The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Objective To observe the influence of felodipine sustained release tablets combined with atorvastatin calcium tablets on electrocardiogram indicators and vascular endothelial function in elderly patients with coronary heart disease(CHD)complicated with angina pectoris(AP).Methods According to cohort methods,elderly patients with CHD and AP were divided into control group(oral administration of atorvastatin calcium tablets,20 mg every time)and treatment group(combined with felodipine sustained release tablets on the basis of control group,with initial dose of 5 mg,and then gradually adjusted to 10 mg each time).The 2 groups were treated for 3 months.The electrocardiogram indicators,vascular endothelial function,blood lipids,inflammatory factors and adverse drug reactionswere compared between groups.Results Sixty cases were enrolled in each group.After 3 months of treatment,the QT interval dispersion(QTd)in treatment group and control group were(37.38±4.25)and(42.05±4.74)ms,the corrected QT interval dispersion(QTcd)values were(38.53±4.66)and(43.78±4.87)ms,the QRS duration limits were(92.13±6.29)and(98.79±6.31)ms,serum nitric oxide(NO)levels were(81.31±5.68)and(77.08±4.94)μmol·L-1,endothelin-1(ET-1)were(51.87±3.48)and(56.19±3.53)pg·mL-1,interleukin(IL)-6 levels were(9.17±1.48)and(11.42±2.13)pg·mL-1,vascular cell adhesion molecule(VCAM-1)levels were(120.51±12.45)and(133.76±13.64)pg·mL-1,C-reactive protein(CRP)levels were(0.95±0.11)and(1.08±0.14)pg·mL-1,respectively,with slalistically significanl dillerence(all P＜0.05).After treatment,the total cholesterol levels in treatment group and control group were(3.65±0.47)and(3.81±0.51)mmol·L-1,triglyceride levels were(1.65±0.28)and(1.71±0.33)mmol·L-1,low density lipoprotein cholesterol levels were(2.34±0.31)and(2.45±0.39)mmol·L-1,respectively,without statistically significant diference between the 2 groups(all P＞0.05).During treatment,the incidence rates of adverse reactions in treatment group and control group were 10.00％(6 cases/60 cases)and 6.67％(4 cases/60 cases)respectively,without statistically significant diference between the groups(P＞0.05).Conclusion Felodipine sustained release tablets combined with atorvastatin calcium tablets can effectively improve the electrocardiogram indicators of elderly patients with CHD and AP,reduce inflammatory factors levels and blood lipids levels,and improve the vascular endothelial function,and has good safety.

ObjectiveTo observe the therapeutic effects of Qishao Huoxue prescription on patients with lumbar disc herniation due to Qi stagnation and blood stasis and the effects of this prescription on hemorheological parameters and serum levels of inflammatory mediators. MethodA total of 86 patients with lumbar disc herniation due to Qi stagnation and blood stasis treated in the Wangjing Hospital of China Academy of Chinese Medical Sciences from January 2023 to February 2024 were selected and assigned according to the random number table into observation and control groups （n=43）. Patients in both groups received lumbar traction treatment. In addition， the observation group was orally treated with Qishao Huoxue prescription and the control group with celebrex for 3 weeks. The visual analogue scale （VAS） score， Oswestry disabilitiy index （ODI） score， 12-item Short-Form Survey （SF-12） score， traditional Chinese medicine （TCM） symptom score， hemorheological parameters ［whole blood high shear viscosity， middle shear viscosity， low shear viscosity， plasma viscosity （PV）， and fibrinogen （FIB）］， and the serum levels of inflammatory mediators ［tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and transforming growth factor-β₁ （TGF-β₁）］ were determined before and after treatment. In addition， the clinical efficacy and adverse reactions were observed and compared between the two groups. ResultAfter treatment， both groups showed declined VAS， ODI， and TCM symptom scores （P<0.05）， increased SF-12 physical component summary （PCS） and mental component summary （MCS） scores （P<0.05）. After treatment， the whole blood high shear viscosity， middle shear viscosity， low shear viscosity， PV， and FIB decreased in the observation group （P<0.05）， while they did not show significant variations in the control group. After treatment， both groups of patients showed reductions in TNF-α， IL-6， and IL-1β levels and an elevation in the TGF-β₁ level （P<0.05）. Compared with the control group after treatment， the observation group showed decreases in VAS， ODI， TCM symptom scores and main symptom scores （P<0.05）， no significant differences in the secondary symptom scores， increased PCS and MCS scores （P<0.05）. The observation group outperformed the control group in terms of recovering whole blood high shear viscosity， middle shear viscosity， low shear viscosity， PV， FIB， TNF-α， IL-6， IL-1β， and TGF-β₁ （P<0.05）. The total response rate in the observation group was 97.5% （40/41）， which was higher than that （88.1%， 37/42） in the control group （P<0.05）. No serious adverse reaction was observed in the two groups during the observation period. One case in the observation group showed subcutaneous bruising on the lower limbs， which gradually disappeared after withdrawal. ConclusionQishao Huoxue prescription demonstrated definite effect in treating lumbar disc herniation due to qi stagnation and blood stasis by recovering hemorheological parameters and inhibiting the expression of inflammatory mediators in the serum without inducing adverse reactions. It is worth applying in clinical practice.

