Clinical characteristics of 17 patients with COVID-19 and systemic autoimmune diseases: a retrospective study.

OBJECTIVES: Increasing data about COVID-19 have been acquired from the general population. We aim to further evaluate the clinical characteristics of COVID-19 in patients with systemic autoimmune diseases (AIDs). METHODS: We included all confirmed inpatients with COVID-19 and systemic AIDs in Wuhan Tongji Hospital from 29 January to 8 March 2020. We retrospectively collected and analysed information on epidemiology of 1255 inpatients and additional clinical characteristics of patients with systemic AIDs. Outcomes were followed up until 16 April 2020. RESULTS: Of the 1255 patients with COVID-19, the median age was 64.0 years and 53.1% were male. More than half (63.0%) had chronic comorbidities. The proportions of elderly, male and patients with comorbidities were significantly higher in intensive care unit (ICU) than in the general ward (p<0.001). 17 (0.61%) patients with systemic AIDs were further screened and analysed from 2804 inpatients. The median age was 64.0 years and 82.4% were female. All patients were living in Wuhan and two family clusters were found. 1 (5.9%) patient was admitted to ICU and one died. 10 (62.5%) of 16 patients changed or stopped their anti-AIDs treatments during hospitalisation, and 5 of them felt that the disease had worsened after the quarantine. CONCLUSIONS: Older males with chronic comorbidities are more vulnerable to severe COVID-19. The lower proportion of COVID-19 in patients with systemic AIDs needs more high-quality human clinical trials and in-depth mechanism researches. Of note, the withdrawal of anti-AIDs treatments during hospitalisation can lead to flares of diseases.

Application of surface-imprinted polymers supported by hydroxyapatite in the extraction of zearalenone in various cereals.

Surface-imprinted polymers supported by hydroxyapatite (HAP@MIPs) were prepared using coumarin-3-carboxylic acid and naringenin as dummy template molecules of zearalenone (ZEA). HAP@MIPs were characterized by Fourier-transform infrared spectroscopy, scanning electron microscopy, particle size distribution analysis, energy-dispersive X-ray spectroscopy, and X-ray diffraction. The adsorption performance was studied. The results showed that it could reach the adsorption equilibrium within 6 min. The adsorption amount could reach 6.77 µg mg-1, while the concentration was 20 µg mL-1. The self-made solid-phase extraction (SPE) columns were prepared with HAP@MIPs as sorbents for the separation and purification of ZEA in cereal samples. The method was established by high-performance liquid chromatography (HPLC). The recoveries were in the range of 70.09-101.88%; the relative standard deviation was 2.06-8.47%. Finally, millet, coix lachryma, and corn were placed under extreme conditions to produce ZEA. The method was used to extract and analyze ZEA in the above samples. The results showed that self-made SPE columns with HPLC could be used for the separation and enrichment of ZEA in real samples. Graphical abstract.

Tetra-proline-modified calix[4]arene-bonded silica stationary phase for simultaneous reversed-phase/hydrophilic interaction mixed-mode chromatography.

A new water-soluble tetra-proline-modified calix[4]arene-bonded silica stationary phase was prepared straightforwardly by an indirect method and characterized by elemental analysis, energy dispersive Spectrometry, solid-state 13 C NMR spectroscopy, Fourier-transform infrared spectroscopy, and thermogravimetric analysis. Due to the simultaneous introduction of polar tetra-proline and nonpolar calix[4]arene, the developed column possessing a double retention mode of reverse-phase liquid chromatography and hydrophilic interaction liquid chromatography. A series of hydrophobic and hydrophilic test samples, including nucleosides and nucleotides, amines, monosubstituted benzenes, chiral compounds, and phenols, were used to evaluate the developed stationary phase. A rapid separation capability, high separation efficiency, and selectivity were achieved based on the multiple interactions between solutes and tetra-proline-modified calix[4]arene-bonded silica stationary phase. Moreover, the developed stationary phase was further used to detect and separate hexamethylenetetramine in rice flour. All the results indicated the potential merits of the developed stationary phase for simultaneous separation of complex hydrophobic and hydrophilic samples with high selectivity.

