High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

OBJECTIVES: To investigate the therapeutic mechanism of Huoxue Shufeng Granules (HXSFG) for alleviating central sensitization in a mouse model of chronic migraine (CM). METHODS: We analyzed the main chemical components of HXSFG through literature review and explored their pharmacological mechanisms by bioinformatics analyses. In a male C57BL/6J mouse model of CM established by intraperitoneal injections of nitroglycerin (10 mg/kg) every other day (5 injections), the effects of gavage with low, and high doses of HXSFG or intraperitoneal injections of topiramate for ameliorating central sensitization were evaluated using Von Frey test and a hot plate apparatus; the changes in expressions of inflammatory factors, the proteins in the TLR4/NF‑κB signaling pathway, and activation of c-Fos and CGRP were detected using RT-qPCR, Western blotting and immunofluorescence staining. RESULTS: Network pharmacology analysis suggested that the main active components in HXSFG for alleviating CM included formononetin, paeoniflorin, quercetin, and tanshinone. Gene Ontology (GO) enrichment analysis identified 492 GO entries, comprising 366 biological processes, 46 cellular components, and 80 molecular functions. KEGG pathway enrichment analysis indicated that the Toll-like receptor and NF‑κB signaling pathways were crucial in mediating the therapeutic effects of HXSFG on CM. In the mouse models of CM, both topiramate and HXSFG treatments alleviated the symptoms of central sensitization, evidenced by improved mechanical and thermal pain thresholds in the mice. HXSFG significantly reduced the expression of c-Fos and CGRP, improved inflammatory markers, and downregulated the expressions of TLR4, p-NF‑κB, IL-1β, and TNF‑α proteins in the mouse models. CONCLUSIONS HXSFG effectively alleviates central sensitization in CM mice by modulating the inflammatory pathways and inhibiting the TLR4/ NF-κB signaling pathway, suggesting its potential as a therapeutic option for CM.
Animals ; Toll-Like Receptor 4/metabolism* ; NF-kappa B/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Mice ; Male ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Migraine Disorders/metabolism* ; Disease Models, Animal ; Inflammation

OBJECTIVES: To investigate the mechanisms of Modified Chaihu Guizhi Decoction (MCGD) for ameliorating anxiety- and depression-like behaviors in a mouse model of chronic unpredictable mild stress (CUMS). METHODS: The main chemical constituents of MCGD were identified through literature review, and network pharmacology analysis was performed to predict the potential pharmacological mechanisms of MCGD. For in vivo validation, male C57BL/6J mice were randomized into control group, CUMS model group, fluoxetine (FLX) treatment group, and low- and high-dose MCGD treatment groups (n=15), and in all but the control group, CUMS models were established by daily exposure to two randomized stressors for 28 consecutive days. Starting from 3 days prior to modeling, MCGD and fluoxetine treatments were administered daily via gavage and intraperitoneal injection, respectively. Depression- and anxiety-like behaviors of the mice were assessed using sucrose preference test, forced swim test, open field test and elevated plus maze test. The changes in mRNA expressions of the clock genes and inflammatory markers and expressions of the JAK2/STAT3 signaling proteins were detected using RT-qPCR and Western blotting, and immunofluorescence staining was used to detect microglia activation in the mice. RESULTS: The key active compounds in MCGD identified by network pharmacology analysis included quercetin, acacetin, formononetin, nobiletin, and baicalein. GO analysis identified 607 enriched pathways, and KEGG pathway enrichment revealed significant involvement of the JAK2/STAT3 and NF-κB signaling pathways. In the mouse models of CUMS, treatment with both fluoxetine and MCGD significantly alleviated anxiety- and depression-like behaviors. MCGD treatment significantly reduced Iba1 expression, improved the inflammatory markers, reversed the decrease in clock gene circadian rhythm amplitude, and obviously downregulated the expressions of JAK2, p-STAT3, p-NF-κB, IL-1β, and IL-6 proteins. CONCLUSIONS MCGD effectively alleviates anxiety- and depression-like behaviors in CUMS mice by modulating the inflammatory pathways and inhibiting the JAK2/STAT3 signaling pathway.
Animals ; Janus Kinase 2/metabolism* ; STAT3 Transcription Factor/metabolism* ; Signal Transduction/drug effects* ; Depression/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Male ; Mice, Inbred C57BL ; Anxiety/drug therapy* ; Stress, Psychological ; Disease Models, Animal

