Heparin-binding protein (HBP) is a pro-inflammatory granule protein released by activated neutrophils, known for its role in modulating vascular permeability and its pathological significance in infectious diseases. In recent years, HBP has garnered attention due to its immune-activating effects in contexts such as sepsis, acute lung injury and organ transplantation. It has been proposed as a potential biomarker for early detection of infection and inflammation. While preliminary progress has been made in animal studies, clinical evidence remains limited. Therefore, this article focuses on the mechanism of action of HBP in transplantation-related complications, explores its potential pathways for predicting infection risk, mediating ischemia-reperfusion injury and rejection, and evaluates the feasibility of intervention strategies such as neutralizing antibodies, heparin derivatives and albumin. The pivotal role of HBP in regulating inflammatory responses post-transplant may offer a novel target for postoperative infection monitoring and personalized therapeutic interventions.

Tenosynovial giant cell tumor (TGCT) is a rare mesenchymal tumor that clinically presents as nodular-type or diffuse-type (D-TGCT). D-TGCT is more aggressive, has a higher surgical recurrence rate, and can potentially lead to severe joint destruction. The traditional treatment is primarily through surgical intervention. Recent advancements in understanding the molecular mechanisms of the disease and the development of new drugs have significantly changed TGCT treatment strategies. Drug therapy and active surveillance have become important treatment options for unresectable or high-recurrence-risk TGCT. Imaging examinations and patient-reported outcome tools play a crucial role in evaluating efficacy and guiding treatment decisions. Comprehensive management by a multidisciplinary team and utilizing individualized treatment plans can significantly improve the quality of life and treatment outcomes of patients. Future research should explore the molecular mechanisms of TGCT, enhance multidisciplinary collaboration, and emphasize long-term management to improve treatment efficacy and patient prognosis.

Background Work-related musculoskeletal disorders (WMSDs) are one of the major occupational health problems faced by bus drivers and should receive special attention. Objective To explore the associations of weekly working hours and sleep quality with neck and lower back WMSDs among bus drivers, as well as assess the potential mediating role of sleep quality. Methods From June to December 2022, we recruited bus drivers from 5 subsidiaries of the Shenzhen Bus Group by convenient sampling method. Demographic characteristics, lifestyles, and work-related features of the bus drivers were collected through a questionnaire survey. The Pittsburgh Sleep Quality Index (PSQI) scale and the Musculoskeletal Disorders Survey Questionnaire were used to assess sleep quality and WMSDs respectively. Logistic regression models were applied to analyze the associations of weekly working hours and sleep quality with WMSDs in neck and lower back. Furthermore, mediation analysis was performed to investigate the role of sleep quality in the associations between weekly work hours and neck and lower back WMSDs. Results A total of 1792 valid questionnaires were collected, with a response rate of 95.07%. Among these, 89.3% of the bus drivers worked more than 40 h per week, and the positive rate of poor sleep quality was 28.2%. The overall positive rate of WMSDs within one year before the survey was 69.12%. Among different body regions, the leading positive rates were identified in neck and lower back regions, at 55.92% and 53.68%, respectively. The logistic regression model showed that compared to the bus drivers with weekly work hours ≤40 h, those weekly worked (40~48] h (OR=1.43, 95%CI: 1.02, 2.01; OR=1.65, 95%CI: 1.17, 2.34), (48~56] h (OR=2.69, 95%CI: 1.89, 3.83; OR=2.30, 95%CI: 1.62, 3.29) and ＞56 h (OR=2.63, 95%CI: 1.86, 3.74; OR=3.23, 95%CI: 2.27, 4.62) had significantly increased risk of WMSDs in neck and lower back. Additionally, when compared to those with good sleep quality, bus drivers with poor sleep quality had higher risks of both neck and lower back WMSDs (OR=4.08, 95%CI: 3.20, 5.23; OR=4.15, 95%CI: 3.26, 5.30, respectively). Further mediation analysis indicated that sleep quality partially mediated the associations between weekly working hours and both neck and lower back WMSDs, with 36.15% and 33.68% as the respective proportion of mediation. Conclusion The positive rate of WMSDs is high among bus drivers, and the most common WMSDs occur in neck and lower back. Long working hours and poor sleep quality are significantly associated with increased risks of neck and lower back WMSDs. Sleep quality may mediate the associations of weekly working hours with neck and lower back WMSDs.

