ObjectiveTo investigate the role of DEAD-box helicase 3 X-linked （DDX3X） in immune-mediated liver injury （ILI）， and to clarify its mechanism by regulating endoplasmic reticulum stress （ERS）-dependent apoptotic pathway and its association with the clinical progression of hepatitis B. MethodsMice were given injection of concanavalin A （ConA） via the caudal vein to establish a model of ILI， PBS （control group） and different concentrations of ConA were injected into the tail vein of hepatocyte-specific DDX3X-knockout mice （DDX3X^ΔHep and DDX3X-flox mice （DDX3X^fl/fl）， respectively.. The log-rank survival analysis， measurement of the serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT）， and HE staining of liver tissue were performed to assess liver injury， and qRT-PCR and Western Blot were used to measure the mRNA and protein expression levels of glucose-regulated protein 78 （GRP78）， CCAAT/enhancer-binding protein homologous protein （CHOP）， and DDX3X in liver tissue. Intraperitoneal injection of 4-phenylbutyric acid （4-PBA， 100 mg/kg） was performed to inhibit ERS. Serum samples （n=30） and liver tissue samples （n=6） were collected from healthy controls， chronic hepatitis B （CHB） patients， and hepatitis B virus-associated liver failure （HBV-LF） patients； ELISA was used to measure the serum level of DDX3X， and qRT-PCR/Western Blot was used to analyze the expression of targets in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the control group of mice， the expression of DDX3X in the liver of mice induced by ConA was significantly increased after liver injury （P<0.05）， and hepatocyte-specific DDX3X knockout increased the 72-hour survival rate of mice by 55% （compared with 20% in the DDX3X^fl/fl group）， with significant reductions in the serum levels of ALT and AST （P<0.000 1） and the expression levels of the ERS markers GRP78 and CHOP （P<0.05）. After ERS was inhibited by 4-PBA， there was alleviation of liver injury （with reductions in ALT and AST， P <0.001） and a reduction in DDX3X expression （P<0.01）. The analysis of clinical samples showed that the mRNA and protein expression levels of liver DDX3X in CHB patients and HBV-LF patients were significantly higher than those in healthy controls （all P<0.01）， and there was a significant increase in the serum level of DDX3X in HBV-LF patients （P<0.000 1）. ConclusionDDX3X exacerbates ILI by regulating the ERS-dependent apoptotic pathway （GRP78/CHOP）， and its expression is associated with the progression of hepatitis B. Therefore， it can be used as a potential therapeutic target.

Objective To investigate the expression profile, prognostic value, gene co-expression network, and immunomodulatory role of BRF1 in a pan-cancer context, and to explore its biological functions and molecular regulatory mechanisms in esophageal squamous cell carcinoma (ESCC). Methods The pan-cancer dataset from The Cancer Genome Atlas (TCGA) was utilized to analyze the differential expression of BRF1 in tumor versus normal tissues, its association with patient survival, pathway enrichment for co-expressed genes, and immune features (including immune checkpoints, cytokines, and immune cell infiltration). The expression profile of BRF1 in ESCC was validated using the Gene Expression Omnibus (GEO) database. In vitro, BRF1 was knocked down in ESCC cells using siRNA. Cell proliferation and migration were assessed by MTT and Transwell assays, respectively. The expression levels of proliferation- and migration-related proteins were detected by Western blotting. The correlation between BRF1 and ferroptosis was analyzed using TCGA data. Results BRF1 was significantly upregulated in over 20 types of cancer, and its high expression was associated with poor prognosis in patients with adrenocortical carcinoma and prostate adenocarcinoma. BRF1 was found to positively regulate the T-cell-mediated cell death pathway in esophageal adenocarcinoma and was associated with the circadian rhythm regulation pathway in pancreatic adenocarcinoma. The correlation of BRF1 with immune checkpoints, cytokine networks, and immune cell infiltration was found to be cancer type-specific. In vitro experiments demonstrated that knocking down BRF1 significantly inhibited the proliferation of ESCC cells, accompanied by the downregulation of the proliferation marker PCNA. Cell migration was also significantly impaired, with decreased expression of Vimentin and MMPs and increased expression of E-cadherin. Furthermore, the expression of BRF1 was positively correlated with that of ferroptosis-antagonizing genes, such as GPX4, HSPA5, and SLC7A11. Conclusion BRF1 plays complex roles in pan-cancer, participating in the regulation of tumorigenesis, progression, and immune infiltration. BRF1 promotes the proliferation and migration of ESCC cells, a mechanism potentially associated with the regulation of ferroptosis resistance. These findings suggest that BRF1 could be a potential therapeutic target for ESCC.

