Ferroptosis is a key driver of the onset and progression of chronic obstructive pulmonary disease （COPD）. By exploring the role of ferroptosis in COPD from the perspective of "qi deficiency with retention and stagnation"， it is considered that mitochondrial dysfunction and imbalanced antioxidant defenses are the microscopic manifestations of "qi deficiency"， whereas iron accumulation and lipid peroxide deposition constitute the pathological basis of "retention and stagnation". In traditional Chinese medicine （TCM）， the treatment principle is tonifying deficiency and benefiting qi， scattering retention and unblocking stagnation. Its mechanism involves improving the antioxidant system and mitochondrial function to enhance cellular resistance to ferroptosis， as well as relieving pulmonary iron overload， excessive lipid peroxidation， and inflammatory factor release to reduce the accumulation of pathological products， thereby exerting therapeutic effects on COPD.

This article summarizes Professor HAN Mingxiang's clinical experience in treating lung cancer based on the theory of "deficiency-phlegm-stasis-toxin". It is believed that depletion of healthy qi， together with binding of phlegm and stasis forming into toxin is the core pathogenesis of lung cancer occurrence and development. In clinical practice， the core treatment principle should be reinforcing healthy qi， resolving phlegm， removing stasis， and relieving toxins. The treatment should be given based on syndrome differentiation. For the syndrome of lung-spleen qi deficiency， the self-formulated Jianpi Huatan Zhike Decoction （健脾化痰止咳汤） can be applied to fortify the spleen and replenish qi， thereby reinforcing healthy qi. For the syndrome of deficiency of both qi and yin， the self-formulated Shenmai Yuzhu Decoction （参麦玉竹汤） is used to nourish yin and moisten the lungs， thereby clearing the source. For the syndrome of phlegm-dampness accumulating in the lungs， the self-formulated Sizi Wenfei Decoction （四子温肺汤） is applied to warm the lungs and resolve phlegm， thereby diffusing the lung qi. For the syndrome of qi stagnation and blood stasis， the self-formulated Yiqi Zhuyu Decoction （益气逐瘀汤） is used to activate blood and resolve stasis， thereby unblocking the collaterals. For the syndrome of binding of phlegm and stasis， the self-formulated Jiejie Decoction （结节方） is utilized to resolve phlegm and remove stasis， thereby dissipating nodules. For the syndrome of lung deficiency with toxin accumulation， the self-formulated Qiyu Sanlong Decoction （芪玉三龙汤） is applied to reinforce healthy qi and remove toxins， thereby combating cancer. Medications are flexibly prescribed based on syndrome differentiation， with an emphasis on reinforcing healthy qi and eliminating pathogenic factors， and maintaining the balance of zang-fu （脏腑） organ functions as well as qi， blood， yin and yang.

Objective:To compare the preliminary efficacy and adverse events of chemoradiotherapy (CRT) with or without immunotherapy in bladder preservation therapy for localized muscle-invasive bladder cancer (MIBC) confined to the pelvis.Methods:Clinical data of 60 patients with MIBC who received CRT with or without immunotherapy for bladder preservation at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to June 2024 were retrospectively analyzed. Patients were divided into CRT plus immunotherapy group and CRT-alone group. Survival outcomes, bladder function preservation, recurrence and metastasis, as well as early and late radiation toxicities were evaluated. The Mann-Whitney U test was used for between-group comparisons. Overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were estimated by the Kaplan-Meier method, and survival rates were compared by the log-rank test. Results:In the CRT plus immunotherapy group ( n=23), the median follow-up was 20 months. The median OS and median PFS were not reached. The 2-year OS, PFS, LRFS, and DMFS rates were 95.7%, 70.7%, 70.7%, and 92.9%, respectively, and 22 patients (96%) preserved normal bladder function. Patients with programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥1 had significantly higher 1-year PFS rate than those with CPS <1 (100% vs. 66.7%, P=0.004). In the CRT-alone group ( n=37), the median follow-up was 37 months, with median OS and PFS of 68 and 19 months, respectively. The 2-year OS, PFS, LRFS, and DMFS rates were 92.0%, 41.1%, 60.9% and 81.5%, respectively, and 33 patients (89%) preserved normal bladder function. Compared with the CRT-alone group, the CRT plus immunotherapy group showed a significant improvement in PFS ( χ2=4.38, P=0.036), while no significant differences were observed in OS, LRFS, or DMFS (all P>0.05). The incidence of acute hematologic toxicity in the CRT plus immunotherapy group and CRT-alone group were 52% (12/23), 27% (10/37) respectively, and late genitourinary toxicity was 22% (5/23), 8% (3/37), respectively, with no significant differences in overall acute or late toxicities (all P>0.05). Conclusions:For localized MIBC, bladder preservation with CRT combined with immunotherapy significantly improves PFS compared with CRT alone, while maintaining comparable safety. The PD-L1 status may serve as a favorable predictor for immunotherapy efficacy.

