1.Long-term survival outcomes and prognostic factors following radical resection of pancreatic body and tail cancer:a retrospective analysis of 992 patients
Dong XU ; Yang WU ; Kai ZHANG ; Nan LYU ; Qianqian WANG ; Pengfei WU ; Jie YIN ; Baobao CAI ; Guodong SHI ; Jianzhen LIN ; Yazhou WANG ; Lingdi YIN ; Zipeng LU ; Min TU ; Jianmin CHEN ; Feng GUO ; Jishu WEI ; Junli WU ; Wentao GAO ; Cuncai DAI ; Yi MIAO ; Kuirong JIANG
Chinese Journal of Surgery 2026;64(1):46-54
Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.
2.Long-term survival outcomes and prognostic factors following radical resection of pancreatic body and tail cancer:a retrospective analysis of 992 patients
Dong XU ; Yang WU ; Kai ZHANG ; Nan LYU ; Qianqian WANG ; Pengfei WU ; Jie YIN ; Baobao CAI ; Guodong SHI ; Jianzhen LIN ; Yazhou WANG ; Lingdi YIN ; Zipeng LU ; Min TU ; Jianmin CHEN ; Feng GUO ; Jishu WEI ; Junli WU ; Wentao GAO ; Cuncai DAI ; Yi MIAO ; Kuirong JIANG
Chinese Journal of Surgery 2026;64(1):46-54
Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.
3.Proteomic Profiling of Qi-blood Deficiency vs Damp-heat Syndrome in Colorectal Cancer: Therapeutic Targeting by Astragaloside IV-berberine
Zhao-Huan LI ; Jing-Wen ZHAO ; Xin ZHANG ; Jian-Jin GUO ; Jie XU ; Zeng-Qiang YANG ; Hao TU ; Min ZOU ; Ming-Bin GUI ; Feng GAO
Progress in Biochemistry and Biophysics 2026;53(9):2462-2479
ObjectiveColorectal cancer (CRC) is a highly heterogeneous malignancy, and traditional Chinese medicine (TCM) syndrome differentiation is widely used in its clinical management. However, the biological basis underlying different TCM syndromes remains insufficiently understood. This study aimed to investigate the proteomic differences between qi-blood deficiency syndrome (QBDS) and damp-heat syndrome (DHS) in CRC patients and to establish a “syndrome-differential protein-herbal component” network for exploring potential molecular mechanisms and therapeutic targets associated with syndrome-specific treatment strategies. MethodsTumor tissue samples were collected from 10 patients with pathologically confirmed CRC, including 5 patients diagnosed with QBDS and 5 with DHS according to standardized TCM syndrome differentiation criteria. Tandem mass tag (TMT)-based quantitative proteomics was employed to identify differentially expressed proteins (DEPs) between the two syndrome groups. Functional enrichment analyses, including Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, were performed to characterize the biological functions and signaling pathways associated with the identified DEPs. Least absolute shrinkage and selection operator (LASSO) regression analysis was further applied to screen key syndrome-related proteins and construct a core protein prediction model. Subsequently, molecular docking was conducted to evaluate the binding affinities between representative herbal compounds, astragaloside IV and berberine, and the identified core proteins. Finally, cell counting kit-8 (CCK-8) assays were performed in HCT 116 and HT-29 colorectal cancer cell lines to validate the anti-proliferative activities of these compounds in vitro. ResultsA total of 44 DEPs were identified between QBDS and DHS tissues, including 21 upregulated and 23 downregulated proteins in the QBDS group relative to the DHS group. Functional enrichment analyses revealed that these proteins were primarily associated with antiviral immune responses, regulation of inflammatory signaling, NF‑κB signaling pathways, cholesterol metabolism, and other biological processes relevant to tumor progression and host immune regulation. LASSO regression analysis identified eight core proteins with potential syndrome-specific significance. Among them, ST7, GPCPD1, and PODXL were closely associated with QBDS, whereas FAT1, GRB7, KRT7, MAFF, and MMP8 were associated with DHS. Molecular docking demonstrated favorable interactions between astragaloside IV and QBDS-related proteins, with binding energies lower than -5 kcal/mol, indicating stable binding activity. Berberine exhibited even lower binding energies and stronger binding specificity toward DHS-related core proteins. In vitro experiments further confirmed that both compounds inhibited CRC cell proliferation, while berberine displayed significantly greater anti-proliferative efficacy. The lowest 48 h IC50 value of berberine reached 15.21 mg/L in CRC cells, indicating a stronger growth-inhibitory effect than astragaloside IV. ConclusionCRC patients with QBDS and DHS exhibit distinct proteomic characteristics, suggesting that different TCM syndromes possess unique molecular signatures. The identified core proteins may serve as potential biomarkers for syndrome differentiation, while astragaloside IV and berberine may exert therapeutic effects through targeting syndrome-specific molecular networks. These findings provide preliminary proteomic evidence supporting syndrome-guided precision integrative medicine in CRC and offer new insights into the biological basis of TCM syndrome differentiation and individualized therapeutic strategies.
