OBJECTIVE To confirm trigger items for adverse drug reaction （ADR） induced by bevacizumab， to identify and analyze the occurrence of related ADR， and to establish a predictive model for severe adverse reaction （SAR） caused by this drug. METHODS Based on the global trigger tool （GTT） theory， and referencing the GTT White Paper， drug package inserts and relevant literature， trigger items for bevacizumab-related ADR were confirmed using a single-round Delphi method. Utilizing these established items， electronic medical records of relevant patients at Guilin People’s Hospital from January 2020 to September 2024 were actively screened via the China Hospital Pharmacovigilance System. Pharmacists then identified and tallied the occurrence of bevacizumab-induced ADR. Data from patients with any positive trigger item served as the study subjects （divided into training and test sets at a ratio of 7∶3）， candidate feature variables were selected from 39 related variables using the Boruta algorithm， and the multivariable Logistic regression analysis was performed with the occurrence of SAR as the dependent variable. Based on these candidate features， Logistic Regression， Extreme Gradient Boosting， Light Gradient Boosting Machine， Random Forest， and Categorical Boosting models were constructed. Model performance was evaluated using metrics including the area under the curve （AUC） of receiver operating characteristic curve and recall rate. The Shapley Additive exPlanations （SHAP） method was applied to analyze and interpret the contribution of each variable. A nomogram was constructed based on the optimal model. RESULTS A total of 38 trigger items for active monitoring of bevacizumab-related ADR were determined， comprising 17 laboratory indicators， 13 clinical manifestations， and 8 intervention measures. In total， 483 patients with positive trigger items were included， and 318 patients with bevacizumab-induced ADR were identified， including 83 SARs. The positive predictive values for the trigger items and cases were 43.57% （708/1 625） and 63.84% （318/483）， respectively. Bevacizumab-induced ADR involved 7 systems/organs， with the hematological system being the most frequently involved （64.15%）. The Boruta algorithm selected 7 vari ables： serum potassium， hematocrit， albumin-to-globulin ratio， prealbumin， hypertension history， age and red blood cell count. Multivariable Logistic regression showed that elevated serum potassium levels were associated with a decreased risk of bevacizumab-induced SAR （OR＝0.234， P ＝0.002）， while a history of hypertension （OR＝2.642， P ＝0.006） and increased age （OR＝1.040， P ＝0.025） were associated with an increased risk. The Logistic Regression model demonstrated superior performance with higher AUC， F1 score and recall rate （0.761， 0.447， 0.607）， compared to other models. SHAP evaluation results indicated that variables such as serum potassium， hematocrit， and age ranked highest in importance. CONCLUSIONS Totally 38 trigger entries have been successfully identified for active screening of bevacizumab-related ADR. Elevated serum potassium levels are a protective factor against bevacizumab-induced SAR， whereas the hypertension history and increased age are risk factors. The Logistic Regression model is the optimal predictive model.

ObjectiveTo analyze the adverse reactions associated with the clinical use of Banxia （Rhizoma Pinelliae）- Wutou （Aconitum） in the same formula， with the aim of providing a reference for the safety of their clinical application. MethodsLiterature on the clinical application of antagonistic herbs "Banxia-Wutou" used in the same formula， published from January 1st， 2014， to June 30th， 2023， was retrieved from databases including CNKI， VIP， Wanfang， SinoMed， PubMed， Cochrane Library， and Embase. A database was established， and information related to adverse reactions was extracted， including descriptions， classifications， specific manifestations， management and outcomes， patients' primary diseases （western medicine diseases and traditional Chinese medicine diagnoses and syndromes）， and medication information （dosage， ratio， administration routes， and dosage forms）. ResultsA total of 79 researches simultaneously used antagonistic herbs Banxia-Wutou in the same formula and reported associated advers reactions. Gastrointestinal adverse reactions were the most common， with 8 studies reporting management of adverse reactions and 3 studies reporting improvement with no intervention. Among the 11 researches， the adverse reaction relieved to extant， while other 69 researches didn't report the managment of adverse reaction and its prognosis. For the primary disease in western medicine system， chronic bronchitis and chronic obstructive pulmonary disease （COPD） were most common， while gastric pain was the most common symptom in traditional Chinese medicine with spleen and kidney deficiency and spleen stomach cold deficiency being the most frequent syndromes. The most common Banxia dosage was 10 g， while for the Wutou， Fuzi （Radix Aconiti Lateralis Praeparata） was predominant with the highest dose at 15 g. The most frequent herbal combination was Banxia-fuzi， with a 1∶1 ratio. The main administration route was oral， and the primary dosage form was decoction. ConclusionGastrointestinal adverse reactions are the most common in the clinical use of Banxia-Wutou antagonistic herb combinations. Research on the safety of "Banxia-Wutou" combinations should focus on respiratory system diseases and spleen-stomach related conditions.

