Objective: To investigate the microbial mechanisms of Banxia Xiexin Decoction (半夏泻心汤, BXXXD) in the treatment of esophageal precancerous lesions. Methods: A total of 30 specific pathogen-free (SPF) grade female C57BL/6J mice were randomly assigned to a control group (n = 6) and a 4-nitroquinoline 1-oxide (4-NQO)-exposed group (n = 24). Esophageal precancerous lesions were induced by providing the 4-NQO-exposed group with 4-NQO in drinking water (100 μg/mL) for 17 consecutive weeks, whereas control group received sterile drinking water. After model establishment, the mice in 4-NQO-exposed group were further randomized into model group and three BXXXD-treated groups: low-dose (BXXXD-L, 3.7 g/kg), medium-dose (BXXXD-M, 7.4 g/kg), and high-dose (BXXXD-H, 14.8 g/kg) groups (n = 6 per group). During the subsequent intervention period, mice in control and model groups were gavaged with sterile water, while mice in BXXXD groups were gavaged once daily with the corresponding dose of BXXXD aqueous extract for 4 weeks. Histopathological changes in esophageal tissues were observed by hematoxylin and eosin (HE) staining. The fecal and esophageal microbiota were profiled via 16S rDNA high-throughput sequencing to evaluate bacterial diversity, community structure, and co-occurrence networks. BXXXD chemical fingerprints were analyzed using ultra-high-performance liquid chromatography coupled with quadrupole QExactive Orbitrap mass spectrometry (UHPLC-QE-MS). Serum short-chain fatty acids (SCFA) level was quantified by targeted metabolomics using gas chromatography-mass spectrometry (GC-MS). Transcriptomic analysis of esophageal tissues was performed to assess gene expression profiles. Results: Compared with model group, BXXXD-M group exhibited reduced mucosal hyperplasia and more orderly epithelial cell arrangement, with superior therapeutic effects in comparison with both BXXXD-L and BXXXD-H groups (P < 0.01). Microbiota analysis revealed that BXXXD increased the abundance of beneficial Enterococcus and reduced pathogenic Escherichia-Shigella in the esophagus. In the gut, BXXXD elevated the relative abundance of beneficial taxa, including Lactobacillus, Dubosiella, Bacteroides, and Faecalibacterium. Targeted metabolomics showed that BXXXD significantly reduced total serum SCFA level (P < 0.01). Transcriptomic analysis indicated that BXXXD downregulated the expression of genes associated with the progression, migration, and invasion of esophageal cancer, which were identified as kallikrein-related peptidase 6 (Klk6), defensin beta 4 (Defb4), family with sequence similarity 3 member B (Fam3b), carboxypeptidase A4 (Cpa4), serum amyloid A1 (Saa1), and chitinase-like 1 (Chil1) (P < 0.05). Conclusion BXXXD may reduce the expression levels of esophageal cancer-related genes and improve esophageal precancerous lesions through modulation of the gut microbiota and metabolites.

Background: and Purpose In patients with large vessel occlusion (LVO), intravenous thrombolysis (IVT) frequently alters thrombus location; however, the clinical impact of this phenomenon remains unclear. We aimed to compare post-IVT thrombus dynamics between tenecteplase and alteplase and to evaluate the association between thrombus dynamics and 3-month outcomes. Methods: This retrospective study analyzed prospectively collected, multicenter data from consecutive patients with LVO who underwent bridging therapy between January 2022 and December 2024. Thrombus dynamics were classified as resolution, migration, or stability. Analyses incorporated propensity score matching with weighting to balance baseline characteristics. Results: Of the 806 initially included patients, 746 were included after matching (373 treated with tenecteplase and 373 treated with alteplase). The incidence of thrombus migration was significantly higher in the tenecteplase group than in the alteplase group (19.3% vs. 11.3%; odds ratio [OR]: 1.92; 95% confidence interval [CI] 1.27–2.91). The advantage of tenecteplase over alteplase was restricted to patients with an IVT-to-puncture time of <60 minutes (18.6% vs. 6.2%; p=0.001) and was no longer significant when the interval ≥60 minutes (19.7% vs. 15.0%; p=0.204; pinteraction=0.043). Additionally, thrombus migration was associated with a better functional outcome (OR: 1.62; 95% CI 1.04–2.53). Finally, tenecteplase was associated with improved functional independence compared with alteplase (OR: 1.43; 95% CI 1.04–1.95). Conclusions Tenecteplase demonstrated superior efficacy in inducing thrombus migration compared with alteplase, particularly within 60 minutes of IVT administration. Thrombus migration independently predicted improved functional independence. These findings support the preferential use of tenecteplase for bridging therapy in patients with LVO.

