Background/Aims: Lenvatinib resistance remains a critical barrier in advanced hepatocellular carcinoma (HCC) therapy. However, the underlying mechanisms and strategies for reversing resistance remain incompletely understood. Methods: Integrated transcriptomics of lenvatinib-resistant patient tumors and an acquired-resistance murine model identified a novel macrophage subpopulation. Functional validation employed CRISPR-SAM screening, conditioned medium (CM) assays, subcutaneous/orthotopic xenografts, patient-derived organoids (PDOs), and patient-derived xenografts (PDXs). Mechanistic studies included ChIP-qPCR, co-immunoprecipitation, and pharmacologic targeting. Clinical relevance was assessed in a retrospective cohort. Results: Resistant HCC exhibited significant enrichment of a COLEC12high TAM subset , which correlated with poor survival and treatment response. These TAMs secreted neuregulin-1 (NRG1) , activating HER2/HER3-AKT signaling in tumor cells to drive cancer stemness and lenvatinib resistance. Mechanistically, in TAMs COLEC12 sequestered STAT1 in the cytoplasm, preventing its phosphorylation, and thereby derepressing STAT3-mediated NRG1 transcription. Depletion of NRG1 reversed the stemness phenotypes and resensitized tumors to lenvatinib both in vitro and in vivo. Clinically, high NRG1 expression predicted an inferior lenvatinib response and shorter survival. Crucially, the bispecific anti-HER2/HER3 antibody zenocutuzumab restored lenvatinib efficacy in PDOs, PDXs, and murine models. Conclusions Our work establishes the COLEC12high TAM/NRG1 axis as a master regulator of therapeutic resistance and identifies NRG1 as a predictive biomarker, providing a clinically actionable strategy to overcome lenvatinib resistance in HCC.

Objective To explore the clinical value of high frequency ultrasound combined with dermoscopy in preoperative evaluation of cutaneous malignant tumors.Methods A total of 323 patients with suspected cutaneous malignant tumors were selected from Jinhua Municipal Central Hospital from January 2022 to December 2023.The clinical value of high frequency ultrasound,dermoscopy and their combined examination in preoperative diagnosis of cutaneous malignant tumors were analyzed and compared.Results A total of 323 patients with suspected cutaneous malignant tumors,223 patients with confirmed cutaneous malignant tumors by skin pathology,234 skin lesions,and 100 patients with benign skin tumors were included.141 skin lesions were detected by dermoscopy,195 skin lesions by high frequency ultrasound,and 213 skin lesions by the combination of dermoscopy and high frequency ultrasound.The sensitivity,specificity and accuracy of high frequency ultrasound combined with dermoscopy in diagnosis of cutaneous malignant tumors were 87.6％,92.0％and 88.9％,respectively,which was higher than that of single high frequency ultrasound and single dermoscopy.The diagnosis results of dermoscopy combined with high frequency ultrasound were in good agreement with the pathological results(kappa=0.75).Conclusion Dermoscopy and high frequency ultrasound are convenient,non-invasive and sensitive imaging methods for skin detection.They can balance resolution and depth of detection,reveal morphological information of tumors,and predict the risk of tumor recurrence.

With the acceleration of population aging, issues such as multimorbidity, functional decline, and insufficient social support among elderly patients have become increasingly prominent.The traditional single-disease-centered medical model can no longer meet their complex health needs.This paper proposes a novel model of geriatric multidisciplinary service with goal-oriented care (GOC) as the core concept, comprehensive geriatric assessment (CGA) as the transformational hub, and geriatric interdisciplinary team (GIT) as the practical vehicle.Through hierarchical GOC setting, interdisciplinary resource integration, and dynamic goal regulation, it promotes a shift in healthcare paradigm from disease-centered treatment to function maintenance and quality of life improvement.However, the widespread clinical adoption of this model still faces multiple challenges, including lagging medical insurance payment policies, insufficient integration of health data, and a shortage of interdisciplinary compound talents.Future efforts should focus on policy innovation, technological empowerment, and talent cultivation to optimize the geriatric care service system, thereby providing a scientific and sustainable practical pathway towards healthy aging.

