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.

In 2022， Hainan provincial government launched the project for the prevention and control of viral hepatitis with the goals of a hepatitis B screening rate of 90%， a diagnostic rate of 90%， and a treatment rate of 80% among people aged 18 years and above by the year 2025， and the main intervention measures include population-based prevention， case screening， antiviral therapy， and health management. As of December 31， 2024， a total of 6.875 million individuals in the general population had been screened for hepatitis B， with a screening rate of 95.6%. A total of 184 710 individuals with positive HBsAg were identified， among whom 156 772 were diagnosed through serological reexamination， resulting in a diagnostic rate of 84.9%. A total of 50 742 patients with chronic hepatitis B were identified， among whom 42 921 had hepatitis B-specific health records established for health management， with a file establishment rate of 84.6%. A total of 31 553 individuals received antiviral therapy， with a treatment rate of 62.2%. A total of 2.503 million individuals at a high risk of hepatitis C were screened， among whom 4 870 tested positive for HCV antibody and 3 858 underwent HCV RNA testing， resulting in a diagnostic rate of 79.2%， and 1 824 individuals with positive HCV RNA were identified， among whom 1 194 received antiviral therapy， with a treatment rate of 65.5%. In addition， 159 301 individuals with negative HBsAg and anti-HBs and an age of 20 — 40 years were inoculated with hepatitis B vaccine free of charge. Through the implementation of the project for the prevention and control of viral hepatitis， a large number of hepatitis patients have been identified， treated， and managed in the province within a short period of time， which significantly accelerates the efforts to eliminate the crisis of viral hepatitis.

BACKGROUND:Currently,numerous experiments delve into the intricate anatomy and biomechanical behavior of distinct segments of the supraspinatus muscle.However,the impact of shoulder joint stress resulting from damage to various regions of this muscle remains a scarcely explored domain.Understanding the repercussions of supraspinatus muscle injuries across different regions on the stress distribution and magnitude of articular cartilage and the glenoid is crucial for providing some theoretical support for clinical diagnosis and treatment. OBJECTIVE:To ascertain the maximum stress values by simulating different degrees of supraspinatus muscle rupture on the humeral cartilage surface,glenoid lip,and glenoid cartilage joint surface using three-dimensional finite element software. METHODS:Normal and healthy shoulder joint CT or MRI scans were processed through Mimics and Geomagic to extract molds.Subsequently,models were constructed via Solidworks.Varying degrees of supraspinatus muscle damage were simulated for each model to mimic fractures in different regions.Finally,Ansys,mechanical software,was employed for three-dimensional finite element biomechanical analysis,calculating stress values for the humeral cartilage surface,glenoid lip,and glenoid cartilage joint surface. RESULTS AND CONCLUSION:(1)With worsening degrees of supraspinatus muscle injury,the stress on the shoulder joint cartilage surface and glenoid lip escalated.(2)Among various regions,the anterior part of the supraspinatus muscle exhibited paramount significance.(3)While supraspinatus muscle fractures of differing degrees impacted the magnitude of cartilage stress on the glenoid labial surface,the stress distribution remained constant.(4)It is indicated that during the initial stages of horizontal abduction of the shoulder joint,the anterior region assumes a pivotal role,followed by the posterior deep region.Injury to the anterior part of the supraspinatus muscle leads to a significant surge in stress within the shoulder joint's soft tissue,potentially causing damage to the top of the glenoid lip and the anterior part of the glenoid cartilage.

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.

Objective To investigate the expression of pepsin in vocal cord polyps and vocal cord cancer,and to compare the difference of pepsin expression.Methods From May 2020 to December 2021,27 patients with vocal cord polyp,27 patients with vocal cord cancer and 23 healthy volunteers were selected.RSI and RFS scoring scales were used for scoring,pepsin detection kit was used for saliva pepsin detection,and immunohistochemical methods were used to detect the expression of pepsin in vocal cord tissues of patients with vocal cord polyps and vocal cord cancer.Results The RSI score,RFS score and pepsin test kit results of vocal cord polyp group and vocal cord canc-er group were higher than those of non-vocal cord disease group,and the differences of the three indexes were statis-tically significant(P＜0.05).RSI score,pepsin detection kit results and pepsin immunohistochemistry results of vocal cord polyp group showed no significant difference compared with vocal cord cancer group(P＞0.05).The RFS score of vocal cord polyp group was significantly different from that of vocal cord cancer group(P＜0.05).Conclusion Pepsin may be an important pathogenic factor of vocal cord polyp and vocal cord cancer,and play an im-portant role in the occurrence of these two diseases.The difference of pepsin expression in vocal cord polyp and vo-cal cord cancer suggests that pepsin may have different pathogenesis.

