifaceted and poorly understood, resulting in limited treatment options that primarily target disease induction and remission maintenance. Thus, the exploration of novel therapeutic options for IBD among existing medications is advantageous. Mendelian randomization analysis (MR) serves as a valuable tool in investigating the relationship between drugs and diseases. In this study, MR analysis was employed to investigate the potential causal relationship between 23 approved drugs for the treatment of various diseases and IBD. Method: We performed a two-sample MR analysis using publicly available genome-wide association study (GWAS) statistics. The inverse variance weighting (IVW) method was used as the main analysis method, supplemented by the remaining four methods (weighted median, MR Egger regression, simple and weighted models), and Meta-analysis was performed to expand the sample size to obtain a more reliable composite causal effect. Finally, Cochran's Q statistic and the MR-Egger test for directed pleiotropy were applied to determine whether significant heterogeneity or directed pleiotropy existed. Results: In the main MR analysis (IVW), drugs with a negative causal association with the risk of IBD were immunosuppressant {OR (95% CI) = 0.7389 [0.6311-0.8651], p = 0.0046} and diabetes drugs {OR (95% CI) = 0.9266 [0.8876-0.9674], p = 0.0058}. A positive causal association with the risk of IBD was found for salicylic acid and derivatives {OR (95% CI) = 1.2737 [1.0778-1.5053], p = 0.0345}. Negative causal associations with UC risk were identified for immunosuppressants {OR (95% CI) = 0.6660 [0.5133-0.8640], p = 0.0169} and diabetes medications {OR (95% CI) = 0.9020 [0.8508-0.9551], p = 0.0046}; positive causal associations with UC risk were found for ß-receptor blockers {OR (95% CI) = 1.1893 [1.0823-1.3070], p = 0.0046}. A negative causal association with the risk of CD was found for immunosuppressants {OR (95% CI) = 0.6957 [0.5803-0.8341], p = 0.0023}. There was no statistically significant association between the remaining 19 drugs and IBD and subtypes. Conclusion: This MR study provides evidence suggesting that immunosuppressants have a mitigating effect on the risk of IBD and demonstrate consistent efficacy in subtypes of ulcerative colitis (UC) and Crohn's disease (CD). Additionally, diabetes medications show potential in reducing the risk of IBD, particularly in cases of UC, while ß-blockers may elevate the risk of UC. Conversely, salicylic acid and its derivatives may increase the risk of IBD, although this effect is not consistently observed in the subtypes of the disease. These findings offer new insights into the prevention and management of IBD.

Fat mass and obesity-associated protein inhibit the pathology of rheumatoid arthritis through the NSUN2/SFRP1/Wnt/ß-catenin signal axis.

OBJECTIVES: The purpose of this study is to investigate whether fat mass and obesity-associated protein (FTO) and NOL1/NOP2/Sun domain family member 2 (NSUN2) mediated RNA methylation is associated with RA pathology. METHODS: We studied the anti-rheumatoid arthritis (RA) mechanism mediated by FTO and NSUN2 in RA samples and collagen-induced arthritis (CIA) rats using real time qPCR (RT-qPCR), western blot, immunofluorescence, and other methods. KEY FINDINGS: The expression of NSUN2 was significantly increased in both RA patients and CIA rats compared with normal controls. Knockdown of NSUN2 blocked the Wnt/ß-catenin signaling pathway and inhibited RA pathological factors such as MMP3, fibronectin, and interleukins. FTO overexpression inhibited RA by inhibiting the expression of NSUN2, up-regulating the level of SFRP1 protein, and blocking the Wnt/ß-catenin signaling pathway. NSUN2 overexpression interfered with the inhibitory effects of FTO on the Wnt/ß-catenin signaling pathway and RA pathology, which further verified that FTO inhibited RA through the NSUN2/SFRP1/Wnt/ß-catenin signal axis. CONCLUSIONS: FTO and NSUN2 are important factors of RA, and this work provides new potential diagnostic biomarkers and therapeutic targets for RA. We also reveal a gene expression regulation pattern of the interaction between m6A and m5C. revealing the pathogenesis of RA from the perspective of RNA methylation.

Maackiain suppresses the development of cervical cancer via AMPK priming autophagy.

BACKGROUND: Maackiain (Mac), a flavonoid analog isolated from Sophora flavescens, exhibits neuroprotective, anti-allergic, anti-inflammatory, and pro-apoptotic effects. It is not clear whether Mac has a therapeutic effect on cervical cancer. METHOD: In this work, we used RT-qPCR, western blot, immunofluorescence, and related methods to detect the therapeutic mechanism of Mac for cervical cancer. RESULTS: We demonstrated that Mac significantly inhibited the proliferation, migration, and invasion of human cervical cancer cell lines HeLa and SiHa. And, Mac enhanced the pro-apoptotic effects of cisplatin in treating cervical cancer cells. Mac has shown good efficacy in treating cervical cancer. Furthermore, Mac inhibited the mammalian target of the rapamycin (mTOR) pathway, thereby inducing autophagy in cervical cancer cells. The regulation of mTOR/autophagy pathway by Mac relied on the activation of AMP-activated protein kinase (AMPK), and the inhibition of the AMPK reversed the Mac's anti-cervical cancer activity. In addition, experimental study of Mac in mouse xenograft tumor model further confirmed its good anti-cervical cancer activity. CONCLUSION: Mac inhibits human cervical cancer by activating the AMPK/mTOR/autophagy pathway, indicating that it is a potential natural compound for the treatment of cervical cancer. This study also provides a feasible molecular mechanism for the treatment of cervical cancer.

