1.Danggui Shaoyaosan Regulates Nrf2/SLC7A11/GPX4 Signaling Pathway to Inhibit Ferroptosis in Rat Model of Non-alcoholic Fatty Liver Disease
Xinqiao CHU ; Yaning BIAO ; Ying GU ; Meng LI ; Tiantong JIANG ; Yuan DING ; Xiaping TAO ; Shaoli WANG ; Ziheng WEI ; Zhen LIU ; Yixin ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):35-42
		                        		
		                        			
		                        			ObjectiveTo investigate the effect of Danggui Shaoyaosan on ferroptosis in the rat model of non-alcoholic fatty liver disease (NAFLD) and explore the underlying mechanism based on the nuclear factor E2-related factor 2 (Nrf2)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway. MethodsThe sixty SD rats were randomly grouped as follows: control, model, Yishanfu (0.144 g·kg-1), and low-, medium-, and high-dose (2.44, 4.88, and 9.76 g·kg-1, respectively) Danggui Shaoyaosan. A high-fat diet was used to establish the rat model of NAFLD. After 12 weeks of modeling, rats were treated with corresponding agents for 4 weeks. Then, the body weight and liver weight were measured, and the liver index was calculated. At the same time, serum and liver samples were collected. The levels or activities of total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and Fe2+ in the serum and TC, TG, free fatty acids (FFA), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX), and Fe2+ in the liver were measured. Hematoxylin-eosin staining and oil red O staining were employed to observe the pathological changes in the liver. Immunofluorescence was used to assess the reactive oxygen species (ROS) content in the liver. Mitochondrial morphology was observed by transmission electron microscopy. The protein levels of Nrf2, SLC7A11, GPX4, transferrin receptor 1 (TFR1), and divalent metal transporter 1 (DMT1) in the liver were determined by Western blot. ResultsCompared with the control group, the model group showed increases in the body weight, liver weight, liver index, levels or activities of TC, TG, ALT, AST, and Fe2+ in the serum, levels of TC, TG, FFA, MDA, Fe2+, and ROS in the liver, and protein levels of TFR1 and DMT1 in the liver (P<0.01), and decreases in the activities of SOD, GPX and the protein levels of Nrf2, SLC7A11, and GPX4 in the liver (P<0.05, P<0.01). Meanwhile, the liver tissue in the model group presented steatosis, iron deposition, mitochondrial shrinkage, and blurred or swollen mitochondrial cristae. Compared with the model group, all doses of Danggui Shaoyaosan reduced the body weight, liver weight, liver index, levels or activities of TC, TG, ALT, AST, and Fe2+ in the serum, levels of TC, TG, FFA, MDA, Fe2+, and ROS in the liver, and protein levels of TFR1 and DMT1 in the liver (P<0.01), while increasing the activities of SOD and GPX and the protein levels of Nrf2, SLC7A11, and GPX4 in the liver (P<0.01). Furthermore, Danggui Shaoyaosan alleviated steatosis, iron deposition, and mitochondrial damage in the liver. ConclusionDanggui Shaoyaosan may inhibit lipid peroxidation and ferroptosis by activating the Nrf2/SLC7A11/GPX4 signaling pathway to treat NAFLD. 
		                        		
		                        		
		                        		
		                        	
2.Effect Analysis of Different Interventions to Improve Neuroinflammation in The Treatment of Alzheimer’s Disease
Jiang-Hui SHAN ; Chao-Yang CHU ; Shi-Yu CHEN ; Zhi-Cheng LIN ; Yu-Yu ZHOU ; Tian-Yuan FANG ; Chu-Xia ZHANG ; Biao XIAO ; Kai XIE ; Qing-Juan WANG ; Zhi-Tao LIU ; Li-Ping LI
Progress in Biochemistry and Biophysics 2025;52(2):310-333
		                        		
		                        			
		                        			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. 
		                        		