Objective To analyze the ecological suitability of Codonopsis pilosula;To provide theoretical reference for expanding the planting scale of Codonopsis pilosula in Shanxi Province.Methods Information on the distribution of Codonopsis pilosula samples through the fourth survey of TCM resources in Shanxi Province and literature review;the MaxEnt model and ArcGIS 10.8 geographic information system software were used to analyze the ecological factors affecting the distribution of Codonopsis Radix in Shanxi Province,and the suitable distribution areas of Codonopsis pilosula in Shanxi Province were predicted.Results The predicted distribution areas of Codonopsis pilosula in Shanxi Province by the model were highly consistent with the actual distribution area;the AUC of the training set was 0.945,indicating good prediction results.The predominant ecological factors(contributing)impacting the distribution of Codonopsis pilosula included vegetation type(31.1%),the standard deviation of seasonal temperature fluctuations(25.0%),slope(8.3%),mean January precipitation(5.3%),mean May precipitation(5.0%),and elevation(4.9%)etc.The optimal vegetation types conducive to the proliferation of Codonopsis pilosula were identified as temperate deciduous shrubs,temperate grasslands,temperate coniferous forests,and temperate deciduous broad-leaved forests.The standard deviation of seasonal temperature change was within the range of 92 to 108,the slope gradient was from 14° to 30°,mean January precipitation was of 4 to 6.8 mm,mean May precipitation was of 33.5 to 58 mm,and elevation ranged from 1 100 to 2 800 meters.Codonopsis pilosula was mainly distributed in Lucheng,Qinxian and Qinyuan counties in the eastern part of Taiyue Mountain in Changzhi City;Pu County,Fenxi County,Fenyang City of Lyuliang City in the Lyuliang Mountain Range and Yushe County of Jinzhong City in the northern part of Taiyue Mountain.The most suitable area in Shanxi Province was 14 109.67 km2,the suitable area encompassed 22 837.62 km2,the relatively suitable area covered 41 982.96 km2,while the unsuitable area extended over 77 769.75 km2.Conclusion The geographical distribution data of Codonopsis pilosula resources in Shanxi Province may serve as a basis for further examination of regional zoning,with the establishment of wild cultivation bases for Codonopsis pilosula in proximity to various mountain ranges,such as the Taihang Mountains.Moreover,the artificial cultivation conditions can be modified in accordance with the optimal growth environment of Codonopsis pilosula,thereby optimizing the management of Codonopsis resources.

Mechanical thrombectomy,which improves the successful vascular recanalization rate and neurological functional prognosis in patients with acute ischemic stroke(AIS)caused by anterior circulation large vessel occlusion,has become one of the primary therapeutic strategies.Among the pharmacologic adjuvant therapies for mechanical thrombectomy,tirofiban(a platelet glycoprotein Ⅱ b/Ⅲ a receptor antagonist)has attracted significant attention due to its antithrombotic mechanism.This article summarized the research progress of tirofiban in the mechanical thrombectomy treatment of AIS patients from the perspectives of pharmacological mechanisms,administration timing,selection of eligible populations,and dosage regimens.It also analyzed the clinical application value and existing controversies of tirofiban,aiming to provide a scientific basis for optimizing the AIS treatment system.

Objective:To compare the clinical outcomes of APTT-HTO and Biplanar-high tibial osteotomy (Biplanar-HTO) in treating medial compartment knee osteoarthritis.Methods:A non-randomized controlled trial was conducted. Twenty-eight patients with medial compartment knee osteoarthritis who underwent HTO at the Affiliated Hospital of Guizhou Medical University from August 2021 to January 2022 were enrolled. Based on the patients' surgical preference, they were assigned to either the APTT-HTO group ( n=15) or the Biplanar-HTO group ( n=13), followed up for 12 months postoperatively. Postoperative pain Visual Analog Scale (VAS) scores, Knee Society Score (KSS), changes in patellar height (Caton-Deschamps Index, CDI), and posterior tibial slope (PTS) were compared between the two groups. Results:The APTT-HTO group demonstrated a significantly shorter operative time (64.13±4.85 min) compared to the Biplanar-HTO group (81.54±6.09 min) ( P<0.05). No significant differences were observed in intraoperative correction (APTT-HTO: 12.19°±4.85°; Biplanar-HTO: 11.23°±3.02°) or postoperative drainage volume (APTT-HTO: 47.00±13.79 ml; Biplanar-HTO: 47.00±11.17 ml) ( P>0.05). At 12-month follow-up (APTT-HTO: 13.93±2.05 months; Biplanar-HTO: 14.08±2.14 months; no dropouts), the APTT-HTO group showed no significant changes in PTS (9.32°±2.04° vs. preoperative 8.82°±1.89°) or CDI (0.95±0.11 vs. 0.98±0.11) ( P>0.05), while the Biplanar-HTO group exhibited increased PTS (13.27°±1.99° vs. 8.86°±1.99°) and decreased CDI (0.64±0.10 vs. 0.97±0.16) ( P<0.05). The differences in PTS and CDI between the APTT HTO group and the Biplanar HTO group at 12 months after surgery were statistically significant ( P<0.05). Both groups achieved significant clinical improvements: in APTT-HTO, VAS decreased (preopreation 4.80±1.01 to postopreation 1.06±0.88), KSS knee scores increased (47.67±12.03 to 87.93±4.38), and KSS function scores improved (48.00±4.93 to 67.00±5.91); in Biplanar-HTO, VAS reduced (5.08±1.12 to 1.85±1.14), KSS knee scores rose (46.85±11.48 to 85.85±5.11), and KSS function scores enhanced (46.92±5.60 to 66.92±5.22) ( P<0.05 for all). Complications included soft tissue irritation (2 cases per group), with Biplanar-HTO additionally reporting deep vein thrombosis (1 case), hinge fracture (1 case), and patella baja (3 cases). Conclusions:Both APTT-HTO and Biplanar-HTO effectively treat medial compartment knee osteoarthritis. However, APTT-HTO outperforms Biplanar-HTO in preventing postoperative patella infera and minimizing alterations in PTS.

