ObjectiveTo construct and evaluate a mouse model that simulates the pathological progression of immune checkpoint inhibitor-associated pneumonitis (CIP), in order to address the critical issue of the lack of standardized animal models in this research field. MethodsThirty-five SPF-grade 6-week-old male C57BL/6J mice were randomly assigned to a control group (n=5), a bleomycin (BLM) group (n=15), and a BLM+programmed death-1 (PD-1) monoclonal antibody (BLM+PD-1) group (n=15). Corresponding drugs were administered via intraperitoneal injection for intervention. The general condition, body weight changes, survival rate, and pulmonary histopathological alterations were systematically monitored. ResultsCompared with the BLM group, the BLM+PD-1 group exhibited significantly more severe pulmonary fibrosis, characterized by progressive body weight loss and more severe deterioration of general conditions. Histopathological examination showed that pulmonary inflammation was alleviated 4 weeks post-modeling in the BLM group. In contrast, pulmonary lesions continued to worsen in the BLM+PD-1 group, with no evidence of resolution of inflammation 28 days post-modeling. Quantitative immunohistochemical analysis revealed that the positive expression rate of interleukin-17A (IL-17A) in lung tissues reached 34.28% in the BLM+PD-1 group 14 days post-modeling, which was markedly higher than that in the BLM group (24.02%, P < 0.000 1). The positive expression rate of α-smooth muscle actin (α-SMA) was 12.40% in the BLM+PD-1 group 14 days post-modeling, nearly twice the level in the BLM group (5.87%). 28 days post-modeling, the positive expression rate of α-SMA remained at 7.72% in the BLM+PD-1 group, while it declined to 3.38% in the BLM group. ConclusionThe addition of a PD-1 inhibitor to bleomycin treatment accelerates the progression of pulmonary interstitial fibrosis and effectively recapitulates the pathological process of lung injury and fibrosis driven by aberrant immune activation during clinical immunotherapy. Accordingly, this study successfully establishes a dynamic CIP animal model recapitulating the progression from early inflammatory response to pulmonary fibrosis. This model addresses the critical shortage of animal models for this condition and offers an experimental platform for further mechanistic studies and the development of therapeutic strategies.

Objective: This study aimed to assess the prevalence of comorbid of smartphone addiction and depressive symptoms and identify their common and distinct risk factors among college students. Methods: A total of 8,347 Chinese college students participated in the study by completing questionnaires that assessed individual, family, school, and peer factors, as well as smartphone addiction and depressive symptoms. Multivariate logistic regression was conducted to explore the risk of smartphone addiction only, depressive symptoms only, and their comorbidity. Results: The prevalence rates of smartphone addiction only, depressive symptoms only, and their comorbidity were 30.5%, 8.9%, and 25.3%, respectively. Higher frequency of mobile phone use in lessons and lower level of school belonging were associated with the increased risk of all three disease outcomes. There was a dose-response relationship between the number of risk exposures and the three disease outcomes. Conclusion The more risk factors of college students were exposed to, the more likely they were to develop smartphone addiction only, depressive symptoms only, and their comorbidity. Targeted preventive measures and solutions should be implemented to reduce the occurrence of smartphone addiction and depressive symptoms.

Objective Discuss the safety and effectiveness of flow diverter device and traditional stent inthetreatment of unruptured ophthalmic segment aneurysms.Methods A retrospective analysis from January 2017 to January 2023 was performed on the clinical data of 70 cases of unruptured aneurysms in the Department of Neurosurgery of Southern Theater General Hospital treated with stent-assisted embolization.According to the type of implanted stents,theywere divided into flow diverter device group(n = 21)and traditional stent group(n = 49),and the postoperative clinical effects and complications of the two groups were compared.Results The two groups of patients followed 3 to 24 months,with an average of(14.4±1.82)months.The results of periopera-tive and follow-up showed that the inclusion rate was higher in the flow diverter device group and the traditional stent group(93.3%vs.87.9%),with no significant difference(P>0.05),and the incidence of perioperative and short-term complications was lower(0 vs.6.1%)in the flow diverter device group than in the traditional stent group,and there currencies rate in the flow diverter device group was lower than that in the traditional stent group(0 vs.6.1%),but the difference was not significant(P>0.05).Conclusion Flow diverter devices and traditional stents in the treatment of unruptured ophthalmic segment aneurysmsare feasible,safe and effective.Preliminary results suggest that the incidence of short-term complications and retreatment is lower after treatment with flow diverter devices,and the operation time is short,but further studies are needed to validate long-term complica-tions in patients.

Xiaoxuming decoction is one of the classical prescriptions in ancient times,mainly used for treating stroke syndrome,with significant therapeutic effects.Recent studies have found that it is also effective for other neurological diseases besides stroke,such as facial paralysis and vertigo,but there are few reports on related achievements,lacking systematic organization and summary.This article systematically summarizes the application practice and mechanism of Xiaoxuming decoction in the above-mentioned diseases,aiming to provide a solid foundation and scientific reference for deepening the exploration of Xiaoxuming decoction in the field of nervous system disease.