Comprehensive Improvement of the Sensitivity and Detectability of a Large-Aperture Electromagnetic Wear Particle Detector.

The electromagnetic wear particle detector has been widely studied due to its prospective applications in various fields. In order to meet the requirements of the high-precision wear particle detector, a comprehensive method of improving the sensitivity and detectability of the sensor is proposed. Based on the nature of the sensor, parallel resonant exciting coils are used to increase the impedance change of the exciting circuit caused by particles, and the serial resonant topology structure and an amorphous core are applied to the inductive coil, which improves the magnetic flux change of the inductive coil and enlarges the induced electromotive force of the sensor. Moreover, the influences of the resonance frequency on the sensitivity and effective particle detection range of the sensor are studied, which forms the basis for optimizing the frequency of the magnetic field within the sensor. For further improving the detectability of micro-particles and the real-time monitoring ability of the sensor, a simple and quick extraction method for the particle signal, based on a modified lock-in amplifier and empirical mode decomposition and reverse reconstruction (EMD-RRC), is proposed, which can effectively extract the particle signal from the raw signal with low signal-to-noise ratio (SNR). The simulation and experimental results show that the proposed methods improve the sensitivity of the sensor by more than six times.

Magnetic Properties of Ferromagnetic Particles under Alternating Magnetic Fields: Focus on Particle Detection Sensor Applications.

The electromagnetic wear particles detection sensor has been widely studied due to its ability to monitor the wear status of equipment in real time. To precisely estimate the change of the magnetic energy of the sensor coil caused by the wear particles, the magnetic property models of wear particles under the alternating magnetic field was established. The models consider the hysteresis effect and the eddy current effect of the wear particles. The analysis and experimental results show that with the increase of the effective field frequency, the change of the magnetic energy caused by the wear particles gradually decrease, which makes the induced electromotive force output by the sensor reduce with the decrease of the particle speed, so a signal compensation method is presented to obtain a unified signal when the same wear particle passing through the sensor in different speeds. The magnetic coupling effect between the two adjacent wear particles is analyzed. The result illustrates that the change of the magnetic energy caused by the dual wear particles system is larger than the sum of the energy variation caused by two independent wear particles, and with the increase of the interparticle distance, the magnetic coupling effect gradually weakens and disappears.

Dahuang-Wumei decoction protects against hepatic encephalopathy in mice: Behavioural, biochemical, and molecular evidence.

BACKGROUND: Disturbance of the blood‒brain barrier (BBB) and associated inflammatory responses are observed in patients with hepatic encephalopathy (HE) and can cause long-term complications. Dahuang-Wumei decoction (DWD) is a renowned traditional Chinese herbal medicine with a long history of clinical use and has been widely employed as an effective treatment for hepatic encephalopathy (HE). Despite its established efficacy, the precise mechanisms underlying the therapeutic effects of DWD have not been fully elucidated. PURPOSE: The present study aimed to comprehensively explore the potential effects and underlying molecular mechanisms of DWD on HE through an integrated investigation that included both in vivo and in vitro experiments. METHODS: In the present study, carbon tetrachloride (CCl4) and thioacetamide (TAA) were used to establish an HE model in mice. The therapeutic effects of DWD on liver injury, fibrosis, brain injury, behaviour, and consciousness disorders were evaluated in vivo. C8-D1A and bEnd.3 cells were used to construct a BBB model in vitro. The effects of DWD on proinflammatory factor expression, BBB damage and the Wnt/ß-catenin pathway were detected in vivo and in vitro. RESULTS: Our results showed that DWD can improve liver injury and fibrosis and brain damage and inhibit neurofunctional and behavioural disorders in mice with HE. Afterwards, we found that DWD decreased the levels of proinflammatory factors and suppressed BBB disruption by increasing the levels of junction proteins in vivo and vitro. Further studies verified that the Wnt/ß-catenin pathway may play a pivotal role in mediating the inhibitory effect of DWD on HE. CONCLUSION: These results demonstrated that DWD can treat HE by preventing BBB disruption, and the underlying mechanisms involved were associated with the activation of the Wnt/ß-catenin pathway and the inhibition of inflammatory responses.