OBJECTIVE To assess the scientific rigor， clarity and feasibility of the recommendations of the Guidelines for Evidence-based Use of Biological Agents for the Clinical Treatment of Osteoporosis （hereinafter referred to as the Guideline） through external review， in order to further revise and improve the Guideline recommendations. METHODS This study employed a cross-sectional survey research design， a convenience sampling method was adopted to select frontline medical workers in the field of osteoporosis （including clinical doctors， clinical pharmacists， and nurses） as well as patients or their family members. External review was conducted through a combination of closed-ended and open-ended electronic questionnaires to get feedback from them on the appreciation，clarity and feasibility of the 32 preliminary recommendations in the Guideline. RESULTS A total of 90 external review subjects from 15 hospitals were collected， including 45 clinical doctors， 15 clinical pharmacists， 15 nurses and 15 patients or their family members. The overall appreciation degree of recommendations was 99.38%， the overall clarity degree of recommendations was 98.92%， and the overall feasibility degree of recommendations was 99.65%. At the same time， 111 subjective suggestions were collected， which provided an important reference for the further improvement of the Guideline recommendations. Based on the above feedback， the Guideline steering committee and core expert group revised the wording of 12 draft recommendations without deletion， and finally determined 32 recommendations. CONCLUSIONS The external review provides an important basis for the final formation of the Guideline， further improves the scientific rigor， clarity and feasibility of the recommendations， and ensures the standardization， practicality and implementability of the Guideline.

The trillions of commensal microorganisms living in the gut lumen profoundly influence the physiology and pathophysiology of the liver through a unique gut-liver axis. Disruptions in the gut microbial communities, arising from environmental and genetic factors, can lead to altered microbial metabolism, impaired intestinal barrier and translocation of microbial components to the liver. These alterations collaboratively contribute to the pathogenesis of liver disease, and their continuous impact throughout the disease course plays a critical role in hepatocarcinogenesis. Persistent inflammatory responses, metabolic rearrangements and suppressed immunosurveillance induced by microbial products underlie the pro-carcinogenic mechanisms of gut microbiota. Meanwhile, intrahepatic microbiota derived from the gut also emerges as a novel player in the development and progression of liver cancer. In this review, we first discuss the causes of gut dysbiosis in liver disease, and then specify the pivotal role of gut microbiota in the malignant progression from chronic liver diseases to hepatobiliary cancers. We also delve into the cellular and molecular interactions between microbes and liver cancer microenvironment, aiming to decipher the underlying mechanism for the malignant transition processes. At last, we summarize the current progress in the clinical implications of gut microbiota for liver cancer, shedding light on microbiota-based strategies for liver cancer prevention, diagnosis and therapy.

Background/Aims: Transmembrane 4 L six family member 1 (TM4SF1) is highly expressed and contributes to the progression of various malignancies. However, how it modulates hepatocellular carcinoma (HCC) progression and senescence remains to be elucidated. Methods: TM4SF1 expression in HCC samples was evaluated using immunohistochemistry and flow cytometry. Cellular senescence was assessed through SA-β-gal activity assays and Western blot analysis. TM4SF1-related protein interactions were investigated using immunoprecipitation-mass spectrometry, co-immunoprecipitation, bimolecular fluorescence complementation, and immunofluorescence. Tumor-infiltrating immune cells were analyzed by flow cytometry. The HCC mouse model was established via hydrodynamic tail vein injection. Results: TM4SF1 was highly expressed in human HCC samples and murine models. Knockdown of TM4SF1 suppressed HCC proliferation both in vitro and in vivo, inducing non-secretory senescence through upregulation of p16 and p21. TM4SF1 enhanced the interaction between AKT1 and PDPK1, thereby promoting AKT phosphorylation, which subsequently downregulated p16 and p21. Meanwhile, TM4SF1-mediated AKT phosphorylation enhanced PD-L1 expression while reducing major histocompatibility complex class I level on tumor cells, leading to impaired cytotoxic function of CD8+ T cells and an increased proportion of exhausted CD8+ T cells. In clinical HCC samples, elevated TM4SF1 expression was associated with resistance to anti-PD-1 immunotherapy. Targeting TM4SF1 via adeno-associated virus induced tumor senescence, reduced tumor burden and synergistically enhanced the efficacy of anti-PD-1 therapy. Conclusions Our results revealed that TM4SF1 regulated tumor cell senescence and immune evasion through the AKT pathway, highlighting its potential as a therapeutic target in HCC, particularly in combination with first-line immunotherapy.

The trillions of commensal microorganisms living in the gut lumen profoundly influence the physiology and pathophysiology of the liver through a unique gut-liver axis. Disruptions in the gut microbial communities, arising from environmental and genetic factors, can lead to altered microbial metabolism, impaired intestinal barrier and translocation of microbial components to the liver. These alterations collaboratively contribute to the pathogenesis of liver disease, and their continuous impact throughout the disease course plays a critical role in hepatocarcinogenesis. Persistent inflammatory responses, metabolic rearrangements and suppressed immunosurveillance induced by microbial products underlie the pro-carcinogenic mechanisms of gut microbiota. Meanwhile, intrahepatic microbiota derived from the gut also emerges as a novel player in the development and progression of liver cancer. In this review, we first discuss the causes of gut dysbiosis in liver disease, and then specify the pivotal role of gut microbiota in the malignant progression from chronic liver diseases to hepatobiliary cancers. We also delve into the cellular and molecular interactions between microbes and liver cancer microenvironment, aiming to decipher the underlying mechanism for the malignant transition processes. At last, we summarize the current progress in the clinical implications of gut microbiota for liver cancer, shedding light on microbiota-based strategies for liver cancer prevention, diagnosis and therapy.

