Osteoporosis is a common senile bone metabolism disease， clinically characterized by decreased bone mass， destruction of bone microstructure， increased bone fragility， and easy fracture. It tends to occur in the elderly and postmenopausal women， seriously threatening the quality of life and physical and mental health of the elderly. At present， the treatment of osteoporosis is mainly based on oral western medicines， such as calcium， Vitamin D， and bisphosphonates. Still， there are drawbacks such as a long medication cycle and many adverse reactions. In recent years， due to the advantages of multi-component， multi-pathway， and multi-target， some traditional Chinese medicines and effective ingredients can regulate the osteogenic and osteoclastic differentiation process in both directions and are widely used in the prevention and treatment of osteoporosis. Hippophae rhamnoides is a commonly used herbal medicine， and its fruits are rich in flavonoids， polyphenols， fatty acids， vitamins， and trace elements， which have been proven to have a good anti-osteoporosis effect. Isorhamnetin is the main effective ingredient of Hippophae rhamnoides fruits， which has many pharmacological effects such as anti-inflammation， anti-oxidative stress， anti-aging， and anti-tumor. Studies have shown that isorhamnetin can participate in the regulation of bone metabolism and has a good anti-osteoporosis effect. However， the pharmacological effects and related mechanisms of isorhamnetin against osteoporosis have not been systematically summarized. Therefore， this paper reviewed the pharmacological effects and related mechanisms of isorhamnetin against osteoporosis by referring to relevant literature to provide more basis for the development and application of isorhamnetin.

OBJECTIVES: The integrated endoplasmic reticulum stress inhibitor (ISRIB) is a selective inhibitor of the protein kinase R-like endoplasmic reticulum kinase (PERK) signaling pathway within endoplasmic reticulum stress (ERS) and can improve spatial and working memory in aged mice. Although ERS and oxidative stress are tightly interconnected, it remains unclear whether ISRIB alleviates cognitive impairment by restoring the balance between ERS and oxidative stress. This study aims to investigate the effects and mechanisms of ISRIB on lipopolysaccharide (LPS)-induced cognitive impairment in mice. METHODS: Eight-week-old male ICR mice were randomly divided into 3 groups: Normal saline (NS) group, LPS group, and ISRIB+LPS group. NS and LPS groups received daily intraperitoneal injections of normal saline for 7 days; on day 7, LPS group mice received intraperitoneal LPS (0.83 mg/kg) to establish a cognitive impairment model. ISRIB+LPS group received ISRIB (0.25 mg/kg) intraperitoneally for 7 days, with LPS injected 30 minutes after ISRIB on day 7. Cognitive ability was evaluated by the novel place recognition test (NPRT). Real-time fluorogenic quantitative PCR (RT-qPCR) was used to detect changes in nitric oxide synthase (NOS), superoxide dismutase-1 (SOD-1), and catalase (CAT) gene expression in the hippocampus and prefrontal cortex. Oxidative stress markers malondialdehyde (MDA), glutathione (GSH), and oxidized glutathione (GSSG), were measured in hippocampal and prefrontal cortex tissues. RESULTS: Compared with the NS group, mice in LPS group showed a significant reduction in novel place recognition ratio, upregulation of hippocampal NOS-1 and NOS-2 mRNA, downregulation of SOD-1 and CAT mRNA, increased MDA and GSSG, decreased GSH, and reduced GSH/GSSG ratio (all P<0.05). Compared with the LPS group, mice in ISRIB+LPS group exhibited significantly improved novel place recognition, downregulated NOS-1 and NOS-2 mRNA, upregulated SOD-1 and CAT mRNA, decreased MDA and GSSG, increased GSH, and an elevated GSH/GSSG ratio in the hippocampus (all P<0.05). No significant changes were observed in the prefrontal cortex. CONCLUSIONS ISRIB improves LPS-induced cognitive impairment in mice by restoring the oxidative/antioxidant balance in the hippocampus.
Animals ; Lipopolysaccharides ; Male ; Mice, Inbred ICR ; Cognitive Dysfunction/drug therapy* ; Mice ; Oxidative Stress/drug effects* ; Endoplasmic Reticulum Stress/drug effects* ; Hippocampus/drug effects* ; Nitric Oxide Synthase Type II/genetics* ; Guanidines/pharmacology* ; eIF-2 Kinase/antagonists & inhibitors* ; Signal Transduction/drug effects* ; Superoxide Dismutase/metabolism*