Objective:To construct a Harvard cancer index-based risk predictive model for perioperative venous thromboembolism (VTE) in elderly patients with femoral neck fracture and assess its predictive effectiveness.Methods:A retrospective cohort study was conducted to analyze the clinical data of 610 elderly patients with femoral neck fracture admitted to Peking Union Medical College Hospital between January 2013 and December 2022, including 193 males and 417 females, aged 60-99 years [(77.3±9.0)years]. The patients were divided into VTE group ( n=125) and non-VTE group ( n=485) according to occurrence of VTE during the perioperative period. The two groups were compared in terms of gender, age, body mass index, smoking status, alcohol consumption, time from fracture to admission, surgical waiting time, comorbidities, perioperative electrolyte disorders, past or present history of malignancy, past history of deep vein thrombosis (DVT) or pulmonary embolism (PE), and preoperative use of oral anticoagulants. Univariate analysis and multivariable stepwise Logistic regression analysis were conducted to evaluate and identify independent risk factors for perioperative VTE in elderly patients with femoral neck fracture. A perioperative VTE risk predictive model for elderly patients with femoral neck fracture was constructed using the Harvard cancer index: (1) assigning a risk score to each variable according to the corresponding conversion criteria of the Harvard cancer index and risk score, based on the magnitude of their ORs; (2) determining the exposure rate of each risk factor based on the population distribution observed in this study; (3) calculating the average population risk score; (4) computing the individual VTE risk score; (5) deriving the ratio (X) of each individual ′s VTE risk score to the population average. Based on the Harvard cancer index classification criteria for disease risk levels, individual VTE risk categories were determined. The predictive performance of the risk stratification was evaluated by comparing the incidence of VTE across different risk levels. The predictive performance of the model was evaluated based on sensitivity, specificity, and the area under the receiver operating characteristic (ROC) curve (AUC). The calibration of the model was assessed using the Hosmer-Lemeshow (H-L) test and internal validation was performed using the bootstrap resampling method with 1000 iterations. Results:Univariate analysis showed that gender, age, time from fracture to admission, surgical waiting time, previous cerebral infarction, stroke within the past month, Alzheimer′s disease, primary Parkinson′s syndrome, hysterectomy with bilateral adnexectomy, perioperative electrolyte disorders, history of DVT or PE, and preoperative use of oral anticoagulant drug were moderately associated with the occurrence of VTE in elderly patients with femoral neck fracture ( P<0.10). Multivariable stepwise logistic regression analysis demonstrated that female gender ( OR=2.26, 95% CI 1.34, 3.80, P<0.01), time from fracture to admission>1 day ( OR=3.70, 95% CI 2.24, 6.12, P<0.01), surgical waiting time>70 hours ( OR=2.06, 95% CI 1.29, 3.30, P<0.01), previous cerebral infarction ( OR=3.78, 95% CI 1.04, 13.76, P<0.05), stroke within the past month ( OR=11.57, 95% CI 1.21, 110.44, P<0.05), Alzheimer′s disease ( OR=3.26, 95% CI 1.12, 9.49, P<0.05), primary Parkinson ′s syndrome ( OR=3.47, 95% CI 1.22, 9.85, P<0.05), previous hysterectomy with bilateral adnexectomy ( OR=4.75, 95% CI 2.09, 10.80, P<0.01), perioperative electrolyte disorders ( OR=2.73, 95% CI 1.39, 5.35, P<0.01), and preoperative oral anticoagulant use ( OR=3.86, 95% CI 1.18, 12.67, P<0.05) were significantly associated with the occurrence of perioperative VTE in elderly patients with femoral neck fracture. Based on the above 10 risk factors, a perioperative VTE risk predictive model for elderly patients with femoral neck fracture was constructed with the Harvard cancer index. The formula was as follows: X=[10×(female gender)+25×(time from fracture to admission>1 day)+10×(surgical waiting time>70 hours)+25×(previous cerebral infarction)+50×(stroke within the past month)+25×(Alzheimer′s disease)+25×(primary Parkinson′s disease)+25×(previous hysterectomy with bilateral adnexectomy)+10×(perioperative electrolyte disorders)+25×(preoperative use of oral anticoagulant drug)]/33. Individualized VTE risk was classified into five levels: very low, low, moderate, high, and very high, with corresponding VTE rates of 4.8%, 11.8%, 14.9%, 32.3%, and 73.5%, respectively ( χ2=87.71, P<0.01). The VTE risk predictive model demonstrated an AUC of 0.74 (95% CI 0.69, 0.79, P<0.01), with a sensitivity of 63.2% and specificity of 74.8%. The H-L goodness-of-fit test indicated satisfactory model calibration ( P>0.05). The internal validation with the bootstrap method confirmed that the AUC remained 0.74. Conclusions:Female gender, time from fracture to admission>1 day, surgical waiting time>70 hours, previous cerebral infarction, stroke within the past month, Alzheimer′s disease, primary Parkinson′s syndrome, hysterectomy with bilateral adnexectomy, perioperative electrolyte disorders, and preoperative use of oral anticoagulant drug are independent risk factors for perioperative VTE in elderly patients with femoral neck fracture. Based on these factors, the perioperative VTE risk predictive model constructed using the Harvard cancer index demonstrates good clinical predictive value. Individualized VTE risk stratification can effectively identify high-, intermediate-, and low-risk populations, providing a valuable reference for tailoring anticoagulant prophylaxis strategies and enhancing postoperative surveillance.