BACKGROUND:Anterior cruciate ligament injury tends to lead to secondary meniscus injury and osteoarthritis.At present,there are few studies on the mechanics of meniscus and articular cartilage injury caused by anterior cruciate ligament injury. OBJECTIVE:To study the effect of partial rupture of the anterior cruciate ligament on the stress of medial and lateral meniscus and articular cartilage of knee joint by finite element analysis. METHODS:The CT and MRI images of the knee joint of a healthy volunteer were selected,and the scan data were imported into Mimics,Geomagic and SolidWorks software.After registration and fusion,four kinds of three-dimensional knee joint models were established:models of intact anterior cruciate ligament,rupture of the posterior external tract of anterior cruciate ligament,rupture of the anterior internal tract of anterior cruciate ligament,and absence of anterior cruciate ligament.Finally,data were imported into Ansys software to apply four different modes of loads to the knee joint:Longitudinal loads of 750 N were applied to the top of the femur;longitudinal load of 750 N to the top of the femur and forward thrust of 134 N behind tibia;a longitudinal load of 750 N and a varus moment of 10 Nm were applied to the top of the femur to simulate genu varus;750 N longitudinal load and 4 Nm internal rotation moment were applied to the proximal end of the femur to simulate knee internal rotation.The finite element analysis of biomechanical stress changes of the meniscus and articular cartilage of the knee joint was carried out. RESULTS AND CONCLUSION:(1)In the straight position of the knee joint,when the anterior medial tract of the anterior cruciate ligament was broken and the anterior cruciate ligament was missing under longitudinal loads of 750 N at the top of the femur,the total stress and peak value of meniscus increased significantly,but the stress distribution of the meniscus and the stress of articular cartilage did not change significantly.In longitudinal load of 750 N to the top of the femur and forward thrust of 134 N behind tibia,the fracture of the anterior internal tract of the anterior cruciate ligament increased the tibia forward,the compressive stress of posterior angle of the meniscus increased,and the stress of the articular cartilage did not change significantly.During simulating genu varus,the posterior angular stress of the lateral meniscus decreased,the stress of the medial meniscus increased,and the stress of articular cartilage slightly decreased when anterior cruciate ligament injuries were complete.When the anterior internal tract of the anterior cruciate ligament was broken or absent under knee internal rotation,the equivalent stress peak value of femoral cartilage and tibia cartilage shifted from medial cartilage to lateral cartilage,and the stress peak value of meniscus increased significantly.At this time,the anterior internal tract of the anterior cruciate ligament played a leading role in the rotational stability of the knee joint.(2)These results indicate that the risk of secondary meniscus injury in patients with anterior and medial anterior cruciate ligament band rupture was much higher than that in patients with posterior and external anterior cruciate ligament band rupture when the knee was in the upright standing position,varus and pronation,and there was no significant difference in the impact on articular cartilage.

BACKGROUND:The incidence of medial collateral ligament injuries in the knee joint is easy to lead to secondary meniscus and cartilage damage,and long-term chronic damage can lead to the occurrence of osteoarthritis.At present,there are few studies on the mechanics of meniscus and articular cartilage injury caused by medial collateral ligament rupture. OBJECTIVE:To investigate the effect of different degrees of medial collateral ligament injury on the biomechanics of meniscus and cartilage of knee joint. METHODS:The CT and MRI examinations of the knee joint of a healthy volunteer were performed to obtain the image data.The scanning data were imported into Mimics,Geomagic,and Solidworks software in turn.After registration and fusion,a 3D model of normal knee joint was established.On this basis,models of medial collateral ligament injury in different degrees of knee joint were simulated,which were divided into four groups,including:(1)medial collateral ligament was intact;(2)deep medial collateral ligament fracture;(3)superficial medial collateral ligament fracture;(4)complete rupture of medial collateral ligament.Finally,Ansys software was introduced to apply three modes of loads to the knee joint:(1)10 N·m valvaration torque was applied to the top of the femur.(2)A 4 N·m internal torque was applied to the top of the femur.(3)A 4 N·m external torque was applied to the top of the femur.The effects of four groups of models on knee biomechanics under different loads were analyzed. RESULTS AND CONCLUSION:(1)In the extension position of the knee joint,when a 10 N·m valgus torque was applied to the knee joint,the overall stress of the posterolateral meniscus increased with different degrees of medial collateral ligament injuries,while the stress of the articular cartilage did not change significantly.The peak stress of the posterolateral meniscus increased significantly with superficial medial collateral ligament rupture.(2)In the knee extension position,when a 4 N·m internal rotation torque was applied to the knee joint,the overall stress of the medial and lateral meniscus increased after different degrees of medial collateral ligament injury.When superficial medial collateral ligament rupture occurred,the peak stress of the meniscus shifted from the anterior horn of the medial meniscus to the anterior horn of the lateral meniscus.(3)In the knee extension position,applying a 4 N·m external rotation torque to the knee joint,the peak stress of the posterolateral meniscus increased more significantly than that of the medial meniscus,and the stress of the articular cartilage changed less.(4)These results show that the risk of meniscus injury secondary to superficial medial collateral ligament rupture is much higher than that of deep medial collateral ligament rupture when the knee is in extension,and the lateral meniscus is more vulnerable to injury than the medial meniscus.Both superficial medial collateral ligament and deep medial collateral ligament play an important role in the rotational stability of the knee joint.