Background/Aims: Transmembrane 4 L six family member 1 (TM4SF1) is highly expressed and contributes to the progression of various malignancies. However, how it modulates hepatocellular carcinoma (HCC) progression and senescence remains to be elucidated. Methods: TM4SF1 expression in HCC samples was evaluated using immunohistochemistry and flow cytometry. Cellular senescence was assessed through SA-β-gal activity assays and Western blot analysis. TM4SF1-related protein interactions were investigated using immunoprecipitation-mass spectrometry, co-immunoprecipitation, bimolecular fluorescence complementation, and immunofluorescence. Tumor-infiltrating immune cells were analyzed by flow cytometry. The HCC mouse model was established via hydrodynamic tail vein injection. Results: TM4SF1 was highly expressed in human HCC samples and murine models. Knockdown of TM4SF1 suppressed HCC proliferation both in vitro and in vivo, inducing non-secretory senescence through upregulation of p16 and p21. TM4SF1 enhanced the interaction between AKT1 and PDPK1, thereby promoting AKT phosphorylation, which subsequently downregulated p16 and p21. Meanwhile, TM4SF1-mediated AKT phosphorylation enhanced PD-L1 expression while reducing major histocompatibility complex class I level on tumor cells, leading to impaired cytotoxic function of CD8+ T cells and an increased proportion of exhausted CD8+ T cells. In clinical HCC samples, elevated TM4SF1 expression was associated with resistance to anti-PD-1 immunotherapy. Targeting TM4SF1 via adeno-associated virus induced tumor senescence, reduced tumor burden and synergistically enhanced the efficacy of anti-PD-1 therapy. Conclusions Our results revealed that TM4SF1 regulated tumor cell senescence and immune evasion through the AKT pathway, highlighting its potential as a therapeutic target in HCC, particularly in combination with first-line immunotherapy.

The trillions of commensal microorganisms living in the gut lumen profoundly influence the physiology and pathophysiology of the liver through a unique gut-liver axis. Disruptions in the gut microbial communities, arising from environmental and genetic factors, can lead to altered microbial metabolism, impaired intestinal barrier and translocation of microbial components to the liver. These alterations collaboratively contribute to the pathogenesis of liver disease, and their continuous impact throughout the disease course plays a critical role in hepatocarcinogenesis. Persistent inflammatory responses, metabolic rearrangements and suppressed immunosurveillance induced by microbial products underlie the pro-carcinogenic mechanisms of gut microbiota. Meanwhile, intrahepatic microbiota derived from the gut also emerges as a novel player in the development and progression of liver cancer. In this review, we first discuss the causes of gut dysbiosis in liver disease, and then specify the pivotal role of gut microbiota in the malignant progression from chronic liver diseases to hepatobiliary cancers. We also delve into the cellular and molecular interactions between microbes and liver cancer microenvironment, aiming to decipher the underlying mechanism for the malignant transition processes. At last, we summarize the current progress in the clinical implications of gut microbiota for liver cancer, shedding light on microbiota-based strategies for liver cancer prevention, diagnosis and therapy.

Background/Aims: Transmembrane 4 L six family member 1 (TM4SF1) is highly expressed and contributes to the progression of various malignancies. However, how it modulates hepatocellular carcinoma (HCC) progression and senescence remains to be elucidated. Methods: TM4SF1 expression in HCC samples was evaluated using immunohistochemistry and flow cytometry. Cellular senescence was assessed through SA-β-gal activity assays and Western blot analysis. TM4SF1-related protein interactions were investigated using immunoprecipitation-mass spectrometry, co-immunoprecipitation, bimolecular fluorescence complementation, and immunofluorescence. Tumor-infiltrating immune cells were analyzed by flow cytometry. The HCC mouse model was established via hydrodynamic tail vein injection. Results: TM4SF1 was highly expressed in human HCC samples and murine models. Knockdown of TM4SF1 suppressed HCC proliferation both in vitro and in vivo, inducing non-secretory senescence through upregulation of p16 and p21. TM4SF1 enhanced the interaction between AKT1 and PDPK1, thereby promoting AKT phosphorylation, which subsequently downregulated p16 and p21. Meanwhile, TM4SF1-mediated AKT phosphorylation enhanced PD-L1 expression while reducing major histocompatibility complex class I level on tumor cells, leading to impaired cytotoxic function of CD8+ T cells and an increased proportion of exhausted CD8+ T cells. In clinical HCC samples, elevated TM4SF1 expression was associated with resistance to anti-PD-1 immunotherapy. Targeting TM4SF1 via adeno-associated virus induced tumor senescence, reduced tumor burden and synergistically enhanced the efficacy of anti-PD-1 therapy. Conclusions Our results revealed that TM4SF1 regulated tumor cell senescence and immune evasion through the AKT pathway, highlighting its potential as a therapeutic target in HCC, particularly in combination with first-line immunotherapy.