Mechanisms of NLRP3 inflammasome in rheumatoid arthritis and osteoarthritis and the effects of traditional Chinese medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: It has been widely reported that various anti-rheumatic traditional Chinese medicines (TCMs) ameliorate rheumatoid arthritis (RA) and osteoarthritis (OA) through regulating the abnormal production, assembly, and activation of the NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome. These TCMs include monomers isolated from Chinese herbs, extracts of Chinese herbs, and Chinese medical formulae with a lengthy application history. AIM OF THE STUDY: This review aimed to summarize and analyze the published articles about the NLRP3 inflammasome and its role in the pathogenesis of RA and OA. We also reviewed existing knowledge on the therapeutic mechanism of TCMs in RA and OA via the regulation of the NLRP3 inflammasome. MATERIALS AND METHODS: We searched for relevant articles with the keywords "NLRP3 inflammasome", "traditional Chinese medicine," "Chinese herbal drugs," "rheumatoid arthritis," and "osteoarthritis." The information retrieval was conducted in medical Chinese and English databases from the date of construction to April 19, 2023, including PubMed, MEDLINE, Web of Science, Scopus, Ovid, China National Knowledge Infrastructure (CNKI), Chinese Biomedicine Literature Database (CBM), Chinese Science and Technology Periodicals Database (VIP), and China Online Journals (COJ). RESULTS: According to retrieval results, 35 TCMs have been demonstrated to relieve RA by targeting the NLRP3 inflammasome, including six traditional Chinese prescriptions, seven extracts of Chinese herbs, and 22 monomers extracted from traditional Chinese herbs and formulae. Additionally, 23 TCMs have shown anti-OA effects with abilities to modulate the NLRP3 inflammasome, including five traditional Chinese prescriptions, one extract of Chinese herbs, and 17 monomers from Chinese herbs. CONCLUSIONS: We summarized mechanism research about the pivotal roles of the NLRP3 inflammasome in the pathogenesis of RA and OA. Moreover, a review of TCMs with targets of the NLRP3 inflammasome in RA and OA treatment was also conducted. Our work is conducive to a better application of TCMs in complementary and alternative therapies in RA and OA.

Wutou Decoction Alleviates Arthritis Inflammation in CIA Mice by Regulating Treg Cell Stability and Treg/Th17 Balance via the JAK2/STAT3 Pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Wutou Decoction (WTD) is a classic traditional Chinese medicine formula, which has shown clinical efficacy in treating rheumatoid arthritis (RA). The Treg stability and Th17/Treg imbalance is an important immunological mechanism in RA progression. Whether WTD regulates CD4+ T cell subsets has not been thoroughly investigated yet. AIM OF THE STUDY: This study aimed to explore the potential role and mechanisms of WTD in regulating the diminished stability of Treg cells and the imbalance of CD4+ T cell subsets via in vivo and in vitro experiments. MATERIALS AND METHODS: Firstly, the therapeutic effects of WTD on the collagen-induced arthritis (CIA) mouse and its potential regulatory function on CD4+ T cell subsets were evaluated in vivo. Animal specimens were collected after 31 days of treatment with WTD. The anti-arthritic and anti-inflammatory effects of WTD were assessed through arthritis scoring, body weight, spleen index, serum IL-6 levels, and micro-PET/CT imaging. Gene enrichment analysis was performed to evaluate the activation T cell-related signaling pathway. Flow cytometry was used to determine the proportions of CD4+ T cell subsets in vitro and in vitro. Additionally, ELISA was used to assess the secretion of IL-10 and TGF-ß by Treg cells under inflammatory conditions. The suppressive function of Treg cells on cell proliferation under inflammatory conditions was examined using CFSE labeling. Immunofluorescence staining was performed to detect the phosphorylation levels of STAT3 in CD4+ T cells from mouse spleen tissues. Western blotting was used to evaluate the phosphorylation levels of JAK2/STAT3 in Treg cells. RESULTS: WTD significantly alleviated joint inflammation in CIA mice. WTD reduced serum IL-6 levels in CIA mice, improved their body weight and spleen index. WTD treatment inhibited the activation of CD4+ T cell subgroup-related signaling in the joint tissues of CIA mice. In vitro and in vitro experiments showed that WTD increased the proportion of Treg cells and decreased the proportion of Th17 cells in CIA mice spleen. Furthermore, WTD promoted the secretion of IL-10 and TGF-ß by Treg cells and enhanced the inhibitory capacity of Treg cells on cell proliferation under inflammatory conditions. Immunofluorescence detected decreased STAT3 phosphorylation levels in CD4+ T cells from CIA mice spleen, while western blotting revealed a decrease in JAK2/STAT3 phosphorylation levels in Treg cells in vitro. CONCLUSIONS: Inhibiting JAK2/STAT3 phosphorylation is a potential mechanism through which WTD improves Treg cell stability, balances CD4+ T cell subsets, and attenuates RA joint inflammation.

