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.

Nanoparticle delivery systems have good application prospects in the field of precision therapy, but the preparation process of nanomaterial has problems such as short in vivo circulation time, easy recognition, and clearance by the immune system in the body. In recent years, biomimetic nanoparticle delivery systems mediated by natural cell membranes have become a research hotspot to address these issues. The natural membrane biomimetic nanoparticle delivery system cleverly integrates the advantages of natural biofilm "autologous" and "artificial" functional carriers by using endogenous cell membranes to modify the surface of nanocarriers, endowing them with characteristics such as tumor targeting, low immunogenicity, and long blood circulation. Currently, biomimetic nanoparticle delivery systems have been used in the treatment of malignant tumors, cardiovascular diseases, bacterial infections, and other diseases. This paper analyzes the development status and current research hotspots of natural cell membrane camouflaged biomimetic nanoparticle delivery systems mainly reviews the latest research progress of red blood cell membrane camouflaged biomimetic nanoparticle delivery systems in the field of disease treatment in recent years. It focuses on exploring the advantages, future development prospects, and limitations of biomimetic nanoparticle delivery systems based on red blood cell membrane camouflage in improving drug delivery, to provide a reference for the in-depth research and development of this system.

A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.

Diabetic cardiomyopathy is a distinct form of cardiomyopathy that can lead to heart failure, arrhythmias, cardiogenic shock, and sudden death. It has become a major cause of mortality in diabetic patients. The pathogenesis of diabetic cardiomyopathy is complex, involving increased oxidative stress, activation of inflammatory responses, disturbances in glucose and lipid metabolism, accumulation of advanced glycation end products (AGEs), abnormal autophagy and apoptosis, insulin resistance, and impaired intracellular Ca²⁺ homeostasis. Recent studies have shown that adenosine monophosphate-activated protein kinase (AMPK) plays a crucial protective role by lowering blood glucose levels, promoting lipolysis, inhibiting lipid synthesis, and exerting antioxidant, anti-inflammatory, anti-apoptotic, and anti-ferroptotic effects. It also enhances autophagy, thereby alleviating myocardial injury under hyperglycemic conditions. Consequently, AMPK is considered a key protective factor in diabetic cardiomyopathy. As part of diabetes prevention and treatment strategies, both pharmacological and exercise interventions have been shown to mitigate diabetic cardiomyopathy by modulating the AMPK signaling pathway. However, the precise regulatory mechanisms, optimal intervention strategies, and clinical translation require further investigation. This review summarizes the role of AMPK in the prevention and treatment of diabetic cardiomyopathy through drug and/or exercise interventions, aiming to provide a reference for the development and application of AMPK-targeted therapies. First, several classical AMPK activators (e.g., AICAR, A-769662, O-304, and metformin) have been shown to enhance autophagy and glucose uptake while inhibiting oxidative stress and inflammatory responses by increasing the phosphorylation of AMPK and its downstream target, mammalian target of rapamycin (mTOR), and/or by upregulating the gene expression of glucose transporters GLUT1 and GLUT4. Second, many antidiabetic agents (e.g., teneligliptin, liraglutide, exenatide, semaglutide, canagliflozin, dapagliflozin, and empagliflozin) can promote autophagy, reverse excessive apoptosis and autophagy, and alleviate oxidative stress and inflammation by enhancing AMPK phosphorylation and its downstream targets, such as mTOR, or by increasing the expression of silent information regulator 1 (SIRT1) and peroxisome proliferator-activated receptor‑α (PPAR‑α). Third, certain anti-anginal (e.g., trimetazidine, nicorandil), anti-asthmatic (e.g., farrerol), antibacterial (e.g., sodium houttuyfonate), and antibiotic (e.g., minocycline) agents have been shown to promote autophagy/mitophagy, mitochondrial biogenesis, and inhibit oxidative stress and lipid accumulation via AMPK phosphorylation and its downstream targets such as protein kinase B (PKB/AKT) and/or PPAR‑α. Fourth, natural compounds (e.g., dihydromyricetin, quercetin, resveratrol, berberine, platycodin D, asiaticoside, cinnamaldehyde, and icariin) can upregulate AMPK phosphorylation and downstream targets such as AKT, mTOR, and/or the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), thereby exerting anti-inflammatory, anti-apoptotic, anti-pyroptotic, antioxidant, and pro-autophagic effects. Fifth, moderate exercise (e.g., continuous or intermittent aerobic exercise, aerobic combined with resistance training, or high-intensity interval training) can activate AMPK and its downstream targets (e.g., acetyl-CoA carboxylase (ACC), GLUT4, PPARγ coactivator-1α (PGC-1α), PPAR-α, and forkhead box protein O3 (FOXO3)) to promote fatty acid oxidation and glucose uptake, and to inhibit oxidative stress and excessive mitochondrial fission. Finally, the combination of liraglutide and aerobic interval training has been shown to activate the AMPK/FOXO1 pathway, thereby reducing excessive myocardial fatty acid uptake and oxidation. This combination therapy offers superior improvement in cardiac dysfunction, myocardial hypertrophy, and fibrosis in diabetic conditions compared to liraglutide or exercise alone.

