Hepatocellular carcinoma (HCC) is a lethal cancer with high morbidity rates worldwide. It is a major threat to public health in China, due to the combination of known and new risk factors, such as endemic hepatitis B virus (HBV), dietary aflatoxin exposure, and the occurrence of metabolic dysfunction-associated steatotic liver disease (MASLD). Although many methods for surveillance and multimodal therapies, such as surgery, local ablation, transarterial therapy, and new systemic agents, have been available, the survival rates of HCC remains poor. They have very limited durable responses, long post-treatment recurrence rates, and high resistance to treatment. This reflects an imperfect picture of the biological cause of the disease and a need for new mechanistic or targeted techniques. A significant characteristic of HCC, in common with other aggressive cancers, is the presence of reprogrammed, hyperactive cell metabolism. Tumor cells hijack metabolic pathways to promote their uncontrolled growth, stress survival, invasion and metastasis. While classical mechanisms such as the Warburg effect, lipid metabolism and glutamine utilization have been understood, the lysosome, which was once viewed as a static “waste disposal unit” to remove old organelles and proteins, is instead a dynamic signaling and metabolic core. The lysosomes incorporate nutrients, energy and stress signals by master regulators such as mTORC1 (activated on its surface) that balance anabolic growth and catabolic recycling to the cellular demands. In HCC, lysosomes are not passive, but are highly active and dysregulated. HCC cells upregulate lysosomes, which scavenge intracellular components via enhanced autophagy and engulf extracellular proteins via macropinocytosis, crucial for survival in the nutrient-poor, hypoxic tumor microenvironment. In addition to metabolism, lysosomes exhibit pro-invasive functions by secreting hydrolases to remodel the extracellular matrix, promote angiogenesis, and suppress stromal immune cells to foster a pro-tumor microenvironment. In a clinical context, lysosomes play an important role in therapeutic resistance: they sequester and inactivate chemotherapeutics via lysosomal sequestration, and enhanced autophagic flux protects the cell from therapy-induced damage, contributing to relapse, as lysosomal dysfunction is a key cause of treatment failure. This makes lysosomes promising yet challenging therapeutic targets in HCC. Recent preclinical and early clinical studies investigate multiple strategies to exploit the susceptibility of lysosomes: lysosome-specific agents, alkalinizing the lysosome lumen or inducing membrane permeabilization and lysosome-dependent cell death; pharmacological inhibition of key lysosomal enzymes or autophagy to impair nutrient recycling and stress adaptation; smart nanotherapeutic agents or antibody-drug conjugates, specifically activated in the acidic lysosomal environment or utilizing lysosomal pathways for efficient intracellular drug release; and combination strategies of lysosome-targeting agents with tyrosine kinase inhibitors or immunotherapy to overcome resistance and achieve synergistic antitumor effects. In summary, our review systematically presents the role of lysosomes in HCC, from metabolic reprogramming and microenvironmental adaptation to therapeutic resistance. By synthesizing the latest mechanistic insights and preclinical advances, this review highlights the indispensable role of lysosomes in the complex HCC biological network, emphasizing that an in-depth understanding of this dynamic organelle holds great promise for developing innovative, targeted therapies, offering new hope for improving the poor prognosis of global HCC patients.

