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.

Background As a pillar industry in China, the manufacturing sector has a high incidence of non-fatal occupational injuries. The factors influencing non-fatal occupational injuries in this industry are closely related at various levels, including individual, equipment, environment, and management, making the analysis of these influencing factors complex. Objective To identify influencing factors of non-fatal occupational injuries among manufacturing workers, providing a basis for targeted interventions and surveillance. Methods A total of 2243 frontline workers from cable and shipbuilding enterprises were selected as study subjects to investigate the incidence of non-fatal occupational injuries and collect information at four levels: individual, equipment, management, and environment in past 12 months. Data balancing was performed using resampling, and LASSO regression was used to select factors of non-fatal occupational injuries. The influence degree and type of variables were judged based on the magnitude of the estimated coefficients of each variable, where variables with estimated coefficients > 0 are risk factors, and those <0 are protective factors. The area under the receiver operating characteristic (ROC)curve (AUC) was used to test the performance of the model, with an AUC value > 0.7 indicating good model performance. Results Among the 2243 frontline workers, males accounted for 77.7% (1742 out of 2243), with the main age range being 40-49 years old, representing 29.5% (661 out of 2243), 82.7% of the workers (1854 out of 2243) were married, and 55.6% (1248 out of 2243) had a junior middle school education level. The average monthly income for 51.0% (1144 out of 2243) of the workers was between 5000 and 6999 Chinese Yuan. The incidence of non-fatal occupational injuries among the manufacturing workers was 8.4% (189/2243) in the past 12 months. Among the 22 factors associated with the occurrence of non-fatal occupational injuries (P<0.05), 10 were individual-level factors, including gender, smoking, alcohol consumption, colleague relationships, average exercise duration, job burnout, work fatigue, musculoskeletal disorders, cardiovascular diseases, and neurological and sensory organ diseases; 3 were equipment-level factors, including equipment operability, hazardous workpieces, and safety hazards; 5 were environmental-level factors, including low temperatures, special operations, noise, workspace size, and dirty and disorderly environment; and 4 were management-level factors, including daily working hours, weekly working days, overtime, and pre-job technical training. The AUC value of the LASSO regression model was 0.704 and the final model retained a total of 10 variables. Among them, there were 7 risk factors for non-fatal occupational injuries (coefficient > 0), including safety hazards, musculoskeletal disorders, dangerous workpieces, job burnout, dirty and disorderly environment, smoking, and male gender; and 3 protective factors (coefficient < 0), including pre-job technical training, good colleague relationship, and long working days per week. Conclusion Manufacturing enterprises need to focus on the incidence of non-fatal occupational injuries and conduct targeted interventions for non-fatal occupational injuries by controlling potential safety hazards, providing pre-job technical training, reducing dangerous workpieces, rectifying working environment, and reasonably arranging working hours.

Aim To investigate the effect of long non- coding RNA p21 (LncRNA p21) regulating Hippo- Yes-associated protein (Hippo-YAP) signaling pathway on the formation of abdominal aortic aneurysm (AAA) in mice. Methods C57BL/6 ApoE

In addition to providing energy for cells, mitochondria also participate in calcium homeostasis, cell information transfer, cell apoptosis, cell growth and differentiation. Therefore, maintaining mitochondrial homeostasis is very crucial for the body to carry out normal life activities. Ubiquitination, a post-translational modification of proteins, is involved in various physiological and pathological processes of cells by regulating mitochondrial homeostasis. However, the mechanism by which ubiquitination regulates mitochondrial homeostasis has not been summarized, especially the effect of Parkin protein on cardiovascular diseases. In this paper, the specific mechanism of mitochondrial homeostasis regulated by ubiquitination of Parkin protein is discussed, and the influence of mitochondrial homeostasis imbalance on cardiovascular diseases is reviewed, with a view to providing potential therapeutic strategies for the clinical treatment of cardiovascular diseases.