This paper summarizes the experience of professor DING Yuanqing in treating post-stroke depression （PSD） of young and middle-aged patients with the method of regulating qi and promoting blood circulation. PSD is a syndrome resulting by vascular injury and impairment of brain marrow and vital activity after the stroke. Factors such as poor lifestyle， improper control of chronic diseases and sleep disorders，etc.，which can be harmful individually， or they can interact. Over time，these factors can block yang of defensive qi，obstract blood circulationg and disturb qi movement. Reverse ascending of defensive qi can generate wind and fire，generate phlegm and stasis from the fluid the blood. Qi stagnation， phlegm and stasis can combined with stagnation heat， phlegm heat， blood stasis heat which caused by stroke ， which can further aggravate pulse accumulation， damage the blood vessels and block the collaterals. Consequently， defensive qi is floating over and nutrient qi is not smooth， resulting in inadequate nourishment of the brain marrow，and disfunction of vital activity， causing depressive symptoms. Professor DING innovatively applied the method of regulating qi and promoting blood circulation. He selected the classic prescriptions such as Guizhi Decoction（桂枝汤）， Baoyuan Decoction（保元汤）， as well as self-fitting prescriptions like Erdan Decoction（二丹汤）， Erzhu Decoction（二竹汤）， to relieve qi and tonify qi，promote harmonious blood circulation， facilitate vasodilation， ease symptoms of depression， invigorate the mind， and provide an effective treatment for PSD.

This study aimed to investigate the prevalence and clinical characteristics of epilepsy in patients with patent foramen ovale (PFO) and the effect of PFO closure on seizures. Patients diagnosed with PFO were recruited and underwent brain magnetic resonance imaging, electrocardiography, transesophageal echocardiography, and transthoracic echocardiography with right ventriculography. In patients with epilepsy, electroencephalography was performed. A total of 110 patients completed the assessment. A chief complaint of chest tightness or palpitations was proportionately higher in patients aged<18 years, whereas headaches and seizures were higher in patients aged≥18 years ( χ2=4.69 ,P<0.05). Comorbid epilepsy was observed in 20.9% of patients with PFO. The age at admission in the epileptic group (14-66(27±14)years) was significantly lower than that in the non-epileptic group (16-81(38±21)years) and that in patients with headache as the chief complaint (16-68(39±12)years) ( t=3.29, P<0.05). The multivariate analysis found no risk factors related to the prognosis of epilepsy. The incidence of epilepsy was significantly higher in patients with PFO than in the general population.