[Objective] To investigate the antigen and gene frequency distribution of the MNS blood group system in the Han population of voluntary blood donors in Suzhou, and to explore the polymorphism of rare MNS blood group genes, in order to improve the construction of the local rare blood group database. [Methods] A total of 8 034 whole blood samples were randomly collected from Han blood donors at our station from October 2023 to June 2024. The MNS blood group phenotypes were identified using serological methods. Gene frequencies were analyzed and compared with those of ethnic populations in other regions. Rare MNS phenotype samples were subjected to gene sequencing. [Results] The distribution of MNS blood group system phenotypes within the population was as follows: the MM, NN, and MN phenotypes accounted for 23.00%, 27.12%, and 49.88% respectively; the SS, ss, and Ss phenotypes accounted for 0.30%, 90.99%, and 8.70% respectively. The gene frequencies of M, N, S, and s were 0.4794, 0.5206, 0.0465, and 0.9534 respectively. Chi-squared tests confirmed adherence to Hardy-Weinberg equilibrium with P-values of 0.997 and 0.349, showing statistical significance compared to some other regional ethnic populations (P<0.05). Additionally, one rare serological phenotype, S-s-, with a frequency of 0.01%, was identified. [Conclusion] The MNS blood group system in the Han population of voluntary blood donors in Suzhou exhibits polymorphism and regional distribution characteristics. Gene frequencies differ from those observed in other regions of China. It is essential to enhance the establishment of a rare blood type database in Suzhou to provide data support for precise clinical transfusion.

Mechanical thrombectomy,which improves the successful vascular recanalization rate and neurological functional prognosis in patients with acute ischemic stroke(AIS)caused by anterior circulation large vessel occlusion,has become one of the primary therapeutic strategies.Among the pharmacologic adjuvant therapies for mechanical thrombectomy,tirofiban(a platelet glycoprotein Ⅱ b/Ⅲ a receptor antagonist)has attracted significant attention due to its antithrombotic mechanism.This article summarized the research progress of tirofiban in the mechanical thrombectomy treatment of AIS patients from the perspectives of pharmacological mechanisms,administration timing,selection of eligible populations,and dosage regimens.It also analyzed the clinical application value and existing controversies of tirofiban,aiming to provide a scientific basis for optimizing the AIS treatment system.

Objective:To explore the advantages of individualized 3D-printed vaginal cylinder template-guided interstitial brachytherapy (3D-p-VC-ISBT) in locally advanced cervical cancer, aiming to provide reference for clinical adaptive brachytherapy.Methods:Clinical data of 20 patients with locally advanced cervical cancer admitted to Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine from September, 2021 to August, 2023 were retrospectively analyzed. The median age was 54 years old (32-69 years). Among them, 3 patients were diagnosed with adenocarcinoma and 17 cases of squamous cell carcinoma. According to the treatment method, all patients were divided into intracavitary brachytherapy group (ICBT-plan group, n=10) and 3D-p-VC-ISBT group (3D-p-VC-ISBT treatment-plan group, n=10). A pretreatment plan was designed for each patient undergoing 3D-p-VC-ISBT. The pretreatment plans were formed as the pretreatment-plan group. Dose volume histogram was used to evaluate dose distribution of the targets and organs at risk (OAR). Comparison between two groups was analyzed by Mann-Whitney test and comparison among three treatment plans (ICBT, 3D-p-VC-ISBT treatment-plan and 3D-p-VC-ISBT pretreatment-plan) was analyzed by Kruskal-Wallis test. Results:The mean D 90rel (representing the dose received by 90% volume of the target area divided by the prescription dose) of high-risk clinical target volume (HR-CTV) in 3D-p-VC-ISBT, pretreatment-plan and ICBT-plan groups were 100.47%, 104.66% and 85.91%, respectively. The conformity indexes were 0.66, 0.72 and 0.68, respectively. There was no significant difference in D 0.01 cm3, D 2 cm3 and D 5 cm3 of bladder, rectum and sigmoid colon among the three groups (all P>0.05). For the 3D-p-VC-ISBT treatment-plan group, the D 2 cm3 values of the small intestine at 6 Gy and 7 Gy prescription doses were 169.51 cGy and 111.93 cGy respectively, which were superior to those of the ICBT-plan group (343.07 cGy at 6 Gy prescription, P<0.01). Conclusions:Individualized 3D-p-VC-ISBT is superior to ICBT in terms of dose distribution of HR-CTV, and it can adaptively adjust the insertion plan according to changes in tumor volume and position, making the operation safer and more efficient.