		                        		
		                        		
		                        	
3.Clinical efficacy of da Vinci robotic and thoracoscopic transxiphoid approach in the treatment of anterior mediastinal tumors: A retrospective cohort study
Chenhan WANG ; Feng WANG ; Wenteng HU ; Ruijiang LIN ; Qiuhao LIANG ; Bowen YUAN ; Minjie MA ; Biao HAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(02):236-242
		                        		
		                        			
		                        			Objective  To compare the safety and efficacy of the da Vinci robot and thoracoscopic subxiphoid approach for the treatment of anterior mediastinal tumors. Methods  The clinical data of patients who underwent anterior mediastinal tumor resection through the subxiphoid approach admitted to the same medical group in the Department of Thoracic Surgery of the First Hospital of Lanzhou University between June 2020 and April 2022 were retrospectively analyzed. According to the surgery approach, the patients were divided into a robot-assisted thoracoscopic surgery (RATS) group and a video-assisted thoracoscopic surgery (VATS) group. The perioperative data and the incidence of postoperative complications were compared between the two groups. Results A total of 79 patients were enrolled. There were 41 patients in the RATS group, including 13 males and 28 females, with an average age of 45.61±14.99 years. There were 38 patients in the VATS group, including 14 males and 24 females, with an average age of 47.84±15.05 years. All patients completed the surgery successfully. Hospitalization cost and operative time were higher or longer in the RATS group than those in the VATS group, and the difference was statistically significant (P<0.05). Intraoperative bleeding, postoperative hospital stay, postoperative water and food intake time, postoperative off-bed activity time, white blood cell count, neutrophil percentage and visual analogue scale (VAS) score on the first postoperative day, white blood cell count and neutrophil percentage on the third postoperative day, duration of analgesic pump use, the number of voluntary compressions of the analgesic pump, and mediastinal drainage volume were all superior to those in the VATS group (P<0.05). The differences in VAS scores on the third postoperative day, duration of drainage tube retention and postoperative complication rates were not statistically different between the two groups (P>0.05). Conclusion  RATS subxiphoid anterior mediastinum tumor resection is a safe and feasible surgical method with less injury and higher safety, which is conducive to rapid postoperative recovery and has wide clinical application prospects.
		                        		
		                        		
		                        		
		                        	
4.Status of wearable flexible monitoring devices based on organic field effect transistors in biomedical field
Kai GUO ; Cui-Zhi TANG ; Bo SUN ; Duan-Qiang XIAO ; Yuan-Biao LIU ; En-Xiang JIAO ; Jie GONG ; Hai-Jun ZHANG
Chinese Medical Equipment Journal 2024;45(1):93-100
		                        		
		                        			
		                        			The working principle and development of flexible semiconductor devices based on organic field effect transistor(OFET)technology were introduced.The current research status of OFET-based wearable flexible monitoring devices were reviewed,including biomechanical monitoring devices,tattoo biomonitoring devices and cellular detection devices and etc.The deficiencies of OFET-based wearable flexible monitoring devices were analyzed,and it's pointed out that miniaturization,personalization and diversification were the directions for the development of the future OFET-based wearable flexible moni-toring devices.[Chinese Medical Equipment Journal,2024,45(1):93-100]
		                        		
		                        		
		                        		
		                        	
5.Dosimetric study of intensity-modulated radiotherapy and volumetric intensity modulated arc therapy based on the inner edge tangent field for radiotherapy after breast-conserving surgery of left-sided breast cancer
Biao ZHAO ; Qin PU ; Meifang YUAN ; Lishuang MA ; Han LI ; Yi YANG ; Chaoxi SUN
Journal of International Oncology 2024;51(7):441-447
		                        		