Tourette syndrome(TS)is a chronic neurodevelopmental disorder.Acupuncture can effectively improve the clinical symptoms of TS patients.This article systematically summarized the clinical research status of acupuncture for the treatment of TS in recent years from the aspects of characteristic acupuncture methods,characteristic needles and comprehensive therapies,and put forward suggestions and prospects for systematically elaborating the peripheral-central mechanism of acupuncture for TS around the intestinal immunity and brain network mechanism in the future,so as to provide reference for optimizing clinical research and treatment.

Objective To explore the effect of the POC CLOUD intelligent management platform on the training of resi-dent doctors with the principles and operation of various point-of-care testing(POCT)instruments to develop quality control man-agement skills and ensure result accuracy.Methods In alignment with Standardized Training Content and Standards for Resi-dent Trainees(2022 Edition and the development of POCT teaching in departments,the POC CLOUD platform was employed to provide information-based and standardized training for resident trainees.Results The POC CLOUD platform standardized resi-dent trainees'qualifications for operating POCT instruments and facilitated a quick understanding of the instruments'status in ro-tating departments.This approach enhanced resident trainees'learning and quality control management skills,enabling them to analyze and review test results effectively.Conclusion POCT teaching method based on the POC CLOUD platform systematical-ly develops resident trainees'operational and quality control abilities,ensuring the accuracy and reliability of test results and im-proving the overall quality of resident trainees.

In order to establish the isolation,culture and identification method of cow bone marrow-derived macrophages,three different media(RPMI-1640,DMEM,DMEM/F12)were added with 20％fetal bovine serum(FBS),2.4％chlorine-streptomycin,1.2％glutamine(Gln),and M-CSF(20 ng/mL),respectively,to induce the monocytes extracted from the bone marrow of dairy cows to become macrophages.The induced M0 macrophages were polarized into M1-type macrophages by adding lipopolysaccharide(LPS).The morphology of macrophages was observed by optical mi-croscope at day 1,4 and 7,and the differences of differentiated macrophages between the three media were compared.The effects of prostaglandin D2(PGD2)-DP2 receptor pathway on the secre-tion of cytokines(IL-6,TNF-α)induced by Escherichia coli and phagocytosis of macrophages were also investigated.The results showed that the morphological changes of cells cultured in the medium of RPMI-1640 were the most obvious and the number was large.A large number of char-acteristic markers of mononuclear macrophages were detected(M0 markers:CD1 1b,CD14;M1 markers:CD11b,CD80)expression,M0 and M1 macrophage purity were 79.9％and 93.5％,re-spectively.COX-2 and H-PGDS gene expressions were significantly increased in E.coli group com-pared with the blank control group.The secretion of PGD2also increased significantly(P＜0.000 1).DP2 receptor inhibitors(CAY10471,CAY10595)could significantly inhibit the secretion of E.coli in-duced pro-inflammatory cytokines(IL-6,TNF-α)and significantly enhance the killing effect of macrophages on E.coli.The above results showed that the induced cells had the characteristic mor-phology and immunophenotype of macrophages.E.coli can induce the production of PGD2 in mac-rophages,and the PGD2-DP2 pathway regulates the secretion of cytokines in E.coli infected macro-phages.