Objective:To analyze the clinical characteristics and medication options of patients with elderly-onset epilepsy and influencing factors for medication efficacy.Methods:A total of 213 patients with elderly-onset epilepsy (age of onset≥65 years) were selected from Epilepsy Outpatient, Department of Neurology, First Medical Center of Chinese PLA General Hospital from February 1999 to March 2023. General data, imaging findings and follow-up results of these patients were collected. Seizure frequencies and types, medication types, and medication efficacy were analyzed retrospectively. According to medication efficacy, these patients were divided into effective anti-seizure medications (ASMs) group and ineffective ASMs group (effective ASMs was defined as having no seizures or seizure reduction>50% at 6 months after medication, and ineffective ASMs as having seizure reduction≤50% or seizure increase. Univariate and multivariate Logistic regression analyses were used to identify the influencing factor for ASMs efficacy.Results:In these 213 patients with elderly-onset epilepsy, 143 (67.1%) were males and 70 (32.9%) were females. Onset age was 70.0 (67.0, 74.5) years, with duration of 12 (4, 32) months. Time from first onset to treatment was 2.0 (1.0, 10.5) months, with that<2 months enjoying the largest proportion ( n=101). MRI/CT in 102 patients indicated potential epileptogenic abnormal structures, such as post-stroke gliosis/encephalomalacia ( n=67) and post-traumatic gliosis/encephalomalacia ( n=13). MRI/CT in 78 patients indicated non-epileptogenic abnormal structures, such as ischemic changes of small and medium vessels ( n=51) and brain atrophy ( n=15). Structural change was the most common cause ( n=160). Sixty-nine patients (32.4%) did not take medicine and 144 (67.6%) took medicine at the visiting; sodium valproate was mostly used ( n=74), followed by levetiracetam ( n=35) and carbamazepine ( n=24). Five patients had sodium valproate combined with levetiracetam, and 4 patients had sodium valproate combined with carbamazepine. Multivariate Logistic regression analysis showed that disease duration and medication combination were independent influencing factors for ASMs efficacy. Conclusion:Structural change is the main cause for elderly-onset epilepsy; medication efficacy is worse in patients with longer disease course and medication combination therapy.

Opioid receptors μOR,δOR,κOR and NOPR are all G protein-coupled receptors(GPCRs),which mainly function through G protein and β-ar-restin.Recent studies have found that G protein mediates analgesia,while β-arrestin reduces anal-gesia and is related to the side effects of opioids.Oliceridine is the first biased μOR agonist approved for commerce.It mainly exerts analgesic effect by activating G protein.It has rapid onset of action and reliable analgesic effect.Due to its low activity on β-arrestin,the incidence of side effects is low,comparing to the classic opioid morphine.Oliceri-dine can be safely used in patients with liver or kid-ney insufficiency and its metabolite is inactive.This article summarizes the current progress of pharma-cological research and clinical application of oliceri-dine,aiming to provide reference for the clinical practice of oliceridine.

Objective: Sialidosis type 2 has variants that are both catalytically inactive (severe), while sialidosis type 1 has at least one catalytically active (mild) variant. This study aimed to discuss the structural changes associated with these variants in a newly reported family carrying N-acetyl-α-neuraminidase-1 (NEU1) variants and explore the clinical characteristics of different combinations of variants in sialidosis type 1. Methods: First, whole-exome sequencing and detailed clinical examinations were performed on the family. Second, structural analyses, including assessments of energy, flexibility and polar contacts, were conducted for several NEU1 variants, and a sialidase activity assay was performed. Third, previous NEU1 variants were systematically reviewed, and the clinical characteristics of patients in the severe-mild and mild-mild groups with sialidosis type 1 were analyzed. Results: We report a novel family with sialidosis type 1 and the compound heterozygous variants S182G and V143E. The newly identified V143E variant was predicted to be a mild variant through structural analysis and was confirmed by a sialidase activity assay. Cherry-red spots were more prevalent in the severe-mild group, and ataxia was more common in the mild-mild group. Impaired cognition was found only in the severe-mild group. Moreover, patients with cherry-red spots and abnormal electroencephalographies and visual evoked potentials had a relatively early age of onset, whereas patients with myoclonus had a late onset. Conclusion Changes in flexibility and local polar contacts may be indicators of NEU1 pathogenicity. Sialidosis type 1 can be divided into two subgroups according to the variant combinations, and patients with these two subtypes have different clinical characteristics.

