ObjectiveTo investigate the efficacy and safety of Babaodan Capsule （BBD） in the treatment of patients with chronic hepatitis B virus （HBV） infection with damp-heat in the liver and gallbladder comorbid with gallbladder polyps. MethodsA randomized， double-blinded， placebo-controlled single-center trial was conducted among 120 patients with chronic HBV infection who were admitted to Beijing YouAn Hospital， Capital Medical University， from August 2020 to April 2023， and they were divided into treatment group （BBD） and control group （placebo）， with 60 patients in each group. The course of treatment was 24 weeks， and follow-up assessments were conducted every 4 weeks. The primary outcome measures were the number and maximum diameter of gallbladder polyps （assessed by ultrasound）， and the secondary outcome measures included traditional Chinese medicine （TCM） syndrome score， blood lipid levels， and liver function parameters. The independent-samples t test or the Wilcoxon rank-sum test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups； the Wilcoxon rank-sum test was used for comparison of ranked data between two groups； the generalized estimating equation was used to analyze repeated measures data. ResultsAfter 8 weeks of treatment， the treatment group had a significantly smaller diameter of polyps and a significantly lower number of polyps than the control group （Z=-1.76 and -1.80， both P<0.05）， and after 24 weeks of treatment， the treatment group had a significantly higher polyp reduction rate than the control group （30.51% vs 10.91%， P<0.05）. The subgroup analysis showed that patients receiving combined antiviral therapy， male patients， patients with a diameter of polyps of <5 mm， and patients with multiple polyps tended to achieve significantly greater benefits. At week 8 of treatment， the treatment group had a significantly better TCM syndrome score than the control group （Z=-2.35， P<0.05）； after treatment， compared with the control group， the treatment group had a significantly greater increase in high-density lipoprotein （Z=-1.85， P<0.05） and significantly lower levels of alanine aminotransferase （Z=-2.06， P <0.05）， aspartate aminotransferase （Z=-2.13， P<0.05）， total bilirubin （Z=-2.12， P<0.05）， and direct bilirubin （Z=-3.09， P<0.05）. No serious adverse events were reported in either group. ConclusionBBD can effectively reduce the size of gallbladder polyps， improve TCM syndrome score， and reduce the level of bilirubin in patients with chronic HBV infection with damp-heat in the liver and gallbladder， with a favorable safety profile， and it may be more suitable for patients receiving combined antiviral therapy and specific subgroups （male patients， patients with a diameter of polyps of <5 mm， and patients with multiple polyps.

ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

The preferred treatment for adrenal functional tumors is laparoscopic surgical resection. However, in recent years, various ablation techniques have gradually been applied in the treatment of adrenal tumors. This report presents the successful diagnosis and treatment experience of 4 aldosterone-producing adenomas and 1 cortisol-secreting adenoma treated with a combined cold and hot ablation system at Xi’an Daxing Hospital from Dec. 2023 to Dec. 2024, providing a new treatment approach for clinical exploration.

Objective To explore the effect of accelerated intermittent theta burst stimulation(aiTBS)on post-stroke depression(PSD).Methods From July,2021 to July,2023,48 PSD patients in Beijing Bo'ai Hospital were randomly assigned to control group(n=16),high-frequency repetitive transcranial magnetic stimulation(HF-rTMS)group(n=16)and aiTBS group(n=16).aiTBS group received left-sided aiTBS treatment at dorsolateral prefrontal cortex(DLPFC),HF-rTMS group received left-sided 10 Hz rTMS treatment at DLPFC,and the control group received left-sided sham stimulation treatment,for three weeks.They were evaluated with the Hamilton Depression Rating Scale(HAMD),Hamilton Anxiety Rating Scale(HAMA)and Beck Depression Inventory(BDI)before and after treat-ment,and one month of follow-up.Results One case dropped down in each group.The inter-group effect,intra-group effect and interaction effect of HAMD,HAMA and BDI scores were all significant(F>3.235,P<0.05).The post-hoc test results showed that the scores of HAMD,HMMA and BDI were lower in HF-rTMS group and aiTBS group than in the control group(P<0.05),and no significant difference was found between HF-rTMS group and aiTBS group(P>0.05).There was significant difference in the effective rate of depression improvement among three groups(χ2=7.834,P=0.019),the effective rate was higher in aiTBS group than in the control group(P<0.017),and no significant dif-ference was found between HF-rTMS group and aiTBS group(P>0.017).Conclusion aiTBS can improve the depression and anxiety symptoms of patients with PSD,with shorter treatment time,compared with HF-rTMS.