Objective:To explore the clinical characteristics of biliary system diseases complicated by severe acute pancreatitis(SAP) and the risk factors.Methods:This is a retrospective cohort study. A retrospective analysis was conducted on the clinical data of 159 SAP patients admitted to the Department of Pancreatic and Biliary Surgery,the First Affiliated Hospital of Harbin Medical University from January 2019 to October 2024. There were 105 male cases, 54 female cases;aged (42.3±10.8)years (range:20 to 71 years). Grouping was performed according to the presence or absence of concurrent acute acalculous cholecystitis (AAC) and biliary stricture. There were 58 cases in the AAC group,including 40 males and 18 females;aged (43.8±10.6) years (range:28 to 71 years);101 cases in the non-AAC group,including 64 males and 37 females;aged (41.5±10.8) years (range:20 to 64 years);there were statistically significant differences between the two groups in terms of admission total bilirubin,Balthazar-CTSI score,fasting time,and the proportions of concurrent shock and sepsis (all P<0.05);the time from onset of SAP to diagnosis of AAC( M (IQR)) was 10.5 (13.3) days (range: 3 to 34 days). There were 15 cases in the biliary stricture group,including 13 males and 2 females;age (46.5±10.0) years (range:33 to 63 years);141 cases in the non-biliary stricture group,including 89 males and 52 females;age (41.9±10.8) years (range: 20 to 71 years); there were statistically significant differences between the two groups in the proportions of infected pancreatic necrosis,pancreatic head necrosis,and lower extremity venous thrombosis (all P<0.05);the time from the onset of SAP to the diagnosis of biliary stenosis in patients with biliary stenosis was 2.0 (3.0) months (range: 1 to 19 months). Univariate analysis was performed using independent sample t-test, Mann-Whitney U test, χ 2 test,or Fisher′s exact probability method,and variables with P<0.05 in univariate analysis were included in multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic and predictive value of the multivariate logistic regression model for AAC and biliary stricture. Results:There were statistically significant differences in fasting time,Balthazar-CTSI score,admission total bilirubin,and the proportions of concurrent shock and sepsis between the AAC group and non-AAC group ( P<0.05). Multivariate logistic analysis showed that admission total bilirubin ( OR=1.033,95% CI: 1.010 to 1.058, P=0.004),Balthazar-CTSI score ( OR=1.276,95% CI: 1.036 to 1.572, P=0.022),fasting time ( OR=1.127,95% CI: 1.044 to 1.216, P=0.002), and sepsis ( OR=4.033, 95% CI: 1.419 to 11.462, P=0.009) were independent risk factors for AAC complicated by SAP. The area under the curve (AUC) of the ROC curve was 0.820 (95% CI: 0.752 to 0.888). There were statistically significant differences in the proportions of infected pancreatic necrosis,pancreatic head necrosis,and lower extremity venous thrombosis between the biliary stricture group and non-biliary stricture group ( P<0.05). Multivariate logistic analysis showed that infected pancreatic necrosis ( OR=7.376,95% CI:1.566 to 37.750, P=0.012) and pancreatic head necrosis ( OR=3.898,95% CI:1.180 to 12.877, P=0.026) were independent risk factors for biliary stricture complicated by SAP. The AUC of the ROC curve was 0.806 (95% CI:0.715 to 0.898). Conclusions:AAC typically occurs in the early stage of SAP,and biliary stricture usually occurs in the late stage of SAP. Admission total bilirubin,Balthazar-CTSI score,fasting duration,and concurrent sepsis are independent risk factors for AAC complicating SAP. Infected pancreatic necrosis and pancreatic head necrosis are independent risk factors for biliary stricture complicating SAP.

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

Objective:To investigate the differences in clinical outcomes of septic children with varying serum zinc levels,and to analyze the relationship between reduced serum zinc levels and organ dysfunction as well as 28-day mortality in septic children.Methods:This study conducted a retrospective analysis of clinical data from pediatric patients diagnosed with sepsis or septic shock in the Department of critical care medicine of the children's Hospital of Soochow University between January 2017 and December 2022.Clinical characteristics,organ dysfunction,and prognosis were compared between two groups:children with low serum zinc levels and those with normal zinc levels.Results:The serum zinc level of septic children within 24 hours of admission was 9.60(5.52,13.80)μmol/L,with 50.54%(94/186)of the children exhibiting low serum zinc levels(<10.07 μmol/L).Compared to the normal serum zinc group,the low serum zinc group had a significantly lower Pediatric Critical Illness Score(PCIS)[(78.71±9.35)vs.(85.12±8.51),P=0.005]and higher 28-day mortality(46.80%vs.14.13%,P<0.001).The low serum zinc group also had a higher proportion of invasive mechanical ventilation(64.89%vs.47.82%,P=0.019),renal replacement therapy(15.59%vs.3.26%,P=0.003),and use of vasoactive drugs(56.38%vs.30.43%,P<0.001).The rate of underlying conditions in the low serum zinc group was significantly higher than that in the normal serum zinc group(57.44%vs.36.95%,P=0.005).Additionally,the low serum zinc group had a higher incidence of disseminated intravascular coagulation(DIC),respiratory failure,acute kidney injury,shock,and multiple organ dysfunction syndrome(MODS)compared to the normal serum zinc group(P<0.05).Serum zinc levels had predictive value for 28-day mortality in septic children(AUC=0.813;95%CI:0.725～0.902;P<0.001).A serum zinc level of less than 6.950 μmol/L predicted the death of septic children with a sensitivity of 0.618 and a specificity of 0.902.Conclusion:Sepsis in children is commonly associated with low serum zinc levels,especially in those with underlying conditions such as hematologic and oncologic disorders.Sepsis patients hypozincemia with a higher incidence of DIC,respiratory failure,acute kidney injury,shock,and MODS.A serum zinc level below 6.95 μmol/L serves as a significant predictor of 28-day mortality in children with severe sepsis.