Insomnia is the most common sleep disorder in clinical practice， and prolonged insomnia can significantly impact daily life and work. Currently， the clinical treatment of insomnia primarily relies on sedative and hypnotic drugs， which， although fast-acting， come with numerous adverse reactions. Traditional Chinese medicine （TCM） approaches the treatment of insomnia by employing syndrome differentiation and focusing on addressing the root cause of the disease. This approach is characterized by fewer adverse reactions， stable long-term effects， and better patient compliance. Huanglian Ejiaotang was first recorded in Zhang Zhongjing's Treatise on Febrile and Miscellaneous Diseases（《伤寒杂病论》） during the Han dynasty. It has the effects of nourishing Yin， reducing fire， eliminating irritability， and calming the nerves. Clinical studies have shown that Huanglian Ejiaotang is frequently used to treat insomnia and， when combined with other classic prescriptions， Western medicine， or other therapies， it can have a synergistic effect， thereby enhancing therapeutic outcomes. Research indicates that the mechanism of action of Huanglian Ejiaotang in treating insomnia may be related to the regulation of the hypothalamic-pituitary-adrenal （HPA） axis， 5-hydroxytryptamine （5-HT）， norepinephrine （NE）， dopamine （DA）， central neurotransmitters， gut microbiota， and the inhibition of inflammatory factors. The active components of Huanglian Ejiaotang that are effective in treating insomnia include berberine， baicalin， baicalein， total glucosides of paeony， and collagen. This article discussed the treatment of insomnia with Huanglian Ejiaotang from several perspectives， including its theoretical foundation， clinical research， and mechanisms of action， and also summarized the latest research progress on Huanglian Ejiaotang for insomnia， with the aim of providing more comprehensive ideas for the clinical diagnosis and treatment of insomnia.

Vascular dementia （VaD） is a common disease that affects the health of the elderly. Due to the aging of the social population， the incidence of VaD is increasing year by year. There have been no officially approved treatments for this disease， mainly because its pathogenesis is complex， and the mechanism of action of effective drugs is not yet clear， which hinders drug research for the treatment of VaD. Therefore， by reviewing the available literature related to VaD， this study sorted out the pathogenesis of VaD from traditional Chinese medicine （TCM） and western medicine， and concluded that in TCM， VaD was characterized by the deficiency of the spleen and kidney （deficiency） and combination of phlegm and blood stasis （excess）， while in western medicine， the pathogenesis of VaD is mainly inflammatory response， oxidative stress， abnormal expression of related proteins， and dysfunction of signaling pathways. On this basis， this study also summarized the research on the mechanism of action of commonly used single Chinese herbal medicine and Chinese herbal medicine compound， western medicine， and the combination of Chinese herbal medicine and western medicine in the treatment of VaD in recent years. The commonly used single Chinese herbal medicine Ginkgo Folium and Chinese herbal medicine compound Dihuang Yinzi have the multi-component and multi-target characteristics and few adverse reactions in the treatment of VaD， while the commonly used western medicines such as donepezil and memantine have the characteristics of the clear target and quick onset. The combination of Chinese herbal medicine and western medicines can achieve a better effect. This study summarized the research on the pathogenesis and treatment of VaD， aiming to link the pathogenesis of VaD with the mechanism of effective drug therapy， and provide an important reference for future drug development for the treatment of VaD.

Objective To analyze the clinical efficacy of transcatheter hepatic arterial thrombolysis combined with splenic arterial embolization in the treatment of hepatic artery thrombosis (HAT) after liver transplantation. Methods Clinical data of 9 patients diagnosed with HAT after liver transplantation undergoing transcatheter hepatic arterial thrombolysis combined with splenic arterial embolization were retrospectively analyzed. The incidence of HAT and clinical efficacy of thrombolytic therapy were summarized. The incidence of thrombolysis related complications and clinical prognosis were evaluated. The thrombolytic therapy procedures of typical cases were analyzed. Results HAT was diagnosed at 1-66 d after liver transplantation with a median time of 10 d. The formation site of HAT was found at the anastomosis of the main hepatic artery in 8 cases and at the right branch in 1 case. Upon diagnosis, 9 patients received transcatheter hepatic arterial thrombolysis combined with splenic arterial embolization in emergency. The hepatic artery was open during operation in 4 cases and treated with postoperative thrombolytic therapy with indwelling catheter in 3 cases. The opening time for inwelling catheter was 72-96 h. The total successful rate was 7/9. The thrombolysis related complication of abdominal hemorrhage occurred in 1 case after surgery. Three cases died, including 2 cases of liver failure and infection, and 1 case of biliary ischemia and systemic infection at 70 d after interventional therapy. Conclusions Hepatic arterial thrombolysis combined with splenic arterial embolization is an efficacious treatment for HAT after liver transplantation, which can serve as the optimal therapy for patients who are unable to undergo secondary liver transplantation.