T peripheral helper cells in autoimmune diseases: What do we know?

The interactions between T cells and B cells are essential for antibody responses and the development of autoimmune diseases. Recently, a distinct subset of T cells capable of helping B cells was established in synovial fluid, and they were termed peripheral helper T (Tph) cells. PD-1hiCXCR5-CD4+ Tph cells express high levels of CXCL13, which drives the formation of lymphoid aggregates and tertiary lymphoid structures, ultimately facilitating the local production of pathogenic autoantibodies. Tph and T follicular helper cells share some key features but can be distinguished by their surface markers, transcriptional regulation, and migration capability. We summarize recent findings on Tph cells in this review and provide a perspective on their potential roles in a range of autoimmune diseases. More clinical and in-depth mechanistic investigations of Tph cells may help to improve the understanding of pathogenesis and further provide novel therapeutic targets in autoimmune diseases.

Wutou decoction attenuates the synovial inflammation of collagen-induced arthritis rats via regulating macrophage M1/M2 type polarization.

ETHNOPHARMACOLOGICAL RELEVANCE: Thousands of years of clinical practice in the treatment of joint-related diseases support the efficacy and safety of Wutou decoction (WTD). Nevertheless, the lack of pharmacological evidence and unclear mechanisms make it difficult for WTD to become a recognized complementary therapy for the treatment of rheumatoid arthritis (RA). AIM OF THE STUDY: This study aimed to investigate the effect of WTD against synovial inflammation in RA and whether this effect depends on the regulation of macrophage polarization. MATERIALS AND METHODS: Sprague-Dawley rats were used to establish the collagen-induced arthritis (CIA) model. WTD with low and high doses was administered for 45 days. RAW264.7 cells were stimulated by lipopolysaccharide (LPS) or interleukin (IL)-4 to polarize M1 and M2 macrophages, which were pre-treated with WTD extract for 4 h. The anti-arthritic and anti-inflammatory effects of WTD were studied using arthritis score, histopathological staining, immunostaining, and enzyme-linked immunosorbent assay (ELISA). The polarization state of RAW264.7 cells and related pro/anti-inflammatory cytokines was detected by ELISA, reverse transcription quantitative polymerase chain reaction and western blotting. Western blotting and immunofluorescence were used to investigate the effect of WTD on nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and peroxisome proliferator-activated receptors γ (PPARγ) activation both in vivo and in vitro. RESULTS: WTD significantly reduced the arthritis score and the pathological damage of the knee joint and decreased the expression of tumor necrosis factor alpha (TNF-α), IL-6 in serum, TNF-α, IL-1ß, monocyte chemoattractant protein-1 (MCP-1), and matrix metalloproteinase-3 (MMP3) in the knee synovium. WTD inhibited M1 type polarization and promoted M2 type polarization, both in vitro and in vivo, and reduced the expression of pro-inflammatory cytokines while increasing the expression of anti-inflammatory cytokines. Experiments showed that WTD inhibited the phosphorylation of NF-κB and downstream p38 in the synovium of CIA rats and LPS-induced M1 type polarized RAW264.7 cells. In addition, PPARγ expression in the synovium of CIA rats was mainly located in the cytoplasm, and WTD treatment increased the nuclear translocation of PPARγ, which was further verified in RAW264.7 cells. CONCLUSIONS: NF-κB and PPARγ regulating M1 and M2 macrophage polarization and subsequent secretion of pro-inflammatory and anti-inflammatory cytokines are the underlying mechanisms of WTD that ameliorate RA synovial inflammation.