Objective:To evaluate the effect of continuous theta burst stimulation (cTBS) on postoperative cognitive dysfunction (POCD) in mice and its association with the excitability of parvalbumin (PV) neurons in the medial prefrontal cortex (mPFC).Methods:Twenty-four specific pathogen-free healthy male C57BL/6 mice, aged 8 weeks, weighing 18-24 g, in which adeno-associated virus (AAV) for labeling PV neurons was injected into the mPFC using stereotaxic surgery, were used in this study. Three weeks later, the mice were divided into 3 groups ( n=8 each) using a random number table method: control group (group C), POCD group (group P) and cTBS group. Group C received no treatment. A mouse model of POCD was established by performing tibial fracture surgery under sevoflurane anesthesia and the mice received sham stimulation from postoperative day 0 to day 4 in group P. Group cTBS underwent POCD model establishment and received cTBS stimulation from postoperative day 0 to day 4. Cognitive function was assessed using contextual fear conditioning, Y-maze and novel object recognition tests on postoperative day 5. The spontaneous firing frequency of PV neurons in the mPFC was then measured using ex vivo patch-clamp electrophysiology. Results:The results of contextual fear conditioning test showed that compared to group C, the percentage of freezing time was significantly increased in group P ( P<0.05); compared to group P, the percentage of freezing time was significantly decreased in group cTBS ( P<0.05). The results of Y-maze test showed that compared to group C, the alternation accuracy was significantly decreased in group P ( P<0.05); compared to group P, the alternation accuracy was significantly increased in group cTBS ( P<0.05). The results of novel object recognition test showed that compared to group C, the percentage of time spent exploring the novel object was significantly decreased in group P ( P<0.05); compared to group P, this percentage of time spent exploring the novel object was significantly increased in group cTBS ( P<0.05). The results of ex vivo patch-clamp electrophysiology showed that compared to group C, the spontaneous firing frequency of PV neurons in the mPFC was significantly decreased in group P ( P<0.05); compared to group P, the spontaneous firing frequency of PV neurons in the mPFC was significantly increased in group cTBS ( P<0.05). Conclusions:cTBS can ameliorate POCD in mice, and the mechanism is related to the restoration of excitability of PV neurons in the mPFC.