PEGylation is considered one of the most successful techniques to improve the characteristics of protein drugs including to increase the circulating half-life of proteins in blood and to decrease their immunogenicity and antigenicity. One known PEG modification method is to attach PEG to the free amino group, typically at lysine residues or at the N-terminal amino acid with no selectivity, resulting in a heterogeneous product mixture. This lack of selectivity can present problems when a therapeutic PEGylated protein is being developed, because predictability of activity and manufacturing reproducibility are needed for regulatory approval. Enzymatic PEGylation of proteins is one route to overcome this limitation. Transglutaminases (TGase) are enzyme candidates for site-specific PEGylation. We use human interferon alpha 2a (IFN α2a) as a test case, and predict that the potential modification residues are Gln101 by computational approach as it contains 12 potential PEGylation sites. IFN α2a was PEGylated by Y shaped PEG40k-NH2 mediated by microbial transglutaminase. Our results show that the microbial transglutaminase mediated PEGylation of IFN α2a was site-specific only at the site of Gln101 in IFN α2a, yielding the single mono-conjugate PEG-Gln101-IFN α2a with a mass of 59 374.66 Da. Circular dichroism studies showed that PEG-Gln101-IFN α2a preserved the same secondary structures as native IFN α2a. As expected, the bioactivity and pharmacokinetic profile in rats of PEG-Gln101-IFN α2a revealed a significant improvement to unmodified IFN α2a, and better than PEGASYS.
Animals ; Antiviral Agents ; Humans ; Interferon alpha-2 ; metabolism ; Interferon-alpha ; biosynthesis ; pharmacokinetics ; Polyethylene Glycols ; pharmacokinetics ; Protein Structure, Secondary ; Rats ; Recombinant Proteins ; biosynthesis ; pharmacokinetics ; pharmacology ; Reproducibility of Results ; Transglutaminases ; metabolism

OBJECTIVE： To prepare Syringopicroside solid lipid nanoparticles （SYR-SLN）， and optimize the formula and characterize SYR-SLN. METHODS： SYR-SLN were prepared by emulsion evaporation method. Using entrapment efficiency as index， based on single factor， orthogonal design was adopted to optimize the mass ratio of lecithin-monoglyceride， volume ratio of organ phase to water phase， poloxamer 188 （F68） concentration and drug dosage. The optimal formula technology was established to investigate entrapment efficiency， drug-loading amount， morphology， particle size， Zeta potential， stability， etc. RESULTS： The mass ratio of lecithin-monoglyceride was 3 ∶ 1； the volume ratio of organic phase to water phase was 1 ∶ 2； the concentration of F68 was 0.4％； drug dosage was 10 mg. The optimal formula included that monoglyceride 80 mg， lecithin 240 mg， 0.4％ F68， syringopicroside 10 mg， absolute ethyl alcohol 5 mL， distilled water 10 mL， emulsification temperature at 65℃ and stirring at 600 r/min. Encapsulation efficiency of SYR-SLN was （42.35±0.60）％ （n＝3）； drug-loading amount was （5.33±0.03）％ （n＝3）； SYR-SLN had a spherical morphology and was evenly distributed. The average particle size was （180.30±5.31） nm with Zeta potential of （－41.9±0.8） mV， and the SYR-SLN could maintain stable for 15 days at 4℃. CONCLUSIONS： SYR-SLN is prepared successfully， and the technology is simple with high encapsulation efficiency.

Objective To explore the clinical safety and efficacy of self-made single-port retroperitoneoscopic renal pedicle lymphatic disconnection for chyluria. Methods From Feb 2013 to Mar 2016, clinical data of 34 patients were collected. Of them, 16 cases underwent self-made single-port retroperitoneoscopic renal pedicle lymphatic disconnection and 18 cases underwent three port retroperitoneoscopic renal pedicle lymphatic disconnection. No significant difference was shown in age, body mass index between the two groups (P > 0.05). Mean operative time, estimated bleeding volume, drainage time, postoperative hospital stay, postoperative pain evaluation, satisfaction scores of incision were compared between the two groups. Results All procedures were successfully performed without conversion to open surgery. Compared with the three port surgery group, results in the single-port group were superior in terms of mean operative time [(102.3 ± 16.1) versus (132.4 ± 21.6) min, P < 0.05], there were no significant differences in estimated blood loss, drainage time, postoperative hospital stay, the date in postoperative pain evaluation, satisfaction scores of incision shown that single-port group was superior to three port group. Conclusion Our initial experience revealed that single-port retroperitoneoscopic renal pedicle lymphatic disconnection was a safe, effective, cost-effective and less-invasive procedure for chyluria with improved postoperative pain and cosmetic results.