Utilizing Esophageal Motility Tests in Diagnosing and Evaluating Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD), a prevalent clinical condition, is often attributed to aberrant esophageal motility, leading to gastric content reflux and associated symptoms or complications. The rising incidence of GERD presents an escalating healthcare challenge. Endoscopic and esophageal reflux monitoring can provide a basis for the diagnosis of patients with gastroesophageal reflux disease, but when the diagnostic basis is at an inconclusive value, some additional supportive evidence will be needed. Advanced technology is the key to improving patient diagnosis, accurate assessment, and the development of effective treatment strategies. High-resolution esophageal manometry (HREM) and endoscopic functional lumen imaging probe (EndoFLIP) represent the forefront of esophageal motility assessment. HREM, an evolution of traditional esophageal manometry, is considered the benchmark for identifying esophageal motility disorders. Its widespread application in esophageal dynamics research highlights its diagnostic significance. Concurrently, EndoFLIP's emerging clinical relevance is evident in diagnosing and guiding the treatment of coexisting esophageal motility issues. This review integrates contemporary research to delineate the contributions of HREM, EndoFLIP, and novel technologies in GERD. It examines their efficacy in facilitating an accurate diagnosis, differentiating similar gastrointestinal disorders, quantifying the extent of reflux, assessing the severity of the disease, forecasting patient responsiveness to proton pump inhibitor therapy, and guiding decisions for surgical interventions. The overarching aim is to deepen the understanding of GERD's underlying mechanisms and advance the formulation of holistic, efficacious treatment approaches.

Huangqin Qingre Chubi Capsule inhibits rheumatoid arthritis by regulating intestinal flora and improving intestinal barrier.

Background: Changes in intestinal flora and intestinal barrier in patients with preclinical and diagnosed rheumatoid arthritis (RA) suggest that intestinal flora and intestinal barrier play an important role in the induction and persistence of RA. Huangqin Qingre Chubi Capsule (HQC) is a clinically effective herbal formula for the treatment of RA, but its therapeutic mechanism has not been fully clarified. Materials and methods: In this study, real-time qPCR (RT-qPCR), 16SrRNA sequencing, Western blot (WB), immunofluorescence and other methods were used to investigate whether HQC inhibited RA. Results: Based on research in collages-induced arthritis (CIA) model in mice, human colon cancer cell line (Caco-2), and fibroblast-like synoviocytes (FLS) from RA patients, we found that intestinal flora was disturbed in CIA model group, intestinal barrier was damaged, and lipolyaccharide (LPS) level was increased, and HQC could regulate intestinal flora and intestinal barrier and reduce LPS translocation into blood. Antibiotic depletion weakened the anti-RA effect of HQC, and HQC fecal microbiota transplantation alleviated RA pathology. In addition, LPS increased the expression of RA pathologic factors MMP3, Fibronectin and inflammatory factors IL-6, TNF-α, IL-1ß and IL-8, indicating that elevated peripheral blood level of LPS was related to RA pathology. Conclusion: The dysregulation of intestinal flora and the disruption of intestinal barrier are significant factors in the development of RA. HQC improves RA by regulating intestinal flora, intestinal barrier and inhibiting LPS translocation into blood. The study unveiles RA's new pathogenesis and laid a scientific groundwork for advancing HQC therapy for RA.

Lipid accumulation product is a valid predictor of hepatic steatosis and nonalcoholic fatty liver disease.

Aims: To evaluate and compare lipid accumulation product (LAP) with alanine aminotransferase (ALT), aspartate aminotransferase (AST), visceral adiposity index (VAI) and triglyceride-glucose index (TyG) as biomarkers for hepatic steatosis and nonalcoholic fatty liver disease (NAFLD). Methods: LAP, ALT, AST, VAI and TyG were measured in 52 biopsy-proven NAFLD patients and 21 control subjects. Additionally, LAP was also measured in 448 ultrasound-proven NAFLD patients and 1009 control subjects. Results: LAP was positively associated with hepatic steatosis and inflammation in biopsy-proven NAFLD. The risk of NAFLD was positively related to LAP and TyG, but LAP showed a better area under the receiver operating characteristic curve for hepatic steatosis and NAFLD. LAP also performed well in recognizing ultrasound-proven NAFLD. Conclusion: LAP is an ideal biomarker of hepatic steatosis and NAFLD.