Triptolide alleviates collagen-induced arthritis in mice by modulating Treg/Th17 imbalance through the JAK/PTEN-STAT3 pathway.

BACKGROUND: This study aimed to investigate the effects of triptolide (TP) on collagen-induced arthritis (CIA) mice and the related mechanisms. METHODS: CIA mice were administered TP for 35 days. Mouse ankle joints and serum antibodies and cytokines were examined to assess the therapeutic effects of TP. The ratios of Treg, Th1 and Th17 cells were measured by flow cytometry and RT-qPCR. Reverse docking was used to characterize the binding modes of TP against target proteins. The expression of the STAT3 pathway in CIA mice was evaluated by western blotting and immunofluorescence staining. Mouse spleen lymphocytes were extracted, and the expression of the STAT3 pathway after IL-6 stimulation was analysed. RESULTS: TP could significantly alleviate joint swelling, reduce bone destruction and downregulate serum inflammation levels. TP improved the imbalance of Treg/Th17 cells in CIA mice. TP could form stable complexes with target proteins. TP significantly inhibited the activation of the JAK/PTEN-STAT3 pathway in mice. Moreover, TP regulated the activation of the JAK1/2-STAT3 signalling pathway in mouse spleen lymphocytes under inflammatory stimulation. CONCLUSION: TP can inhibit inflammation and alleviate bone destruction in CIA mice. The underlying mechanism is related to the regulation of the imbalance of Treg/Th17 cells through the JAK/PTEN-STAT3 pathway.

Simiao pill attenuates collagen-induced arthritis and bleomycin-induced pulmonary fibrosis in mice by suppressing the JAK2/STAT3 and TGF-ß/Smad2/3 signalling pathway.

ETHNOPHAMACOLOGICAL RELEVANCE: Simiao Pill (SM) as a classic prescription of traditional Chinese medicine treatment of damp-heat arthralgia, the earliest from 'Cheng Fan Bian Du ', written by the Qing Dynasty doctor Zhang Bingcheng. Previous studies have shown that SM has obvious curative effect on rheumatoid arthritis, which provides a basis for the application of SM in rheumatoid arthritis related complications. AIM OF THE STUDY: Interstitial lung disease (ILD), as the most severe complication of rheumatoid arthritis (RA), lacks effective clinical treatments and a corresponding animal model. Simiao pill (SM) is a traditional Chinese medicine prescription extensively used as a complementary and alternative treatment for RA. However, the effect and mechanism of SM on RA-ILD have not yet been reported. This study aimed to investigate an appropriate animal model that can simulate RA-ILD, and the efficacy, safety, and mechanism of SM on RA-ILD. METHODS: Collagen-induced arthritis (CIA) and bleomycin-induced pulmonary fibrosis model were combined to construct the CIA-BLM model. After the intervention of SM, the protective effects of SM on RA-ILD were determined by detecting the CIA mouse arthritis index (AI), Spleen index, and the extent of pulmonary fibrosis. The joint inflammation and pulmonary fibrosis were detected by immunohistochemistry, H&E staining, safranin- O fast green Sirius red staining, trap staining, and Masson staining. Finally, the mechanism was verified by Western blot and immunohistochemistry. RESULTS: Our work showed that SM significantly reduced joint swelling, arthritis index, pulmonary fibrosis score, and spleen index in CIA mice. The pathological examination results indicated Si-Miao Pill suppressed inflammation, pulmonary fibrosis, bone erosion, and cartilage degradation of the ankle joint. Besides, SM up-regulated expressions of E-cadherin, whereas down-regulated expressions of α-SMA. Further studies confirmed that SM regulated JAK2/STAT3 and TGF-ß/SMAD2/3. CONCLUSION: SM can not only effectively improve joint inflammation by JAK2/STAT3 Pathway but also inhibit pulmonary fibrosis by TGF-ß/SMAD2/3. The fibrosis induced by CIA-BLM model was more stable and obvious than that induced by CIA model alone.

