This article presents the diagnosis and treatment processes, and morphological and genetic testing of Gongylonema pulchrum in a case with G. pulchrum found in the oral mucosa. In addition, this article reviews publications pertaining to G. pulchrum human infections by Chinese scientists during the recent 10 years and summarizes the demographic and clinical characteristics, location and number of parasites, diagnosis and treatment processes, and epidemiological surveys of cases infected with G. pulchrum, so as to provide insights into improving the diagnostic capability among clinicians.

This article investigates the collaborative management of metabolic dysfunction-associated fatty liver disease （MAFLD） and chronic kidney disease （CKD）. As major public health issues worldwide， MAFLD and CKD are closely related in terms of epidemiology， pathogenesis， and management strategies， and however， there are still many challenges in the multidisciplinary collaborative management of the two diseases. This article systematically elaborates on the epidemiology of MAFLD and CKD， summarizes their common risk factors such as metabolic disorder， genetic susceptibility， and active metabolites， and reviews the mutual screening strategies and combined management models based on noninvasive imaging， serum markers， FIB-4 score， and liver stiffness measurement. In addition， this article summarizes the advances in the application of lifestyle intervention and new drugs （such as GLP-1 receptor agonists and SGLT-2 inhibitors） and emphasizes the importance of multidisciplinary collaboration in improving the prognosis of patients. Due to the close association between MAFLD and CKD， their joint management is crucial， and therefore， it is necessary to establish a multidisciplinary collaboration mechanism and implement the measures of precise screening， comprehensive treatment， and long-term monitoring， so as to improve the prognosis of patients and reduce the risk of complications. Finally， this article proposes that in the future， more effective combined treatment regimens should be explored to expand the clinical options for the co-management of the liver and the kidney.

In 2020， an international expert panel proposed to replace nonalcoholic fatty liver disease with metabolic associated fatty liver disease （MAFLD）. Recent studies have shown that there is a higher risk of chronic kidney disease （CKD） in the MAFLD population and that MAFLD is an independent risk factor for CKD. However， up to now， there are still no guidelines on the prevention and treatment of MAFLD-related CKD. Based on the Delphi method， the authors led a multidisciplinary team of 50 authoritative experts from 26 countries to reach a consensus on some open-ended research issues about the association between MAFLD and CKD， which can help to clarify the important clinical association between MAFLD and the risk of CKD and improve the understanding of the epidemiology， pathogenesis， management， and treatment of MAFLD and CKD， so as to establish a framework for the early prevention and management of these two common and interrelated diseases.

Humans ; Arthroplasty, Replacement, Knee ; Follow-Up Studies ; Cohort Studies ; Treatment Outcome ; Minimally Invasive Surgical Procedures ; Knee Joint/surgery* ; Knee Prosthesis ; Osteoarthritis, Knee/surgery*

Bacillus subtilis is recognized as a generally-regarded-as-safe strain, and has been widely used in the biosynthesis of high value-added products, including N-acetylneuraminic acid (NeuAc) which is widely used as a nutraceutical and a pharmaceutical intermediate. Biosensors responding to target products are widely used in dynamic regulation and high-throughput screening in metabolic engineering to improve the efficiency of biosynthesis. However, B. subtilis lacks biosensors that can efficiently respond to NeuAc. This study first tested and optimized the transport capacity of NeuAc transporters, and obtained a series of strains with different transport capacities for testing NeuAc-responsive biosensors. Subsequently, the binding site sequence of Bbr_NanR responding to NeuAc was inserted into different sites of the constitutive promoter of B. subtilis, and active hybrid promoters were obtained. Next, by introducing and optimizing the expression of Bbr_NanR in B. subtilis with NeuAc transport capacity, we obtained an NeuAc-responsive biosensor with wide dynamic range and higher activation fold. Among them, P535-N2 can sensitively respond to changes in intracellular NeuAc concentration, with the largest dynamic range (180-20 245) AU/OD. P566-N2 shows a 122-fold of activation, which is 2 times of the reported NeuAc-responsive biosensor in B. subtilis. The NeuAc-responsive biosensor developed in this study can be used to screen enzyme mutants and B. subtilis strains with high NeuAc production efficiency, providing an efficient and sensitive analysis and regulation tool for biosynthesis of NeuAc in B. subtilis.
N-Acetylneuraminic Acid/metabolism* ; Bacillus subtilis/metabolism* ; Promoter Regions, Genetic/genetics* ; Binding Sites ; Biosensing Techniques

