Background Lead is a typical persistent environmental pollutant that can accumulate in bones for decades. During pregnancy, alterations in calcium metabolism promote the mobilization of bone lead, resulting in secondary exposure; however, the mechanisms by which pregnancy-associated bone lead mobilization affects maternal renal function remain unclear. Objective To investigate the role of mitochondrial dysfunction in pregnancy-related bone lead mobilization-induced renal injury. Methods Newly weaned female Wistar rats were randomly assigned to a control or a lead-exposed group administered either 0.05% sodium acetate or 0.05% lead acetate in drinking water. Following a 4-week lead exposure and a 4-week washout period, the females were co-housed with healthy age-matched males for mating. Rats were sacrificed at early (gestational day 3) and late (gestational day 17) pregnancystages, respectively. Renal histopathology was assessed using hematoxylin and eosin staining staining. Mitochondria-related indicators, including oxidative stress, inflammatory responses, and energy metabolism, were measured. Differential metabolites were identified using serum metabolomics. Results Renal injury in the lead-exposed pregnant rats progressed in a time-dependent manner, characterized by degeneration of proximal tubular epithelial cells, glomerular hyaline changes, and interstitial inflammatory cell infiltration. Repeated measures ANOVA indicated a significant interaction between the treatment factor (lead exposure) and the temporal factor (gestational stage) on renal injury (P<0.001). Further analysis of mitochondrial function-related indicators in late-pregnancy renal tissue revealed that the lead exposure group exhibited significantly increased levels of malondialdehyde (MDA) and reactive oxygen species (ROS) (P<0.05), accompanied by a reduction in superoxide dismutase (SOD) and reduced glutathione (GSH) activities (P<0.05); regarding inflammatory markers, levels of interleukin-18 (IL-18) and interleukin-1β (IL-1β) were elevated (P<0.01), whereas interleukin-33 (IL-33) was decreased in the lead-exposed group (P<0.05); energy metabolism-related indicators, including adenosine triphosphate (ATP) level, Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase activities, and mitochondrial respiratory chain complexes I, III, and V activities, were significantly reduced (P<0.05) in the lead-exposed gorup. The typical differential metabolite N-methylisoleucine, identified through serum metabolomics analysis, was negatively correlated with blood lead levels, kidney injury scores, and IL-1β, while positively correlated with catalase (CAT) activity and Ca²⁺-Mg²⁺-ATPase. Conclusions Mitochondrial dysfunction may play a critical role in renal injury induced by bone lead mobilization during late gestation.

Hepatocellular carcinoma (HCC) develops within a profoundly immunosuppressive tumor immune microenvironment (TIME), which limits the efficacy of immunotherapy. Polarization of tumor-associated macrophages (TAMs) toward a pro-tumorigenic M2 phenotype is a major driver of immune escape. Ferroptosis, an iron-dependent regulated cell death program, intersects with hepatic iron metabolism and immune regulation and thus offers promising points of therapeutic intervention. This review systematically elucidates the mechanistic role of TAM ferroptosis in HCC immune evasion and highlights a “bidirectional regulation” intervention strategy grounded in the Traditional Chinese medicine (TCM) principle of “fortifying healthy qi and eliminating pathogens” (Fuzheng Quxie). This strategy employs “eliminating pathogens” (Quxie) approaches to exploit the metabolic vulnerability of M2-like TAMs and precisely induce their ferroptosis. Moreover, it utilizes “fortifying healthy qi” (Fuzheng) approaches to protect M1-like TAMs and CD8⁺ T cells from oxidative damage. This parallel “induction-protection” paradigm demonstrates the unique advantages of TCM in systemically remodeling TIME through multitarget synergistic actions. Accordingly, precision regulation of TAM ferroptosis based on the Fuzheng Quxie theory represents a promising integrative Chinese-Western medicine strategy for overcoming current bottlenecks in HCC immunotherapy, although its clinical translational potential warrants further validation.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