Interaction of gut microbiota with the tumor microenvironment: A new strategy for antitumor treatment and traditional Chinese medicine in colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignancies worldwide and the second leading cause of cancer-related death. In recent years, the relationship between gut microbiota and CRC has attracted increasing attention from researchers. Studies reported that changes in the composition of gut microbiota, such as increase in the number of Fusobacterium nucleatum and Helicobacter hepaticus, impair the immune surveillance by affecting the intestinal mucosal immunity and increase the risk of tumor initiation and progression. The tumor microenvironment is the soil for tumor survival. Close contacts between gut microbiota and the tumor microenvironment may directly affect the progression of tumors and efficacy of antitumor drugs, thus influencing the prognosis of patients with CRC. Recently, many studies have shown that traditional Chinese medicine can safely and effectively improve the efficacy of antitumor drugs, potentially through remodeling of the tumor microenvironment by regulated gut microbiota. This article describes the effect of gut microbiota on the tumor microenvironment and possible mechanisms concerning the initiation and progression of CRC, and summarizes the potential role of traditional Chinese medicine.

A diagnostic challenge of mysterious bone pain caused by tumor-induced osteomalacia with multiple tumors: a case report.

Background: Tumor-induced osteomalacia (TIO) is a rare, tumor-induced, metabolic bone disorder, the exact incidence of which is unknown. The most common cause of TIO is hypersecretion of tumor-derived fibroblast growth factor 23 (FGF23). Surgical resection can cure TIO in most cases, while for patients with TIO who are ineligible for surgery, biologic antibodies targeting FGF23 can be used as treatment. However, the diagnosis of TIO is more difficult than its treatment as the initial presentation can be misleading or nonspecific; thus, diagnosing TIO remains a clinical challenge. Case Description: Herein, we present a case of TIO originating from the nasal cavity neoplasm in which the patient also had a rare, thymic-derived, tumorous lesion. A diagnosis of osteoporosis was subsequently made, and a disorder of phosphorus metabolism was discovered. After determining that the patient was exhibiting signs of TIO, we used gallium-68 dotatate positron emission tomography/computed tomography (68Ga-DOTATATE PET/CT) to locate the tumor position. Conclusions: This case report emphasizes the importance of electrolyte testing, which is potentially helpful for quickly identifying the presence of disorders of phosphorus metabolism in suspected patients. Subsequently, appropriate imaging techniques (e.g., 68Ga-DOTATATE PET/CT) should be used to identify potential TIO lesions. Most patients with TIO can be treated successfully following diagnosis. Keywords: Tumor-induced osteomalacia (TIO); gallium-68 dotatate positron emission tomography/computed tomography (68Ga-DOTATATE PET/CT); phosphaturic mesenchymal tumor (PMTs); weakness; case report.

Triptolide attenuates pulmonary fibrosis by inhibiting fibrotic extracellular matrix remodeling mediated by MMPs/LOX/integrin.

