ObjectiveTo analyze the incidence and spatiotemporal distribution of typhus fever in Baoshan City, Yunnan Province from 2005 to 2023, to identify high-risk populations and regions, so as to provide a scientific basis for optimizing the allocation of local prevention and control resources and developing targeted intervention measures. MethodsData of typhus fever cases in Baoshan City from 2005 to 2023 were obtained from the Infectious Disease Information Management System of the Chinese Center for Disease Control and Prevention. Descriptive epidemiological methods were used to analyze the temporal, spatial and demographic distribution of typhus fever cases. Spatial clustering was assessed using spatial dynamic window scan statistics (circular and elliptical windows), flexible spatial scan statistics, and local spatial autocorrelation methods (including local Moran’s I, local Geary’s C, and Getis-Ord G_i*). Retrospective spatiotemporal scan statistics were employed to detect spatiotemporal clusters. ResultsA total of 1 099 typhus fever cases were reported in Baoshan City from 2005 to 2023. The incidence rate peaked at 6.31/ 100 000 in 2007, followed by a decline until reaching its lowest level at 0.21/100 000 in 2015 , and subsequently rebounded during 2016‒2023. The highest proportion of cases was among children under 10 years of age (31.12%), and the top three occupations of cases were farmers, students, and children, accounting for 88.62% of all cases. Cases occurred predominantly between June and September each year. The incidence was relatively high in Jiucheng Town (62.58/100 000), Yaoguan Town (57.15/100 000), and Dianyang Town (46.81/100 000) of Shidian County. Spatial clustering analyses indicated that high-risk areas were mainly located in the southern part of Baoshan City, showing a south-to-north trend. Spatiotemporal scan analyses identified five clusters, with the most likely cluster centered around Yaoguan Town, covering ten towns (subdistricts) during the period 2007‒2010. ConclusionThe incidence of typhus fever in Baoshan City exhibits a clear seasonal and spatial clustering pattern, with peak incidence occurring in summer and autumn. Spatially, cases are primarily distributed in the southern part of Baoshan City, and high-risk clusters exhibit a south-to-north trend. Farmers, students, and children are the high-risk groups.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Objective:To investigate the views of doctors on the incidence and treatment tactics of mild progression after epithelial growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)treatment in lung adenocarcinoma and provide suggestions to optimize the counter-measure strategies.Methods:Convenience sampling was used to conduct an online questionnaire survey for doctors specializing in onco-logy and respiratory diseases.Results:584 valid questionnaires were collected,and all the doctors expressed concerns regarding mild tumor progression after EGFR-TKI treatment.The coping strategies included maintaining the original TKI treatment,adding other treatments to the original TKI,changing the regimen,and performing secondary tissue biopsy,among which,most doctors chose to add other treatments to the original TKI.Conclusions:Doctors have noticed the enlargement of target lesions in still stable disease(SD)and most frequently chose to add other treatments to the original TKI as a coping strategy.This finding can provide a reference for framing future guidelines for large sample prospective clinical studies that are needed to find the most effective synergistic treatment options.

AIM To investigate the effects of Qifu Yixin Granules on cardiac inflammation in a rat model of heart failure.METHODS The rats were induced into chronic heart failure(CHF)models by 6-week intraperitoneal injection of doxorubicin followed by the random assignment of the successful rat models into the model group,the captopril group(22.5 mg/kg),and the low-dose,medium-dose,and high-dose Qifu Yixin Granules groups(2.84,5.67,11.34 g/kg),in contrast to the normal rats of the blank group.The rats had their body weight monitored;their cardiac function assessed by echocardiography;their serum levels of NT-proBNP,TNF-α,IL-6,IL-1 and CRP measured by ELISA;their cardiac morphological alterations observed by HE and Masson staining;their cardiac protein expressions of TLR4,MyD88 and NF-κB detected by immunohistochemistry and Western blot;and their cardiac mRNA expressions of TLR4,MyD88 and NF-κB measured by RT-qPCR.RESULTS Compared to the blank group,the model group exhibited significantly reduced body weight,LVEF and LVFS(P＜0.01),alongside significantly elevated LVEDD,LVESD,and serum concentrations of NT-proBNP,TNF-α,IL-6,IL-1 and CRP(P＜0.01).Additionally,the model group displayed greater myocardial inflammatory cell aggregation,increased collagen deposition(P＜0.01);and upregulated myocardial protein and mRNA expressions of TLR4,MyD88 and NF-κB(P＜0.01).Compared to the model group,the groups intervened with captopril or medium/high dose Qifu Yixin Granules demonstrated significantly increased body weight,LVEF and LVFS(P＜0.05,P＜0.01);significantly reduced LVEDD,LVESD,and serum levels of the aforementioned indicators(P＜0.05,P＜0.01);mitigated inflammation and collagen deposition(P＜0.05,P＜0.01);and downregulated myocardial protein and mRNA expressions of TLR4,MyD88 and NF-κB(P＜0.05,P＜0.01).CONCLUSION Qifu Yixin Granules attenuate cardiac inflammation and improve cardiac function in doxorubicin-induced CHF rats;this therapeutic effect is mediated by inhibiting the activation of the TLR4/MyD88/NF-κB signaling pathway.