Objective To investigate the correlation between serum levels of long non-coding RNA(Ln-cRNA)-prostate androgen regulated transcript 1(PART1),LncRNA-nucleolar ribonucleic acid host gene 14(SNHG14)and disease stage,cognitive impairment and motor function in patients with Parkinson's disease(PD).Methods A total of 100 PD patients(PD group)who admitted to the Department of Neurology in the hospital from January 2021 to December 2023 and 100 healthy subjects(control group)who underwent the physical examination during the same period of time were selected.According to Hoehn-Yahr staging,PD pa-tients were divided into early stage group(grade 1.0-2.5,20 cases),middle stage group(grade 3.0,48 ca-ses)and late stage group(grade 4.0-5.0,32 cases).According to the Montreal Cognitive Assessment(Mo-CA)score,the patients were divided into normal cognitive group(MoCA score≥26 points,33 cases),PD-mild cognitive impairment group(MoCA score 21-＜26 points,46 cases)and PD dementia group(MoCA score＜21 points,21 cases).According to the Unified Parkinson's Disease Rating Scale(UPDRS)-Ⅲ score,the pa-tients were divided into mild dyskinesia group(0-15 points,29 cases),moderate dyskinesia group(＞15-40 points,46 cases)and severe dyskinesia group(＞40-56 points,25 cases).Real-time fluorescence quantitative PCR was used to detect serum LncRNA-PART1 and LncRNA-SNHG14 levels.Spearman method was used to analyze the correlation between serum LncRNA-PART1,LncRNA-SNHG14 levels and Hoehn-Yahr staging,MoCA score and UPDRS-Ⅲ score in PD patients.Results The level of serum LncRNA-PART1 in PD group was lower than that in control group(P＜0.05),and the level of LncRNA-SNHG14 was higher than that in control group(P＜0.05).The serum levels of LncRNA-PART1 in the middle stage group and late stage groups were lower than those in the early stage group(P＜0.05),and the levels of LncRNA-SNHG14 were higher than those in the early stage group(P＜0.05).In addition,the serum level of LncRNA-PART1 in the late stage group was lower than that in the middle stage group(P＜0.05),and the level of LncRNA-SNHG14 was higher than that in the middle stage group(P＜0.05).The serum LncRNA-PART1 levels in the PD-mild cognitive impairment group and PD dementia group were lower than those in the normal cognitive group(P＜0.05),while the LncRNA-SNHG14 levels were higher than those in the normal cognitive group(P＜0.05).Additionally,the serum LncRNA-PART1 level in the PD dementia group was lower than that in the PD-mild cognitive impairment(P＜0.05),while the LncRNA-SNHG14 level was higher than that in the PD-mild cog-nitive impairment group(P＜0.05).The serum levels of LncRNA-PART1 in the moderate dyskinesia group and severe dyskinesia group were lower than those in the mild dyskinesia group(P＜0.05),and the levels ofLncRNA-SNHG14 were higher than that in the mild dyskinesia group(P＜0.05).In addition,the serum level of LncRNA-PART1 in the severe dyskinesia group was lower than that in the moderate dyskinesia group(P＜0.05),and the level of LncRNA-SNHG14 was higher than that in the moderate dyskinesia group(P＜0.05).Spearman method results showed that serum LncRNA-PART1 level was negatively correlated with Hoehn-Yahr staging and UPDRS-Ⅲ score in PD patients,and positively correlated with MoCA score(P＜0.05).The level of serum LncRNA-SNHG14 was positively correlated with Hoehn-Yahr staging and UPDRS-Ⅲ score in PD patients,and negatively correlated with MoCA score(P＜0.05).Conclusion The level of ser-um LncRNA-PART1 in PD patients is decreased,and the level of LncRNA-SNHG14 is increased,both of them are related to the disease stage,cognitive impairment and motor function of PD patients,which may be-come evaluation indicators for PD progression.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

This paper uses literature and network data to systematically sort out the theoretical and practical foundations of global public health cooperation,combines expert interviews to conduct empirical analyses,and further explores China's strategies for participating in global public health cooperation through quantitative statistics and text mining of interview data,and proposes a plan for China's participation in global public health cooperation under the current international situation.Under the countercurrents to globalization,China should take its own public health capacity building as the foundation,put global security and health equity at the core,with a philosophy of open cooperation and sustainable development,actively promote bilateral and multilateral cooperation,focus on cultivating global health talents,and enhance the effectiveness of disease prevention and control by making use of existing platforms,international mechanisms and digital health technologies,so as to help build a Global Community of Health for All.

