ObjectiveTo evaluate a novel nomogram based on contrast-enhanced MRI radiomics combined with clinical variables for the preoperative prediction of perineural invasion （PNI） in intrahepatic cholangiocarcinoma （ICC）. MethodsThe clinical data of 59 ICC patients were retrospectively collected. According to postoperative pathology reports， the patients were divided into the non-PNI group （n = 33） and the PNI group （n = 26）. Regions of interest （ROI） were delineated from five MRI sequences. Radiomics features were then extracted and filtered to select those with the strongest discriminative power for PNI identification. These selected features were used to construct a radiomics model， which subsequently generated a quantitative radiomics score （radiomics score， Radscore）. Univariate analysis was applied to identify clinical variables associated with PNI， and the glm function was subsequently used to construct clinical and combined models. Finally， the models were evaluated using receiver operating characteristic （ROC） curves， calibration curves， and decision curve analysis （DCA）. The combined model was then visualized as a nomogram. ResultsThe clinical model included age， carbohydrate antigen 19-9 （CA19-9）， red blood cell distribution width， and albumin， whereas the Radscore included five radiomic features. The areas under the ROC curves （AUCs） for the clinical and radiomics models were 0.717 （95%CI： 0.586-0.848） and 0.896 （95%CI： 0.820-0.973）， respectively， whereas the combined model further improved its AUC to 0.917 （95% CI：0.848-0.987）. The calibration curves and DCA showed that the nomogram was well calibrated and provided the greatest net clinical benefit. ConclusionThe novel nomogram may serve as a basis for preoperative prediction of PNI status， thereby assisting clinical decision-making and guiding personalized treatment.

Malaria remains one of the most serious public health problems worldwide. After China achieved the target for malaria elimination, thousands of imported malaria cases are still reported annually. Timely and accurate diagnosis is critical to clinical treatment of cases and prevention of re-establishment of imported malaria. Detection of Plasmodium antigens is one of the criteria for definitive diagnosis of malaria. Malaria rapid diagnostic tests (RDTs) based on the immunochromatographic assay have become an important tool for clinical diagnosis of malaria due to convenient procedures and rapid detection. Nevertheless, there are still multiple misunderstandings pertaining to use of malaria RDTs among workers in medical and disease control and prevention institutions at all levels across China. To standardize technical guidelines and operational procedures for detection of Plasmodium spp., the National Disease Control and Prevention Administration has arranged the formulation of a recommended health industry standard Detection of Plasmodium spp. Immune-chromatographic test (WS/T 10029—2025), which has been officially iming immunochromatographic assays, including the testing principles, sample collection and detection procedures, and result interpretation, which provides the technical basis and operational specifications for detection of Plasmodium antigens in medical and disease control and prevention institutions at all levels. Based on analysis of the epidemiological characteristics of imported malaria in China, this article interprets the core content of this standard, aiming to promote its dissemination, implementation, and practical applications.

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

AIM:This study aims to investigate the effects of baicalin on the hypoxia-inducible factor-1α(HIF-1α)/solute carrier family 7 member 11(SLC7A11)/glutathione peroxidase 4(GPX4)axis and the ferroptosis induced by oxidized low-density lipoprotein(ox-LDL)in RAW264.7 macrophage-derived foam cells.METHODS:RAW264.7 cells were categorized into five groups:control,ox-LDL,baicalin+ox-LDL,ferrostatin-1(Fer-1;ferroptosis inhibitor)+ox-LDL,and baicalin+Fer-1+ox-LDL.To induce foam cell formation,RAW264.7 macrophages were exposed to 100 μg/mL ox-LDL for 24 h.Oil red O staining was employed to visualize lipid droplet formation in each group.The ultrastructure of the mitochondria was examined using transmission electron microscopy.Fluorescence microscopy was utilized to assess the fluorescence intensity of intracellular reactive oxygen species(ROS),lipid peroxides,and Fe2+.A colorimetric assay facilitated the measurement of malondialdehyde(MDA)and glutathione(GSH)levels.Additionally,Western blot analy-sis was conducted to quantify protein levels of HIF-1α,SLC7A11,and GPX4.RESULTS:The model group exhibited foam cell formation,abundant lipid droplets,significant swelling of mitochondrial structures,and observable shortening or disappearance of cristae.There was a marked increase in intracellular fluorescence intensity of ROS,lipid peroxides,and Fe2+,alongside elevated MDA levels and decreased GSH levels.HIF-1α protein expression was significantly increased,while SLC7A11 and GPX4 protein expressions were notably decreased(P<0.05).In comparison to the model group,both the baicalin+ox-LDL and Fer-1+ox-LDL groups demonstrated a significant reduction in lipid droplets,improved mitochon-drial structures,decreased fluorescence intensity of ROS,lipid peroxides,and Fe2+,as well as lower MDA levels and higher GSH levels.Additionally,HIF-1α expression significantly decreased,while SLC7A11 and GPX4 expressions sig-nificantly increased(P<0.05).Furthermore,the baicalin+Fer-1+ox-LDL group showed a more pronounced reduction in lipid droplets,near-normal mitochondrial structures,lower fluorescence intensity of ROS,lipid peroxides,and Fe2+,de-creased MDA levels,and increased GSH levels compared to the baicalin+ox-LDL group;HIF-1α,SLC7A11,and GPX4 protein expressions were also significantly reduced(P<0.05).CONCLUSION:Baicalin modulates the HIF-1α/SLC7A11/GPX4 axis,thereby inhibiting ox-LDL-induced ferroptosis in macrophage-derived foam cells.