Objective To evaluation the bioequivalence of telmisartan tablets(80 mg)between test formulation and reference formulation in Chinese healthy subjects.Methods A single-center,randomized,open-label,two-preparations,single administration,partial repeat crossover of three sequences in three postprandial cycles and complete repeat crossover of two sequences in four fasting cycles,bioequivalence test was designed.Chinese healthy subjects were included in the bioequivalence trial,with 33 randomly assigned to the postprandial group and 32 randomly assigned to the fasting group.In each period,blood samples was collected before and after administration.The plasma concentration of the drug was determined by LC-MS/MS,using WinNonlin version 8.3 calculate the pharmacokinetic parameters and perform a statistical analysis using SAS version 9.4.Results The main pharmacokinetic parameters of telmisartan tablets after oral administration of test or reference were as follows.Fasting group Cmax were(556.10±456.06)and(580.99±533.50)ng·mL-1;AUC0-t were(3 475.15±3 785.16)and(3 450.54±3 681.02)ng·mL-1·h;AUC0-∞ were(3 214.06±2 272.06)and(3 194.84±2 187.45)ng·mL-1·h.The 90％confidence intervals of the geometric mean ratio of Cmax,AUC0-t,AUC0-∞ were within the requirements of the equivalent range of bioequivalence(80.00％-125.00％).Postprandial group Cmax were(299.26±124.72)and(291.29±126.34)ng·mL-1;AUC0-t were(3 682.24±2 799.72)and(3 636.71±2 158.42)ng·mL-1·h;AUC0-were(3 544.53±1 553.06)and(3 969.38±2 528.22)ng·mL-1·h.The 90％confidence intervals of the geometric mean ratio of Cmax,AUC0-t,AUC0-∞ were within the requirements of the equivalent range of bioequivalence(80.00％-125.00％).Conclusion Under fasting and fed conditions,two kinds of telmisartan tablets are bioequivalent in Chinese healthy subjects.

Objective To explore the effect of rifampicin on the pharmacokinetics of linezolid in mice and provide pharmacokinetic evidence for the formulation of safe drugs for clinical use of pulmonary tuberculosis.Methods Fifty male KM mice were randomly divided into 2 groups:Control group,rifampicin group;the control group was given 15 mg·kg-1 linezolid;the rifampicin group was given 100 mg·mL-1 rifampicin,continuous administration for 7 days,followed by gavage,administration of 15 mg·kg-1 linezolid;blood and lung tissue were collected from mouse at different time points after administration.High performance liquid mass spectrometry(LC-MS/MS)was used to determine plasma concentration of linezolid and compared the pharmacokinetics between groups.Pharmacokinetic parameters were calculated using DAS 2.0 software.Results Main pharmacokinetic parameters of plasma linezolid in control group,rifampicin group were as follows:AUC0_t were(23.88±1.16)and(19.06±2.56)pg·mL-1·h,respectively;t1/2 were((1.15±0.11)and(1.11±0.10)h,respectively;Cmax were(9.93±0.46)and(7.74±1.17)μg·mL-1,respectively.The main pharmacokinetic parameters of the lungs in the control group and the rifampicin group were as follows:AUC0_t were(18.76±4.29)and(14.90±1.52)μg·mL-1·h,respectively;t1/2 were(1.94±0.50)and(1.44±0.07)h,respectively;Cmax were(8.28±2.67)and(6.82±1.57)μg·mL-1,respectively.AUC0_t and Cmax in plasma and AUC0_t in lung tissue of control group were significantly different from those of rifampicin group(all P＜0.05).Conclusion After the combination of rifampicin,linezolid plasma and lung tissue exposure decreased significantly,and attention should be paid to monitoring linezolid trough concentration when the two drugs were combined to avoid treatment failure caused by low effective concentration.