Objective To evaluate the quality of ketoconazole lotion produced by different domestic companies.Methods Legal standards and exploratory research were used to conduct a comprehensive evaluation of 45 batches(40 batch numbers)of ketoconazole lotion for national drug sampling inspection in 2024,including related substances,antioxidant content,packaging oxygen permeability,in vitro permeation test,and viscosity,antibacterial efficacy,irritation,microstructure,etc.Results The legal standard inspection pass rate was 100.0%.Correlation analysis found that the main factors affecting the quality of this product are prescription technology and packaging.Conclusion It is recommended that manufacturers optimize the prescription process as soon as possible,and pay attention to choose suitable packaging materials,effectively improve the quality of ketoconazole lotion.

Background and purpose:Tumor necrosis factor alpha-induced protein 8(TNFAIP8),also called TIPE,plays critical regulatory roles in various malignancies,yet its molecular mechanisms in metabolic reprogramming of triple-negative breast cancer(TNBC)remain elusive.This study aimed to elucidate how TIPE regulates the expression of the glycolytic key enzyme lactate dehydrogenase A to influence TNBC cell proliferation and glycolytic reprogramming,thereby providing potential molecular targets for TNBC therapy.Methods:Stable TIPE-knockdown MDA-MB-231 cell lines were established using a lentiviral shRNA system and selected with puromycin.Transcriptome sequencing was used to analyze TIPE's impact on TNBC glycolytic pathways.Extracellular acidification rate(ECAR)was measured using the Seahorse XF Analyzer,complemented by lactate production assays to evaluate glycolytic capacity.Co-IP/MS was carried out to identify TIPE-interacting proteins,with subsequent validation of TIPE-LDHA interaction through co-transfection of TIPE-Myc and LDHA-Flag plasmids in HEK-293T cells.Protein stability was assessed via cycloheximide(CHX)chase and ubiquitination assays.The cell counting kit-8(CCK-8)assay and animal experiments(Approval Number for Animal Ethics:202212007)were conducted to investigate how TIPE affects the proliferation and glucometabolic reprogramming of TNBC by mediating LDHA.Results:TIPE promoted glycolytic metabolic reprogramming in TNBC.Knockdown of TIPE significantly inhibited TNBC glycolytic activity and glycolytic capacity(P＜0.001).TIPE interacted with the key glycolytic enzyme LDHA and suppressed its degradation rate through a ubiquitination-dependent mechanism.Cellular experiments demonstrated that TIPE mediated LDHA to enhance TNBC cell proliferation(P＜0.001)and glycolytic activity(P＜0.001).Animal studies confirmed that TIPE knockdown significantly suppressed tumor volume(P＜0.05)and weight(P＜0.01),with a positive correlation between TIPE and LDHA expression levels in tumor tissues.Conclusion:TIPE enhances TNBC cell proliferation and glycolytic capacity by inhibiting LDHA ubiquitination-mediated degradation.