[摘 要] 目的：探究雷公藤甲素（TPL）通过miR-34b-5p调控Notch1表达对骨肉瘤U2OS细胞铁死亡影响的机制。方法：常规培养U2OS细胞，将其分为对照组、TPL（10 μmol/L）组、TPL（10 μmol/L）+Fer-1（铁死亡抑制剂，20 μmol/L） 组、miR-NC组、miR-34b-5p组、miR-34b-5p+Fer-1（20 μmol/L）组、TPL（10 μmol/L）+anti-miR-34b-5p组、anti-miR-34b-5p+Fer-1（20 μmol/L）组。qPCR法、CCK-8法、铁离子检测试剂、DHE-荧光探针和WB法分别检测各组U2OS细胞中miR-34b-5p的表达、增殖能力、Fe2+水平、ROS水平以及铁死亡相关蛋白（GPX4、SLC7A11及Notch1蛋白）的表达，双萤光素酶报告基因实验验证miR-34b-5p与Notch1的靶向结合关系。结果： TPL可促进U2OS细胞中miR-34b-5p表达，Fer-1和anti-miR-34b-5p则抑制miR-34b-5p的表达（均P<0.05）。TPL明显抑制U2OS细胞的增殖、GPX4、SLC7A11、Notch1蛋白的表达、增加细胞中Fe2+和ROS的含量，Fer-1可逆转TPL对U2OS细胞的作用（均P<0.05）。过表达miR-34b-5p与TPL对U2OS细胞的作用相似（均P<0.05）。miR-34b-5p可靶向结合Notch1（均P<0.05）。miR-34b-5p抑制剂可明显抑制TPL对U2OS细胞的影响，Fer-1可增强miR-34b-5p抑制剂的作用（均P<0.05）。结论：TPL可抑制U2OS细胞的增殖能力并促进其铁死亡，其作用机制可能与miR-34a-5p靶向调节Notch1表达有关。

Objective To analyze diagnostic value of 18F-fluorode-oxyglucose(18F-FDG)positron emission tomography and computed tomography(PET/CT)in elderly patients with colon cancer.Methods A total of 102 patients with colon cancer admitted to Jingdezhen Hospital of Traditional Chinese Medicine from January 2021 to December 2022 were retrospectively selected to analyze the relationship between 18F-FDG PET/CT imaging and clinical features and its diagnostic value.Results The typical 18F-FDG PET/CT imaging of colon cancer was mainly concentrated in ascending colon,transverse colon,descending colon,and sigmoid colon.The glucose metabolism of each part increased,the intestinal wall thickened,and standardized uptake value(SUV)increased.There were statistically significant differences in SUV among colon cancer patients with different vertical thickness of the lesion,gender and lymph node metastasis(P<0.05).SUV was positively correlated with vertical thickness of the lesion and lymph node metastasis(P<0.05).Receiver operating characteristic curve results showed that the area under the curve of 18F-FDG PET/CT for diagnosis of colon cancer lymph node metastasis was 0.993,the sensitivity was 97.2%,and the specificity was 100%.Conclusion 18F-FDG PET/CT for the diagnosis of elderly patients with colon cancer has a high clinical application value.

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.