Objective:To compare the efficacy and safety of extended-field versus reduced-field radiotherapy in upper tract urothelial carcinoma (UTUC) patients after radical operation.Methods:A retrospective analysis was conducted on the data of 210 UTUC patients who underwent full-length nephrectomy and received postoperative adjuvant radiotherapy in Peking University First Hospital from January 2013 to November 2023, and follow-up continued until June 2024. According to the target area of postoperative radiotherapy, patients were divided into the extended-field radiotherapy group (127 cases) and the reduced-field radiotherapy group (83 cases). The overall survival (OS), distant metastasis free survival (DMFS), local recurrence free survival (LRFS) and adverse reactions were compared. In the same period, 114 patients with recurrent abdominal and pelvic lymph nodes who did not receive adjuvant therapy after surgery for UTUC in our center were prospectively collected, and the coverage of the reduced-field target area was analyzed. Chi square test was used to compare the clinical characteristics, Kaplan-Meier method was used to analyze survival outcomes, log-rank test was used to compare the survival rate, and Cox multivariate regression analysis was performed on the influencing factors of survival.Results:The median follow-up was 24.5 (range: 3-74) months. There were no significant differences between the extended-field and reduced-field radiotherapy groups in terms of 2-year LRFS (93.3% vs. 98.1%, P=0.156), 2-year DMFS (84.8% vs. 91.2%, P=0.176), and 2-year OS (90.4% vs. 90.7%, P=0.707). The most common toxicities of adjuvant radiotherapy were nausea and leukopenia, with significantly higher grade 1-2 incidence in the extended-field group compared to the reduced-field group ( P<0.05). According to the analysis of patients with retroperitoneal lymph node recurrence after surgery, the reduced-field target designed according to the location of the primary tumor can cover more than 90% of the postoperative metastatic lymph node area Multivariate analysis revealed that variant histology ( HR=2.180,95% CI: 1.021-4.658, P=0.044) was an independent predictor of worse DMFS, while variant histology ( HR=3.825,95% CI: 1.514-9.662, P=0.005) and T 3-4 stage ( HR=4.452,95% CI: 1.025-19.339, P=0.046) were independent predictors of poorer OS. Conclusions:Compared with extended-field radiotherapy, reduced-field radiotherapy designed based on primary tumor location significantly reduced treatment-related toxicities without compromising postoperative therapeutic efficacy, and the reduced-field can cover more than 90% of local recurrent lesions.

Objective To investigate the abnormal changes characteristics of the degree centrality(DC)of the brain functional network in patients with benign paroxysmal positional vertigo(BPPV)in the classical frequency band(0.010-0.080 Hz),the slow-4 frequency band(0.027-0.073 Hz),and the slow-5 frequency band(0.010-0.027 Hz).Methods Twenty patients with BPPV(BPPV group)and 14 healthy controls(HC)(HC group)were selected.Resting-state functional magnetic resonance imaging(rs-fMRI)scans were performed,and the clinical data were analyzed.The DC method was used to analyze the changes of centrality of resting state network in patients with BPPV.Results Compared with the HC group,the BPPV group showed an increase in DC in the left caudate nucleus in the classical frequency band(P＜0.05),and a decrease in DC in the right auxiliary motor region in the classical frequency band(P＜0.05);within the slow-4 frequency band,no significant differences were observed in brain regions(P＞0.05);within the slow-5 frequency band,the BPPV group showed an increase in DC in the left thalamus(P＜0.05),while the left anterior cingulate and paracingulate gyrus showed a decrease in DC(P＜0.05).Conclusion Patients with BPPV have spontaneous activity disorders in multiple brain regions at resting states,and these changes show frequency band specificity.