Objective:To investigate the clinical manifestations, pathological features, and genetic variant characteristics of children with glycogen storage disease type Ⅸa (GSD Ⅸa).Methods:A retrospective case series analysis was conducted to collected and analyzed the medical history, biochemical markers, liver ultrasound results, liver histopathological findings, genotypes, treatment regimens, and follow-up data of 4 pediatric patients diagnosed with GSD IXa in the Department of Infectious Diseases at Xiamen Children′s Hospital from January 2018 to May 2024. All patients were confirmed by genetic testing.Results:All 4 pediatric patients diagnosed with GSD Ⅸa were male. The ages of onset were 8 months, 2 years, 3 years and 3 months, 1 year and 5 months, respectively, with initial presentations including chronic diarrhea (Case 1), incidentally detected transaminase elevation during routine examinations (Cases 2 and 3), and delayed motor development (Case 4). Diagnosis was confirmed at ages 10 months, 3 years, 3 years 4 months and 1 year 6 months, respectively.At diagnosis, anthropometric parameters and biochemical profiles revealed:Height: 68 cm (< P3), 96 cm ( P25-50), 94 cm ( P3-10), and 94 cm ( P3-10).Weight: 7 kg (< P3), 17 kg ( P90-97), 14.4 kg ( P25-50), and 10.5 kg ( P25-50).Alanine aminotransferase: 299, 500, 271, and 313 U/L (reference range 0-40 U/L).Aspartate aminotransferase: 285, 543, 337 and 357 U/L (reference range 0-40 U/L).Fasting glucose: 2.80, 3.67, 2.98, and 3.66 mmol/L (reference range 3.90-6.10 mmol/L).Lactate: 4.3, 2.1, 1.3, and 2.6 mmol/L (reference range 0.5-2.2 mmol/L).Triglycerides: 5.22, 1.38, 1.32, and 1.88 mmol/L (reference range 0.56-1.70 mmol/L).Case 1 exhibited poor adherence to uncooked cornstarch therapy during initial treatment, with no significant improvement in biochemical parameters. Follow-up imaging at age 4 revealed hepatic adenoma. Subsequent improvement in therapeutic compliance led to biochemical normalization, reduced hepatic adenoma size, and growth parameters of 113 cm ( P10-25) and 26 kg ( P90-97) at 6 years 2 months. Cases 2-4 demonstrated biochemical improvement with regular uncooked cornstarch therapy and no evidence of hepatic adenoma.Liver histopathology in Cases 1-3 confirmed glycogen accumulation consistent with GSD, without cirrhotic changes. Genetic analysis identified PHKA2 variations in all cases: 2 missense variants, 1 frameshift variant and 1 nonsense variant. The c.2839dup and c.3267G>A variants represent novel pathogenic mutations. Conclusions:GSD Ⅸa in pediatric patients is predominantly characterized by hepatomegaly, hepatic dysfunction, and hypoglycemia. While uncooked cornstarch therapy typically yields favorable prognoses, a subset of patients may develop hepatic adenomas. Notably, children with hepatic adenoma exhibited younger age of onset, significant growth retardation, and more severe metabolic disturbances, suggesting that hepatic adenoma development may be closely linked to the severity of metabolic dysregulation.

Objective:To assess the anti-tumor immune response after combined cryoablation and granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment.Methods:A mouse model of colorectal liver metastases (CLM) was established using 80 BALB/c mice. All tumor-bearing mice were divided into a control group ( n=20), a GM-CSF group ( n=20), a cryoablation group ( n=20), and a cryoablation+GM-CSF group ( n=20). Cryoablation was applied using a 1.7-mm diameter cryosurgery needle from an argon-helium cryosurgery system. Tumor size and survival time were observed. Changes in the number of dendritic cells (DCs) in tumors were assessed by immunohistochemistry. Serum cytokine (IFN-γ, IL-4) levels were analyzed by enzyme-linked immunosorbent assay (ELISA), and the Th1/Th2 ratio was estimated from the IFN-γ/IL-4 ratio. One-way analysis of variance was used for data analysis. Results:Our findings showed that combining cryoablation and GM-CSF synergistically increased infiltrating DC numbers. Among the four groups, cryoablation+GM-CSF group exhibited the highest DC count post-treatment (control group: 1.4±0.5/HPF, GM-CSF group: 15.3±1.8/HPF, cryoablation group: 9.6±1.5/HPF, cryoablation+GM-CSF group:17.4±1.3/HPF; F=138.60, P<0.05). Cryoablation, alone or combined with GM-CSF, elevated serum IFN-γ and reduced serum IL-4. IFN-γ levels of cryoablation group increased from 45.6±2.4 pg/ml to 57.8±3.3 pg/ml, F=170.09, P<0.05,and IFN-γ levels of cryoablation+GM-CSF group increased from 45.6±2.4 pg/ml to 86.3±1.9 pg/ml, F=664.31, P<0.05;and IL-4 levels of cryoablation group decreased from 7.21±0.63 pg/ml to 6.35±0.25 pg/ml, F=5.77, P<0.05,IL-4 levels of cryoablation+GM-CSF group decreased from 7.21±0.63 pg/ml to 6.42±0.21 pg/ml, F=10.93, P<0.05. Conversely, GM-CSF alone decreased serum IFN-γ and increased serum IL-4. Notably, combined cryoablation and GM-CSF significantly boosted Th1/Th2 ratios (cryoablation+GM-CSF group: from 6.32±0.45 to 13.43±0.64; F=379.95, P<0.05). Conclusion:Combined cryoablation with GM-CSF treatment exerted a promising anti-tumor immune effect in the treatment of colorectal cancer liver metastases. This approach increased the number of DCs in the tumor microenvironment and improved the anti-tumor immunologic response in tumor-bearing mice.