Objective:To explore the application value of three-dimensional visualization reconstruction technology in robot-assisted laparoscopic partial nephrectomy（RAPN）for the treatment of highly complex（R.E.N.A.L. score≥10）renal hilar tumors.Methods:The clinical data of 87 patients with highly complex renal hilar tumors with R.E.N.A.L. scores ≥10 who were treated in First Affiliated Hospital of Nanchang University from January 2021 to December 2024 were retrospectively analyzed，of which 36 underwent 3D visualization reconstruction and 51 underwent conventional CT. The 3D visualization reconstruction method was to import the patient’s enhanced CT images in DICOM format into the 3D reconstruction image data processing software to produce a 3D visualization model. There were 22 males and 14 females in the 3D visualization group，with an average age of（54.2 ± 9.5）years，a body mass index of（24.8 ± 4.5）kg/m 2，and a tumor size of（4.3 ± 1.0）cm. Tumors were located on the left side in 16 cases and on the right side in 20 cases. Tumor stages were classified as T 1a in 11 cases，T 1b in 21 cases，and T 2a in 4 cases. The R.E.N.A.L. scores were distributed as follows：10 points in 21 cases，11 points in 12 cases，and 12 points in 3 cases. The estimated glomerular filtration rate（eGFR）before operation was（78.2±9.6）ml/（min·1.73 m 2）. There were 35 males and 16 females in the conventional CT group，with an average age of（51.3±8.9）years，a body mass index of（25.4 ± 3.9）kg/m 2，and a tumor size of（4.1 ± 1.2）cm. Tumors were located on the left side in 25 cases and on the right side in 26 cases. Tumor stages were classified as T 1a in 12 cases，T 1b in 33 cases，and T 2a in 6 cases. The R.E.N.A.L. scores were distributed as follows：10 points in 31 cases，11 points in 18 cases，and 12 points in 2 cases . The preoperative eGFR was（80.6 ± 8.8）ml/（min·1.73 m 2）. There was no statistical difference in general data and preoperative renal function between the two groups（ P > 0.05）. Both groups underwent RAPN. The two groups were analyzed and compared in terms of operation time，warm ischemia time，intraoperative blood loss，postoperative hospital stay，postoperative complications，and changes in renal function 3 months after surgery. Results:There were no cases of conversion to radical treatment or open surgery in both the 3D visualization group and the conventional CT group. The 3D visualization group had shorter operation time［（94.6 ± 18.5）min vs.（110.2 ± 17.2）min， P < 0.001］，shorter renal artery occlusion time［（23.3 ± 4.0）min vs.（27.2 ± 3.3）min， P < 0.001］，less intraoperative blood loss［120（100，250）ml vs. 150（120，300）ml， P = 0.018］，and a lower proportion of intraoperative collecting system incision（19/36 vs. 38/51， P = 0.042）than the conventional CT group. There was no significant statistical difference in the time of postoperative drainage tube removal and postoperative hospital stay between the two groups（ P > 0.05）. One case in the 3D visualization group had postoperative fever，and two cases in the conventional CT group had postoperative obvious macroscopic hematuria. Postoperative pathological diagnosis of the patients was clear cell carcinoma in 78 cases，papillary cell carcinoma in 6 cases，chromophobe cell carcinoma in 2 cases，and oncocytoma in 1 case. No positive resection margin was found in both groups. Three months after surgery，there was no significant statistical difference in eGFR between the two groups［（70.6 ± 8.5）ml/（min·1.73 m 2）vs.（71.4 ± 9.2）ml/（min·1.73 m 2）， P = 0.681］. During the median follow-up of 17.8 months，no tumor recurrence or metastasis was observed in either group. Conclusions:RAPN has good safety and feasibility in the treatment of highly complex（R.E.N.A.L. score ≥10）renal hilar tumors. Preoperative three-dimensional visualization reconstruction technology helps to reduce RAPN operation time，renal artery occlusion time and intraoperative blood loss，and has good clinical application value.

Malnutrition is one of the main complications for gastric cancer patients, with an incidence rate as high as 65% to 85%, severely affecting their quality of life and survival rate. This issue is particularly prominent during out-of-hospital treatment, as patients often lack nutritional knowledge and do not receive continuous nutritional management. Therefore, ensuring that patients continue to receive effective nutritional management after discharge is crucial. This study explored three primary models of nutritional management for gastric cancer patients after discharge: the multidisciplinary team collaboration model, three-level nutritional management model, and the Internet+ model. It also analyzed the shortcomings and challenges these models face in practice, with the aim of providing a reference for clinical work.