Objective:To explore the clinical characteristics and healthcare burden in patients with McCune-Albright syndrome (MAS).Methods:A cross-sectional study was conducted at the Children′s Hospital, Zhejiang University School of Medicine. Clinical and healthcare burden data were systematically collected through structured questionnaires in 164 children with MAS from February 2022 to May 2023. According to the clinical characteristics, patients were categorized into 3 groups: monosymptomatic, bisymptomatic and trisymptomatic groups. Patients were also divided into 3 groups according to the age of <7, 7-<10 and 10-18 years. Comparative analyses of clinical characteristics and healthcare burden were conducted across age, sex, and symptom categories.Results:The cohort comprised 59 males (36.0%) and 105 females (64.0%) with an age of 4.6 (2.0, 7.4) years. Age stratification revealed 117 cases (71.3%) aged 0-<7 years, 29 cases (17.7%) aged 7-<10 years, and 18 cases (11.0%) aged 10-<18 years. Among monosymptomatic (67 cases, 40.9%), the cohort comprised 32 females (47.8%) and 35 males (52.2%), predominantly presenting with fibrous dysplasia (57 cases, 85.1%). This subgroup showed peak prevalence in the 0-<7 years age range (29 cases (50.9%)). The bisymptomatic cohort (56 cases, 34.1%) consisted of 39 females (69.6%) and 17 males (30.4%), predominantly manifesting fibrous dysplasia with skin hyperpigmentation (25 cases, 44.6%). Peak prevalence occurred in the 0-<7 years subgroup(16 cases (64.0%)). The trisymptomatic cohort (41 cases, 25.0%) consisted of 34 females (82.9%) and 7 males (17.1%), with peak prevalence occurring in the 0-<7 years subgroup (36 cases (87.8%)). The diagnostic journey analysis revealed 94 cases (57.3%) required 1-3 referrals, and 34 cases (20.7%) necessitated >3 referrals from symptom onset to definitive diagnosis. Healthcare expenditure analysis revealed 69 families (42.1%) incurred direct medical costs of 10 000-100 000 CNY, with 11 families (6.7%) exceeding >100 000 CNY. Direct non-medical costs reached of 10 000-100 000 CNY for 62 families (37.8%) and >100 000 CNY for 4 families (2.4%). Productivity loss affected 58 families (35.4%) at 10 000-100 000 CNY and 8 families (4.9%) above 100 000 CNY during the study period.Conclusion:MAS requires increased attention to skeletal manifestations, especially in children aged 0-<7 years. Moreover, the significant financial burden on families necessitates a society-wide support system.