Objective To investigate the efficacy and safety of Tubridge flow diverter(TFD)in the treatment of ruptured intracranial aneurysms.Methods The clinical data of 13 patients with aneurysmal subarachnoid hemorrhage,who received TFD treatment at the First Affiliated Hospital of Zhengzhou University between March 2019 and Jul 2022,were retrospectively collected.The perioperative materials and follow-up results were summarized and analyzed.Results Successful operation was accomplished in all the 13 patients(13 aneurysms in total).TFD and coil embolization were simultaneously performed in 10 patients(simultaneous treatment),spring coil filling followed by selective staged TFD placement was adopted in 2 patients(staged treatment),and pure TFD placement was employed in one patient.The incidence of perioperative complications was 15.4%(2/13),including asymptomatic ischemic event in one patient and extra-ventricular drainage-related postoperative bleeding in another patient,which caused death of the patient.The median follow-up time was 6.5 months,and 83.3%of patients(10/12)completed cerebral angiography reexamination with DSA.OKM grade D(complete occlusion of the aneurysm)was obtained in 8 patients(80%),and OKM grade C(residual aneurysm neck)in 2 patients.Conclusion For ruptured intracranial aneurysms,TFD implantation is a clinically feasible treatment with favorable safety and efficacy.

Schimke immuno-osseous dysplasia (SIOD)caused by SMARCAL1 gene mutations is a rare genetic disorder characterized by multi-system involvement, including T-cell dysfunction, skeletal dysplasia, disproportionate short stature, nephrotic syndrome, and kidney failure. This multidisciplinary consultation involved a 9-year-old boy with intrauterine growth retardation, presenting with short stature, T-cell lymphopenia, proteinuria, and degenerative bone and joint disease. Treatment primarily focused on symptomatic and supportive care. Through the multidisciplinary rare disease consultation, holistic support was provided to the patient, offering comprehensive care from various specialtiesx.We also aim to use this case report to enhance clinicians′ under-standing of SIOD and improve the management and treatment of rare diseases.

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 study the pharmacokinetic characteristics of etoricoxib tablets in healthy Chinese subjects and to evaluate the bioequivalence and safety of the test and reference formulations.Methods In a randomised,single-dose,two-period,two-sequence crossover trial,28 healthy subjects were enrolled under the fasting and fed conditions,respectively,who received a single oral dose of 60 mg of etoricoxib tablets in the test or reference formulation.The concentration of etoricoxib in plasma was detected by LC-MS/MS,and the main pharmacokinetic parameters were calculated to evaluate bioequivalence and using WinNonlin 8.2 software.Results The main pharmacokinetic parameters of the test and reference preparations were as follows:The fasting condition Cmax of etoricoxib were(1 176.96±287.95)and(1 164.93±189.65)ng·mL-1;AUC0-t were(18 651.95±6 100.27)and(19 241.39±6 107.48)ng·h·mL-1;and AUC0-∞ were(19 939.15±7 553.27)and(20 536.31±7 223.40)ng·h·mL-1.The fed condition Cmax of etoricoxib were(913.50±184.72)and(878.59±164.35)ng·mL-1;and AUC0-t were(19 085.22±5 155.01)and(18 669.54±4 508.21)ng·h·mL-1;AUC0-∞ were(20 103.77±5 567.02)and(19 528.05±4 989.74)ng·h·mL-1.The 90％confidence intervals for the geometric mean ratios of the main pharmacokinetic parameters in the fasting and fed conditions fell between 80.00％and 125.00％.The incidence of adverse events in the fasting and fed conditions were 28.57％and 21.43％,respectively.Conclusion Two kinds of etoricoxib tablets are bioequivalent,and have similar safety in healthy Chinese subjects.

Pafolacianine is a fluorescent agent that specifically targets folate receptors,employed in the treatment of adult ovarian cancer patients to support the detection of malignant growths during surgical interventions.Pafolacianine binds to cancer cells expressing folate receptors,accumulating within folate-receptor-positive tumor tissue through receptor-mediated endocytosis.It can be excited by near-infrared fluorescence imaging,facilitating the surgical removal of tumors during procedures.This article gives an introduction to the mechanism of action,pharmacokinetics,clinical studies,and safety aspects of Pafolacianine.

On May 27,2021,the U.S.Food and Drug Administration(FDA)officially approved Lantheus'PYLARIFY?(Piflufolastat F 18,18 F-labeled imaging agent),which can be used for positron emission computed tomography(PET)of prostate-specific membrane antigen(PSMA)-positive lesions in prostate cancer patients to accurately identify prostate cancer with suspected metastasis or recurrence.Piflufolastat F 18 is approved by FDA for two indications.The first is the initial staging for suspected metastatic lesions in men with newly diagnosed prostate cancer.The second is restaging,with the goal of identifying lesions in the setting of biochem ical recurrence.