		                        			
		                        			Objective:To explore the dosimetry difference between intensity-modulated radiotherapy (IMRT) and volumetric intensity modulated arc therapy (VMAT) based on the inner edge tangent field (IETF) after left-sided breast conserving surgery.Methods:The localization CT and target organ at risk (OAR) data of 35 patients with left-sided breast cancer treated with IMRT after breast conserving surgery at Department of Radiotherapy in Yunnan Cancer Hospital from June 2022 to June 2023 were selected. The IETF-IMRT and the IETF-VMAT plans were designed for the same patient based on IETF, the dosimetry differences of target areas and OAR, as well as the planned execution time were compared between the two groups.Results:Dosimetry of target areas: for IETF-IMRT and IETF-VMAT, the D 98% of the planning target volume were (47.92±0.51) and (48.21±0.33) Gy, respectively, while the D 50% were (52.04±0.22) and (51.91±0.26) Gy, respectively, and the D 2% were (53.93±0.36) and (53.62±0.41) Gy, respectively, the conformity index were 0.84±0.03 and 0.87±0.02, respectively, while the homogeneity index were 0.12±0.01 and 0.10±0.01, respectively, with statistically significant differences ( t=-3.87, P<0.001; t=3.53, P=0.001; t=5.30, P<0.001; t=-13.60, P<0.001; t=6.24, P<0.001). Dosimetry of OAR: for IETF-IMRT and IETF-VMAT, the left lung V 5 were (31.91±6.28) % and (33.99±6.31) %, respectively, and the V 20 were (11.71±2.06) % and (9.73±2.12) %, respectively, with statistically significant differences ( t=-4.18, P<0.001; t=12.40, P<0.001). The right lung V 5 were (0.11±0.08) % and (7.13±3.12) %, respectively, and the D mean were (1.05±0.12) and (2.71±0.27) Gy, respectively, with statistically significant differences ( t=-33.62, P<0.001; t=-13.30, P<0.001). The spinal cord D 2% were (1.08±0.11) and (4.83±1.40) Gy, respectively, with a statistically significant difference ( t=-15.99, P<0.001). The left lung D mean were (7.45±1.08) and (7.37±1.03) Gy, the heart D mean were (4.21±0.96) and (4.41±0.48) Gy, and the right-sided breast D mean were (3.74±1.52) and (3.48±1.11) Gy, respectively, with no statistically significant difference ( t=1.16, P=0.253; t=-1.76, P=0.088; t=1.41, P=0.169). Planned execution time: the execution time of IETF-IMRT and IETF-VMAT was (10.73±1.21) and (2.18±0.17) min, respectively, with a statistically significant difference ( t=44.71, P<0.001) . Conclusion:Both IETF-IMRT and IETF-VMAT can meet clinical requirements, however the two techniques have their own characteristics. IETF-VMAT has better conformity and homogeneity of target region. The planned OAR dosimetry in both plans are significantly lower than the dose limit of postoperative radiotherapy for breast cancer, among which the left lung V 5, the right lung V 5, D mean and spinal cord D 2% of IETF-IMRT are slightly lower, the left lung V 20 of IETF-VMAT is slightly lower. IETF-VMAT significantly reduces the planned execution time compared with IETF-IMRT, thus can greatly reduce the dose deviation caused by patient position change, and significantly improve patients experience and comfort of radiotherapy. Taken together, IETF-VMAT has advantages over IETF-IMRT in radiotherapy after breast conserving surgery of left-sided breast cancer.
		                        		
		                        		
		                        		
		                        	
6.One-stage posterior debridement and spinal internal fixation for the treatment of lumbar Brucellar spondylitis
Xian-Shuai KOU ; Wei SHE ; Gui-Fu MA ; Xing-Yu PU ; Yun-Biao WU ; Yang QI ; Wen-Yuan LUO
China Journal of Orthopaedics and Traumatology 2024;37(8):764-771
		                        		