Objective To provide reference for the clinical use of Baihui acupoint(GV20)in treating diseases,the rules of clinical application of GV20 in ancient literature through data mining technology was analyzed.Methods"Zhong Hua Yi Dian"was searched by computer for relevant papers involving GV20 in the main treatment of illnesses,the main treatment of illnesses by combining other acupoints,and the treatment methods.After organizing the included articles into a database,Microsoft Excel 2021 was used to analyze the frequency of diseases and the use of acupoint pairing,attribution to meridians and special points,and IBM SPSS STATISTIC 27 software was used to analyze the cluster analysis of high-frequency compatible acupoints.Results Valid prescriptions from 209 medical books,including Zhen Jiu Da Cheng(The Great Compendium of Acupuncture and Moxibustion),containing 311 compatible acupoints,were screened and summarized.The main treatment conditions of GV20 mainly included internal medicine,surgery,gynecology,pediatrics and other disciplines,with the brain and liver and gallbladder systems of internal medicine as the main diseases.The top 5 frequency acupoints were Quchi(LI11),Hegu(LI4),Shenting(GV24),Zusanli(ST36),and Shangxing(GV23),and the most frequently involved meridians were Bladder Meridian of Foot-Taiyang,Governor Vessel,and Gallbladder Meridian of Foot-Shaoyang.The compatible acupoints mainly distributed in the head and neck.The special points with the highest frequency of collocation were Five-Shu acupoints,confluent acupoints,and Back-Shu acupoints.In the cluster analysis,the icicle diagram showed 2 effective clusters and the dendrogram 4 clusters of acupoints.Conclusion The main treatment range of GV20 in ancient medical texts is wide,and the main treatment range can be enlarged by pairing,emphasizing the use of moxibustion,which can provide a reference for modern clinical treatment.

Objective:To investigate the clinical effect of indocyanine green angiography (ICGA)-assisted design and harvest of expanded flaps for scar reconstruction.Methods:This study was a retrospective observational study. From April 2019 to August 2023, 19 patients with scars (8 males, 11 females; aged 3-38 years) treated at the Plastic Surgery Hospital of Peking Union Medical College and Chinese Academy of Medical Sciences met the inclusion criteria. The scars were distributed on the head, face, trunk, and extremities. In stage Ⅰ surgery, skin soft tissue expanders were implanted in suitable areas around the scars for skin soft tissue expansion. In stage Ⅱ surgery, the scar tissue was excised, resulting in wound areas ranging from 100 to 210 cm 2, and expanded flaps were designed. ICGA was used to identify target perforators and their accompanying veins, and the flap design was adjusted to ensure the inclusion of complete arterial and venous axes. The expanded flap with an area of 120 to 240 cm2 was harvested using unilateral back-cut technique and transferred to the recipient site, and the donor site wound was sutured directly. The durations of the arterial and venous phases of ICGA during flap design were recorded. The length-to-width ratios of the back-cut flaps were calculated for different regions. After stage Ⅱ surgery, the blood perfusion and survival of the flap, the wound healing at the donor site, and the occurrence of complications were observed. During follow-up, the appearance, color, and texture of the patient's flap were observed. Results:The arterial phase of ICGA lasted 10-27 (18±5) s, and the venous phase lasted 78-116 (100±10) s. The length-to-width ratios of the back-cut flaps were 1.22±0.32, 1.63±0.12, and 1.15±0.21 for the head and neck, trunk, and limb regions, respectively. After stage Ⅱ surgery, one patient had a large area of insufficient blood perfusion in the flap. By comparing ICGA images before and after flap transfer, the sutures at the oral commissure were loosened, the blood flow of the flap was restored. The blood perfusion of the flaps in other patients was good. All flaps survived completely, with well-healed donor site wounds and no complications. During 0.5-14.0 months of follow-up, all flaps of patients demonstrated excellent appearance, with color and texture matching the surrounding skin.Conclusions:As a means of superficial blood flow visualization, ICGA can not only clearly show the microvascular distribution of the expanded flap before operation, assist in optimizing the design of the flap, but also evaluate the blood perfusion of the flap after operation, reduce the occurrence of complications, and provide a full-process navigation for the harvesting of expanded flaps, thereby improving the safety of flap transfer for scar reconstruction.