Objective:To explore the effects of proton FLASH irradiation (FLASH-IR) and conventional irradiation (CONV-IR) on the cell cycle, apoptosis, and pyroptosis of renal cancer cells.Methods:Renal cancer cells (769-P) were irradiated with 8 Gy of protons at a dose rate of 40 Gy/s for FLASH-IR and 0.4 Gy/s for CONV-IR, Ctrl group was treated without irradiation. Cells were collected 24 h after irradiation. The changes in the cell cycle were measured using flow cytometry. The expression of genes and proteins related to the cell cycle, apoptosis, and pyroptosis signaling pathways in renal cancer cells was measured using quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot.Results:Proton FLASH-IR increased the proportion of renal cancer cells in the G 0/G 1 phase [FLASH-IR group vs. Ctrl group, (67.01±0.44)% vs. (38.68±0.63)%, t = -63.99, P<0.05], while CONV-IR increased the proportion of renal cancer cells in the G 2/M phase [CONV-IR group vs. Ctrl group, (56.65±1.52)% vs. (23.67±0.51)%, t = -29.17, P<0.05]. Both proton FLASH-IR and CONV-IR caused apoptosis of renal cancer cells ( tFLASH= -16.24 to -5.01, P <0.05; tCONV=-20.08 to 6.11, P < 0.05) and CONV-IR activated the P53/P21 pathway ( t = -16.86 to -9.74, P < 0.05). Both proton FLASH-IR and CONV-IR induced pyroptosis of renal cancer cells ( tFLASH= -23.36 to 20.18, P <0.05; tCONV=-41.62 to 13.95, P <0.05), and the former exhibited a greater effect (FLASH-IR group vs. CONV-IR group, 0.96±0.01 vs. 0.68±0.44, t = -10.46, P <0.05). Conclusions:Both proton FLASH-IR and CONV-IR bring about changes in the cell cycle of renal cancer, promoting apoptosis and pyroptosis. However, there are differences between the two mechanisms that require further exploration. Proton FLASH-IR holds promise for the treatment of renal cancer.