Objective To observe the effect of Bushen Huoxue formula on interleukin-17(IL-17)in rats with recurrent spontaneous abortion(RSA).Methods RS A model rats were constructed by intraperitoneal injection of estradiol benzoate.Forty RSA model rats were randomly divided into model group,control group and experimental-L,-H groups,with 10 rats per group.Another 10 healthy pregnant rats were set as blank group.The experimental-L,-H groups were given 7.77 and 15.54 g·kg-1 of Bushen Huoxue formula solution by gavage.The control group was given 2.10 mg·kg-1of dydrogesterone solution by gavage.The blank group and the model group were given equal amount of 0.9％NaCl by gavage.The dose of administration for the five groups was 10 mL·kg-1,once a day,for 9 days.The number of live fetuses,embryo loss,and embryo loss rate in each group were observed.The proportion of Th 17 cells in the peripheral blood was detected by flow cytometry.The expression levels of interleukin-6(IL-6),IL-17 and IL-23 proteins in the decidual tissues were detected by Western blotting.Results The number of live fetuses in the experimental-H,control,model and blank groups were 11.50±2.84,11.50±3.10,6.30±1.25 and 12.50±3.24;the number of embryos lost were 1.80±0.42,1.90±0.57,4.90±1.37 and 0;the rates of embryo loss were(14.01±4.52)％,(14.79±6.06)％,(43.50±9.49)％and 0;the proportions of Th17 cells in the peripheral blood were(3.12±0.47)％,(3.10±0.59)％,(5.31±1.16)％and(2.54±0.71)％;the relative expression levels of IL-6 protein were 0.19±0.04,0.18±0.05,0.85±0.16 and 0.11±0.03;the relative expression levels of IL-17 protein were 0.28±0.04,0.29±0.05,0.84±0.12 and 0.09±0.01;the relative expression levels of IL-23 protein were 0.35±0.04,0.34±0.06,0.90±0.11 and 0.08±0.01,respectively.Comparing experimental-H group and model group,comparing control group and blank group,the above indexes were statistically significant(all P＜0.05).Conclusion Bushen Huoxue formula can reduce embryo loss,improve placental tissue pathology,reduce Th 17 cell proportion and its related cytokines IL-6,IL-17,IL-23 expression in rats with RSA.

Exploring the risk "time interval window" of sequential medication of Reduning injection (RDN) and penicillin G injection (PG) by detecting the correlation between serum biochemical indexes and plasma metabonomic characteristics, in order to reduce the risk of adverse reactions caused by the combination of RDN and PG. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). The changes of biochemical indexes in serum of rats were detected by enzyme-linked immunosorbent assay. It was determined that RDN combined with PG could cause pseudo-allergic reactions (PARs) activated by complement pathway. Further investigation was carried out at different time intervals (1.5, 2, 3.5, 4, 6, and 8 h PG+RDN). It was found that sequential administration within 3.5 h could cause significant PARs. However, PARs were significantly reduced after administration interval of more than 4 h. LC-MS was used for plasma metabolomics analysis, and the levels of serum biochemical indicators and plasma metabolic profile characteristics were compared in parallel. 22 differential metabolites showed similar or opposite trends to biochemical indicators before and after 3.5 h. And enriched to 10 PARs-related pathways such as arachidonic acid metabolism, steroid hormone biosynthesis, linoleic acid metabolism, glycerophospholipid metabolism, and tryptophan metabolism. In conclusion, there is a risk "time interval window" phenomenon in the adverse drug reactions caused by the sequential use of RDN and PG, and the interval medication after the "time interval window" can significantly reduce the risk of adverse reactions.

Background Workers in printing jobs are exposed to a variety of organic solvents at low levels for a long period of time. Previous studies have focused on the main components in Material Safety Data Sheet or high-risk occupational hazardous agents, but have not been able to comprehensively and accurately identify the volatile organic compounds (VOCs) in printing jobs. Objective To qualitatively analyze the VOCs in ink, detergent, varnish, fountain solution, and other raw and auxiliary materials by headspace gas chromatography-mass spectrometry, and to accurately identify the occupational hazardous agents in printing jobs. Methods Raw and auxiliary materials used in printing jobs in 6 printing enterprises in Shanghai were sampled by headspace sampling, analyzed by gas chromatography-mass spectrometry, identified by National Institute of Standards & Technology ( NIST) Standard Library and retention time, and quantified by peak area percentage. Results A total of 181 VOCs were reported in the headspace of 25 organic solvent samples, with a total detection frequency of 337 items and 13.2±12.3 VOCs per sample. The most frequently detected VOCs category was naphthene, with a total of 69 items detected (22.5%), dominated by cyclohexane. The characteristics of VOCs components in the headspace of different types of samples were different. The largest number of VOCs was detected in the headspace of detergent samples, with an average of 31.5 VOCs detected. The characteristic components in detergent were aromatic hydrocarbons and ester compounds; alcohols were the characteristic components in varnish; and ester compounds were the characteristic components in ink. The results of cluster analysis showed that ethanol, toluene, ethyl acetate, cyclohexane, and acetone were occupational hazardous agents with high levels of exposure in printing jobs. Conclusion Many kinds of organic solvents used in printing process are difficult to identify by traditional methods. Headspace gas chromatography-mass spectrometry can help to accurately identify VOCs in the workplace, so as to more accurately assess the occupational hazards, and to provide a technical basis for guiding occupational health monitoring and implementing corresponding occupational health risk management and control.