Objective To explore the effects of commonly used rapid imaging techniques on the image quality of cerebral three-dimensional time-of-flight magnetic resonance angiography(3D-TOF-MRA)and to select the optimal imaging technique for clinical use.Methods Thirty subjects were prospectively recruited,and five sets of 3D-TOF-MRA images were acquired as follows:non-acceleration(reference group),intra-layer parallel imaging(PI)(1D group),inter-layer PI(2D group),compressed sensing(CS)group,and artificial intelligence-assisted compressive sensing(ACS)group.The metrics including clarity,pseudo-stenosis,signal-to-noise ratio(SNR),contrast-to-noise ratio(CNR),and edge sharpness of the intracranial proximal,middle,and distal blood vessels were quantitatively or qualitatively assessed.Results There were no significant differences in the clarity of intracranial proximal and middle blood vessels between the groups(P＞0.05).The clarity of distal blood vessels in the ACS group was superior to that in the other groups,and the CS and 2D groups were superior to the 1D group.Compared to the reference group,no stenosis was observed in any segment of the blood vessels in the ACS group,while the incidence of stenosis in the distal blood vessels of the 1D,2D,and CS groups was 36.67％,13.33％,and 6.67％,respectively.The SNR of the proximal and middle blood vessels in the ACS group did not differ from the reference group,and the SNR of the proximal,middle,and distal segments was higher than that in the 1D and CS groups,and higher than the 2D group for the proximal and distal segments.The CNR of the proximal,middle,and distal segments in the ACS group did not differ from the reference group,and was higher than that of the 1D and CS groups,and higher than the 2D group for the proximal and distal segments.The edge sharpness of the ACS group was significantly higher than that of the other groups.Conclusion ACS technology can accelerate the imaging speed and improve the image quality of cerebral 3D-TOF-MRA.It is recommended for use.

Objective:To evaluate the effect of the radiation dose of thoracic cage bone structure on clinical prognosis in patients with locally advanced non‐small cell lung cancer (LA‐NSCLC) receiving chemoradiotherapy, and to develop and verify a combined model combining the radiation dose of bone structure, the estimated radiation dose of immune cells (EDRIC) and other related factors to predict the prognosis of LA‐NSCLC.Methods:Clinical data of 197 patients with LA‐NSCLC who underwent chemoradiotherapy were retrospectively analyzed. All patients were randomly divided into the training set and testing set at a ratio of 7:3 using computer random partitioning. The EDRIC value was calculated using the model developed by Jin et al. and modified by Ladbury et al. The scope of the thoracic cage structure includes the ribs, sternal manubrium, sternal body, thoracic vertebral body, thoracic vertebral appendages, and thoracic vertebrae. The tumor volume, ERDIC, and average bone structure dose (D mean) were categorized into two groups using the P25, P50, P75 value from the quartile method. Univariate and multivariate Cox proportional hazards regression were used to analyze the influencing factors of overall survival (OS), local progression‐free survival (LPFS), and distant metastasis‐free survival (DMFS) for predicting the outcome, and significant correlated variables were retained to construct a combined prediction model with EDRIC. The receiver operating characteristic (ROC) curve, decision curve analysis (DCA), and calibration curves were plotted for subjects at the 2‐year time point of the combined model to evaluate the predictive performance. The model was visualized through a nomograph. Results:In the thoracic cage bone structure, D mean > 47.3 Gy of the sternal manubrium was an independent risk factor of OS, LPFS, and DMFS of LA-NSCLC patients. D mean > 23.1 Gy of thoracic vertebral body was an independent risk factor of OS, and D mean > 14.4 Gy of thoracic vertebral body was an independent risk factor of DMFS. Among other variables, gross tumor volume (GTV) >50.2 cm 3 was a risk factor for OS, and GTV >87.0 cm 3 was a risk factor for LPFS. Planning target volume >571.9 cm 3 was a risk factor for DMFS. A combined prediction model for OS, LPFS, and DMFS was established with EDRIC using features significantly associated with these three predicted outcomes. The area under the ROC curve (AUC) of OS combined model in the training set and test set were 0.708 and 0.696, respectively, and the AUC of DMFS combined model were 0.675 and 0.639, respectively. The calibration curve and DCA curve of the two prediction endpoints showed that the combined model had good prediction accuracy and clinical benefit. However, the LPFS model was not good in accuracy and clinical applicability. Conclusions:The radiation dose of sternal manubrium and thoracic vertebral body in the thoracic cage bone structure is an independent influencing factor for the prognosis of LA‐NSCLC patients after chemoradiotherapy. The combined model has good predictive performance for OS and DMFS.