To summarize the clinical features of pancreatic tuberculosis, analyze its endoscopic ultrasonography (EUS) findings, aspiration histopathology and etiological results, the medical history, clinical manifestations, laboratory tests, imaging findings, EUS findings, pathological and etiological results of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) biopsy, of 14 patients with pancreatic tuberculosis in Wuhan Union Hospital from January 2018 to January 2022 were retrospectively analyzed. Among the patients with pancreatic tuberculosis, 7 were male and 7 were female with the age of 39.7±16.0 years. The main clinical manifestations were abdominal distention, abdominal pain, loss of appetite, weight loss, abdominal mass, obstructive jaundice, skin pruritus, asymptomatic. Seven patients with pancreatic tuberculosis were complicated with tuberculosis in other organs, including 3 patients with pulmonary tuberculosis. Laboratory examination results showed 7 patients with anemia, 3 with elevated serum amylase, 2 with elevated bilirubin and 10 with positive anti-tuberculosis antibody, 12 positive for tuberculosis T-SPOT. Levels of CA19-9 in all patients were within normal range. Imaging examination results showed that 9 cases were solid mass, 4 cystic solid mass, 1 cystic mass, 4 with enlarged peripancreatic lymph node, and 2 with dilated bile duct. EUS showed that head of pancreas was the most common location of pancreatic tuberculosis. All the lesions were hyperechoic without vascular invasion, including 8 cases with homogeneous hyperecho, 6 cases with inhomogeneous hyperecho, 2 cases with hyperechoic calcification and 1 case of echoless colliquative necrosis area. The diameter of the mass was 3.9±1.6 cm, with 5 cases <3 cm and 9 cases ≥3 cm. Pathological biopsy showed 12 cases of caseous granuloma. Etiological examination results showed that 11 cases were positive for polymerase chain reaction for mycobacterium tuberculosis, 3 positive for acid-fast stain, 1 positive for culture. All the patients were treated with regular anti-tuberculosis drugs, and 3 patients with jaundice were treated with endoscopic retrograde cholangiopancreatography and biliary stent placement. All patients showed good prognosis during the follow-up period. For patients with pancreatic space-occupying lesions, the possibility of pancreatic tuberculosis should be considered. The current diagnostic method relies on tissue biopsy and aetiological examination. EUS-FNA is the preferred method for obtaining pancreatic tissue to avoid unnecessary surgery, and to provide timely and accurate diagnosis. Regular anti-tuberculosis treatment is the main treatment for pancreatic tuberculosis.

Inflammatory injury of the intestine is often accompanied by symptoms such as damage to intestinal mucosa, increased intestinal permeability, and intestinal motility dysfunction. Inflammatory factors spread throughout the body via blood circulation, and can cause multi-organ failure. Pyroptosis is a newly discovered way of programmed cell death, which is mainly characterized by the formation of plasma membrane vesicles, cell swelling until the rupture of the cell membrane, and the release of cell contents, thereby activating a drastic inflammatory response and expanding the inflammatory response cascade. Pyroptosis is widely involved in the occurrence of diseases, and the underlying mechanisms for inflammation are still a hot spot of current research. The caspase-1 mediated canonical inflammasome pathway of pyroptosis and caspase-4/5/8/11-mediated non-canonical inflammasome pathway are closely related to the occurrence and development of intestinal inflammation. Therefore, investigation of the signaling pathways and molecular mechanisms of pyroptosis in intestinal injury in sepsis, inflammatory bowel diseases, infectious enteristic, and intestinal tumor is of great significance for the prevention and treatment of intestinal inflammatory injury.
Humans ; Pyroptosis ; Inflammasomes/metabolism* ; Apoptosis ; Caspase 1 ; Inflammation

T cell infiltration and proliferation in tumor tissues are the main factors that significantly affect the therapeutic outcomes of cancer immunotherapy. Emerging evidence has shown that interferon-gamma (IFNγ) could enhance CXCL9 secretion from macrophages to recruit T cells, but Siglec15 expressed on TAMs can attenuate T cell proliferation. Therefore, targeted regulation of macrophage function could be a promising strategy to enhance cancer immunotherapy via concurrently promoting the infiltration and proliferation of T cells in tumor tissues. We herein developed reduction-responsive nanoparticles (NPs) made with poly (disulfide amide) (PDSA) and lipid-poly (ethylene glycol) (lipid-PEG) for systemic delivery of Siglec15 siRNA (siSiglec15) and IFNγ for enhanced cancer immunotherapy. After intravenous administration, these cargo-loaded could highly accumulate in the tumor tissues and be efficiently internalized by tumor-associated macrophages (TAMs). With the highly concentrated glutathione (GSH) in the cytoplasm to destroy the nanostructure, the loaded IFNγ and siSiglec15 could be rapidly released, which could respectively repolarize macrophage phenotype to enhance CXCL9 secretion for T cell infiltration and silence Siglec15 expression to promote T cell proliferation, leading to significant inhibition of hepatocellular carcinoma (HCC) growth when combining with the immune checkpoint inhibitor. The strategy developed herein could be used as an effective tool to enhance cancer immunotherapy.