4.Prokaryotic expression, purification and immunogenicity of SARS-CoV-2 omicron variant nucleocapsid protein.
Zewen TU ; Quansheng WANG ; Shiguo LIU ; Haosen LIU ; Chunyan ZENG ; Juanjuan XIE ; Mingzhi LI ; Jingcai LI ; Min WANG ; Shiqi WENG ; Lumei KANG ; Lingbao KONG
Chinese Journal of Cellular and Molecular Immunology 2025;41(8):735-743
Objective The study aims to investigate the immunological functions of the nucleocapsid (N) protein of the novel coronavirus Omicron (BA.1, BA.2) and evaluate the differences among different N proteins of mutant strains in immunogenicity. Methods By aligning sequences, the mutation sites of the Omicron (BA.1, BA.2) N protein relative to prototype strain of the novel coronavirus (Wuhan-Hu-1) were determined. The pET-28a-N-Wuhan-Hu-1 plasmid was used as template to construct pET-28a-BA.1/BA.2-N through single point mutation or homologous recombination. The three kinds of N protein were expressed in prokaryotic system, purified through Ni-NTA affinity chromatography, and then immunized into mice. The titer and reactivity of the polyclonal antibody, as well as the expression level of IL-1β and IFN-γ in mouse spleen cells, were detected using indirect ELISA and Western blot assay. Results The constructed prokaryotic expression plasmids were successfully used to express the Wuhan-Hu-1 N, BA.1 N, and BA.2 N proteins in E.coli BL21(DE3) at 37 DegreesCelsius for 4 hours. The indirect ELISA test showed that the titers of polyclonal antibody prepared by three N proteins were all 1:51 200. All three N proteins can increase the expression of IFN-γ and IL-1β cytokines, but the effect of Omicron N protein in activing two cytokines was more obvious than that of Wuhan-Hu-1 N protein. Conclusion The study obtained three new coronavirus N proteins and polyclonal antibodies, and confirmed that mutations in the amino acid sites of the N protein can affect its immunogenicity. This provides a basis for developing rapid diagnostic methods targeting N protein of different novel coronavirus variants.