Osteosarcopenia (OS) is a multifactorial, multiaetiologic degenerative metabolic syndrome in which sarcopenia coexists with osteoporosis, and its influences are related to aging-induced mechanics, genetics, inflammatory factors, endocrine disorders, and irregular lifestyles. With the accelerated aging process in our country, osteosarcopenia has become a public health problem that cannot be ignored, with a higher risk of falls, fractures, impaired mobility and death. In recent years, scholars at home and abroad have conducted a lot of research on osteosarcopenia, but their pathogenesis is still unclear. Understanding the signaling pathways associated with osteosarcopenia is of great significance for further research on the pathogenesis of these disorders and for finding new targets for treatment. Studies have shown that activation of the PI3K/Akt signaling pathway promotes osteoblast differentiation as well as skeletal muscle regeneration, indicating that inhibition of thePI3K/Akt signaling pathway is closely related to the development of osteosarcopenia. Muscle factor-mechanical stress interactions can maintain osteoblast viability by activating the Wnt/β-catenin signaling pathway, suggesting that Wnt signaling is important in muscle and bone crosstalk. The Notch signaling pathway also plays an important role in improving bone and muscle mass and function, but different researchers hold different views, which need to be further validated and refined in subsequent studies. Exercise, as an existing non-pharmacological treatment with strong and sustained effects on physical function and muscle strength, also significantly increases bone density in osteoporosis patients, which may be mainly due to the fact that exercise induces changes in the form and function of bones, in the form of muscular pulling and indirectly improves the bone mass, and changes in the bone strength can also change the number, shape as well as the function of the muscles. At the same time, the mechanism of different exercise modalities focuses on different aspects, and there are differences in exercise time, exercise intensity, and therapeutic effects in the implementation of interventions. Aerobic exercise can improve the quality of skeletal muscle and increase the expression of osteogenesis-related genes by stimulating mitochondrial biosynthesis, as well as improve the quality and strength of bones and muscles through the Wnt/β- catenin and PI3K/Akt signaling pathways, effectively preventing and controlling the occurrence of musculoskeletal disorders. High-intensity resistance exercise has a significant effect on improving the quality of muscles and bone mineral density, but older people with osteosarcopenia suffer from a decline in muscle quality and strength, and a decline in bone mineral density, which makes them very susceptible to fracture, so they should select the intensity of the training in a gradual and orderly manner, from small to large. What kind of exercise intensity and exercise modalities are most effective in improving the occurrence and development of osteosarcopenia needs to be further investigated. Therefore, this paper mainly reviews the epidemiology of osteosarcopenia, diagnostic criteria, the related signaling pathways (PI3K/Akt pathway, Wnt/β-catenin pathway, Notch pathway, NF-κB pathway) that jointly regulate the metabolic process of myocytes and skeletal cells, as well as the interventional effects of different exercise modes on osteosarcopenia, with the aim of providing theoretical bases for the clinical treatment of osteosarcopenia, as well as enhancing the preventive capacity of the disease in old age.

Objective To investigate the efficacies of proximal femoral nail anti-rotation(PFNA)internal fixation in traction bed supine position and non-traction bed lateral position in the treatment of elderly unstable femoral intertrochanteric fractures.Methods The clinical data of patients with unstable femoral intertrochanteric fractures treated with PFNA internal fixation in our hospital were retrospec-tively analyzed,41 patients received treatment in traction bed supine position were included in the supine position group,and 55 patients treated received treatment in non-traction bed lateral position were included in the lateral position group.The perioperative related indicators,surgical reduction,hip Harris score,and incidence of complications in the two groups were analyzed.Results The operation time and incision length of patients in the lateral position group were shorter than those in the supine position group,and the intraoperative blood loss and fluoroscopy times were less than those in the supine position group,with statistically significant differences(P<0.05).There was no significant difference in the anesthesia mode,blood transfusion or hospital stay of patients between the two groups(P>0.05).There was no significant difference in the incidence of postoperative complications of patients between the two groups(P>0.05).There was no significant difference in neck-shaft angle,tip-apex distance or hip Harris score of patients between the two groups(P>0.05).Conclusion PFNA internal fixation in traction bed supine position and non-traction bed lateral position have the same effect in the treatment of elderly unstable femoral intertrochanteric fractures,while the non-traction bed lateral position for treatment has more advantages in shortening operation time,decreasing intraoperative blood loss,and reducing radiation exposure.