Objective: To investigate the effect of salidroside(Sal) on ischemia reperfusion(IR) in isolated rat heart and explore the underlying mechanisms on endoplasmic reticulum stress(ERS) and apoptosis. Methods: The isolated rat hearts underwent Langendorff perfusion subjected to IR. After ischemia for 45 min and reperfusion for 2 h, the isolated rat hearts were randomly divided into four groups(n=10): Control group, Sal treatment group(Sal), ischemia reperfusion group(IR) and Sal treatment with ischemia reperfusion group(IR+Sal). Myocardial infarct size was detected by TTC staining. Lactate dehydrogenase(LDH) activity in the coronary flow was determined by ELISA. The cardiac function was evaluated by left ventricular peak systolic pressure(LVSP) and left ventricular end diastolic pressure(LVEDP). The expressions of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X(Bax),protein kinase R-like endoplasmic reticulum kinase(PERK), C/EBP homologous protein(CHOP) and activating transcription factor 6(ATF6) were detected by Western blot, and apoptosis was observed by TUNEL staining. Results: There was no significant difference in all indexes between Sal group and Control group. Compared with Control group, the infarct size and LDH activity in the coronary flow increased in IR group. The LVSP value decreased, and the LVEDP value increased. The expression of Bax and the TUNEL-positive cells increased, while the expression of Bcl-2 decreased. Meanwhile, the expressions of ERS related proteins including PERK, CHOP and ATF6 also increased. Compared with IR group, the infarct size and LDH activity in the coronary flow increased in IR+Sal group. The LVSP value increased, and the LVEDP value decreased. The expression of Bax and the TUNEL-positive cells decreased, while the expression of Bcl-2 increased. In addition, the expressions of PERK, CHOP and ATF6 decreased. Conclusion Sal can improve myocardial IR injury by inhibiting ERS and apoptosis in isolated rat hearts.

Objective: To investigate the role and mechanisms of empagliflozin(EMPA) on myocardial ischemia/reperfusion(MI/R) injury. Methods : Forty male SD rats were randomly divided into Control group, MI/R group,2. 5 μmol/L EMPA combined with MI/R group(EMPA + MI/R) as well as EMPA and 10 μmol/L SIRT1 inhibitor EX527 combined with MI/R group(EMPA + EX527 + MI/R). Cardiac function, myocardial fiber morphology and infarct size were detected. The content of malonaldehyde(MDA), the activities of superoxide dismutase(SOD)and succinodehydrogenase(SDH) in myocardium were determined by ELISA. The protein expressions of Cytochrome c, Cleaved caspase-3, SOD2, gp91phoxand SIRT1 were observed by Western blot. The ROS level was detected by DHE staining. Results: Compared with Control group, MI/R group manifested the decreased cardiac function and myocardial fiber rupture. Myocardial infarction area, the expressions of Cytochrome c, Cleaved caspase-3 and gp91phox, as well as the MDA content and ROS level increased, while decreased the activities of SOD and SDH, and the expressions of SOD2 and SIRT1. Compared with MI/R group, EMPA + MI/R group improved cardiac function and inhibited myocardial fiber rupture, myocardial infarction area, the expressions of Cytochrome c and Cleaved caspase-3. The expression of gp91phox, the MDA content and ROS level were also downregulated,while the activities of SOD and SDH and the expressions of SOD2 and SIRT1 were upregulated. However, the protective effects of EMPA on MI/R heart were blocked by EX527. Conclusion EMPA alleviates MI/R injury by inhibiting mitochondrial oxidative stress and apoptosisviaactivating SIRT1.