Animals
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Mice
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SARS-CoV-2/genetics*
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Coronavirus Nucleocapsid Proteins/immunology*
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Nucleocapsid Proteins/isolation & purification*
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COVID-19/immunology*
;
Antibodies, Viral/immunology*
;
Mice, Inbred BALB C
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Interferon-gamma/metabolism*
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Interleukin-1beta/metabolism*
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Female
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Escherichia coli/metabolism*
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Mutation
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Humans
5.Reconstruction of lacunar bone defect caused by giant cell tumor of the distal femur with a 3D printed modular supporting prosthesis
Minxun LU ; Linyun TAN ; Xin HU ; Zihan PENG ; Zhuangzhuang LI ; Wacili DA ; Xuanhong HE ; Weiyi WANG ; Yitian WANG ; Yi LUO ; Chongqi TU ; Li MIN
Chinese Journal of Orthopaedics 2025;45(10):686-692
Objective:To observe the early clinical efficacy of 3D-printed modular supporting prosthesis for reconstruction of lacunar bone defect caused by giant cell tumor of the distal femur.Methods:From May 2018 to July 2023, a total of 9 patients with giant cell tumor of the distal femur were treated with 3D-printed modular supporting prosthesis to reconstruct lacunar bone defects in the Department of Orthopedics, West China Hospital, Sichuan University. There were 4 males and 5 females, aged 30.8±6.1 years (range, 24-44 years), 5 cases on the left side, 4 cases on the right side, 2 cases of Campanacci grade I, 7 cases of Campanacci grade II. The anteroposterior and lateral X-ray films and T-SMART tomosynthesis imaging of the knee joint were taken to observe the bone graft healing and osseointegration after operation. Musculoskeletal Tumor Society (MSTS)-93 was used to evaluate knee function, and visual analogue scale (VAS) was used to evaluate knee pain.Results:All patients were successfully operated and followed up for an average of 30.8±7.5 months (range, 18-42 months). The operation time was 124.2±23.6 min, and the intraoperative blood loss was 105.6±17.4 ml. All autografts showed bony union at the graft-host junction, and the healing time was 3.3±0.4 months (range, 3.0-4.0 months). At 6 months after surgery, T-SMART tomosynthesis imaging showed that the gap between the prosthesis-bone interface was less than 1 mm in all patients. At the last follow-up, the thickness of residual subchondral bone was 5.7±1.3 mm, which was greater than that before operation 2.2±0.8 mm, and the difference was statistically significant ( t=10.823, P<0.001). At the last follow-up, the score of MSTS-93 was 26.7±2.4, which was higher than that before operation 18.8±3.7, and the difference was statistically significant ( t=5.367, P<0.001). At the last follow-up, the range of motion of the knee joint was 122.8°±9.1°, which was higher than that before operation 108.3°±6.1°, and the difference was statistically significant ( t=3.970, P<0.001). All patients were able to walk normally, go up and down stairs and other daily activities, and 7 patients were able to complete squats. At the last follow-up, there was no local tumor recurrence, distant metastasis, death, joint infection, pain (VAS score was 0), delayed wound healing, joint degeneration, prosthesis loosening or articular surface collapse. Conclusion:Reconstruction of lacunar bone defect caused by giant cell tumor of distal femur with 3D-printed modular supporting prosthesis can effectively improve knee joint function and osseointegration, and the short-term clinical results are satisfactory.
6.The early and mid-term efficacy of three-dimensional printed customized porous prosthesis with preserved articular in the reconstruction of ultra-long segmental bone defect around the metaphysis of peri-knee
Jinyang LI ; Zhuangzhuang LI ; Taojun GONG ; Xin HU ; Linyun TAN ; Yong ZHOU ; Yi LUO ; Minxun LU ; Chongqi TU ; Li MIN
Chinese Journal of Orthopaedics 2025;45(11):735-741
Objective:To explore the early and mid-term efficacy of three-dimensional printed customized porous prosthesis with preserved articular in the reconstruction of ultra-long segmental bone defect around the metaphysis of peri-knee.Methods:A retrospective analysis was conducted on the data of 24 patients who underwent reconstruction of ultra-long segmental bone defect around the metaphysis of peri-knee using 3D-printed customized porous prostheses at West China Hospital of Sichuan University from June 2015 to June 2021. There were 14 female cases and 10 male cases, with an average age of 28.9±16.5 years (range, 12-61 years), 12 cases at the distal end of the femur and 12 cases at the proximal end of the tibia. Tumor types: 16 cases of osteosarcoma, 4 cases of Ewing's sarcoma, 2 cases of chondrosarcoma, and 2 case of parosteal