Objective To investigate the relieving effects of knockdown of long non-coding RNA(lncRNA)taurine up-regulated gene 1 (TUG1) on inhibiting nucleotide binding oligomerization domain like receptor protein 1 (NLRP1) inflammasome and the progression of Alzheimer’ s disease. Methods Wild-type (WT group, 10 mice) or amyloid precursor protein (APP) / presenilin-1 (PS1) transgenic mice (30 mice) with a genetic background of C57 / BL6 aged 9-10 weeks were used in this study. APP / PS1 transgenic mice were randomly divided into model group, model+lncRNA TUG1 short hairpin RNA (shRNA) group and model + shRNA non target (NT) group (n = 10) . Blood samples, cerebral cortex tissues, primary microglial cells and primary astrocytes were collected from mice 12 weeks of age on day 1 (3-month-old) and 32 weeks of age on day 1 (8-month-old), with 5 mice per group at each time point. Real-time PCR analysis was used to detect the expression levels of lncRNA TUG1 and macrophage migration inhibitory factor (MIF) mRNA in cerebral cortex tissues and primary microglial cells, and C1r and C1s mRNA levels in primary astrocytes of 3-month-old and 8-month-old mice in the above 4 groups, respectively. ELISA was used to determine the MIF in plasma samples of the above 4 groups of mice. Primary microglia and astrocytes from the cerebral cortex of 3-month-old and 8-month-old mice were co-cultured. CCK-8 method was used to determine the proliferation ability of the above cells. Western blotting was used to determine the expression levels of MIF, pro interleukin-1β (pro-IL-1β), apoptosis associated speck-like protein containing a caspase recrult domain(ASC), Caspase-1 (p20), Caspase-1 (full), NLRP1 and NLRP3 in cerebral cortex tissues of 3-month-old and 8-month-old mice. Immunofluorescent staining was used to determine amyloid beta(Aβ) in cerebral cortex of 8-month-old mice. Results At the age of 3-month-old and 8-month-old, compared with the WT group, the relative expression level of lncRNA TUG1 and MIF in cerebral cortex tissues and primary microglia of model group mice was significantly up-regulated, with primary microglial cells and astrocytes proliferation ability enhanced (P<0. 05) . Compared with the model group, the relative expression level of lncRNA TUG1 and MIF cerebral cortex tissues and primary microglia of model + lncRNA TUG1 shRNA group were significantly down-regulated, with primary microglial cells and astrocytes proliferation ability decreased (P<0. 05) . Compared with the WT group, MIF factor in the peripheral plasma of model group increased significantly, with pro-IL-1β,ASC,Caspase-1 (p20),Caspase-1 (full), NLRP1 and NLRP3 expression level up-regulated in the model group mice cerebral cortex tissues, with increased Aβ immunofluorescent indensity (P<0. 05) . Compared with the model group, MIF factor in the peripheral plasma, and pro-IL-1β, ASC, Caspase-1 (p20), Caspase-1 (full) and NLRP1 expression in the model + lncRNA TUG1 shRNA group mice cerebral cortex tissues were down-regulated, and Aβ immunofluorescent indensity decreased (P<0. 05), while NLRP3 expression level were not changed (P>0. 05) . There was no significant difference between the model group and the model+shRNA NT group mice of all the above factors (P>0. 05) . Conclusion In APP / PS1 transgenic mice, up-regulation of lncRNA TUG1 and MIF are positively associated with the activation of NLRP1 inflammasome in mice cerebral cortex tissues and primary microglia. Knock-down of lncRNA TUG1 can ameliorate the progression of Alzheimer’ s disease.

The discoid meniscus is a common congenital meniscal malformation that is prevalent mainly in Asians and of-ten occurs in the lateral discoid meniscus.Patients with asymptomatic discoid meniscus are usually treated by conservative methods such as observation and injury avoidance,while patients with symptoms and tears need to be treated surgically.Arthroscopic saucerization combined with partial meniscectomy and meniscus repair is the most common surgical approach.,and early to mid-term reports are good.The prognostic factors are the patient's age at surgery、follow-up time and type of surgery.Some patients experience complications such as prolonged postoperative knee pain,early osteoarthritis,retears and Osteochondritis dissecans.The incidence of prolonged postoperative knee pain was higher and the incidence of Osteochondritis dissecans was the lowest.Retears of the lateral meniscus is the main reason for reoperation.