The preferred treatment for adrenal functional tumors is laparoscopic surgical resection. However, in recent years, various ablation techniques have gradually been applied in the treatment of adrenal tumors. This report presents the successful diagnosis and treatment experience of 4 aldosterone-producing adenomas and 1 cortisol-secreting adenoma treated with a combined cold and hot ablation system at Xi’an Daxing Hospital from Dec. 2023 to Dec. 2024, providing a new treatment approach for clinical exploration.

Objective To explore the effect of accelerated intermittent theta burst stimulation(aiTBS)on post-stroke depression(PSD).Methods From July,2021 to July,2023,48 PSD patients in Beijing Bo'ai Hospital were randomly assigned to control group(n=16),high-frequency repetitive transcranial magnetic stimulation(HF-rTMS)group(n=16)and aiTBS group(n=16).aiTBS group received left-sided aiTBS treatment at dorsolateral prefrontal cortex(DLPFC),HF-rTMS group received left-sided 10 Hz rTMS treatment at DLPFC,and the control group received left-sided sham stimulation treatment,for three weeks.They were evaluated with the Hamilton Depression Rating Scale(HAMD),Hamilton Anxiety Rating Scale(HAMA)and Beck Depression Inventory(BDI)before and after treat-ment,and one month of follow-up.Results One case dropped down in each group.The inter-group effect,intra-group effect and interaction effect of HAMD,HAMA and BDI scores were all significant(F>3.235,P<0.05).The post-hoc test results showed that the scores of HAMD,HMMA and BDI were lower in HF-rTMS group and aiTBS group than in the control group(P<0.05),and no significant difference was found between HF-rTMS group and aiTBS group(P>0.05).There was significant difference in the effective rate of depression improvement among three groups(χ2=7.834,P=0.019),the effective rate was higher in aiTBS group than in the control group(P<0.017),and no significant dif-ference was found between HF-rTMS group and aiTBS group(P>0.017).Conclusion aiTBS can improve the depression and anxiety symptoms of patients with PSD,with shorter treatment time,compared with HF-rTMS.

Objective To analyze the correlation between serum interleukin-37(IL-37)and nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)with disease severity in chronic obstructive pulmonary disease(COPD)patients with systemic inflammatory response syndrome(SIRS),and evaluate their combined predictive value for prognosis.Methods A total of 150 patients with COPD and SIRS in Zigong First People's Hospital from January 2023 to March 2024 were selected as the study group,and 150 patients with COPD were selected as the control group.The groups were compared for general data and serum IL-37 and NLRP3 levels upon admission.The serum IL-37 and NLRP3 levels of patients with different disease severities in the study group were compared to analyze their correlation with disease severity.28-day prognosis of both groups was compared,and the serum IL-37 and NLRP3 levels of patients with poor and good prognosis in the study group were analyzed.Univariate and multivariate Logistic regression was used to assess factors influencing poor prognosis in COPD patients with SIRS.The predictive value of serum IL-37 and NLRP3 for poor prognosis was evaluated,and their interactive effects on patient outcomes were analyzed.Results The study group's serum IL-37 and NLRP3 levels were higher upon admission compared to the control group(P<0.05);serum IL-37 and NLRP3 levels in extremely severe patients were higher than those in severe,moderate,and mild patients,with severe patients higher than moderate and mild patients,and moderate patients higher than mild patients(P<0.05);serum IL-37 and NLRP3 levels at admission were positively correlated with the disease severity of COPD patients with SIRS(P<0.05);patients with poor prognosis had higher serum IL-37 and NLRP3 levels upon admission compared to those with good prognosis(P<0.05);serum IL-37 and NLRP3 levels at admission were independent risk factors for poor prognosis in COPD patients with SIRS(P<0.05);the AUC for predicting poor prognosis using serum IL-37 and NLRP3 alone were 0.805 and 0.834,respectively,while the combined AUC was 0.920,which was higher than the individual AUCs(P<0.05);interaction analysis showed that high serum IL-37 and NLRP3 levels exhibited a positive super-multiplicative interaction in the prognosis of COPD patients with SIRS(P<0.05).Conclusion Serum IL-37 and NLRP3 levels in COPD patients with SIRS were positively correlated with disease severity,and the combined serum IL-37 and NLRP3 showed high predictive efficacy for patient prognosis.