		                        			
		                        			Objective To explore the clinical efficacy and safety of one-stage posterior lesion removal and internal spinal fixation in patients with lumbar Brucellosis spondylitis.Methods The clinical data of 24 patients admitted from October 2017 to October 2022 were retrospectively analyzed,2 patients were lost to follow-up at 10 months after surgery,at the final 22 cases were included in the study,including 13 males and 9 females with an average age of(52.00±6.89)years old,were treated with one-stage posterior lesion removal and internal spinal fixation.The operation time,intraoperative bleeding,follow-up time,ery-throcyte sedimentation rate(ESR)and C-reactive protein(CRP)before and after operation were recorded.The pain visual ana-logue scale(VAS),Oswestry disability index(ODI),the Japanese Orthopaedic Association(JOA)score for neurofunction,American Spinal Injury Association(ASIA)spinal cord injury grade and modified MacNab criteria were ussed to evaluate the efficacy.Results All patients were followed up from 12 to 30 months with an average of(17.41±4.45)months.The operation time was 70 to 155 min with an average of(1 16.59±24.32)min;the intraoperative bleeding volume was 120 to 520 ml with an average of(275.00±97.53)ml.CRP and ESR levels decreased more significantly at 1 week and at the final follow-up than pre-operative levels(P<0.05).VAS,JOA score and ODI at 1 week and at the latest follow-up were more significantly improved than preoperative results(P<0.05).There was no significant difference between ASIA preoperative and 1 week after operation(P>0.05),and a significant difference between preoperative and last follow-up(P<0.05).In the final follow-up,21 patients had ex-cellent efficacy,1 patient had fair,and there was no recurrence during the follow-up.Conclusion One-stage transpedicular le-sion removal and internal spinal fixation,with few incisions and short operation time,helps the recovery of neurological func-tion,and the prognosis meets the clinical requirements,which can effectively control Brucella spondylitis.
		                        		
		                        		
		                        		
		                        	
7.Application of multidisciplinary small-class teaching in general surgery residency training
Shuai WANG ; Guangsheng DU ; Dan BIAO ; Yujiao CAI ; Jie MEI ; Yuan QIU ; Weidong XIAO
Chinese Journal of Medical Education Research 2024;23(4):568-572
		                        		
		                        			
		                        			Objective:To investigate the effects of multidisciplinary small-class teaching on expertise and skill acquisition and learning experience in standardized residency training in general surgery.Methods:Sixty residents of grade 2021 rotating in general surgery from January to August 2023 were divided into multidisciplinary teaching group ( n=30) and traditional teaching group ( n=30, to receive tradition one-on-one teaching). All the residents underwent a theoretical examination and Mini-Clinical Evaluation Exercise (Mini-CEX) skill assessment before admission, and the scores were compared between the two groups. At the end of training, the two groups were compared in terms of theoretical and Mini-CEX skill assessment scores and the degree of satisfaction with teaching. Statistical analysis was conducted using SPSS 26.0. Results:There were no significant differences in the theoretical assessment and Mini-CEX skill assessment scores before admission between the two groups ( P>0.05). At the end of training, the multidisciplinary teaching group had a significantly higher theoretical examination score [(88.15±3.45) vs. (72.25±4.36), P<0.05] and a significantly higher Mini-CEX score [(86.35±2.24) vs. (76.28±3.92), P<0.05] compared with the traditional teaching group. According to the survey, the residents in the multidisciplinary teaching group were more satisfied with teaching and more likely to recognize the teaching effects. Conclusions:Multidisciplinary small-class teaching can help improve the quality of standardized general surgery residency training on gastrointestinal tumor treatment, which is a highly accepted and effective attempt at standardized residency training.
		                        		
		                        		
		                        		
		                        	
8.The clinical efficacy of Da Vinci robot versus video-assisted thoracoscopic surgery in the treatment of posterior mediastinal tumors: A retrospective cohort study
Feng WANG ; Yuhang YUAN ; Chenhan WANG ; Wenteng HU ; Li HE ; Wenwen YANG ; Shuo SUN ; Min ZHANG ; Biao HAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(05):695-701
		                        		