Post-stroke spasticity is a series of symptoms after stroke,such as hand and foot urgency,unflexion and extension of muscles,etc.In order to deeply understand the cognition of post-stroke spasticity of ancient Chinese physicians and comb out their therapeutic thoughts,this study took the General Catalogue of Chinese Ancient Books of Traditional Chinese Medicine as a bibliographic reference,all the ancient Chinese literature on spasms after stroke was retrieved manually and by computer,and then sorted and analyzed,and classified them by longitudinal time,and extracted the description about post-stroke spasticity,including medical classics,prescriptions,clinical evidence,medical records and so on.And this paper verified and summarized the etiology,pathogenesis,functional and indications and prescription characteristics of spasticity after stroke,in order to deeply understand systematic theories and treatment ideas of the ancient medical practitioners in the bud,development and mature stages of their understanding of spasticity after stroke,and provide the theoretical basis for the later doctors to understand this disease and the modern clinical treatment of traditional Chinese medicine.

With the acceleration of population aging, issues such as multimorbidity, functional decline, and insufficient social support among elderly patients have become increasingly prominent.The traditional single-disease-centered medical model can no longer meet their complex health needs.This paper proposes a novel model of geriatric multidisciplinary service with goal-oriented care (GOC) as the core concept, comprehensive geriatric assessment (CGA) as the transformational hub, and geriatric interdisciplinary team (GIT) as the practical vehicle.Through hierarchical GOC setting, interdisciplinary resource integration, and dynamic goal regulation, it promotes a shift in healthcare paradigm from disease-centered treatment to function maintenance and quality of life improvement.However, the widespread clinical adoption of this model still faces multiple challenges, including lagging medical insurance payment policies, insufficient integration of health data, and a shortage of interdisciplinary compound talents.Future efforts should focus on policy innovation, technological empowerment, and talent cultivation to optimize the geriatric care service system, thereby providing a scientific and sustainable practical pathway towards healthy aging.

Post-stroke spasticity is a series of symptoms after stroke,such as hand and foot urgency,unflexion and extension of muscles,etc.In order to deeply understand the cognition of post-stroke spasticity of ancient Chinese physicians and comb out their therapeutic thoughts,this study took the General Catalogue of Chinese Ancient Books of Traditional Chinese Medicine as a bibliographic reference,all the ancient Chinese literature on spasms after stroke was retrieved manually and by computer,and then sorted and analyzed,and classified them by longitudinal time,and extracted the description about post-stroke spasticity,including medical classics,prescriptions,clinical evidence,medical records and so on.And this paper verified and summarized the etiology,pathogenesis,functional and indications and prescription characteristics of spasticity after stroke,in order to deeply understand systematic theories and treatment ideas of the ancient medical practitioners in the bud,development and mature stages of their understanding of spasticity after stroke,and provide the theoretical basis for the later doctors to understand this disease and the modern clinical treatment of traditional Chinese medicine.

Objective To provide reference for the clinical use of Baihui acupoint(GV20)in treating diseases,the rules of clinical application of GV20 in ancient literature through data mining technology was analyzed.Methods"Zhong Hua Yi Dian"was searched by computer for relevant papers involving GV20 in the main treatment of illnesses,the main treatment of illnesses by combining other acupoints,and the treatment methods.After organizing the included articles into a database,Microsoft Excel 2021 was used to analyze the frequency of diseases and the use of acupoint pairing,attribution to meridians and special points,and IBM SPSS STATISTIC 27 software was used to analyze the cluster analysis of high-frequency compatible acupoints.Results Valid prescriptions from 209 medical books,including Zhen Jiu Da Cheng(The Great Compendium of Acupuncture and Moxibustion),containing 311 compatible acupoints,were screened and summarized.The main treatment conditions of GV20 mainly included internal medicine,surgery,gynecology,pediatrics and other disciplines,with the brain and liver and gallbladder systems of internal medicine as the main diseases.The top 5 frequency acupoints were Quchi(LI11),Hegu(LI4),Shenting(GV24),Zusanli(ST36),and Shangxing(GV23),and the most frequently involved meridians were Bladder Meridian of Foot-Taiyang,Governor Vessel,and Gallbladder Meridian of Foot-Shaoyang.The compatible acupoints mainly distributed in the head and neck.The special points with the highest frequency of collocation were Five-Shu acupoints,confluent acupoints,and Back-Shu acupoints.In the cluster analysis,the icicle diagram showed 2 effective clusters and the dendrogram 4 clusters of acupoints.Conclusion The main treatment range of GV20 in ancient medical texts is wide,and the main treatment range can be enlarged by pairing,emphasizing the use of moxibustion,which can provide a reference for modern clinical treatment.

