ObjectiveTo investigate the features of serum HBV RNA in different stages of the natural history of chronic hepatitis B virus （HBV） infection without antiviral treatment， as well as its correlation with serum HBV DNA and HBsAg. MethodsA total of 306 treatment-naïve patients with chronic HBV infection who attended Department of Infections Diseases and Hepatoloty， the Second Hospital of Shandong University from January 2023 to June 2024 were divided into six groups based on the different stages of natural history， i.e.， HBeAg-positive chronic HBV infection group with 29 patients， HBeAg-positive chronic hepatitis B （CHB） group with 107 patients， HBeAg-negative chronic HBV infection group with 18 patients， HBeAg-negative CHB group with 60 patients， HBeAg-positive indeterminate-phase chronic HBV infection group with 7 patients， and HBeAg-negative indeterminate-phase chronic HBV infection group with 85 patients. Real-time isothermal RNA amplification was used to measure serum high-sensitivity HBV RNA. The Kruskal-Wallis H test was used for comparison between multiple groups of continuous data， while the Mann-Whitney U test was used for comparison between two groups. The Spearman method was used to investigate the correlation of HBV RNA with HBV DNA and HBsAg. ResultsThe HBeAg-positive chronic HBV infection group showed the highest level of serum HBV RNA ［7.5 （7.4‍ ‍—‍ ‍7.9） log₁₀ copies/mL］， followed by the HBeAg-positive CHB group ［7.4 （6.4‍ ‍—‍ ‍7.9） log₁₀ copies/mL］， the HBeAg-negative CHB group ［4.5 （3.0‍ ‍—‍ ‍5.7） log₁₀ copies/mL］， and the HBeAg-negative chronic HBV infection group ［1.0 （1.0‍ ‍—‍ ‍2.0） log₁₀ copies/mL］； the HBeAg-positive indeterminate-phase chronic HBV infection group had a serum HBV RNA level of 3.9 （3.7‍ ‍—‍ ‍5.7） log₁₀ copies/mL， and the HBeAg-negative indeterminate-phase chronic HBV infection group had a serum HBV RNA level of 2.0 （1.0‍ ‍—‍ ‍3.0） log₁₀ copies/mL； there was a significant difference in serum HBV RNA level between the six groups （H=830.770， P<0.001）. There was a significant difference in HBV RNA level between the HBeAg-positive chronic HBV infection group and all the other groups except the HBeAg-positive CHB group （all P<0.001）. In the 306 patients with HBV infection， HBV RNA was strongly correlated with HBV DNA （r=0.92， P<0.001） and was moderately correlated with HBsAg （r=0.67， P<0.001）. The correlation between serum HBV RNA and HBsAg in HBeAg-positive patients （r=0.61， P<0.001） was stronger than that in HBeAg-negative patients （r=0.31， P<0.001）. For the patients with HBeAg-positive chronic HBV infection， the male patients with ALT>30 U/L and the female patients with ALT>19 U/L had a significantly lower serum HBV RNA level than the male patients with ALT≤30 U/L and the female patients with ALT≤19 U/L （P<0.001）， and there was no significant difference in serum HBV RNA level between the latter group of patients and the HBeAg-positive CHB group （P>0.05）. ConclusionIn patients with chronic HBV infection who do not receive antiviral therapy， there is a difference in serum HBV RNA level in different stages of natural history， and serum HBV RNA level has the strongest correlation with HBV DNA and a relatively weak correlation with HBsAg. In patients with HBeAg-positive chronic HBV infection， serum HBV RNA level in male patients with ALT>30 U/L and female patients with ALT>19 U/L are in the transition stage between HBeAg-positive chronic HBV infection and HBeAg-positive CHB.

Objective To analyze the levels of serum CTCs and ctDNA in NSCLC patients receiving first-line EGFR-TKI treatment, and to explore the clinical value of CTCs and ctDNA detection in assessing the efficacy of treatment for advanced lung cancer. Methods A total of 109 NSCLC patients receiving first-line EGFR-TKI treatment were enrolled. Serum tumor markers CEA, CTCs, and ctDNA were detected at baseline and after one month of treatment. Chest CT scans were performed, and treatment efficacy was evaluated based on RECIST1.1 criteria. CTCs were counted by enrichment-staining-computational algorithm to analyze malignant features, while ctDNA was assessed using digital PCR. Results Survival rate was low in patients with abnormal CEA and ctDNA tests at baseline and in patients with reduced serum CTCs after treatment. In the SD subgroup of patients with brain metastases and advanced stage, the PFS benefit was low. Conclusion Patients in the SD subgroup have significantly higher recurrence risks than those in the PR or CR subgroups. Therefore, CTC and ctDNA testing should be applied to patients in the SD subgroup to identify high-risk patients with poor response to EGFR-TKI treatment, intervene with additional treatment promptly, and obtain long progression-free survival.