OBJECTIVE: To investigate the anti-coronavirus potential and the corresponding mechanisms of the two ingredients of Reduning Injection: quercetin and luteolin. METHODS: A pseudovirus system was designed to test the efficacy of quercetin and luteolin to inhibit SARS-CoV-2 infection and the corresponding cellular toxicity. Luteolin was tested for its activities against the pseudoviruses of SARS-CoV-2 and its variants. Virtual screening was performed to predict the binding sites by Autodock Vina 1.1.230 and PyMol. To validate docking results, surface plasmon resonance (SPR) was used to measure the binding affinity of the compounds with various proteins of the coronaviruses. Quercetin and luteolin were further tested for their inhibitory effects on other coronaviruses by indirect immunofluorescence assay on rhabdomyosarcoma cells infected with HCoV-OC43. RESULTS: The inhibition of SARS-CoV-2 pseudovirus by luteolin and quercetin were strongly dose-dependent, with concentration for 50% of maximal effect (EC₅₀) of 8.817 and 52.98 µmol/L, respectively. Their cytotoxicity to BHK21-hACE2 were 177.6 and 405.1 µmol/L, respectively. In addition, luetolin significantly blocked the entry of 4 pseudoviruses of SARS-CoV-2 variants, with EC₅₀ lower than 7 µmol/L. Virtual screening and SPR confirmed that luteolin binds to the S-proteins and quercetin binds to the active center of the 3CLpro, PLpro, and helicase proteins. Quercetin and luteolin showed over 99% inhibition against HCoV-OC43. CONCLUSIONS The mechanisms were revealed of quercetin and luteolin inhibiting the infection of SARS-CoV-2 and its variants. Reduning Injection is a promising drug for COVID-19.
Humans ; SARS-CoV-2 ; COVID-19 ; Luteolin ; Quercetin

Chronic pancreatitis (CP) is a progressive and irreversible fibroinflammatory disorder, accompanied by pancreatic exocrine insufficiency and dysregulated gut microbiota. Recently, accumulating evidence has supported a correlation between gut dysbiosis and CP development. However, whether gut microbiota dysbiosis contributes to CP pathogenesis remains unclear. Herein, an experimental CP was induced by repeated high-dose caerulein injections. The broad-spectrum antibiotics (ABX) and ABX targeting Gram-positive (G⁺) or Gram-negative bacteria (G^-) were applied to explore the specific roles of these bacteria. Gut dysbiosis was observed in both mice and in CP patients, which was accompanied by a sharply reduced abundance for short-chain fatty acids (SCFAs)-producers, especially G⁺ bacteria. Broad-spectrum ABX exacerbated the severity of CP, as evidenced by aggravated pancreatic fibrosis and gut dysbiosis, especially the depletion of SCFAs-producing G⁺ bacteria. Additionally, depletion of SCFAs-producing G⁺ bacteria rather than G^- bacteria intensified CP progression independent of TLR4, which was attenuated by supplementation with exogenous SCFAs. Finally, SCFAs modulated pancreatic fibrosis through inhibition of macrophage infiltration and M2 phenotype switching. The study supports a critical role for SCFAs-producing G⁺ bacteria in CP. Therefore, modulation of dietary-derived SCFAs or G⁺ SCFAs-producing bacteria may be considered a novel interventive approach for the management of CP.

The biofilms formed by pathogenic microorganisms seriously threaten human health and significantly enhance drug resistance, which urgently call for developing drugs specifically targeting on biofilms. Chitooligosaccharides extracted from shrimp and crab shells are natural alkaline oligosaccharides with excellent antibacterial effects. Nevertheless, their inhibition efficacy on biofilms still needs to be improved. Spirulina (SP) is a microalga with negatively charged surface, and its spiral structure facilitates colonization in the depth of the biofilm. Therefore, the complex of Spirulina and chitooligosaccharides may play a synergistic role in killing pathogens in the depth of biofilm. This research first screened chitooligosaccharides with significant bactericidal effects. Subsequently, Spirulina@Chitooligosaccharides (SP@COS complex was prepared by combining chitooligosaccharides with Spirulina through electrostatic adsorption. The binding of the complex was characterized by zeta potential, z-average size, and fluorescence labeling. Ultraviolet-visible spectroscopy (UV-Vis) showed the encapsulation efficiency and the drug loading efficiency reached up to 90% and 16%, respectively. The prepared SP@COS2 exhibited a profound synergistic inhibition effect on bacterial and fungal biofilms, which was mainly achieved by destroying the cell structure of the biofilm. These results demonstrate the potential of Spirulina-chitooligosaccharides complex as a biofilm inhibitor and provide a new idea for addressing the harm of pathogenic microorganisms.
Humans ; Spirulina ; Anti-Bacterial Agents/chemistry* ; Chitosan/pharmacology* ; Biofilms ; Chitin/pharmacology*