Gestational supplementation of Bifidobacterium, Lactobacillus, and Streptococcus thermophilus attenuates hepatic steatosis in offspring mice through promoting fatty acid ß-oxidation.

Currently, Bifidobacterium, Lactobacillus, and Streptococcus thermophilus (BLS) are widely recognized as the crucially beneficial bacteria in the gut. Many preclinical and clinical studies have shown their protective effects against non-alcoholic fatty liver disease (NAFLD). However, whether gestational BLS supplementation could alleviate NAFLD in the offspring is still unknown. Kunming mice were given a high-fat diet (HFD) for 4 weeks before mating. They received BLS supplementation by gavage during pregnancy. After weaning, offspring mice were fed with a regular diet up to 5 weeks old. Gestational BLS supplementation significantly increased the abundance of Actinobacteriota, Bifidobacterium, and Faecalibaculum in the gut of dams exposed to HFD. In offspring mice exposed to maternal HFD, maternal BLS intake significantly decreased the ratio of Firmicutes to Bacteroidetes as well as the relative abundance of Prevotella and Streptococcus, but increased the relative abundance of Parabacteroides. In offspring mice, maternal BLS supplementation significantly decreased the hepatic triglyceride content and mitigated hepatic steatosis. Furthermore, maternal BLS supplementation increased the glutathione content and reduced malondialdehyde content in the liver. In addition, mRNA and protein expression levels of key rate-limiting enzymes in mitochondrial ß-oxidation (CPT1α, PPARα, and PGC1α) in the livers of offspring mice were significantly increased after gestational BLS supplementation. Thus, gestational BLS supplementation may ameliorate maternal HFD-induced steatosis and oxidative stress in the livers of offspring mice by modulating fatty acid ß-oxidation.

Simultaneous passivation on both A and X sites of halogen perovskite with magnesium benzoate.

Surface modification engineering is a well-known effective passivation method for making efficient and stable perovskite solar cells (PSCs). However, to our knowledge, little attention has been paid to simultaneously passivating the A and X sites of halogen perovskites. Herein, we introduced an organometallic salt (C6H5COO)2Mg (MgBEN) as a passivator, and as a result, the C6H5COOMg+ passivates the A site and C6H5COO- the X site on the perovskite layer, significantly reducing the trap-state density and nonradiative recombination. Moreover, the modification induces the perovskite film quality to improve, which may decrease the charge accumulation and facilitate carrier transport. By optimizing the concentration of the MgBEN, the perovskite film showed an increased grain size (from 1.18 µm to 1.61 µm), and the best device exhibited an enhanced power conversion efficiency (PCE) of 22.24%. Meanwhile, the device after modification performed with good long-term stability.

Circular RNA in autoimmune diseases: special emphasis on regulation mechanism in RA and SLE.

BACKGROUND: Autoimmune diseases are diseases caused by tissue damage caused by the body's immune response to autoantibodies. Circular RNAs (CircRNAs) are a kind of special endogenous non-coding RNA that play a biological role by regulating gene transcription. METHODS: In this work, we searched the PubMed, Web of Science (SCIE), National Science and Technology Library (NSTL), and ScienceDirect Online (SDOL) databases to summarize the impact of circRNAs on autoimmune diseases, especially the results of circRNAs in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). RESULTS: The study on the function of circRNAs and autoimmune diseases further deepened our understanding of the development and pathogenesis of autoimmune diseases. CircRNAs may act as miRNA sponges to regulate biological processes and affect the occurrence and development of autoimmune diseases. CircRNAs are closely related to the pathogenesis of RA and SLE and may become potential biomarkers for the diagnosis and treatment of RA and SLE. CONCLUSION: CircRNAs play an important role in the pathogenesis of RA, SLE and other autoimmune diseases, and are expected to provide new biomarkers for the diagnosis and treatment of autoimmune diseases. However, the function and mechanism of circRNAs in autoimmune diseases need more comprehensive research.

CircRnas in atherosclerosis, with special emphasis on the spongy effect of circRnas on miRnas.

Atherosclerosis (AS) is a chronic inflammatory disease, which leads to atherosclerotic rupture, lumen stenosis and thrombosis, and often endangers life. Circular RNAs (circRNAs) are a special class of non-coding RNA molecules, whose abnormal expression has been proved to be closely related to human diseases, including AS. Both the abnormal regulation of circRNAs and the sponging effect on miRNAs would lead to changes in gene expression in the form of epigenetic modification, ultimately leading to the formation of AS. CircRNAs can be used as peripheral blood markers of AS, and play an important regulatory role in the proliferation, migration, inflammation and apoptosis of vascular smooth muscle cells, endothelial cells and macrophage, which are key cells for the development of AS. The in-depth understanding of circRNAs in AS not only provides a new method for the diagnosis of AS, but also provides a new idea for the treatment of AS.