Objective To observe the effects of melatonin on autophagy in cortical neurons of neonatal rats with hypoxic-ischemic brain damage(HIBD)and to explore its mechanisms via the PI3K/AKT signaling pathway,aiming to provide a basis for the clinical application of melatonin.Methods Seven-day-old Sprague-Dawley neonatal rats were randomly divided into a sham operation group,an HIBD group,and a melatonin group(n=9 each).The neonatal rat HIBD model was established using the classic Rice-Vannucci method.Neuronal morphology in the neonatal rat cerebral cortex was observed with hematoxylin-eosin staining and Nissl staining.Autophagy-related protein levels of microtubule-associated protein 1 light chain 3(LC3)and Beclin-1 were detected by immunofluorescence staining and Western blot analysis.Phosphorylated phosphoinositide 3-kinase(p-PI3K)and phosphorylated protein kinase B(p-AKT)protein expression levels were measured by immunohistochemistry and Western blot.The correlation between autophagy and the PI3K pathway in the melatonin group and the HIBD group was analyzed using Pearson correlation analysis.Results Twenty-four hours post-modeling,neurons in the sham operation group displayed normal size and orderly arrangement.In contrast,neurons in the HIBD group showed swelling and disorderly arrangement,while those in the melatonin group had relatively normal morphology and more orderly arrangement.Nissl bodies were normal in the sham operation group but distorted in the HIBD group;however,they remained relatively intact in the melatonin group.The average fluorescence intensity of LC3 and Beclin-1 was higher in the HIBD group compared to the sham operation group,but was reduced in the melatonin group compared to the HIBD group(P<0.05).The number of p-PI3K+and p-AKT+cells decreased in the HIBD group compared to the sham operation group but increased in the melatonin group compared to the HIBD group(P<0.05).LC3 and Beclin-1 protein expression levels were higher,and p-PI3K and p-AKT levels were lower in the HIBD group compared to the sham operation group(P<0.05);however,in the melatonin group,LC3 and Beclin-1 levels decreased,and p-PI3K and p-AKT increased compared to the HIBD group(P<0.05).The correlation analysis results showed that the difference of the mean fluorescence intensity of LC3 and Beclin-1 protein in the injured cerebral cortex between the melatonin and HIBD groups was negatively correlated with the difference of the number of p-PI3K+and p-AKT+cells between the two groups(P<0.05).Conclusions Melatonin can inhibit excessive autophagy in cortical neurons of neonatal rats with HIBD,thereby alleviating HIBD.This mechanism is associated with the PI3K/AKT pathway.

This study investigated the role of Echinococcus multilocularis vesicle-derived extracellular vesicles(EVs)con-taining emu-miR-10-5p in regulating HSC activation in vitro.Mice were injected intraperitoneally with protoscoleces to con-struct a secondary alveolar echinococcosis model,and E.multilocularis vesicles were cultured in mice and identified by PCR.The EV structure in cultured vesicle tissue was observed by transmission electron microscopy.EVs were isolated from vesicle culture supernatants through differential-ultracentrifugation,and identified by transmission electron microscopy,nanoparticle size analysis,and western blotting.The activity of HSCs treated with different EV concentrations was detected with CCK-8 assays.The expression levels of α-SMA,and collagen Ⅰ and Ⅲ were detected by RT-qPCR and western blotting after EV treatment of HSCs.Bioinformatics analysis identified the specific miRNA emu-miR-10-5p.The proliferation of HSCs was detected with EdU after overexpression of emu-miR-10-5p,and the expression levels of α-SMA,collagen Ⅰ,and collagen Ⅲ in cells were detected by RT-qPCR and western blotting.Detection of α-SMA,collagen Ⅰ,and collagen Ⅲ expression levels in HSCs was performed after EVs were extracted from the culture supernatant of vesicular tissues with emu-miR-10-5p knockdown.E.multilocularis vesicles were successfully cultured from focal material in mice,and the E.multilocularis origin was confirmed through PCR amplification of specific genes.TEM observation of culture vesicles in-dicated abundant surface vesicular structures.E.multilocularis vesicle-derived EVs were isolated by differential-ultracentrifu-gation,and confirmed by TEM to be spherical and membrane like-structures.Vesicle-derived EVs were internalized by HSCs,and promoted the proliferation and activation of HSCs.Comprehensive analysis of miRNA sequencing results revealed emu-miR-10-5p expression in E.multilocularis-infected mouse serum,metacestode tissue,E.multilocularis-derived EVs,germi-nal layer cells,and protoscoleces.Moreover emu-miR-10-5p was confirmed to be present in higher amounts in E.multilocu-laris-derived EVs,according to RT-qPCR.Further studies confirmed that overexpression of emu-miR-10-5p promoted HSC proliferation and increased α-SMA,collagen Ⅰ,and collagen Ⅲ mRNA and protein expression levels in HSCs.In contrast,EVs extracted from culture supernatants after emu-miR-10-5p knockdown in vesicles did not increase a-SMA,collagen Ⅰ,and colla-gen Ⅲ mRNA and protein expression levels.E.multilocularis vesicle-derived EVs and emu-miR-10-5p thus promote the acti-vation of HSCs.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.