Background/Aims: Disrupted bile acid regulation and accumulation in the liver can contribute to progressive liver damage and fibrosis. However, the effects of bile acids on the activation of hepatic stellate cells (HSCs) remain unclear. This study investigated the effects of bile acids on HSC activation during liver fibrosis, and examined the underlying mechanisms. Methods: The immortalized HSCs, LX-2 and JS-1cells were used for the in vitro study. in vitro, the adeno-associated viruses adeno-associated virus-sh-S1PR2 and JTE-013 were used to pharmacologically inhibit the activity of S1PR2 in a murine model of fibrosis induced by a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet. Histological and biochemical analyses were performed to study the involvement of S1PR2 in the regulation of fibrogenic factors as well as the activation properties of HSCs. Results: S1PR2 was the predominant S1PR expressed in HSCs and was upregulated during taurocholic acid (TCA) stimulation and in cholestatic liver fibrosis mice. TCA-induced HSC proliferation, migration and contraction and extracellular matrix protein secretion were inhibited by JTE-013 and a specific shRNA targeting S1PR2 in LX-2 and JS-1 cells. Meanwhile, treatment with JTE-013 or S1PR2 deficiency significantly attenuated liver histopathological injury, collagen accumulation, and the expression of fibrogenesis-associated genes in mice fed a DDC diet. Furthermore, TCAmediated activation of HSCs through S1PR2 was closely related to the yes-associated protein (YAP) signaling pathway via p38 mitogen-activated protein kinase (p38 MAPK). Conclusions TCA-induced activation of the S1PR2/p38 MAPK/YAP signaling pathways plays a vital role in regulating HSC activation, which might be therapeutically relevant for targeting cholestatic liver fibrosis.

OBJECTIVE: To observe preventive effect of Caprini based thrombosis risk evaluation model on venous thromboembolism (VTE) after total knee replacement (TKA). METHODS: Totally 257 TKA patients were admitted from May 2017 to December 2021 were selected. They were divided into conventional intervention strategies (121 patients in control group) and intervention strategies based on Caprini thrombosis risk evaluation model (136 patients in observation group), based on whether Caprini thrombosis risk evaluation model was introduced in May 2019. In normal gourp, there were 79 males and 42 females aged from 50 to 78 years old with an average of (63.10±11.86) years old;body mass index (BMI) ranged from 19 to 32 with an average of (25.21±4.95) kg/m2;55 patients on the left side and 66 on the right side. In observation group, there were 81 males and 55 females aged from 50 to 78 years old with an average of (64.35±10.54) years old;BMI ranged from 19 to 32 with an average of (24.43±5.18) kg/m²;87 patients on the left side and 49 on the right side. The incidence of VTE, visual analogue scale (VAS), Hospital for Special Surgery (HSS) score, affected limb swelling, mean velocity(Vm), peak velocity (PV), D-dimer (D-D), prothrombin time(PT), and incidence of complications were analyzed and compared. RESULTS: The incidence of VTE in observation group was 1.47%(2/136), and 9.09%(11/121) in control group, and there was statistically difference between two groups (χ²=6.976, P=0.008). At 7 days after operation, VAS, HSS score and the difference in circumference of the affected limb in observation group were significantly better than those in control group, and had statistically differences (P<0.05). Blood flow Vm and PV levels between two groups were significantly increased (P<0.001), and blood flow Vm and PV levels in observation group were significantly higher than those in control group on the 7th day after operation, and had differences (P<0.001). The serum D-D level in observation group was significantly lower than that of in control group on the 7th day after operation, and PT level was significantly higher than that of in control group, and had difference(P<0.05). There was no difference in total incidence of complications between two groups (χ²=4.488, P=0.034). CONCLUSION Intervention strategy based on caprini thrombus risk evluation model could effectively reduce incidence of VTE and complications in TKA patients, improve swelling, hemodynamics and coagulation function of the affected limbs, and contribute to recovery of knee joint function.
Male ; Female ; Humans ; Middle Aged ; Aged ; Arthroplasty, Replacement, Knee/adverse effects* ; Venous Thromboembolism/prevention & control* ; Thrombosis/complications* ; Hospitalization ; Incidence ; Retrospective Studies ; Risk Factors