Objective:To evaluate the efficacy and safety of once-daily tacrolimus extended-release capsules (OD-TAC) in pediatric liver transplant recipients after conversion from twice-daily tacrolimus (TD-TAC).Methods:A retrospective analysis was performed on pediatric liver transplant recipients at Tianjin First Center Hospital between January 2014 and December 2020 who were converted from TD-TAC to OD-TAC with a follow-up of at least 12 months. After conversion, all patients received OD-TAC monotherapy. The daily dose conversion ratio from TD-TAC to OD-TAC ranged from 2∶1 to 1∶2. Clinical data including demographics, tacrolimus dosage, trough concentrations, liver function, and adverse events were collected. Continuous variables with normal distribution were expressed as Mean±SD and compared using independent-samples t-test or ANOVA; non-normally distributed variables were expressed as median ( Q1, Q3) and compared using Mann-Whitney U or Kruskal-Wallis H tests. Categorical variables were expressed as frequency and percentage, and compared using χ 2 test or Fisher's exact test. P<0.05 was considered statistically significant. Results:A total of 290 children were enrolled, including 140 males (48.3%) and 150 females (51.7%). The median age at transplantation was 7.34 (6.03, 12.34) months, and the median time to conversion was 36 (29, 48) months post-transplant. Tacrolimus daily doses at 3, 6, and 12 months after conversion were slightly higher than before conversion, but without statistical significance (all P>0.05). Trough tacrolimus levels at 6 and 12 months after conversion were 2.34±1.02 μg/L and 2.23±1.07 μg/L, respectively, both lower than pre-conversion (2.77±1.43 μg/L), with statistical significance ( P=0.02 and P<0.01). Serum creatinine levels at 6 and 12 months post-conversion were 2.63±0.63 mmol/L and 2.76±0.68 mmol/L, respectively, both higher than before conversion (2.57±1.90 mmol/L, P<0.05). Triglyceride level at 12 months post-conversion was 0.87±0.25 mmol/L, significantly lower than pre-conversion (1.05±0.55 mmol/L, P<0.05). Two patients developed transient bilirubin elevation at 3 months, and another two developed transient triglyceride elevation at 6 months; all recovered without intervention. No new-onset diabetes was observed during follow-up. Thirteen patients experienced acute rejection. One patient (0.3%) died three years after conversion due to hepatic venous outflow obstruction, while all others survived. Conclusion:In pediatric liver transplant recipients, OD-TAC provides comparable efficacy and safety to TD-TAC.

Background and purpose:Tumor necrosis factor alpha-induced protein 8(TNFAIP8),also called TIPE,plays critical regulatory roles in various malignancies,yet its molecular mechanisms in metabolic reprogramming of triple-negative breast cancer(TNBC)remain elusive.This study aimed to elucidate how TIPE regulates the expression of the glycolytic key enzyme lactate dehydrogenase A to influence TNBC cell proliferation and glycolytic reprogramming,thereby providing potential molecular targets for TNBC therapy.Methods:Stable TIPE-knockdown MDA-MB-231 cell lines were established using a lentiviral shRNA system and selected with puromycin.Transcriptome sequencing was used to analyze TIPE's impact on TNBC glycolytic pathways.Extracellular acidification rate(ECAR)was measured using the Seahorse XF Analyzer,complemented by lactate production assays to evaluate glycolytic capacity.Co-IP/MS was carried out to identify TIPE-interacting proteins,with subsequent validation of TIPE-LDHA interaction through co-transfection of TIPE-Myc and LDHA-Flag plasmids in HEK-293T cells.Protein stability was assessed via cycloheximide(CHX)chase and ubiquitination assays.The cell counting kit-8(CCK-8)assay and animal experiments(Approval Number for Animal Ethics:202212007)were conducted to investigate how TIPE affects the proliferation and glucometabolic reprogramming of TNBC by mediating LDHA.Results:TIPE promoted glycolytic metabolic reprogramming in TNBC.Knockdown of TIPE significantly inhibited TNBC glycolytic activity and glycolytic capacity(P＜0.001).TIPE interacted with the key glycolytic enzyme LDHA and suppressed its degradation rate through a ubiquitination-dependent mechanism.Cellular experiments demonstrated that TIPE mediated LDHA to enhance TNBC cell proliferation(P＜0.001)and glycolytic activity(P＜0.001).Animal studies confirmed that TIPE knockdown significantly suppressed tumor volume(P＜0.05)and weight(P＜0.01),with a positive correlation between TIPE and LDHA expression levels in tumor tissues.Conclusion:TIPE enhances TNBC cell proliferation and glycolytic capacity by inhibiting LDHA ubiquitination-mediated degradation.