Objective To explore the clinical and pathological characteristics and oncological outcomes of clear cell borderline ovarian tumor(CCBOT),and provide guidance for the diagnosis and treatment of this disease in the future.Methods A total of 23 CCBOT patients who underwent surgical treatment in our hospital from May 2011 to Aug 2022 were enrolled,and the clinical information of 19 CCBOT patients in the Ricotta's cohort was integrated.The clinical pathological characteristics and oncological outcomes of these 42 patients were retrospectively analyzed.Results This study enrolled 42 CCBOT patients,including 23 from our cohort and 19 from the Ricotta G's cohort.Compared with the Ricotta's cohort,the proportion of CCBOT patients with endometriosis in our cohort(34.8%)was significantly higher than that in the Ricotta's cohort(5.3%)(P<0.05).In our cohort,22 patients had information on intraoperative frozen section evaluation,and the accuracy of intraoperative frozen section evaluation was 50%(11/22).The other 50%(11/22)of patients were underestimated by intraoperative frozen section evaluation.The merged cohort indicated that the median age of the patients was 60 years old,occuring more common in postmenopausal women(66.7%).Most cases presented with pelvic masses(59.5%)and abdominal pain or distension(19.0%).This disease mostly involved unilateral ovaries(90.5%).Information on preoperative tumor markers was largely missed,making it difficult to draw an accurate evaluation for them.Ten cases(23.8%)underwent fertility sparing surgery,and 32 cases(76.2%)underwent radical surgery.The pathologic report indicated that all patients were stage I patients and 21.4%patients had endometriosis.Among these patients,32 patients underwent total hysterectomy,of which 10(31.3%)had concurrent endometrial lesions.The median follow-up time was 68 months,with a minimum follow-up of one month and a maximum follow-up of 231 months,and no recurrence or death was observed.Conclusion CCBOT patients usually had an good prognosis with a low recurrence rate.Fertility sparing surgery was safe and feasible,but attention should be paid to exclude concurrent endometrial lesions.Given the rarity of CCBOT,future multicenter prospective studies are needed to better elucidate the clinical pathological features and prognosis of patients with CCBOT.

OBJECTIVE: To investigate the anti-inflammatory effect of rutaecarpine (RUT) on monosodium urate crystal (MSU)-induced murine peritonitis in mice and further explored the underlying mechanism of RUT in lipopolysaccharide (LPS)/MSU-induced gout model in vitro. METHODS: In MSU-induced mice, 36 male C57BL/6 mice were randomly divided into 6 groups of 8 mice each group, including the control group, model group, RUT low-, medium-, and high-doses groups, and prednisone acetate group. The mice in each group were orally administered the corresponding drugs or vehicle once a day for 7 consecutive days. The gout inflammation model was established by intraperitoneal injection of MSU to evaluate the anti-gout inflammatory effects of RUT. Then the proinflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA) and the proportions of infiltrating neutrophils cytokines were detected by flow cytometry. In LPS/MSU-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and proinflammatory cytokines were measured by ELISA. The percentage of pyroptotic cells were detected by flow cytometry. Respectively, the mRNA and protein levels were measured by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot, the nuclear translocation of nuclear factor κB (NF-κB) p65 was observed by laser confocal imaging. Additionally, surface plasmon resonance (SPR) and molecular docking were applied to validate the binding ability of RUT components to tumor necrosis factor α (TNF-α) targets. RESULTS: RUT reduced the levels of infiltrating neutrophils and monocytes and decreased the levels of the proinflammatory cytokines interleukin 1β (IL-1β) and interleukin 6 (IL-6, all P<0.01). In vitro, RUT reduced the production of IL-1β, IL-6 and TNF-α. In addition, RT-PCR revealed the inhibitory effects of RUT on the mRNA levels of IL-1β, IL-6, cyclooxygenase-2 and TNF-α (P<0.05 or P<0.01). Mechanistically, RUT markedly reduced protein expressions of tumor necrosis factor receptor (TNFR), phospho-mitogen-activated protein kinase (p-MAPK), phospho-extracellular signal-regulated kinase, phospho-c-Jun N-terminal kinase, phospho-NF-κB, phospho-kinase α/β, NOD-like receptor thermal protein domain associated protein 3 (NLRPS), cleaved-cysteinyl aspartate specific proteinase-1 and cleaved-gasdermin D in macrophages (P<0.05 or P<0.01). Molecularly, SPR revealed that RUT bound to TNF-α with a calculated equilibrium dissociation constant of 31.7 µmol/L. Molecular docking further confirmed that RUT could interact directly with the TNF-α protein via hydrogen bonding, van der Waals interactions, and carbon-hydrogen bonding. CONCLUSION RUT alleviated MSU-induced peritonitis and inhibited the TNFR1-MAPK/NF-κB and NLRP3 inflammasome signaling pathway to attenuate gouty inflammation induced by LPS/MSU in THP-1 macrophages, suggesting that RUT could be a potential therapeutic candidate for gout.
Animals ; NF-kappa B/metabolism* ; Male ; Indole Alkaloids/therapeutic use* ; Signal Transduction/drug effects* ; Mice, Inbred C57BL ; Inflammation/complications* ; Uric Acid ; Quinazolines/therapeutic use* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Gout/chemically induced* ; Inflammasomes/metabolism* ; Cytokines/metabolism* ; THP-1 Cells ; Mitogen-Activated Protein Kinases/metabolism* ; Mice ; Molecular Docking Simulation ; Lipopolysaccharides ; Quinazolinones