osteosarcoma. All patients were classified as Enneking stage IIB. Record the oncology results of the patients, the length of tumor segment resection, and the remaining bone length at the distal femur or proximal tibia, as well as complications, systemic metastasis and imaging changes. The bone integration at the prosthesis-bone interface was evaluated by tomosynthesis-shimadzu metal artifact reduction technology (T-SMART). Limb function was evaluated using the Musculoskeletal Tumor Society (MSTS)-93 score and knee range of motion assessment.Results:All 24 patients successfully completed the surgery and were followed up, with an average follow-up time of 51.8±12.7 months (range, 32-99 months). The length of femoral osteotomy was 241.1±66.2 mm (range, 150.6-333.4 mm), and the length of tibial osteotomy was 198.6±35.6 mm (range, 156.6-287.6 mm). The remaining bone length at the epiphyseal end around the knee joint (from the knee joint plane to the osteotomy plane of the distal femur or proximal tibia) was 52.6±11.0 mm (range, 31.1-77.5 mm). At the last follow-up, 23 patients survived tumor-free, while one patient died due to lung metastasis 54 months after the operation. One patient had prosthesis fracture 75 months after the operation, two patients had aseptic loosening 6 and 8 months after the operation, and the T-SMART of the remaining 20 patients showed that the implanted prostheses all achieved good osseointegration. At the last follow-up, the range of motion of the knee joint was 126.2°±7.5° (range, 110.0°-140.0°), and the MSTS-93 score was 26.7±1.8 points (range, 23-30 points). Among them, the MSTS-93 score of the femoral prosthesis was 26.7±1.6 points (range, 24-29 points), and the MSTS-93 score of the tibial prosthesis was 26.9±1.9 points (range, 23-30 points). The average knee range of motion was 126.2°±7.5° (range, 110°-140°), and the MSTS-93 functional score was 26.7±1.8 points (range, 23-30 points) at the last follow-up. The femoral component had an average score of 26.7±1.6 points (range, 24-29 points), while the tibial component had an average score of 26.9±1.9 points (range, 23-30 points).Conclusion:The application three-dimensional printed customized porous prosthesis with preserved articular in the reconstruction of ultra-long segmental bone defect around the metaphysis of peri-knee can preserve the joint, restore limb function well, and have a low incidence of prosthesis complications, with good clinical efficacy in the early and middle stages.
7.Design and application of a pressure ulcer prevention nursing device for critically ill patients
Jing LI ; Yan YUE ; Shuhan TU ; Mengling XIANG ; Min DENG ; Jing LIU ; Guojin XIAO
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2025;32(3):361-363
Pressure ulcer is a common complication of long-term bed rest in intensive care unit(ICU)patients,which can increase the risk of infection and prolong ICU hospitalization.They are an important indicator of patient safety and nursing quality in medical institutions.Early prevention of pressure ulcer is an important means of controlling their development.At present,the prevention of pressure ulcer mainly involves timed flipping and the use of pressure reducing devices.However,during the flipping process,it often requires two or more nursing staff to complete,which increases the workload and also exacerbates the occurrence of occupational lower back pain among nursing staff.In addition,existing pressure reducing devices still have certain limitations in use,and their functions are single,often requiring the combination of multiple tools to increase material and financial resources.Based on this,the research team from the department of critical care medicine of Hospital of Chengdu University of Traditional Chinese Medicine,has designed a nursing device for preventing pressure ulcer in critically ill patients,and has obtained a National Utility Model Patent of China(Patent Number:ZL 202320609787.6).It has several inflation components and connecting structures.The inflation components are equipped with a connected air inlet,a connected air outlet,and a discharge port on the side;the inflatable components are fitted together and can be detachably connected through a connecting structure.The connected air inlet of one inflatable component corresponds to the connected air outlet of adjacent inflatable components.This device is connected by multiple inflation components,which lower or raise the height of the airbag through inflation and deflation,adjust the pressure on various parts of the patient's body,and solve the problem of labor-intensive and heavy workload in nursing work;In addition,multiple inflatable components can be detachably connected to form an inflatable mattress.When in use,the number of inflatable component connections can be selected according to the specific needs of different patients or nursing areas.The device is easy to operate,flexible in combination,and suitable for timed flipping pressure reduction regulation in pressure ulcer high-risk areas under various postures.It has good clinical application value.
