Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Objective To evaluate the value of miniprobe endoscopic ultrasound(EUS)in guiding endoscopic treatment of small-diameter(maximum diameter less than 1 cm)and low-grade(G1 grade)rectum neuroendocrine neoplasm(R-NEN),and to provide evidence and clues for its clinical application and further research.Methods The clinical data of 85 cases of low-grade(G1 grade)R-NEN with a maximum diameter of less than 1 cm who underwent endoscopic treatment in our center from January 2014 to December 2020 were retrospectively analyzed.The patients were divided into the EUS group(37 cases)and control group(48 cases)according to whether EUS was performed before endoscopic treatment.The positive rate of incision margin,the incidence of complications,the recurrence rate,the hospital stay,the cost of hospitalization and endoscopic therapy were compared between the two groups.Results The positive rate of incision margin in the EUS group was significantly lower than that in control group(P<0.05).There was no significant difference in the incidence of complications,tumor recurrence rate,hospital stay or hospital costs between the two groups(P>0.05).There was statistically significant difference in the endoscopic therapy between the two groups(P<0.05).Conclusion Evaluating the lesion depth of small-diameter and low-grade(G1 grade)R-NEN before surgery by miniprobe EUS and selecting endoscopic surgery according to its results of can significantly reduce the residual risk of resection margin tumors.

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.

Adequate inflammation can effectively eliminate harmful substances and prevent disease as a self-protective measure to prevent further damage to the body,while abnormally activated inflammation is detrimental to the body.Nucleotide binding and oligomerization domain-like receptor protein 3(NLRP3)inflammasome that participates in inflammatory responses are closely related to many physiological and pathological processes and play an important role in the occurrence and development of pulmonary diseases.This article mainly reviewed the activation mechanism and hypothesis of NLRP3 inflammasome,as well as the research on treating respiratory diseases by interfering with NLRP3 inflammasome.

Objective To construct an artificial intelligence assisted diagnosis model based on deep learning for dynamically recognizing gastric lesions and their locations under gastroscopy in real time,and to evaluate its ability to detect and recognize gastric lesions and their locations.Methods The gastroscopy videos of 104 patients in our hospital was retrospectively analyzed,and the video frames were manually annotated.The annotated picture frames of lesion category were divided into the training set and the validation set according to the ratio of 8∶2,and the annotated picture frames of location category were divided into the training set and the validation set according to the patient sources at the ratio of 8∶2.These sets were utilized for training and validating the respective models.YoloV4 model was used for the training of lesion recognition,and ResNet152 model was used for the training of location recognition.The accuracy,sensitivity,specificity,positive predictive value,negative predictive value and location recognition accuracy of the auxiliary diagnostic model were evaluated.Results A total of 68 351 image frames were annotated,with 54 872 frames used as the training set,including 41 692 frames for lesion categories and 13 180 frames for location categories.The validation set consisted of 13 479 frames,comprising 10 422 frames for lesion categories and 3 057 frames for location categories.The lesion recognition model achieved an overall accuracy of 98.8%,with a sensitivity of 96.6%,specificity of 99.3%,positive predictive value of 96.3%,and negative predictive value of 99.3% in validation set.Meanwhile,the location recognition model demonstrated an top-5 accuracy of 87.1% .Conclusion The artificial intelligence assisted diagnosis model based on deep learning for real-time dynamic recognition of gastric lesions and their locations under gastroscopy has good ability in lesion detection and location recognition,and has great clinical application prospects.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive dysfunction and behavioral impairment, and there is a lack of effective drugs to treat AD clinically. Existing medications for the treatment of AD, such as Tacrine, Donepezil, Rivastigmine, and Aducanumab, only serve to delay symptoms and but not cure disease. To add insult to injury, these medications are associated with very serious adverse effects. Therefore, it is urgent to explore effective therapeutic drugs for AD. Recently, studies have shown that a variety of enzyme inhibitors, such as cholinesterase inhibitors, monoamine oxidase (MAO)inhibitors, secretase inhibitors, can ameliorate cholinergic system dysfunction, Aβ production and deposition, Tau protein hyperphosphorylation, oxidative stress damage, and the decline of synaptic plasticity, thereby improving AD symptoms and cognitive function. Some plant extracts from natural sources, such as Umbelliferone, Aaptamine, Medha Plus, have the ability to inhibit cholinesterase activity and act to improve learning and cognition. Isochromanone derivatives incorporating the donepezil pharmacophore bind to the catalytic active site (CAS) and peripheral anionic site (PAS) sites of acetylcholinesterase (AChE), which can inhibit AChE activity and ameliorate cholinergic system disorders. A compound called Rosmarinic acid which is found in the Lamiaceae can inhibit monoamine oxidase, increase monoamine levels in the brain, and reduce Aβ deposition. Compounds obtained by hybridization of coumarin derivatives and hydroxypyridinones can inhibit MAO-B activity and attenuate oxidative stress damage. Quinoline derivatives which inhibit the activation of AChE and MAO-B can reduce Aβ burden and promote learning and memory of mice. The compound derived from the combination of propargyl and tacrine retains the inhibitory capacity of tacrine towards cholinesterase, and also inhibits the activity of MAO by binding to the FAD cofactor of monoamine oxidase. A series of hybrids, obtained by an amide linker of chromone in combine with the benzylpiperidine moieties of donepezil, have a favorable safety profile of both cholinesterase and monoamine oxidase inhibitory activity. Single domain antibodies (such as AAV-VHH) targeted the inhibition of BACE1 can reduce Aβ production and deposition as well as the levels of inflammatory cells, which ultimately improve synaptic plasticity. 3-O-trans-p-coumaroyl maslinic acid from the extract of Ligustrum lucidum can specifically inhibit the activity of γ-secretase, thereby rescuing the long-term potentiation and enhancing synaptic plasticity in APP/PS1 mice. Inhibiting γ-secretase activity which leads to the decline of inflammatory factors (such as IFN-γ, IL-8) not only directly improves the pathology of AD, but also reduces Aβ production. Melatonin reduces the transcriptional expression of GSK-3β mRNA, thereby decreasing the levels of GSK-3β and reducing the phosphorylation induced by GSK-3β. Hydrogen sulfide can inhibitGSK-3β activity via sulfhydration of the Cys218 site of GSK-3β, resulting in the suppression of Tau protein hyperphosphorylation, which ameliorate the motor deficits and cognitive impairment in mice with AD. This article reviews enzyme inhibitors and conformational optimization of enzyme inhibitors targeting the regulation of cholinesterase, monoamine oxidase, secretase, and GSK-3β. We are hoping to provide a comprehensive overview of drug development in the enzyme inhibitors, which may be useful in treating AD.