BACKGROUND: Pre-transplant exposure to immune checkpoint inhibitors (ICIs) significantly increases the risk of allograft rejection after liver transplantation (LT); however, whether ICI-related rejection leads to increased graft loss remains controversial. Therefore, this study aimed to investigate the association between ICI-related allograft rejection and perioperative graft loss. METHODS: This was a retrospective analysis of adult liver transplant recipients with early biopsy-proven T-cell-mediated rejection (TCMR) at Liver Transplantation Center of Sun Yat-sen Memorial Hospital from June 2019 to September 2024. The pathological features, clinical characteristics, and perioperative graft survival were analyzed. RESULTS: Twenty-eight patients who underwent early TCMR between June 2019 and September 2024 were included. Based on pre-LT ICI exposure, recipients were categorized into ICI-related TCMR (irTCMR, n = 12) and conventional TCMR (cTCMR, n = 16) groups. Recipients with irTCMR had a higher median Banff rejection activity index (RAI) (6 vs . 5, P = 0.012) and more aggressive tissue damage and inflammation. Recipients with irTCMR showed higher proportion of treatment resistance, achieving a complete resolution rate of only 8/12 compared to 16/16 for cTCMR. Graft loss occurred in 5/12 of irTCMR recipients within 90 days after LT, with no graft loss in cTCMRs recipients. Cox analysis demonstrated that irTCMR with an ICI washout period of <30 days was an independent risk factor for perioperative graft loss (hazard ratio [HR], 6.540; 95% confidence interval [CI], 1.067-40.067, P = 0.042). CONCLUSION IrTCMR is associated with severe pathological features, increased resistance to treatment, and higher graft loss in adult liver transplant recipients.
Humans ; Liver Transplantation/adverse effects* ; Male ; Female ; Middle Aged ; Retrospective Studies ; Graft Rejection/immunology* ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; T-Lymphocytes/drug effects* ; Graft Survival/immunology* ; Aged

In a healthy human, the airway mucus forms a thin, protective liquid layer covering the surface of the respiratory tract. It comprises a complex blend of mucin, multiple antibacterial proteins, metabolic substances, water, and electrolytes. This mucus plays a pivotal role in the lungs' innate immune system by maintaining airway hydration and capturing airborne particles and pathogens. However, heightened mucus secretion in the airway can compromise ciliary clearance, obstruct the respiratory tract, and increase the risk of pathogen colonization and recurrent infections. Consequently, a thorough exploration of the mechanisms driving excessive airway mucus secretion is crucial for establishing a theoretical foundation for the eventual development of targeted drugs designed to reduce mucus production. Across a range of lung diseases, excessive airway mucus secretion manifests with unique characteristics and regulatory mechanisms, all intricately linked to mucin. This article provides a comprehensive overview of the characteristics and regulatory mechanisms associated with excessive airway mucus secretion in several prevalent lung diseases.
Humans ; Mucus/metabolism* ; Mucins/physiology* ; Lung Diseases/metabolism* ; Respiratory Mucosa/metabolism* ; Pulmonary Disease, Chronic Obstructive/physiopathology* ; Asthma/physiopathology* ; Cystic Fibrosis/physiopathology* ; Mucociliary Clearance/physiology*

OBJECTIVE: To explore the morphological characteristics of the postero-superior protuberance of the calcaneus and to explore its relationship with Haglund malformation. METHODS: Ankle lateral X-ray films of 391 hospitalized patients between May 2021 and June 2024 were retrospectively collected. The morphological parameters of the postero-superior protuberance of the calcaneus were measured, including the length of the base, the height of the base, and the tip angle of the postero-superior protuberance of the calcaneus, and the morphological types were classified according to the above parameters, including the peak type, the hill type, and the flat type. The related parameters of Haglund malformation were measured, including Fowler-Philipp angle (FPA), calcaneal pitch angle (CPA), parallel pitch line (PPL), Chauveaux-Liet angle (CLA), and X/Y ratio (total calcaneal length/length of greater tuberosity of calcaneus). The differences of the morphological parameters of the postero-superior protuberance of the calcaneus and the related indicators of Haglund deformity among the three types and between the males and the females were compared and analyzed, and the differences of the positive numbers of the related indicators of Haglund deformity among the three types were compared. RESULTS: According to the morphological parameters of the postero-superior protuberance of the calcaneus, there were 64 cases of peak type, 245 cases of hill type, and 82 cases of flat type. There was no significant difference in the length of the base of the postero-superior protuberance of the calcaneus, CPA, CLA, and X/Y ratio among the three types ( P>0.05). Among the three types, the peak type had the largest FPA and the flat type had the smallest ( P<0.05); the peak type had the smallest tip angle of the postero-superior protuberance of the calcaneus and the flat type had the largest ( P<0.05); the positive rate of PPL in the hill type was significantly higher than that in the peak type and flat type ( P<0.05); the height of the base of the postero-superior protuberance of the calcaneus in the flat type was the smallest ( P<0.05). FPA, CPA, CLA, PPL, and X/Y ratio were positive in 2, 42, 172, 142, and 77 patients, respectively. There was no significant difference in the number of positive Haglund deformity indicators among the three types ( P>0.05). There was no significant difference between male and female patients in the tip angle of the postero-superior protuberance of the calcaneus, FPA, the positive rate of PPL, and X/Y ratio ( P>0.05). The length and the height of the base of the postero-superior protuberance of the calcaneus, CPA, and CLA in male patients were significantly higher than those in female patients ( P<0.05). CONCLUSION The postero-superior protuberance of the calcaneus can be divided into three types: the peak type, the hill type, and the flat type. The peak type is more likely to suffer from Haglund deformity, and the males are more likely to suffer from Haglund deformity than the females.
Humans ; Calcaneus/anatomy & histology* ; Male ; Female ; Retrospective Studies ; Adult ; Middle Aged ; Adolescent ; Young Adult ; Radiography ; Child ; Aged

