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*

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.

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.

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.

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.

Objective To investigate the clinical outcomes of acupuncture and motion therapy combined with Chinese medicine rubbing and low frequency wave in the rehabilitation of hemiplegia patients after stroke.Methods From May 2019 to March 2022,86 patients with hemiplegia after stroke were prospectively selected and divided into study group(n=43)and control group(n=43)by random number table method.The control group was treated with Chinese medicine rubbing and low frequency wave,and the study group was treated with acupuncture and motion therapy on the basis of the control group.The treatments continued for 4 weeks.The National Institutes of Health Stroke Scale(NIHSS)score,Fugl-Meyer Motor Function Scale(FMA)score,Modified Barthel Index(MBI)score and walking ability were compared between the two groups.Results The NIHSS score was decreased after treatment in both groups(P＜0.05),and the NIHSS score in the study group was significantly lower than that in the control group(P＜0.05).The FMA score and MBI score were increased after treatment in both groups(P＜0.05),and the scores in the study group were significantly higher than those in the control group(P＜0.05).There were significant differences in the grade distribution of walking ability after treatment between the two groups(P＜0.05).Conclusion Acupuncture and motion therapy combined with Chinese medicine rubbing and low frequency wave therapy can improve the nerve function,motor function,daily living ability and walking ability of patients with hemiplegia after stroke.

Objective To investigate the therapeutic effect of functional electrical stimulation combined with traditional Chinese medicine liniment and compulsory exercise therapy on upper limb dysfunction in patients with hemiplegia after stroke.Methods From February 2017 to March 2022,86 stroke patients with hemiplegia after stroke were selected and divided into study group(43 cases)and control group(43 cases)by random number table method.The control group was treated with functional electrical stimulation and traditional Chinese medicine liniment,and the study group was treated with compulsory exercise therapy on the basis of the control group.Both groups were treated for 1 months.The scores of Wolf Motor Function Test(WMFT),Fugl-Meyer Assessment-Upper Extremity(FMA-UE),Modified Barthel Index(MBI),Action Research Arm Test(ARAT),National Institutes of Health Stroke Scale(NIHSS),and Stroke Specific Quality of Life Scale(SS-QOL)were compared between the two groups.Results After treatment,the scores of WMFT,FMA-UE,MBI,ARAT and SS-QOL were increased in both groups(P<0.05),and these scores in the study group were higher than those in the control group(P<0.05).After treatment,NIHSS scores were decreased in both groups(P<0.05),and the score in the study group was lower than that in the control group(P<0.05).Conclusion Functional electrical stimulation combined with traditional Chinese medicine liniment and compulsory exercise therapy can improve the function of upper limbs,the activity of daily living,neurological function and quality of life of patients with hemiplegia after stroke.

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.