Objective To investigate the effect of splenectomy on the repair of full-thickness skin tissue defects,as well as the impact of different recovery times after splenectomy on the healing of skin tissue defects.Methods According to a random number table,39 8-week-old female C57 mice were randomly divided into three groups:sham surgery group(sham group,n=13),splenectomy group with 3 days of recovery(Spx3d group,n=13),and splenectomy group with 3 weeks of recovery(Spx3w group,n=13).Full-thickness skin defects were created on the backs of the mice in each group.The wound healing conditions at different times after skin defects were observed,and the wound healing rates after the injury were calculated.Peripheral blood cell analysis was performed on day 14 after the defect,and tissue samples from the wound area were taken for hematoxylin and eosin(HE)staining to observe the granulation tissue thickness at the defect site and the re-epithelialization rate.Masson's trichrome staining was used to observe the proportion of collagen fibers.Results After splenectomy and sham surgery,the mice recovered well without significant discomfort.From 1 to 14 days after the skin defect modeling,the wound areas of the mice in all three groups gradually decreased.Compared with sham group,the wound areas were smaller in Spx3d and Spx3w groups at 3,5 and 7 days after the injury,and the differences were statistically significant(P<0.05).The wound healing rates were also significantly higher(P<0.05).Moreover,at 3 days and 5 days after the injury,the wound healing rates of Spx3d group were significantly higher than those of Spx3w group(P<0.05 or P<0.01).The peripheral blood white blood cell(WBC)count in Spx3w group was significantly higher than that in sham group and Spx3d group(P<0.01).The platelet counts in both sham group and Spx3w group were significantly higher than that in Spx3d group(P<0.05).Additionally,the lymphocyte and neutrophil counts in Spx3w group were markedly higher than those in sham group(P<0.05).No statistically significant differences in red blood cell(RBC)counts were observed among the three groups(P>0.05).HE staining results showed that compared with sham group,the wound healing of the mice in Spx3d and Spx3w groups were better,and the thickness of the granulation tissue in Spx3d group were better than that in Spx3w group.At 7 days,the thickness of the granulation tissue in Spx3d and Spx3w groups was significantly higher than that in sham group(P<0.01,P<0.05)and the re-epithelialization rate in Spx3d group was significantly higher than that in sham group and Spx3w group(P<0.05).At 14 days,the re-epithelialization rates of Spx3d and Spx3w groups were significantly higher than those of sham group(P<0.05).The results of Masson's staining showed that the collagen fiber proportion in the wounds of Spx3d group at 7 and 14 days and that of Spx3w group at 14 days were significantly higher than that in sham group(P<0.05).Conclusion The healing of skin defects in mice is accelerated after splenectomy,and the recovery time after splenectomy has a certain effect on the healing of skin defects.

Objective:To explore screening pathways and practical implementation strategies for primary care disease groups un-der the Diagnosis-Intervention Packet(DIP)payment.Methods:Matching and expert consultation methods were used to select primary care conditions,and experts included DIP National Steering Group experts,DIP experts from a sample municipal health-care security bureau,health policy researchers,coders from a tertiary hospital in Beijing,and big data engineers.Results:The DIP primary disease of"conservative treatment groups"in primary and secondary medical institutions were 104 and 105,repective-ly.The DIP primary disease of"primary can be completed groups"were 74 and 171,respectively.The final number of primary diseases in primary and secondary hospital was determined to be 178 and 276,respectively.Conclusions:The number of primary care disease groups varies from place to place,but it still needs to be dynamically adjusted and optimized in conjunction with big data methods and expert consultation,evaluated and corrected in a timely manner to ensure scientificity and effectiveness.The pri-mary care disease groups implement"same price for the same disease"across different levels of medical institutions,eliminating the differentiation of medical institution grade coefficients to promote hierarchical diagnosis and treatment.Cost-value measurement of disease group,scientific development of payment criteria for disease group,lack of regulatory tools for big data,and high sets of codes are key barriers to primary care implementation.

Objective:To explore screening pathways and practical implementation strategies for primary care disease groups un-der the Diagnosis-Intervention Packet(DIP)payment.Methods:Matching and expert consultation methods were used to select primary care conditions,and experts included DIP National Steering Group experts,DIP experts from a sample municipal health-care security bureau,health policy researchers,coders from a tertiary hospital in Beijing,and big data engineers.Results:The DIP primary disease of"conservative treatment groups"in primary and secondary medical institutions were 104 and 105,repective-ly.The DIP primary disease of"primary can be completed groups"were 74 and 171,respectively.The final number of primary diseases in primary and secondary hospital was determined to be 178 and 276,respectively.Conclusions:The number of primary care disease groups varies from place to place,but it still needs to be dynamically adjusted and optimized in conjunction with big data methods and expert consultation,evaluated and corrected in a timely manner to ensure scientificity and effectiveness.The pri-mary care disease groups implement"same price for the same disease"across different levels of medical institutions,eliminating the differentiation of medical institution grade coefficients to promote hierarchical diagnosis and treatment.Cost-value measurement of disease group,scientific development of payment criteria for disease group,lack of regulatory tools for big data,and high sets of codes are key barriers to primary care implementation.