Objective:To analyze the effects of fluorine exposure on calcium ion metabolism and the expression of related calcium-regulating proteins in the kidneys of rats.Methods:Forty-five 5-week-old specific pathogen-free male Wistar rats (weighed 90 - 120 g) were selected and divided into three groups according to the randomized numeric table: 0 (control), 50, and 100 mg/L fluorine exposure groups, with 15 rats in each group. The control group was given deionized water, while the 50 and 100 mg/L fluorine exposure groups were given sodium fluoride solutions containing 50 and 100 mg/L fluorine ions, respectively. After 12 weeks, urine samples were collected, and kidneys and blood were harvested. Urinary fluorine levels were measured using a fluoride ion-selective electrode method. Calcium ion levels in the urine, kidneys, and serum were determinated using the methylthymol blue microplate method. The protein expression levels of transient receptor potential vanilloid receptor 5 (TRPV5), calbindin-D28K (CB-D28K), sodium-calcium exchanger-1 (NCX1), Klotho and plasma membrane calcium ATPase 1b (PMCA1b) in the kidneys were detected by Western blotting and immunohistochemistry.Results:The urinary fluorine levels in the control group and the 50 and 100 mg/L fluorine exposure groups were (0.48 ± 0.09), (20.01 ± 1.68), (37.45 ± 2.45) mg/L, respectively, with statistically significant differences between the groups ( F = 929.58, P < 0.001). Significant differences in calcium ion levels in urine, kidneys, and serum were observed among the three groups ( F = 14.66, 11.09, 10.31, P < 0.05). Compared with the control group, the 100 mg/L fluorine exposure group exhibited higher levels of calcium ion in the urine and kidneys, and lower serum calcium ion levels ( P < 0.05). The results of Western blotting analysis revealed that the protein expression levels of TRPV5 and CB-D28K in the kidneys increased with the increase of fluorine exposure level ( Z = 2.11, 2.11, P = 0.035). The protein expression level of NCX1 in the kidneys showed a decreasing trend with increasing fluorine exposure level ( Z = - 2.11, P = 0.035). Significant differences were also observed in the protein expression levels of Klotho and PMCA1b among the three groups ( F = 8.93, 7.08, P < 0.05). Compared with the control group, the 100 mg/L fluorine exposure group showed higher level of Klotho protein expression and lower level of PMCA1b protein expression in the kidneys ( P < 0.05). Immunohistochemical results indicated significant differences in the protein expression levels of TRPV5, CB-D28K, NCX1, and Klotho in the kidneys of the three groups ( F = 27.56, 24.94, 16.05, 32.72, P < 0.05). Compared with the control group, the protein expression levels of TRPV5, CB-D28K, and Klotho in kidneys of 50 and 100 mg/L fluorine exposure groups were higher, while the protein expression levels of NCX1 were lower ( P < 0.05). Conclusion:Fluorine exposure may cause calcium ion metabolism disorders by regulating the expression levels of Klotho and other calcium-regulating proteins in the kidneys.

Alzheimer's disease (AD) is characterized by cognitive and functional deterioration, with pathological features such as amyloid-beta (Aβ) aggregates in the extracellular spaces of parenchymal neurons and intracellular neurofibrillary tangles formed by the hyperphosphorylation of tau protein. Despite a thorough investigation, current treatments targeting the reduction of Aβ production, promotion of its clearance, and inhibition of tau protein phosphorylation and aggregation have not met clinical expectations, posing a substantial obstacle in the development of drugs for AD. Recently, artificial intelligence (AI), computational biology (CB), and systems biology (SB) have emerged as promising methodologies in AD research. Their capacity to analyze extensive and varied datasets facilitates the identification of intricate patterns, thereby enriching our comprehension of AD pathology. This paper provides a comprehensive examination of the utilization of AI, CB, and SB in the diagnosis of AD, including the use of imaging omics for early detection, drug discovery methods such as lecanemab, and complementary therapies like phototherapy. This review offers novel perspectives and potential avenues for further research in the realm of translational AD studies.