Objective:Using the impact of chronic graft-versus-host disease (cGVHD) on overall survival after hematopoietic stem cell transplantation as an example, this study aims to introduces and critically appraises five statistical approaches for handling time-dependent events in survival analysis.Methods:This study was based on data from the Center for International Blood and Marrow Transplant Research (CIBMTR) GV18-03 study. A total of 4361 patients with acute myeloid leukemia or myelodysplastic syndrome were included, who were aged ≥40 years and had received an HLA 8/8 matched sibling donor transplant between 2008 and 2017. Five analytical approaches were used, treating cGVHD as: ① a baseline fixed covariate, ② a time-dependent covariate, ③ a time-dependent event via landmarking analysis, ④ a transitional event in a multi-state model, and ⑤ an exposure in the parametric g-formula. For each approach, we presented its core concept and results, and elaborated on its rationale, strengths, limitations, and applicable scenarios.Results:The five approaches showed significant differences in bias control, modeling flexibility, and clinical interpretability. Method 1 was prone to immortal time bias. Method 2 partially corrected this bias but was vulnerable to informative censoring and estimation instability due to insufficient sample sizes in the early-onset cGVHD group. Method 3 was straightforward but dependent on a predefined landmark time point and unable to account for cGVHD occurring after this point. Method 4 allowed for a comprehensive description of the impact of time-dependent events on survival prognosis by modeling dynamic clinical transitions. Method 5 could simultaneously handle both time-dependent events and confounders, making it suitable for estimating population-level effects of specific exposure strategies.Conclusion:Researchers should select the appropriate method based on their specific study objectives to ensure that the estimation of the impact of time-dependent events on outcomes is both statistically valid and clinically meaningful.

Objective:To investigate the protective effect of myrislignan（MRL）on concanavalin A（Con A）-induced autoimmune hepatitis（AIH）.Methods:C57BL/6J mice were divided into the following groups using a random number table，with five mice in each group：control group，MRL group，model group（Con A group），and MRL pretreatment group（MRL+Con A group）. MRL was injected intraperitoneally at a dose of 30 μg/g；3 h after pretreatment，Con A（18 μg/g）was administrated by intravenous injection；mouse livers and serum samples were collected 12 h after injection for measuring serum transaminase levels and liver cell apoptosis. The mRNA and protein expression levels of IL-6，IL-12，and TNF-α were measured using qRT-PCR and ELISA. Flow cytometry was performed to detect the proportion and activation status of macrophages in liver tissues. Bone marrow-derived macrophages（BMDMs）were isolated and induced in vitro to analyze the regulatory effect of MRL on macrophages. One-way analysis of variance was used to compare the differences in various indicators among groups. Results:Compared with the Con A group，MRL（30 μg/g）pretreatment significantly reduced alanine aminotransferase（ P<0.05）and aspartate transaminase（ P<0.01）levels，attenuated liver oxidative stress（increased superoxide dismutase activity，while decreased levels of malondialdehyde and myeloperoxidase；all P<0.05），and suppressed hepatocyte apoptosis（ P<0.01）. Both in vivo and in vitro experiments confirmed that MRL（30 μg/g）could reduce the proportion of M1 macrophages（ in vivo： P<0.05； in vitro：all P<0.001）and inhibit macrophage activation（ in vivo： P<0.01； in vitro：all P<0.05）. Conclusion:MRL effectively prevents Con A-induced autoimmune hepatitis by inhibiting liver cell apoptosis，attenuating liver oxidative stress，suppressing M1 macrophage polarization，and reducing inflammatory cytokine expression.