BACKGROUND: Fibrotic extracellular matrix (ECM) remodeling characterized different types of pulmonary fibrosis, and its regulation could be a potential shared treatment strategy for pulmonary fibrosis. PURPOSE: We aimed to investigate the effect of triptolide on pulmonary fibrosis through the inhibition of several important aspects of fibrotic ECM remodeling. METHODS: Bleomycin-induced pulmonary fibrosis mice and TGF-ß1-induced primary lung fibroblasts were used. The effect of triptolide on pulmonary fibrosis was detected using histopathology, immunostaining, RT-qPCR, western blotting, ELISA, and protein activity assay. RESULTS: Triptolide significantly alleviated bleomycin-induced pulmonary fibrosis in mice. It inhibited the expression of fibrotic genes α-SMA, collagen I, fibronectin, and vimentin and blocked the TGF-ß-SMAD signaling pathway both in vivo and in vitro. In addition, triptolide regulated the expression and activity of MMPs during fibrosis. Interestingly, it suppressed the expression of lysyl oxidase, which was responsible for matrix cross-linking and elevated ECM stiffness. Furthermore, triptolide blocked the biomechanical stress transduction pathway integrin-ß1-FAK-YAP signaling and attenuated the pro-fibrotic feedback of fibrotic ECM on fibroblasts via integrin inhibition. CONCLUSION: These findings show that triptolide prevents the key linkages of fibrotic ECM remodeling, including deposition, degradation, cross-linking, and pro-fibrotic feedback and, therefore, has potential therapeutic value for pulmonary fibrosis.

Dyslipidemia in rheumatoid arthritis: the possible mechanisms.

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease, of which the leading cause of death is cardiovascular disease (CVD). The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) in RA decrease especially under hyperinflammatory conditions. It is conflictive with the increased risk of CVD in RA, which is called "lipid paradox". The systemic inflammation may explain this apparent contradiction. The increased systemic proinflammatory cytokines in RA mainly include interleukin-6(IL-6)、interleukin-1(IL-1)and tumor necrosis factor alpha(TNF-α). The inflammation of RA cause changes in the subcomponents and structure of HDL particles, leading to a weakened anti-atherosclerosis function and promoting LDL oxidation and plaque formation. Dysfunctional HDL can further worsen the abnormalities of LDL metabolism, increasing the risk of cardiovascular disease. However, the specific mechanisms underlying lipid changes in RA and increased CVD risk remain unclear. Therefore, this article comprehensively integrates the latest existing literature to describe the unique lipid profile of RA, explore the mechanisms of lipid changes, and investigate the impact of lipid changes on cardiovascular disease.

Multifaceted oncostatin M: novel roles and therapeutic potential of the oncostatin M signaling in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a self-immune inflammatory disease characterized by joint damage. A series of cytokines are involved in the development of RA. Oncostatin M (OSM) is a pleiotropic cytokine that primarily activates the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, and other physiological processes such as cell proliferation, inflammatory response, immune response, and hematopoiesis through its receptor complex. In this review, we first describe the characteristics of OSM and its receptor, and the biological functions of OSM signaling. Subsequently, we discuss the possible roles of OSM in the development of RA from clinical and basic research perspectives. Finally, we summarize the progress of clinical studies targeting OSM for the treatment of RA. This review provides researchers with a systematic understanding of the role of OSM signaling in RA, which can guide the development of drugs targeting OSM for the treatment of RA.

Trigonella foenum-graecum L. and Psoralea corylifolia L. Improve Erectile Dysfunction in Streptozotocin-Induced Diabetic Rats through Suppression of Oxidative Stress.