Deactivation of the mitochondrial pyruvate dehydrogenase complex (PDC) is important for the metabolic switching of cancer cell from oxidative phosphorylation to aerobic glycolysis. Studies examining PDC activity regulation have mainly focused on the phosphorylation of pyruvate dehydrogenase (E1), leaving other post-translational modifications largely unexplored. Here, we demonstrate that the acetylation of Lys 488 of pyruvate dehydrogenase complex component X (PDHX) commonly occurs in hepatocellular carcinoma, disrupting PDC assembly and contributing to lactate-driven epigenetic control of gene expression. PDHX, an E3-binding protein in the PDC, is acetylated by the p300 at Lys 488, impeding the interaction between PDHX and dihydrolipoyl transacetylase (E2), thereby disrupting PDC assembly to inhibit its activation. PDC disruption results in the conversion of most glucose to lactate, contributing to the aerobic glycolysis and H3K56 lactylation-mediated gene expression, facilitating tumor progression. These findings highlight a previously unrecognized role of PDHX acetylation in regulating PDC assembly and activity, linking PDHX Lys 488 acetylation and histone lactylation during hepatocellular carcinoma progression and providing a potential biomarker and therapeutic target for further development.
Humans ; Acetylation ; Carcinoma, Hepatocellular/genetics* ; Liver Neoplasms/genetics* ; Pyruvate Dehydrogenase Complex/genetics* ; Gene Expression Regulation, Neoplastic ; Animals ; Mice ; Cell Line, Tumor ; Protein Processing, Post-Translational ; Histones/metabolism* ; Disease Progression

The application of mechanics in clinical wound healing has a long history;however,the systematic underlying mechanisms remain unclear.With recent advancements in biomechanics and mechanobiology,the principles regarding how mechanical factors influence the formation,progression,and healing of wounds have gradually been elucidated.Herein,based on progress in theories,technologies,and clinical practices concerning the interplay between mechanics and wound healing,this study introduces the concept of wound-repairing mechanomedicine.Relevant research is systematically reviewed from the perspectives of biomechanics,mechanobiology,and mechanotherapy.Additionally,potential future development directions are prospectively analyzed to provide novel insights into wound care and strategies for preventing scar formation.

Purpose This study aims to analyze genetic mutations in patients with BCR ∷ABL negative myelopro-liferative neoplasms(MPN)and to explore their relationship with clinical features.Methods We retrospectively ana-lyzed the clinical data of 208 patients diagnosed with BCR ∷ABL negative MPN,which included 34 patients with poly-cythemia vera(PV),33 with essential thrombocytopenia(ET),and 141 with primary myelofibrosis(PMF).Mutations in driver genes were assessed in all patients.A total of 72 patients underwent next-generation sequencing(NGS)with 69-gene panel,and the relationship between gene mutations and clinical features were analyzed.Results Among the 208 MPN patients,at least one driver gene mutation(JAK2,CALR,MPL)was detected in 96.15％(200/208)of the patients.Only 0.48％(1/208)of the patients exhibited both JAK2 and CALR driver mutations.We analyzed the clinical data of 136 patients with only driver gene mutations to compare the relationship between the most common JAK2 mutations(identified in 110 patients)and clinical outcomes.The JAK2 mutation group demonstrated higher white blood cell(WBC)counts and lower platelet(PLT)counts compared to the group without JAK2 mutations.173 muta-tions in 40 genes were detected in 72 patients,per capita carried(2.40±1.40)mutations.TET2,ASXL1,and TP53 are the most prevalent non-driver gene mutations,with 44.4％(32/72)of patients exhibiting at least one mutation in these three genes.In comparison to patients without detected mutations in TET2,ASXL1,and TP53,those with muta-tions in these genes demonstrated lower hemoglobin(HGB)levels,a higher incidence of splenomegaly,and more se-vere bone marrow fibrosis.High-molecular risk category(HMR)mutations were detected in 22.22％(16/72)of the patients,and patients with HMR exhibited lower hemoglobin(HGB)levels,lower PLT counts,a higher likelihood of peripheral blood primitive cell percentage ≥ 1％,a greater incidence of splenomegaly,and more severe myelofibrosis.Mutations in the ASXL1 gene were exclusively observed in patients with PMF.Among the PMF patients with ASXL1 mutations(12 patients),there was a higher likelihood of having a peripheral blood primitive cell percentage of ≥1％,as well as a more severe degree of myelofibrosis.Conclusion Approximately 97％of patients with myeloproliferative neoplasms(MPN)exhibit positivity for driver genes,with a notably high mutation rate of the JAK2 gene.Each sub-group of MPN is characterized by distinct gene mutation patterns.Notably,ASXL1 mutations are exclusive to patients with primary myelofibrosis(PMF).Furthermore,PMF patients harboring ASXL1 mutations tend to demonstrate more pronounced bone marrow fibrosis and a greater proportion of blast cells in peripheral blood.