Objective:To investigate the clinical efficacy of autologous adipose-derived stem cell gel (SVF-gel) grafting in the treatment of depressed acne scars.Methods:A retrospective analysis was conducted on data collected from 28 patients who underwent SVF-gel grafting treatment for depressed acne scars in the Department of Dermatology, Xijing Hospital, Air Force Medical University from October 2018 to May 2021. There were 17 males and 11 females, aged 17 - 38 (26 ± 4.86) years. As for clinical types, 8 patients were diagnosed with boxcar acne scars, 14 with rolling acne scars, and 6 with acne scars with characteristics of the two types. The clinical acne scar weighted scale (ECCA scale) was used to evaluate the appearance improvement after the treatment, and patients′ subjective satisfaction scores and incidence of adverse reactions were recorded.Results:After the SVF-gel grafting, the facial appearance of patients with depressed acne scars significantly improved, and the ECCA scores significantly decreased 6 months after surgery (before surgery: 52.5 ± 15.8 points; 6 months after surgery: 23.8 ± 10.2 points; t = 11.68, P < 0.001). The subjective satisfaction rate of patients was 82.14% (23/28), the incidence rate of adverse reactions was 17.86% (5/28), and 5 patients experienced mild inflammatory reactions after surgery, including 2 with subcutaneous nodules. The secondary grafting rate was 67.86% (19/28) . Conclusion:The SVF-gel grafting was markedly effective for the treatment of depressed acne scars, which is worthy of clinical promotion and application.

Objective: To analyze the epidemiological characteristics of mumps in Shanxi Province from 2014 to 2023, so as to provide scientific evidence for targeted prevention strategies. Methods: Mumps case data in Shanxi Province were obtained from the China Information System for Disease Prevention and Control. Descriptive epidemiological analysis and age-period-cohort (APC) analysis were carried out on the reported incidence of mumps from 2014 to 2023. Results: A total of 44 360 mumps cases were reported in Shanxi Province from 2014 to 2023, with an average annual incidence rate of 11.78/100 000. The incidence rates were high during 2017-2019, which were 21.00/100 000, 16.76/100 000, and 19.51/100 000, respectively. Males had a higher incidence rate (13.50/100 000) than females (9.98/100 000). Children aged 5-9 years were the most affected group, accounting for 47.29% of total cases. In 2017 and 2019, incidence rates among the 5-15-year-old group were particularly high, reaching 155.08/100 000 and 131.78/100 000, respectively. The APC model age effect, period effect and cohort effect of the reported incidence rate in the high-incidence population aged 0-20 years all had statistical significance ( P <0.05). The age-relative risk ( RR ) decreased from 1.75 in the 0-year-old group to 0.33 in the 20-year-old group, and the birth cohort RR decreased from 2.58 in 1994 to 0.26 in 2023. The morbidity risk of the population aged 0-20 years showed a trend of first increasing and then decreasing over time, among which it was the highest in 2017 ( RR =1.23) and the lowest in 2023 ( RR =0.29). Conclusions Shanxi exhibits cyclical mumps epidemics, with school-aged children as the high-risk population. School health management work should be carried out, and the surveillance of mumps in high-risk areas and the routine vaccination of two doses of mumps-containing vaccines for eligible children should be strengthened.

Objective To investigate the cognition level and behavior compliance of blood pressure measurement in community residents and analyze the related influencing factors, and to provide evidence for community health management and blood pressure control. Methods A questionnaire survey was conducted to investigate 4470 community patients. Questionnaires included basic personal information，blood pressure measurement cognition, and blood pressure measurement behavior related issues. SPSS 19.0 was used to analyze the basic information, blood pressure measurement cognition, and pressure measurement behavior of the survey subjects. Logistic regression was performed to analyze relevant factors affecting blood pressure measurement cognition and behavior compliance. Results The overall cognitive compliance rate for blood pressure measurement among the visiting community patients was 31.52%. Age, education level, and chronic disease had a statistically significant impact on the cognitive knowledge (P<0.05). The overall behavior compliance rate of blood pressure measurement among the community patients was 23.69%. The cognition, age and education had a statistically significant impact on the overall behavior compliance rate of blood pressure measurement (P<0.05). Conclusion The cognitive level and standardized behavior of blood pressure measurement of community patients need to be improved. More attention should be paid to the elderly, low education level residents and community residents without chronic diseases, to promote community residents to form correct and standardized behavior of blood pressure measurement through health education.