Objective:To explore the application value of three-dimensional visualization reconstruction technology in robot-assisted laparoscopic partial nephrectomy（RAPN）for the treatment of highly complex（R.E.N.A.L. score≥10）renal hilar tumors.Methods:The clinical data of 87 patients with highly complex renal hilar tumors with R.E.N.A.L. scores ≥10 who were treated in First Affiliated Hospital of Nanchang University from January 2021 to December 2024 were retrospectively analyzed，of which 36 underwent 3D visualization reconstruction and 51 underwent conventional CT. The 3D visualization reconstruction method was to import the patient’s enhanced CT images in DICOM format into the 3D reconstruction image data processing software to produce a 3D visualization model. There were 22 males and 14 females in the 3D visualization group，with an average age of（54.2 ± 9.5）years，a body mass index of（24.8 ± 4.5）kg/m 2，and a tumor size of（4.3 ± 1.0）cm. Tumors were located on the left side in 16 cases and on the right side in 20 cases. Tumor stages were classified as T 1a in 11 cases，T 1b in 21 cases，and T 2a in 4 cases. The R.E.N.A.L. scores were distributed as follows：10 points in 21 cases，11 points in 12 cases，and 12 points in 3 cases. The estimated glomerular filtration rate（eGFR）before operation was（78.2±9.6）ml/（min·1.73 m 2）. There were 35 males and 16 females in the conventional CT group，with an average age of（51.3±8.9）years，a body mass index of（25.4 ± 3.9）kg/m 2，and a tumor size of（4.1 ± 1.2）cm. Tumors were located on the left side in 25 cases and on the right side in 26 cases. Tumor stages were classified as T 1a in 12 cases，T 1b in 33 cases，and T 2a in 6 cases. The R.E.N.A.L. scores were distributed as follows：10 points in 31 cases，11 points in 18 cases，and 12 points in 2 cases . The preoperative eGFR was（80.6 ± 8.8）ml/（min·1.73 m 2）. There was no statistical difference in general data and preoperative renal function between the two groups（ P > 0.05）. Both groups underwent RAPN. The two groups were analyzed and compared in terms of operation time，warm ischemia time，intraoperative blood loss，postoperative hospital stay，postoperative complications，and changes in renal function 3 months after surgery. Results:There were no cases of conversion to radical treatment or open surgery in both the 3D visualization group and the conventional CT group. The 3D visualization group had shorter operation time［（94.6 ± 18.5）min vs.（110.2 ± 17.2）min， P < 0.001］，shorter renal artery occlusion time［（23.3 ± 4.0）min vs.（27.2 ± 3.3）min， P < 0.001］，less intraoperative blood loss［120（100，250）ml vs. 150（120，300）ml， P = 0.018］，and a lower proportion of intraoperative collecting system incision（19/36 vs. 38/51， P = 0.042）than the conventional CT group. There was no significant statistical difference in the time of postoperative drainage tube removal and postoperative hospital stay between the two groups（ P > 0.05）. One case in the 3D visualization group had postoperative fever，and two cases in the conventional CT group had postoperative obvious macroscopic hematuria. Postoperative pathological diagnosis of the patients was clear cell carcinoma in 78 cases，papillary cell carcinoma in 6 cases，chromophobe cell carcinoma in 2 cases，and oncocytoma in 1 case. No positive resection margin was found in both groups. Three months after surgery，there was no significant statistical difference in eGFR between the two groups［（70.6 ± 8.5）ml/（min·1.73 m 2）vs.（71.4 ± 9.2）ml/（min·1.73 m 2）， P = 0.681］. During the median follow-up of 17.8 months，no tumor recurrence or metastasis was observed in either group. Conclusions:RAPN has good safety and feasibility in the treatment of highly complex（R.E.N.A.L. score ≥10）renal hilar tumors. Preoperative three-dimensional visualization reconstruction technology helps to reduce RAPN operation time，renal artery occlusion time and intraoperative blood loss，and has good clinical application value.

Malnutrition is one of the main complications for gastric cancer patients, with an incidence rate as high as 65% to 85%, severely affecting their quality of life and survival rate. This issue is particularly prominent during out-of-hospital treatment, as patients often lack nutritional knowledge and do not receive continuous nutritional management. Therefore, ensuring that patients continue to receive effective nutritional management after discharge is crucial. This study explored three primary models of nutritional management for gastric cancer patients after discharge: the multidisciplinary team collaboration model, three-level nutritional management model, and the Internet+ model. It also analyzed the shortcomings and challenges these models face in practice, with the aim of providing a reference for clinical work.