8.Application of indocyanine green combined with autologous blood and methylene blue in localizing pulmonary nodules in lung wedge resection
Zijie WANG ; Zhi FENG ; Min LIN ; Yuanrong TU ; Quan DU ; Jianfeng CHEN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(06):792-797
Objective To explore the feasibility and safety of using indocyanine green combined with autologous blood and methylene blue for localization of small lung nodules during thoracoscopic wedge resection. Methods Patients who underwent CT-guided percutaneous lung puncture injection of localization agents to locate lung nodules at the First Affiliated Hospital of Fujian Medical University from November 2023 to January 2024 were selected. Under thoracoscopy, lung nodules were located by white light mode, fluorescence mode, or near-infrared mode and wedge resection was performed. The feasibility of using indocyanine green combined with autologous blood and methylene blue for localization of small lung nodules was preliminarily verified by evaluating whether the localization agent concentrated around the nodules, and the safety of this method was verified by analyzing the incidence of adverse reactions during patient puncture and surgery. Results A total of 30 patients with lung nodules were included, including 10 males and 20 females, with an average age of (55.5±11.2) years. In 26 patients, the amount of localization agent used was moderate, the localization agent concentrated around the nodules, and successful precise localization of small lung nodules was achieved. In 4 patients, due to excessive use of localization agent, the marker was diffuse with pleural staining. The overall localization success rate was 86.7%, and when the injection volume of localization agent was 0.2-0.5 mL, the localization success rate was 100.0%. All patients successfully completed thoracoscopic wedge resection and found nodule lesions, with negative margins and a distance from the margin to the lesion that met the requirements. There were no complications. Conclusion Thoracoscopic surgery using indocyanine green combined with autologous blood and methylene blue for localization of small lung nodules is safe and feasible.
9.Prognosis analysis of R2 intervention surgery in patients with primary craniofacial hyperhidrosis: A retrospective cohort study
Hong CHEN ; Zhi FENG ; Yuanrong TU ; Min LIN ; Zijie WANG ; Quan DU ; Jianfeng CHEN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(07):1013-1021
Objective To investigate the prognosis and satisfaction of the R2 intervention procedure and develop related predictive models. Methods The clinical data of 64 patients with primary craniofacial hyperhidrosis who underwent R2 intervention surgery at the First Affiliated Hospital of Fujian Medical University from November 2018 to October 2022 were retrospectively analyzed. By statistically analyzing the risk factors for compensatory hyperhidrosis (CH) and satisfaction, and conducting feature screening, a relevant prediction model was established. Results Finally, 51 patients were collected, including 43 (84.3%) males and 8 (15.7%) females, with an average age of (30.27±7.22) years. Overall postoperative satisfaction was high, with only 5.9% of patients expressing regret about the surgery. However, 92.2% of patients experienced CH. The onset of postoperative CH was most prominent within the first 3 months postoperatively, with the incidence rate stabilizing thereafter. Preoperative heart rate and R2 sympathetic nerve clipping were identified as independent risk factors for severe CH. The preoperative body mass index, the degree of sweating in the chest and abdomen, are significantly correlated with postoperative satisfaction. Conclusion The R2 intervention surgery effectively alleviates the symptoms of primary craniofacial hyperhidrosis, and patient satisfaction is high.
10.Ablation of macrophage transcriptional factor FoxO1 protects against ischemia-reperfusion injury-induced acute kidney injury.
Yao HE ; Xue YANG ; Chenyu ZHANG ; Min DENG ; Bin TU ; Qian LIU ; Jiaying CAI ; Ying ZHANG ; Li SU ; Zhiwen YANG ; Hongfeng XU ; Zhongyuan ZHENG ; Qun MA ; Xi WANG ; Xuejun LI ; Linlin LI ; Long ZHANG ; Yongzhuo HUANG ; Lu TIE
Acta Pharmaceutica Sinica B 2025;15(6):3107-3124
Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

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