OBJECTIVE: To study the clinical effects of pomalidomide-based regimen in the treatment of relapsed and refractory multiple myeloma (RRMM). METHODS: 60 patients with RRMM in hematology department of the First Affiliated Hospital of Xinxiang Medical University from November 2020 to January 2023 were selected. Among them, 15 cases were treated with PDD regimen (pomalidomide + daratumumab + dexamethasone), and 45 cases were treated with PCD regimen (pomalidomide + cyclophosphamide + dexamethasone). The clinical effects were evaluated. RESULTS: The median number of treatment cycles for the entire cohort was 5 (2-11), with an overall response rate (ORR) of 75.0%. The ORR of patients treated with PDD regimen was 73.3%, while the ORR of patients treated with PCD regimen was 75.6%. The ORR of 46 patients with non high-risk cytogenetic abnormalities (non-HRCA) was 86.9%, significantly higher than the 35.7% of 14 patients with HRCA (χ² =15.031, P < 0.05). The median PFS for all patients was 8.0(95%CI : 6.8-9.1) months and the median OS was 14.0 (95%CI : 11.3-16.7) months. Among patients treated with PDD regimen, the PFS and OS of patients with non-HRCA were significantly higher than those of patients with HRCA [PFS: 7.0(95%CI : 4.6-9.3) months vs 4.0(95%CI : 3.1-4.8) months, χ² =5.120, P < 0.05; OS: not reached vs 6.0(95%CI : 1.1-10.9) months, χ² =9.870, P < 0.05]. Among patients treated with PCD regimen, the PFS and OS of patients with non-HRCA were significantly higher than those of patients with HRCA [PFS: 9.0(95%CI : 6.2-11.8) months vs 6.0(95%CI : 5.4-6.6) months, χ²=14.396, P < 0.05; OS: not reached vs 11.0(95%CI : 6.4-15.6) months, χ² =7.471, P < 0.05]. CONCLUSION The pomalidomide-based regimen has a good clinical effect and safety in the treatment of RRMM.
Humans ; Multiple Myeloma/drug therapy* ; Thalidomide/administration & dosage* ; Dexamethasone/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Female ; Male ; Middle Aged ; Recurrence ; Aged ; Cyclophosphamide/therapeutic use* ; Treatment Outcome ; Antibodies, Monoclonal

Objective To investigate the current status of symptom burden and psychological distress among lung cancer patients in the diagnostic phase, and to explore the chain mediating role of social support and resilience between symptom burden and psychological distress. Methods The patients with lung cancer in the diagnostic phase who were treated in the Department of Thoracic Surgery of the Second Xiangya Hospital of Central South University from October 2022 to June 2023 were investigated by a general information questionnaire using the MD Anderson Symptom Inventory, the Social Support Rating Scale, the Connor-Davidson Resilience Scale, and the Distress Thermometer. The chain mediating role of social support and resilience between symptom burden and psychological distress was analyzed. Results A total of 413 lung cancer patients were enrolled, including 173 males and 240 females, aged (54.69±10.82) years. The detection rate of psychological distress among lung cancer patients in the diagnostic phase was 48.18%, and the average score was (3.84±2.50) points. Psychological distress was positively correlated with symptom burden (P<0.01), and negatively correlated with social support and resilience (P<0.01). The mediating effect of resilience between symptom burden and psychological distress was significant. The chain mediating effect of social support and resilience between symptom burden and psychological distress was also significant. Conclusion Lung cancer patients in the diagnostic phase have a high detection rate of psychological distress. Symptom burden can directly impact psychological distress, and can affect psychological distress through the indirect path of resilience as well as the chain mediating path between social support and resilience among lung cancer patients in the diagnostic phase.