Objective:To explore the independent risk factors for bleeding in patients following percutaneous liver biopsy examination.Methods:The clinicopathological data of patients who underwent percutaneous liver biopsy examination at Nanjing Second Hospital from January 2012 to December 2021 were retrospectively collected. Univariate and multivariate logistic regression analysis were used to investigate the effect of age, gender, lesion type (diffuse liver parenchymal lesions, focal liver lesions), number of biopsies, tissue length, presence or absence of cirrhosis, presence or absence of portosystemic shunt, erythrocytes, white blood cells, hemoglobin, platelets, prothrombin time, fibrinogen, international normalized ratio, and liver biochemical indicators on bleeding following liver biopsy, as well as to screen independent risk factors.Results:A total of 3 331 patients were examined by percutaneous liver biopsy, and 3 060 cases were actually included by excluding 271 cases who took consultation from other hospitals. The overall postoperative hemorrhagic rate was 1.6% (49/3 060). Of which, forty-four cases (1.4%) had overt bleeding (hemodynamic changes or hemoglobin decreased by more than 20 g/L), five cases (0.2%) had minor bleeding, three cases had subcapsular hepatic hemaotma, and two cases had local bleeding from liver biopsy. Among the overt bleeding cases, two cases were in the off-label group (platelet<50×10 9/L or international normalized ratio>1.5), and the rest were in the non-off-label group. The results of univariate analysis showed that factors such as focal liver lesions, portosystemic shunt, prolonged prothrombin time, increased international normalized ratio, bilirubin, and alkaline phosphatase were associated with bleeding after liver biopsy in the non-off-label group. The multivariate collinearity diagnosis revealed statistically significant differences for the indicators. Multivariate logistic regression analysis finally included factors such as lesion type, portosystemic shunt, international normalized ratio, total bilirubin, and alkaline phosphatase. The results showed that patients with focal liver lesions were more prone to bleed after surgery than patients with diffuse liver parenchymal lesions ( OR=3.396, P=0.002, 95% CI: 1.596-7.228). Patients with portosystemic shunt were more prone to bleed than those without portosystemic shunt ( OR=3.301, P=0.018, 95% CI: 1.232-8.845). Patients were more likely to experience bleeding following liver biopsy when their total bilirubin levels were elevated ( OR=1.006, P<0.001, 95% CI:1.003-1.008). Conclusion:Focal liver lesions, portosystemic shunts, and elevated total bilirubin are independent risk factors for bleeding after percutaneous liver biopsy.

Objective:To explore the efficacy of long intramedullary nails versus short intramedullary nails in the treatment of AO/OTA 31-A3 intertrochanteric fractures.Methods:A retrospective analysis was conducted on 60 patients with AO/OTA 31-A3 intertrochanteric femur fractures treated between March 2019 and August 2022. The patients were randomly divided into two groups (the long nail group and the short nail group). Thirty-four patients were treated with long intramedullary nails, including 16 males and 18 females, aged 68.41±17.84 years old (range 31-96 years). Twenty-six patients were treated with short intramedullary nails, including 13 males and 13 females, aged 72.23±13.97 years old (range 31-90 years). The causes of injury, fracture classification (AO/OTA classification), intraoperative blood loss, operation time, fracture healing time, imaging indexes (fracture reduction quality, postoperative neck trunk angle, and medial support), Harris score of the hip joint at the last follow-up, one-year mortality rates and complications were compared between the two groups.Results:The follow-up time was 24.26±6.67 months in the long nail group and 24.31±5.60 months in the short nail group, and the general information of the two groups were comparable. Between the long nail and short nail group, the intraoperative blood loss was 281.47±235.28 ml vs. 121.92±84.14 ml and the operation time was 110.44±24.63 min vs. 81.15±28.54 min with significant differences ( P<0.05). While the length of hospital stay was 12.35±4.81 d vs. 10.89±4.30 d, the good rate of fracture reduction was 55.9% vs. 61.53%, the fracture healing time was 120.44±16.43 d vs. 128.07±18.33 d, the presence rate of medial support was 67.6% vs. 79.4%, and the excellent rate of Harris score was 65.4% vs. 65.4% with no significant difference between the two groups ( P>0.05). One-year mortality rates was 5.3% vs. 7.1% and complications was 11.7% vs. 15.4% with no significant difference between the two groups ( P>0.05). Conclusion:Both long intramedullary nails and short intramedullary nails are effective in the treatment of AO/OTA 31-A3 intertrochanteric femur fractures. However, surgical time and intraoperative blood loss was less in the short nail group.