		                        			
		                        			Objective To compare the short-term clinical effects of Da Vinci robot-assisted thoracic surgery (RATS) and video-assisted thoracoscopic surgery (VATS) in the treatment of posterior mediastinal tumors, and to explore the advantages of RATS posterior mediastinal tumor resection. Methods The clinical data of patients who underwent posterior mediastinal tumors resection through the lateral chest approach admitted to the same medical group in the Department of Thoracic Surgery of the First Hospital of Lanzhou University between January 2019 to January 2023 were retrospectively analyzed. According to the different surgical methods, the patients were divided into a RATS group and a VATS group. The clinical data were compared between the two groups. Results A total of 85 patients were included in this study. There were 39 patients in the RATS group, including 25 females and 14 males, with an average age of 47.6±13.0 years, and 46 patients in the VATS group, including 14 males and 32 females, with an average age of 45.3±14.7 years. All patients completed the operation successfully. The hospitalization cost in the RATS group was significantly higher than that in the VATS group (P<0.001), and the white blood cell count and neutrophilic granulocyte percentage on the first day after operation in the RATS group were lower than those in the VATS group, and the differences were statistically significant (P<0.05). The operative time, intraoperative bleeding, postoperative hospital stay, white blood cell count and neutrophil percentage on the third postoperative day, visual analogue scale score on the first and third postoperative days, duration of analgesic pump use, postoperative 12 h oxygen saturation (no oxygen inhalation), postoperative down bed time, total thoracic drainage volume, duration of drainage tube retention, and postoperative complication rates were not statistically different between the two groups (P>0.05). There was no perioperative death, conversion to thoracotomy or serious perioperative complications in both groups. Conclusion RATS resection of posterior mediastinal tumor via lateral thoracic approach is safe and feasible, and its short-term effect is similar to that of VATS via lateral thoracic single-hole approach. It is worth further comparative study to explore its benefit and cost performance.
		                        		
		                        		
		                        		
		                        	
9.Epidemiological characteristics of elderly malignant tumors in Tongren City in 2018 - 2022
Ruinian ZHENG ; Yamin TIAN ; Dan YANG ; Yingjun LEI ; Lei TIAN ; Yinjiao YUAN ; Xiarong HU ; Ruijuan LUO ; Linxuan HUANG ; Biao YAO
Journal of Public Health and Preventive Medicine 2024;35(5):85-88
		                        		
		                        			
		                        			Objective  To analyze the epidemiological characteristics of new elderly malignant tumor cases in Tongren City from 2018 to 2022, so as to provide a theoretical basis for the prevention and control of elderly malignant tumor in this area.  Methods  A retrospective analysis of the epidemiological characteristics of cases aged 60 and above who were first diagnosed with malignant tumors by pathology in our hospital from 2018 to 2022 was conducted based on the International Classification of Diseases (ICD-10).  Results  The incidence rate of elderly malignant tumors in Tongren City increased from 123.83/100 000 in 2018 to 126.14/100 000 in 2022, and the incidence rate showed a trend of first rising and then declining. The top five tumors in incidence rate are lung cancer, rectal cancer, liver cancer, stomach cancer and cervical cancer. The tumor order has changed over the years except lung cancer, which was the first. Lung cancer was the main high incidence tumor among the elderly of all ages. With the increase of age, the number of bladder cancer patients increases significantly, and the number of colon cancer patients also shows an upward trend. The prevalence rate of lung cancer(χ2=16.032,P=0.014) , liver cancer(χ2=8.099,P=0.030) , bladder cancer(χ2=11.274 , P=0.018) , and gastric cancer(χ2=19.387 , P=0.011) in elderly people of different sexes was generally higher in men than in women, and the difference was statistically significant (P<0.05).  Conclusion  Lung cancer , rectal cancer and liver cancer, as the malignant tumors with high case composition and rapid increase in the elderly, can be the focus of early screening and prevention of malignant tumors in the elderly in Tongren City, and men should pay more attention.
		                        		
		                        		
		                        		
		                        	
10.Application Study of Enzyme Inhibitors and Their Conformational Optimization in The Treatment of Alzheimer’s Disease
Chao-Yang CHU ; Biao XIAO ; Jiang-Hui SHAN ; Shi-Yu CHEN ; Chu-Xia ZHANG ; Yu-Yu ZHOU ; Tian-Yuan FANG ; Zhi-Cheng LIN ; Kai XIE ; Shu-Jun XU ; Li-Ping LI
Progress in Biochemistry and Biophysics 2024;51(7):1510-1529
		                        		
		                        			
		                        			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. 
		                        		
		                        		
		                        		
		                        	
            

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