Objective:To explore the effects of early electroacupuncture(EA)intervention on the high mobility group box 1(HMGB1)/Toll-like receptor 4(TLR4)signaling pathway-related protein expression and oligodendrocytes in mice with amyotrophic lateral sclerosis(ALS),and uncover the potential molecular mechanisms underlying the improvement of motor function in ALS mice by early EA intervention.Methods:ALS mice carrying the SOD1G93A gene were randomly divided into a model group and an EA group,with 10 mice in each group;10 littermate mice with a negative SOD1G93A genotype served as the control group.In the EA group,Baihui(GV20),Tianzhu(BL10),and Tianshu(ST25)were selected with needles retained for 10 min,5 consecutive days per week,with 2 days of rest.One week constituted a course of treatment,and a total of 3 consecutive courses were performed.The other groups were grasped and fixed similarly,but without intervention.Motor function was assessed using the open field test(OFT)and Morris water maze(MWM).Subsequently,hematoxylin-eosin staining was used to observe neuron morphology in the M1 region of the cerebral cortex.Immunofluorescence was performed to detect the positive cell rate of TAR DNA-binding protein 43(TDP-43),and double immunofluorescence staining was used to observe the positive cell rate and cell states of ionized calcium-binding adaptor molecule 1(Iba-1)and myelin basic protein(MBP)in the M1 region of the cerebral cortex.Western blotting was used to detect the relative expression levels of TDP-43,tumor necrosis factor(TNF)-α,HMGB1,and TLR4 proteins.Results:Compared to the control group,the model group exhibited a reduced total movement distance in the OFT,and an increased escape latency,as well as fewer platform crossings in the MWM,with statistically significant differences(P<0.01).In the model group,the number of degenerated and necrotic neurons in the M1 region of the ALS mouse cerebral cortex increased,with significant nuclear shrinkage and cytoplasmic vacuolization;the percentage of TDP-43 immunofluorescence positive cells in the M1 region of the cerebral cortex increased(P<0.01),and the relative expression level of TDP-43 protein in the cerebral cortex showed a significant increase(P<0.01);the Iba-1 positive cell percentage increased,while the MBP positive cell percentage decreased(P<0.01);the relative expression levels of TNF-α,HMGB1,and TLR4 proteins increased(P<0.05).Compared to the model group,the EA group showed an increased total movement distance(P<0.01),and a reduced escape latency,and more platform crossings in the MWM,with statistically significant differences(P<0.05).In the EA group,neurons showed improvement,with reduced degeneration and necrosis,and larger,clearer nuclei;the percentage of TDP-43 immunofluorescence positive cells in the M1 region of the cerebral cortex decreased(P<0.05),and the relative expression level of TDP-43 protein also decreased(P<0.05);the percentage of Iba-1 positive cells in the M1 region of the cerebral cortex decreased,while the percentage of MBP positive cells increased(P<0.01);the relative expression levels of TNF-α,HMGB1,and TLR4 proteins decreased(P<0.05).Conclusion:EA intervention can suppress microglial activation,improve the state of oligodendrocytes,and reduce abnormal TDP-43 aggregation in the M1 region of the cerebral cortex in ALS model mice;its mechanism of action may be related to the HMGB1/TLR4 signaling pathway.