Objective To screen the anti-Helicobacter pylori gastritis active components of the ethyl acetate extract of Alpinia officinarum Hance.Methods The"knock-out"strategy combined with high-performance liquid chromatography(HPLC)detection was developed to separate the components of the ethyl acetate extract of A.officinarum while obtaining the negative samples without the components.A human gastric epithelial cell(GES-1)model of H.pylori gastritis was established,and the levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),interleukin-8(IL-8)and interleukin-1β(IL-1β)in the supernatant of the cells were determined by enzyme-linked immunosorbent assay(ELISA).Results The total flavonoid fraction,the negative fraction without total diphenylheptanoids,the negative fraction without 5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-phenyl-3-heptanone(DHPA),and galangin significantly reduced IL-6 levels in the supernatant of H.pylori infected GES-1 cells at a concentration of 8 μg·mL-1 with 24 h incubation.The total flavonoid fraction strongly inhibited the release of IL-6,TNF-α,IL-8,and IL-1β from H.pylori gastritis GES-1 cells at a concentration of 16 μg·mL-1.Conclusions The total flavonoid fraction is the major anti-H.pylori gastritis active component of the ethyl acetate extract of A.officinarum.The results lay the foundation for further elucidation of the material basis of A.officnarum against H.pylori gastritis.

This study aims to explore the mechanism of Zhuanggu Jianxi Decoction in reducing synovial tissue inflammation in human knee osteoarthritis(KOA) via the liver X receptors(LXRs)/nuclear factor(NF)-κB signaling pathway. The synovial tissue samples were collected from 5 healthy volunteers and 30 KOA synovitis patients and cultured in vitro. The samples from the heathy volunteers were set as the normal group, and those from KOA synovitis patients were randomized into synovitis, Zhuanggu Jianxi Decoction, LXRα inhibitor, and N-CoR inhibitor groups. The synovitis tissue samples of the 5 groups were treated with 10% blank serum, 10% blank serum, 10% drug-containing serum, 10% drug-containing serum+LXRα inhibitor, and 10% drug-containing serum+N-CoR inhibitor, respectively, for 7 days. After intervention, the synovial tissue samples of each group were collected and stained with hematoxylin-eosin for observation and scoring of the pathological changes. The expression intensity of the fibroblast-specific marker α-smooth musle actin(α-SMA) in the synovial tissue was observed by immunofluorescence staining. The levels of interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), matrix metalloproteinase-3(MMP-3), and matrix metalloproteinase-13(MMP-13) in the supernatant of synovium homogenate were determined by ELISA. The mRNA and protein levels of LXRα, N-CoR, P50, and P65 in the synovial tissue were determined by RT-qPCR and Western blot, respectively. The results showed that compared with the normal group, the synovitis group showcased obvious synovial lining cell proliferation, inflammatory cell infiltration, synovial cell disarrangement, increased histopathological score(P<0.05), enhanced α-SMA fluorescence intensity and increased number of synovial fibroblasts(P<0.05), elevated levels of IL-1β, TNF-α, MMP-3, and MMP-13 in the synovial tissue(P<0.05), down-regulated mRNA and protein levels of LXRα and N-CoR, and up-regulated mRNA and protein levels of P50 and P65(P<0.05). Compared with the synovitis group, the Zhuanggu Jianxi Decoction group showed alleviated pathological changes, declined histopathological score of the synovial tissue(P<0.05), decreased α-SMA fluorescence intensity and number of synovial fibroblasts(P<0.05), lowered levels of IL-1β, TNF-α, MMP-3, and MMP-13(P<0.05), up-regulated mRNA and protein levels of LXRα and N-CoR, and down-regulated mRNA and protein levels of P50 and P65(P<0.05) in the synovial tissue. Compared with the Zhuanggu Jianxi Decoction group, the LXRα inhibitor group and N-CoR inhibitor group showed aggravated pathological changes, risen histopathological score of the synovial tissue(P<0.05), enhanced α-SMA fluorescence intensity and increased number of synovial fibroblasts(P<0.05), elevated levels of IL-1β, TNF-α, MMP-3, and MMP-13(P<0.05), down-regulated mRNA and protein levels of LXRα and N-CoR, and up-regulated mRNA and protein levels of P50 and P65(P<0.05). The results above indicated that Zhuanggu Jianxi Decoction could alleviate the synovial tissue inflammation in KOA patients by upregulating the mRNA and protein levels of LXRα and N-CoR in the LXRs/NF-κB pathway to downregulate the mRNA and protein levels of P50 and P65 and reduce the activity of the NF-κB pathway in the synovial tissue.
Humans ; Osteoarthritis, Knee/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Male ; Liver X Receptors/immunology* ; Middle Aged ; NF-kappa B/metabolism* ; Female ; Synovial Membrane/metabolism* ; Aged ; Adult