Background: and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture. Methods: A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture. Results: The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05). Conclusion The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.

Background: and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture. Methods: A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture. Results: The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05). Conclusion The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.

Background: and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture. Methods: A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture. Results: The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05). Conclusion The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.

Objective: To explore the mediating effect of life meaning and subjective well being during college students values influence depression, providing insights for reducing college students depression. Methods: Utilizing a longitudinal approach, the study employed four scales of assessing Chinese adolescent values, sense of life meaning, subjective wellbeing, and depression to conduct a twoyear followup survey of 576 university students (September 2021 T1; September 2023 T2). Three multiple chained mediation models were constructed and analyzed using PROCESS Model 6. Results: Across the two waves, students endorsement of collective responsibility [(3.74±0.67)(3.64±0.65)] and self improvement [(3.78±0.75)(3.54±0.73)] decreased, while personal happiness [(3.46±0.77)(3.70±0.71)] and depression levels [(0.92±0.43)(0.99±0.50)] increased. Personal happiness T1 negatively predicted depression T2 ( β =-0.21) by enhancing subjective well being T2 ( β =0.20), with a mediation effect of -0.04 (95% CI =-0.07 to -0.02)(all P <0.01). Self improvement T1 negatively predicted depression T2( β =-0.08,-0.20) by increasing sense of life meaning T2 ( β =0.49) and through a serial mediation (sense of life meaning T2 →subjective well being T2, β =0.29), with mediation effects of -0.04 (95% CI =-0.06 to -0.02) and -0.03 (95% CI =-0.04 to -0.02)(all P <0.01). Collective responsibility negatively T1 predicted depression T2 ( β =-0.08,-0.21) via separate pathways (sense of life meaning T2: β = 0.29 ; subjective well being T2: β =0.17) and a serial mediation (sense of life meaning T2→ subjective well being T2, β =0.28), with mediation effects of -0.02 (95% CI =-0.04 to -0.01), -0.04 (95% CI = -0.07 to -0.01) and -0.02 (95% CI =-0.03 to -0.01 )(all P <0.01). Conclusion The three values influence depression through distinct psychological mechanisms, providing a basis for mental health interventions and values education.

ObjectiveTo explore the protective effect and mechanism of Gegen Qianliantang （GQT） on intestinal mucosal barrier function in dextran sulfate sodium （DSS）-induced ulcerative colitis （UC） model mice. MethodsA UC model was established in C57BL/6 mice using a 2.5% DSS solution. Mice were randomly divided into five groups （n=8 per group）： blank group， model group， mesalazine sustained-release granule group （0.52 g·kg^-1）， high-dose GQT group （2.23 g·kg^-1）， and low-dose GQT group （1.12 g·kg^-1）. Fecal characteristics and body weight changes were observed before and after treatment. The body weight loss and disease activity index （DAI） of UC mice were calculated to evaluate symptom severity. Hematoxylin-eosin （HE） staining and Alizarin blue-periodic acid-Schiff （AB-PAS） staining were used to detect histological changes in colon tissue. Immunohistochemistry was used to detect the expression of zonula occludens-1 （ZO-1） and mucin 2 （MUC2）. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of pro-inflammatory cytokines interferon-γ （IFN-γ）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， IL-17A， and anti-inflammatory cytokine IL-10. Flow cytometry was used to detect the activation of helper T lymphocyte subsets （Th1， Th17）， regulatory T cells （Treg）， and regulatory B cells （Breg） in spleen and colon tissues. Western blot was used to detect the expression levels of T-bet， forkhead box protein P3（FoxP3）， nuclear transcription factor（NF）-κB p65， phosphorylated NF-κB p65 （p-NF-κB p65）， signal transducer and activator of transcription 3（STAT3）， and phosphorylated STAT3 （p-STAT3）. ResultsCompared with the model group， both high- and low-dose GQT groups significantly improved the body weight loss and DAI scores （P<0.05）， alleviated colonic inflammation， and showed optimal efficacy in the high-dose group. AB-PAS staining showed that compared with the model group， both the high- and low-dose GQT groups significantly increased goblet cell proliferation and mucin secretion， indicating improved mucosal barrier function. GQT upregulated the expression of ZO-1 and MUC2 in colon tissue （P<0.05）， suppressed IFN-γ， IL-6， and TNF-α secretion （P<0.05）， elevated IL-10 secretion （P<0.05）， but had no significant effect on IL-17A. At the same time， high- and low-dose GQT intervention increased the activation of CD4⁺ FoxP3⁺ Treg cells （P<0.05） and suppressed activation of CD4⁺ IFN-γ⁺ Th1 cells （P<0.05）. Western blot showed that GQT downregulated T-bet， NF-κB p65， and STAT3 protein expression （P<0.05）， upregulated FoxP3 （P<0.05）， and also reduced phosphorylation levels of p-NF-κB p65 and p-STAT3 （P<0.05）. ConclusionGQT can upregulate the activation of CD4⁺ FoxP3⁺ Treg cells， reduce the activation of CD4⁺ IFN-γ⁺ Th1 cells， inhibit the secretion of IFN-γ， IL-6， and TNF-α， and increase the secretion of IL-10. It enhances the expression of MUC2 and ZO-1 in colon tissue， thereby alleviating inflammatory damage to the intestinal mucosa and restoring mucosal barrier integrity. These effects may be related to its regulation of NF-κB p65 and STAT3 signaling pathways， ultimately regulating the activation of transcription factors T-bet and FoxP3.

Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity. However, no reliable method is currently available to assess its impact on delivery performance. In this study, a biomimetic nasal model based on three-dimensional (3D) reconstruction and three-dimensional printing (3DP) technology was developed for visualizing the deposition of drug powders in the nasal cavity. The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females. The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test. The experimental device produced the most satisfactory results with five spray times. Furthermore, particle sizes and spray angles were found to significantly affect the experimental device's performance and alter drug distribution, respectively. Additionally, mometasone furoate (MF) nasal spray (NS) distribution patterns were investigated in a goat nasal cavity model and three male goat noses, confirming the in vitro and in vivo correlation. In conclusion, the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.

ObjectiveThe correlation of Pueraria lobata producing areas， climate factors， total flavonoids of P. lobata， polysaccharide content of P. lobata， and antioxidant activity of P.lobata for medicinal application was analyzed， and the relationship between climate factors and the formation of P. lobata quality was evaluated. MethodThe scavenging rates of 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl（DPPH） and 2, 2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)（ABTS） radicals by total flavonoids and polysaccharides of P. lobata were detected， and the correlation between the contents of each component and the information of producing areas and climate factors was analyzed. ResultThe ABTS⁺ scavenging rate by total flavonoids of P.lobata was negatively correlated with altitude （P<0.05） and positively correlated with annual sunshine hours （P<0.05）. The altitude was positively correlated with the total flavonoid content， while the annual sunshine hours were negatively correlated with the total flavonoid content. There was a negative correlation between total flavonoid content and ABTS⁺ scavenging rate by total flavonoids. In other words， lower altitude and longer annual sunshine hours indicated lower total flavonoid content and higher ABTS⁺ scavenging rate by total flavonoids. The ABTS⁺ scavenging rate by polysaccharides of P. lobata was negatively correlated with the frost-free period （P<0.05） and the mean temperature in July （P<0.01）. There was a positive correlation between the polysaccharide content of P. lobata and the frost-free period. The mean temperature in July was positively correlated with the polysaccharide content of P. lobata （P<0.05）. The polysaccharide content of P. lobata was negatively correlated with the ABTS⁺ scavenging rate by polysaccharides of P. lobata. In other words， a shorter frost-free period in the producing area and lower mean temperature in July indicated lower polysaccharide content of P. lobata and higher ABTS⁺ scavenging rate by polysaccharides of P. lobata. The mean temperature in July was significantly correlated with the contents of total flavonoids and polysaccharides in P. lobata samples （P<0.05）. The lower mean temperature in July was often accompanied by lower total flavonoid content of P. lobata， lower polysaccharide content of Pueraria lobata， and stronger antioxidant activity of P. lobata samples. ConclusionThe ability of P. lobata to remove ABTS⁺ is stronger than that of DPPH⁺. There is a significant correlation between climate factors， content， and antioxidant capacity in each producing area. Further research on the internal law of the formation of medicinal active components of P. lobata induced by core climate factors will provide a scientific basis for revealing the formation mechanism of genuine P. lobata and the subsequent control of P. lobata quality according to the environment of producing areas.

The etiology of central nervous system(CNS)diseases is complex and mostly unknown,and patients are often left with sequelae and poor prognosis.Recently,ferroptosis has emerged as a unique oxidative stress-induced cell death pathway and is important in various CNS diseases.It is an important mode of neuronal cell death.This article summarizes the molecular mechanism of ferroptosis,research progress of ferroptosis in CNS diseases,and application of ferroptosis inhibitors in CNS diseases to provide new targets and clini-cal references for CNS disease treatment.