Background: Diabetes mellitus-induced erectile dysfunction (DMED) is one of the most common complications of diabetes and is mainly attributed to oxidative stress. Hu-Lu-Ba-Wan (HLBW) is a classic Chinese formulation consisting of Trigonella foenum-graecum L. (TFG) and Psoralea corylifolia L. (PC). HLBW has been used not only for the treatment of diabetes but also for the treatment of erectile dysfunction in clinics. This study aimed to explore the efficacy and underlying mechanism of HLBW in ameliorating erectile function in streptozotocin-induced diabetic rats. Methods: The diabetic model was established by tail vein injection of streptozotocin (26 mg/kg), and then DMED rats screened by the apomorphine test were randomly divided into two groups: the model group and the HLBW group. The rats in the HLBW group were administered HLBW granules daily for 12 weeks. Fasting blood glucose and fasting insulin were tested by a commercial kit. Intracavernous pressure (ICP) and mean arterial pressure (MAP) were measured by cavernous nerve electrostimulation before the rats were killed. Erectile function was evaluated with ICP/MAP. The markers of oxidative stress in the corpus cavernosum (CC) were assayed by assay kits. Apoptosis in cavernosal tissue was detected by Western blotting (WB). The expression levels of vascular endothelial marker (vWF), α-smooth muscle actin (α-SMA), endothelial nitric oxide synthase (eNOS), and NADPH oxidase subunit P47phox were determined by WB and PCR. Furthermore, the structure of the CC was further confirmed by Masson's trichrome staining. Results: The results showed that HLBW significantly reduced blood glucose and increased insulin sensitivity. HLBW reduced oxidative stress and apoptosis. In addition, we observed that the expression levels of vWF, α-SMA, and eNOS as well as the ratio of smooth muscle to collagen increased in the HLBW group. Conclusions: Our results demonstrated that HLBW could reduce oxidative stress damage in CC to improve diabetes mellitus-induced erectile dysfunction in rats by inhibiting NADPH oxidase.

Hyperprogressive Disease in Cancers Treated With Immune Checkpoint Inhibitors.

Immunotherapy, which takes advantage of the immune system to eliminate cancer cells, has been widely studied and applied in oncology. Immune checkpoint inhibitors (ICIs) prevent the immune system from being turned off before cancer cells are eliminated. They have proven to be among the most promising and effective immunotherapies, with significant survival benefits and durable responses in diverse tumor types. However, an increasing number of retrospective studies have found that some patients treated with ICIs experience unusual responses, including accelerated proliferation of tumor cells and rapid progression of the disease, with poor outcomes. Such unexpected adverse events are termed hyperprogressive disease (HPD), and their occurrence suggests that ICIs are detrimental to a subset of cancer patients. HPD is common, with an incidence ranging between 4 and 29% in several cancer types. However, the mechanisms of HPD remain poorly understood, and no clinical predictive factors of HPD have been identified. In this review, we summarize current findings, including retrospective studies and case reports, and focus on several key issues including the defining characteristics, predictive biomarkers, potential mechanisms of HPD, and strategies for avoiding HPD after ICI treatment.

Covalent Triazine Framework Sorbent for Solid Phase Extraction of Fipronil and its Metabolite in Eggs with Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry.

A solid-phase extraction (SPE) method was established for fipronil and its metabolite residues (fipronil desulfinyl, fipronil sulphone and fipronil sulphide) in eggs with a covalent triazine framework (CTF) porous material as the adsorbent followed by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) detection. Multiple probes and quantum chemistry theory calculations were conducted to describe the versatile adsorption property directly and quantifiably. The conjugated structure of CTF and N-containing triazine generated π-π interactions and hydrogen bonds between the CTF and the targets, which led to high extraction efficiency and recoveries. The solid-phase extraction parameters, including amount of the adsorbent, type of eluent, amount of eluent and loading rate were investigated. Under the optimal experimental conditions, the recoveries of the analytes were between 85.5% and 103.2%, and the RSD (n = 5) was between 1.8% and 3.6%. The LODs and LOQs were 0.13-0.2 ng g-1 and 0.5-0.8 ng g-1, respectively. The sorbent can effectively reduce the interference of the matrix and meet the detection requirements of fipronil and its metabolites in eggs. These results imply that the CTF as adsorbents have great potential in the analysis of trace targets in samples with complex matrices.