OBJECTIVE To investigate whether electroacupuncture(EA)ameliorates abnormal trigeminal neuralgia(TN)orofacial pain and anxiety-like behavior by altering synaptic plasticity in the hippocampus CA1.METHODS A mouse infraorbital nerve transection model(pT-ION)of neuropathic pain was established,and EA or sham EA was used to treat ipsilateral acu-puncture points(GV20-Baihui and ST7-Xia-guan).Golgi-Cox staining and transmission elec-tron microscopy(TEM)were administrated to observe the changes of synaptic plasticity in the hippocampus CA1.RESULTS Stable and per-sistent orofacial allodynia and anxiety-like behav-iors induced by pT-ION were related to changes in hippocampal synaptic plasticity.Golgi stain-ings showed a decrease in the density of dendritic spines,especially mushroom-type dendritic spines,in hippocampal CA1 neurons of pT-ION mice.TEM results showed that the density of synapses,membrane thickness of the postsynap-tic density,and length of the synaptic active zone were decreased,whereas the width of the synap-tic cleft was increased in pTION mice.EA attenu-ated pT-ION-induced orofacial allodynia and anx-iety-like behaviors and effectively reversed the abnormal changes in dendritic spines and syn-apse of the hippocampal CA1 region.CONCLU-SION EA modulates synaptic plasticity of hippo-campal CA1 neurons,and reduces abnormal oro-facial pain and anxiety-like behavior,providing evidence for a TN treatment strategy.

Objective To explore the efficacy of the resolving depression and tranquilizing herbal sachets in alleviating sleep disorders of soldiers in naval vessels. Methods Fifty-nine soldiers with sleep disorders (PSQI scale score ≥8 and SAS scale score ≥50) were selected before training at sea, and were randomly divided into sachet treatment group, mindfulness meditation group and control group. During the training period, the sachet treatment group was given traditional Chinese medicine sachet treatment, the mindfulness meditation group was trained in mindfulness meditation, and the control group was not given any intervention. Results Compared with the control group, the PSQI and SAS scores of soldiers in both the experimental sachet treatment group and the positive meditation group were significantly improved; compared with the pre-intervention data, the PSQI and SAS scores of both the positive meditation group and the sachet treatment group were significantly decreased, and the degree of decrease was comparable. Conclusion The homemade improving depression and tranquilizing TCM sachets have the effect of alleviating the sleep disorders of naval troops served on vessels, which is equivalent to mindfulness meditation. It is easy to use and operate, which is suitable for promotion in the military.

Acute pancreatitis (AP) is a devastating disease characterized by an inflammatory disorder of the pancreas. P-selectin glycoprotein ligand-1 (PSGL-1) plays a crucial role in the initial steps of the adhesive at process to inflammatory sites, blockade of PSGL-1 might confer potent anti-inflammatory effects. In this study, we generated two non-human primate derived monoclonal antibodies capable of efficiently targeting human PSGL-1, RH001-6 and RH001-22, which were screened from immunized rhesus macaques. We found that RH001-6, can effectively block the binding of P-selectin to PSGL-1, and abolish the adhesion of leukocytes to endothelial cells in vitro. In vivo, we verified that RH001-6 relieved inflammatory responses and pancreatic injury in both caerulein and l-arginine induced AP models. We also evaluated the safety profile after RH001-6 treatment in mice, and verified that RH001-6 did not cause any significant pathological damages in vivo. Taken together, we developed a novel non-human primate derived PSGL-1 blocking antibody with high-specificity, named RH001-6, which can interrupt the binding of PSGL-1 and P-selectin and attenuate inflammatory responses during AP. Therefore, RH001-6 is highly potential to be further developed into therapeutics against acute inflammatory diseases, such as AP.