Cholesterol(CH)plays a crucial role in enhancing the membrane stability of drug delivery systems(DDS).However,its association with conditions such as hyperlipidemia often leads to criticism,overshadowing its influence on the biological effects of formulations.In this study,we reevaluated the delivery effect of CH using widely applied lipid microspheres(LM)as a model DDS.We conducted comprehensive in-vestigations into the impact of CH on the distribution,cell uptake,and protein corona(PC)of LM at sites of cardiovascular inflammatory injury.The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage.Then,the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy.Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma(PPAR-γ)expression in vascular endothelial cells and estrogen receptor alpha(ERα)protein levels in myocardial cells,thereby enhancing LM uptake at cardiovascular inflam-mation sites.Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V(Apoa5);this may be a major contributing factor to their prolonged circu-lation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites.It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations.The findings enhance the conceptualization of CH and LM delivery,providing novel strategies for investigating prescription factors' bioactivity.

OBJECTIVES: To investigate the mechanism by which transforming growth factor‑β (TGF‑β) regulates major histocompatibility complex class I (MHC-I) expression in hepatocellular carcinoma (HCC) cells and its role in immune evasion of HCC. METHODS: HCC cells treated with TGF‑β alone or in combination with SB-431542 (a TGF-β type I receptor inhibitor) were examined for changes in MHC-I expression using RT-qPCR and Western blotting. A RNA interference experiment was used to explore the role of miR-23a-3p/IRF1 signaling in TGF‑β‑mediated regulation of MHC-I. HCC cells with different treatments were co-cultured with human peripheral blood mononuclear cells (PBMCs), and the changes in HCC cell proliferation was assessed using CCK-8 and colony formation assays. T-cell cytotoxicity in the co-culture systems was assessed with lactate dehydrogenase (LDH) release and JC-1 mitochondrial membrane potential assays, and T-cell activation was evaluated by flow cytometric analysis of CD69 cells and ELISA for TNF-α secretion. RESULTS: TGF‑β treatment significantly suppressed MHC-I expression in HCC cells and reduced T-cell activation, leading to increased tumor cell proliferation and decreased HCC cell death in the co-culture systems. Mechanistically, TGF-β upregulated miR-23a-3p, which directly targeted IRF1 to inhibit MHC-I transcription. Overexpression of miR-23a-3p phenocopied TGF‑β‑induced suppression of IRF1 and MHC-I. CONCLUSIONS We reveal a novel immune escape mechanism of HCC, in which TGF‑β attenuates T cell-mediated antitumor immunity by suppressing MHC-I expression through the miR-23a-3p/IRF1 signaling axis.
Humans ; MicroRNAs/genetics* ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Interferon Regulatory Factor-1/metabolism* ; Transforming Growth Factor beta/metabolism* ; Signal Transduction ; Histocompatibility Antigens Class I/metabolism* ; Cell Line, Tumor ; Tumor Escape ; Coculture Techniques

OBJECTIVE: To investigate the therapeutic potential of octaarginine (R8)-modified essential oil from Fructus Alpiniae zerumbet (EOFAZ) lipid microspheres (EOFAZ@^R8LM) for cardiovascular therapy. METHODS: EOFAZ@^R8LM was developed by leveraging the volatilization of EOFAZ and integrating it with the oil phase of LM, followed by surface modification with cell-penetrating peptide R8 to target the site of vascular endothelial injury. The therapeutic effects of this formulation in alleviating lipopolysaccharide-induced vascular endothelial inflammation were evaluated by assessing mitochondrial membrane potential (MMP), intracellular reactive oxygen species (ROS) levels, as well as inflammatory factors interleukin-6 (IL-6) and interleukin-1β (IL-1β) levels. RESULTS: EOFAZ@^R8LM effectively delivered EOFAZ to the site of injury and specifically targeted the mitochondria in vascular endothelial cells, thereby ameliorating mitochondrial dysfunction through regulation of MMP and reduction of intracellular ROS levels. Moreover, it attenuated the expression levels of IL-6 and IL-1β, exerting protective effects on the vascular endothelium. CONCLUSION Our findings highlight the significant therapeutic potential of EOFAZ@^R8LM in cardiovascular therapy, providing valuable insights for developing novel dosage forms utilizing EOFAZ for effective treatment against cardiovascular diseases.