Phosphodiesterase 4 (PDE4) is an important member of the phosphodiesterase enzyme family that specifically catalyzes the hydrolysis of cyclic adenosine monophosphate (cAMP), activates the downstream phosphorylation cascade pathway by altering cAMP concentration, and is strongly associated with multiple diseases. Inhibition of PDE4 is clinically investigated as a therapeutic strategy in a broad range of disease areas, including respiratory system diseases, autoimmune disorders, central nervous system diseases, and dermatological conditions. However, the incidence of adverse reactions such as nausea and vomiting is relatively high in the marketed PDE4 inhibitors, which has stalled their clinical development. In this review, we provide an overview of the clinical progression and safety issues of the marketed PDE4 inhibitors. We also review the main causes underlying PDE4-mediated adverse effects by combining the structural analysis of the PDE4 protein, the mechanism of action of PDE4 inhibitors, and the related side effect mechanism research, aiming to provide a reference for the development of safe and effective PDE4 inhibitors.

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Moderate and deep sedation can effectively relieve or eliminate the pain and body discomfort during wound dressing change in pediatric burn patients, relieve anxiety, agitation, and even delirium of the children, reduce the metabolic rate of the children, make them in a quiet, comfortable, and cooperative state, which is conducive to the smooth completion of dressing change. This paper summarized the three aspects of moderate and deep sedation in pediatric burn patients, including the overview, main points of implementation, and effects, and further introduced the moderate and deep sedation medication regimens for different routes of administration, as well as the content of evaluation and monitoring. Suggestions on the prevention and management of related complications and the management of moderate and deep sedation implementation procedures were put forward, in order to provide references for the development of moderate and deep sedation for wound dressing change in pediatric burn patients in China.
Child ; Humans ; Bandages/adverse effects* ; Burns/therapy* ; Deep Sedation ; Pain/complications* ; Pain Management/methods*

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.

OBJECTIVE: To summarize the surgical treatment of different proximal clavicle fractures, and discuss the classification of proximal clavicle fractures. METHODS: Total of 24 patients with displaced proximal clavicle fractures were treated from January 2017 to December 2020 including 16 males and 8 females, aged 28 to 66 years old. Among them, 20 cases were fresh fractures and 4 cases were old fractures. According to the Edinburgh classification, 14 cases were type 1B1 fractures and 10 cases were type 1B2 fractures. The different internal fixation methods were selected for internal fixation treatment according to different fracture types.The operation time, blood loss, preoperative and postoperative displacement difference, fracture healing time and Rockwood scoring system were recorded. RESULTS: All patients were followed up for 12 to 24 months. There were no patients with infection or loss of reduction after the operation. Three patients had internal fixation failure after operation, and the internal fixation device was removed. Results The operation time was 30 to 65 min, and the blood loss was 15 to 40 ml. No important nerves, blood vessels, or organs were damaged. The imaging healing time was 3 to 6 months. According to the Rockwood functional score, the total score was (13.50±1.86), pain (2.57±0.50), range of motion (2.78±0.41), muscle strength (2.93±0.28), restricted daily activity (2.85±0.35), subjective results (2.63±0.61);the results were excellent in 20 cases, good in 3 cases, fair in 1 case. CONCLUSION Proximal clavicular fracture is a type of fracture with low incidence. According to different fracture types, different internal fixation methods and treatment methods can be selected, and satisfactory surgical results can be achieved.
Male ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Clavicle/surgery* ; Treatment Outcome ; Bone Plates ; Fractures, Bone/surgery* ; Fracture Fixation, Internal/methods* ; Retrospective Studies