AIM:This study aims to investigate the effects of baicalin on the hypoxia-inducible factor-1α(HIF-1α)/solute carrier family 7 member 11(SLC7A11)/glutathione peroxidase 4(GPX4)axis and the ferroptosis induced by oxidized low-density lipoprotein(ox-LDL)in RAW264.7 macrophage-derived foam cells.METHODS:RAW264.7 cells were categorized into five groups:control,ox-LDL,baicalin+ox-LDL,ferrostatin-1(Fer-1;ferroptosis inhibitor)+ox-LDL,and baicalin+Fer-1+ox-LDL.To induce foam cell formation,RAW264.7 macrophages were exposed to 100 μg/mL ox-LDL for 24 h.Oil red O staining was employed to visualize lipid droplet formation in each group.The ultrastructure of the mitochondria was examined using transmission electron microscopy.Fluorescence microscopy was utilized to assess the fluorescence intensity of intracellular reactive oxygen species(ROS),lipid peroxides,and Fe2+.A colorimetric assay facilitated the measurement of malondialdehyde(MDA)and glutathione(GSH)levels.Additionally,Western blot analy-sis was conducted to quantify protein levels of HIF-1α,SLC7A11,and GPX4.RESULTS:The model group exhibited foam cell formation,abundant lipid droplets,significant swelling of mitochondrial structures,and observable shortening or disappearance of cristae.There was a marked increase in intracellular fluorescence intensity of ROS,lipid peroxides,and Fe2+,alongside elevated MDA levels and decreased GSH levels.HIF-1α protein expression was significantly increased,while SLC7A11 and GPX4 protein expressions were notably decreased(P<0.05).In comparison to the model group,both the baicalin+ox-LDL and Fer-1+ox-LDL groups demonstrated a significant reduction in lipid droplets,improved mitochon-drial structures,decreased fluorescence intensity of ROS,lipid peroxides,and Fe2+,as well as lower MDA levels and higher GSH levels.Additionally,HIF-1α expression significantly decreased,while SLC7A11 and GPX4 expressions sig-nificantly increased(P<0.05).Furthermore,the baicalin+Fer-1+ox-LDL group showed a more pronounced reduction in lipid droplets,near-normal mitochondrial structures,lower fluorescence intensity of ROS,lipid peroxides,and Fe2+,de-creased MDA levels,and increased GSH levels compared to the baicalin+ox-LDL group;HIF-1α,SLC7A11,and GPX4 protein expressions were also significantly reduced(P<0.05).CONCLUSION:Baicalin modulates the HIF-1α/SLC7A11/GPX4 axis,thereby inhibiting ox-LDL-induced ferroptosis in macrophage-derived foam cells.

Objective:To explore the effects of proton FLASH irradiation (FLASH-IR) and conventional irradiation (CONV-IR) on the cell cycle, apoptosis, and pyroptosis of renal cancer cells.Methods:Renal cancer cells (769-P) were irradiated with 8 Gy of protons at a dose rate of 40 Gy/s for FLASH-IR and 0.4 Gy/s for CONV-IR, Ctrl group was treated without irradiation. Cells were collected 24 h after irradiation. The changes in the cell cycle were measured using flow cytometry. The expression of genes and proteins related to the cell cycle, apoptosis, and pyroptosis signaling pathways in renal cancer cells was measured using quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot.Results:Proton FLASH-IR increased the proportion of renal cancer cells in the G 0/G 1 phase [FLASH-IR group vs. Ctrl group, (67.01±0.44)% vs. (38.68±0.63)%, t = -63.99, P<0.05], while CONV-IR increased the proportion of renal cancer cells in the G 2/M phase [CONV-IR group vs. Ctrl group, (56.65±1.52)% vs. (23.67±0.51)%, t = -29.17, P<0.05]. Both proton FLASH-IR and CONV-IR caused apoptosis of renal cancer cells ( tFLASH= -16.24 to -5.01, P <0.05; tCONV=-20.08 to 6.11, P < 0.05) and CONV-IR activated the P53/P21 pathway ( t = -16.86 to -9.74, P < 0.05). Both proton FLASH-IR and CONV-IR induced pyroptosis of renal cancer cells ( tFLASH= -23.36 to 20.18, P <0.05; tCONV=-41.62 to 13.95, P <0.05), and the former exhibited a greater effect (FLASH-IR group vs. CONV-IR group, 0.96±0.01 vs. 0.68±0.44, t = -10.46, P <0.05). Conclusions:Both proton FLASH-IR and CONV-IR bring about changes in the cell cycle of renal cancer, promoting apoptosis and pyroptosis. However, there are differences between the two mechanisms that require further exploration. Proton FLASH-IR holds promise for the treatment of renal cancer.