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 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.

Objective:To investigate the effect of overexpression of T cell restricted intracellular antigen 1(TIA1)gene in M2-type tumor-associated macrophages(M2-TAMs)on invasion and migration of gastric cancer cells and its mechanism.Methods:Primary TAMs were extracted from gastric cancer tissues and induced to differentiate into M2-TAMs using IL-4 and IL-13.The TIA1 overex-pression plasmid(oe-TIA1)and its empty vector were transfected into M2-TAMs.The expression levels of TIA1 mRNA and protein were detected by qRT-PCR and Western blot.The expression levels of CD206 and CD163 were detected by flow cytometry.The levels of IL-10,TGF-β,VEGF-A and Arg-1 in cell culture supernatant were detected by ELISA.The transfected M2-TAMs were co-cultured with gastric cancer BGC-823 cells by Transwell co-cultivation system,and PI3K agonist 740Y-P was used to intervene in parallel.The cell migration ability was detected by scratch assay.Transwell assay was used to detect cell invasion ability.Protein expression levels of PI3K,p-PI3K,AKT,p-AKT,MMP-2 and MMP-9 in the cells were detected by Western blot.Results:①Compared with primary TAMs,the levels of CD206 and CD163 expression in M2-TAMs cells and IL-10,TGF-β,VEGF-A and Arg-1 in cell culture superna-tant were significantly increased(P<0.05),while the expression levels of TIA1 mRNA and protein were significantly decreased(P<0.05).Overexpression of TIA1 gene significantly decreased the expression levels of CD206 and CD163 in M2-TAMs and IL-10,TGF-β,VEGF-A and Arg-1 in cell culture supernatant(P<0.05).②Overexpression of TIA1 gene in M2-TAMs could significantly reduce the migration and invasion ability and the expression levels of p-PI3K/PI3K,p-AKT/AKT,MMP-2 and MMP-9 proteins in BGC-823 cells(P<0.05).③740Y-P could significantly reverse the inhibitory effects of overexpression of TIA1 gene in M2-TAMs on migration,inva-sion and PI3K/AKT signaling pathway of BGC-823 cells.Conclusion:Overexpression of TIA1 gene in M2-TAMs can affect the inva-sion and migration of gastric cancer cells by blocking the PI3K/AKT signaling pathway.

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]

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

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.

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.

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.