Objective: To investigate the clinicopathologic and molecular genetic characteristics of myxoid pleomorphic liposarcoma (MPLPS). Methods: Six cases of MPLPS diagnosed and consulted in Fujian Provincial Hospital from 2015 to 2021 were collected for histomorphological observation, immunohistochemistry, and fluorescence in situ hybridization (FISH) detection of DDIT3 (CHOP) gene translocation and MDM2/CDK4 gene amplification. Results: There were four males and two females, aged 26-74 years (mean 53.8 years). The tumor size was 3.8-16.0 cm (mean 11.8 cm). All six cases had similar histopathologic features, showing overlapping histologic morphology of myxoid liposarcoma and pleomorphic liposarcoma. Four cases (4/6) were positive for S-100 protein, and the Ki-67 index was 50%-95%. All cases (6/6) were negative for DDIT3 (CHOP) translocation and MDM2/CDK4 amplification by FISH. TP53 (p.R248w) germline mutation was found in one case. Conclusions: MPLPS is a rare subtype of liposarcoma, characterized by overlapping morphology of myxoid liposarcoma and pleomorphic liposarcoma. Genetically, a few of them have TP53 gene germline mutations, but they lack of DDIT3 (CHOP) translocation or MDM2/CDK4 amplification.
Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Liposarcoma/pathology* ; Liposarcoma, Myxoid/diagnosis* ; Male ; Molecular Biology ; Proto-Oncogene Proteins c-mdm2/genetics* ; Translocation, Genetic

Objective     To investigate the influence of prior percutaneous coronary intervention (PCI) on the outcome of coronary artery bypass grafting (CABG). Methods     Clinical data of 5 216 patients from Jiangsu Province CABG registry who underwent primary isolated CABG from 2016 to 2019 were retrospectively analyzed. Patients were divided into a PCI group (n=673) and a non-PCI group (n=4 543) according to whether they had received PCI treatment. The PCI group included 491 males and 182 females, aged 62.6±8.2 years, and the non-PCI group included 3 335 males and 1 208 females, aged 63.7±8.7 years. Multivariable logistic regression and propensity score matching (PSM) were used to compare 30-day mortality, incidence of major complications and 1-year follow-up outcomes between the two groups. Results     Both in original cohort and matched cohort, there was no statistical difference in the 30-day mortality [14 (2.1%) vs. 77 (1.7%), P=0.579; 14 (2.1%) vs. 11 (1.6%), P=0.686], or the incidence of major complications (myocardial infarction, stroke, mechanical ventilation≥24 h, dialysis for new-onset renal failure, deep sternal wound infection and atrial fibrillation) (all P>0.05). The rate of reoperation for bleeding in the PCI group was higher than that in the non-PCI group [19 (2.8%) vs. 67 (1.5%), P=0.016; 19 (2.8%) vs. 7 (1.0%), P=0.029]. Both in original cohort and matched cohort, there was no statistical difference in 1-year survival rate between the two groups [613 (93.1%) vs. 4 225 (94.6%), P=0.119; 613 (93.1%) vs. 630 (95.2%), P=0.124], while the re-admission rate in the PCI group was significantly higher than that in the non-PCI group [32 (4.9%) vs. 113 (2.5%), P=0.001; 32 (4.9%) vs. 17 (2.6%), P=0.040]. Conclusion     This study shows that a history of PCI treatment does not significantly increase the perioperative mortality and major complications of CABG, but increases the rate of cardiogenic re-admission 1 year postoperatively.