Objective:To discuss the inhibitory effect of microRNA-487a(miR-487a)on the M2 polarization of tumor-associated macrophages(TAMs)in gastric cancer,and to clarify its effect on the proliferation,invasion,and migration of the gastric cancer AGS cells.Methods:The TAMs from gastric cancer tissue and adjacent normal tissue macrophages(NTMs)from adjacent tissue of the primary gastric cancer patients were isolated and cultured.The human monocyte THP-1 cells were induced in vitro to differentiate into TAMs,and the differentiated M0,M1,and M2 macrophages were cultured for 24 h by conditioned medium(CM)to obtain the TAMs,M1-TAMs,and M2-TAMs respectively.The TAMs were transfected and then divided into blank group,inhibitor-NC group,miR-487a inhibitor group,miR-487a inhibitor+si-NC group,and miR-487a inhibitor+si-TIA1 group.The transfection efficiencies of the cells in various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods.The M2-TAMs were co-cultured with the AGS cells,and divided into AGS group,AGS+inhibitor-NC group,AGS+miR-487a inhibitor group,AGS+miR-487a inhibitor+si-NC group,and AGS+miR-487a inhibitor+si-TIA1 group.RT-qPCR method was used to detect the expression levels of miR-487a and lymphocyte intracytoplasmic antigen-1(TIA1)mRNA in TAMs from gastric cancer tissue and NTMs from adjacent normal tissue in various groups;Western blotting method was used to detect the expression level of TIA1 protein in TAMs from gastric cancer tissue and NTMs from adjacent normal tissue and TAMs in various groups;flow cytometry was used to detect the levels of CD206 and CD163 in TAMs in various groups;enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of interleukin-10(IL-10),transforming growth factor-beta(TGF-β),vascular endothelial growth factor A(VEGF-A),and arginase-1(Arg-1)in culture supernatant of the TAMs cells;CCK-8 assay was used to detect the proliferative activity of the AGS cells in various groups;wound healing assay was used to detect the migration rates of the AGS cells in various groups;Transwell assay was used to detect the number of invasion AGS cells in various groups.Results:The RT-qPCR results shoued that compared with NTMs from adjacent tissue,the expression level of miR-487a in the TAMs from gastric cancer tissue was significantly increased(P<0.01)and the expression level of TIA1 mRNA was significantly decreased(P<0.01).Compared with TAMs,the expression level of miR-487a in M1-TAMs was significantly decreased(P<0.01),and the expression level of TIA1 mRNA was increased(P<0.01);the expression level of miR-487a in M2-TAMs was significantly increased(P<0.01),and the expression level of TIA1 mRNA was decreased(P<0.01).After transfection,compared with blank group and inhibitor-NC group,the expression level of miR-487a in the cells in miR-487a inhibitor group was significantly decreased(P<0.01),indicating successful transfection.The Western blotting results showed that compared with NTMs from adjacent normal tissue,the expression level of TIA1 protein in TAMs from gastric cancer tissue was decreased(P<0.01);compared with TAMs,the expression level of T1A1 protein in M1-TAMs was significantly increased(P<0.01),and the expression of TIA1 protein in M2-TAMs was significantly decreased(P<0.01);after co-transfection,compared with inhibitor-NC group,the expression level of TIA1 protein in the cells in miR-487a inhibitor group was significantly increased(P<0.01);compared with miR-487a inhibitor+si-NC group,the expression level of TIA1 protein in the cells in miR-487a inhibitor+si-TIA1 group was significantly decreased(P<0.01).The flow cytometry results showed that compared with blank group and inhibitor-NC group,the levels of CD206 and CD163 in the cells in miR-487a inhibitor group were significantly decreased(P<0.01);after co-transfection,compared with inhibitor-NC group,the levels of CD206 and CD163 in the cells in miR-487a inhibitor group were significantly decreased(P<0.01);compared with miR-487a inhibitor+si-NC group,the levels of CD206 and CD163 in the cells in miR-487a inhibitor+si-TIA1 group were significantly increased(P<0.01).The ELISA results showed that compared with blank group and inhibitor-NC group,the levels of IL-10,TGF-β,VEGF-A,and Arg-1 in culture supernatant of the TAMs in miR-487a inhibitor group were significantly decreased(P<0.01);after co-transfection,compared with inhibitor-NC group,the levels of IL-10,TGF-β,VEGF-A,and Arg-1 in culture supernatant of the TAMs in miR-487a inhibitor group were significantly decreased(P<0.01);compared with miR-487a inhibitor+si-NC group,the levels of IL-10,TGF-β,VEGF-A,and Arg-1 in culture supernatant of the TAMs in miR-487a inhibitor+si-TIA1 group were significantly increased(P<0.01).The CCK-8 assay results showed that compared with AGS group,the proliferation activity of the cells in AGS+inhibitor-NC group was significantly increased(P<0.01);compared with AGS+inhibitor-NC group,the proliferation activity of the cells in AGS+miR-487a inhibitor group was significantly decreased(P<0.01);compared with AGS+miR-487a inhibitor+si-NC group,the proliferation activity of the cells in AGS+miR-487a inhibitor+si-TIA1 group was significantly increased(P<0.01).The wound healing assay results showed that compared with AGS group,the migration rate of the cells in AGS+inhibitor-NC group was significantly(P<0.05);compared with AGS+inhibitor-NC group,the migration rate of the cells in AGS+miR-487a inhibitor group was significantly decreased(P<0.01);compared with AGS+miR-487a inhibitor+si-NC group,the migration rate of the cells in AGS+miR-487a inhibitor+si-TIA1 group was significantly increased(P<0.05).The Transwell assay results showed that compared with AGS group,the number of invasion AGS cells in AGS+inhibitor-NC group was significantly increased(P<0.01);compared with AGS+inhibitor-NC group,the number of invasion AGS cells in AGS+miR-487a inhibitor group was significantly decreased(P<0.01);compared with AGS+miR-487a inhibitor+si-NC group,the number of invasion AGS cells in AGS+miR-487a inhibitor+si-TIA1 group was significantly increased(P<0.01).Conclusion:Silencing the miR-487a expression can inhibit the M2 polarization of the gastric cancer-associated macrophages by targeted upregulation of TIA1,and suppress the proliferation,migration,and invasion of the gastric cancer cells.

Colonoscopy is an important technical means for screening early colorectal cancer lesions.Accurate segmentation of intestinal polyps helps improve the accuracy of screening.Early screening for lesions is of great significance for the prevention of colorectal cancer,and the segmentation of intestinal polyps is an important research direction.Although intestinal polyp segmentation based on deep learning has achieved acceptable performance,the color variation among intestinal endoscopic images significantly affects it.Based on the ResNet architecture,this study proposes an advanced PE-ResNet in which histogram equalization is used to reduce color influence.Experimental results on five datasets,including ClinicDB,demonstrate that the PE-ResNet model achieves improved performance in intestinal polyp segmentation.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Objective To investigate the effect of quality control circle(QCC)activities on reducing the incidence of non-failure alarms of heated humidifiers in the intensive care unit(ICU).Methods Firstly,a QC circle team was formed,and the activity theme of reducing the incidence of non-faulty alarms of heated humidifiers in the ICU was selected to inves-tigate the current status of the use of heated humidifiers in the ICU during the period of December 1-15,2021,and to set improvement goals.Secondly,pareto charts and fishbone diagrams were drawn to analyze the causes for the occurrence of non-faulty alarms.Finally,the countermeasures were formulated and implemented according to the PDCA principle.The inciden-ces of non-faulty alarms of heated humidifiers and the comprehensive capabilities of the circle members were compared before and after the implementation of the QC circle activities.Results After the implementation of the QCC activities,the incidence of non-failure alarms of heated humidifiers decreased from 48.57％to 8.23％,the target achievement rate was 119.7％,the progress rate was 83.06％,and the comprehensive capabilities of circle members were improved obviously.Conclusion The QCC activities effectively reduces the incidence of non-failure alarms of heated humidifiers in the ICU,and thus is worthy promoting for standardizing medical equipment management.[Chinese Medical Equipment Journal,2024,45(6):87-92]