Inflammatory diseases (IDs) are a general term of diseases characterized by chronic inflammation as the primary pathogenetic mechanism, which seriously affect the quality of patient′s life and cause significant social and medical burden. Current drugs for IDs include nonsteroidal anti-inflammatory drugs, corticosteroids, immunomodulators, biologics, and antioxidants, but these drugs may cause gastrointestinal side effects, induce or worsen infections, and cause non-response or intolerance. Given the outstanding performance of metal polyphenol network (MPN) in the fields of drug delivery, biomedical imaging, and catalytic therapy, its application in the diagnosis and treatment of IDs has attracted much attention and significant progress has been made. In this paper, we first provide an overview of the types of IDs and their generating mechanisms, then sort out and summarize the different forms of MPN in recent years, and finally discuss in detail the characteristics of MPN and their latest research progress in the diagnosis and treatment of IDs. This research may provide useful references for scientific research and clinical practice in the related fields.

Objective: Huntington’s disease (HD) is characterized by motor, cognitive, and neuropsychiatric symptoms. Oculomotor impairments and gait variability have been independently considered as potential markers in HD. However, an integrated analysis of eye movement and gait is lacking. We performed multiple examinations of eye movement and gait variability in HTT mutation carriers, analyzed the consistency between these parameters and clinical severity, and then examined the associations between oculomotor impairments and gait deficits. Methods: We included 7 patients with pre-HD, 30 patients with HD and 30 age-matched controls. We collected demographic data and assessed the Unified Huntington’s Disease Rating Scale (UHDRS) score. Examinations, including saccades, smooth pursuit tests, and optokinetic (OPK) tests, were performed to evaluate eye movement function. The parameters of gait include stride length, walking velocity, step deviation, step length, and gait phase. Results: HD patients have significant impairments in the latency and velocity of saccades, the gain of smooth pursuit, and the gain and slow phase velocities of OPK tests. Only the speed of saccades significantly differed between pre-HD patients and controls. There are significant impairments in stride length, walking velocity, step length, and gait phase in HD patients. The parameters of eye movement and gait variability in HD patients were consistent with the UHDRS scores. There were significant correlations between eye movement and gait parameters. Conclusion Our results show that eye movement and gait are impaired in HD patients and that the speed of saccades is impaired early in pre-HD. Eye movement and gait abnormalities in HD patients are significantly correlated with clinical disease severity.

Objective: Huntington’s disease (HD) is characterized by motor, cognitive, and neuropsychiatric symptoms. Oculomotor impairments and gait variability have been independently considered as potential markers in HD. However, an integrated analysis of eye movement and gait is lacking. We performed multiple examinations of eye movement and gait variability in HTT mutation carriers, analyzed the consistency between these parameters and clinical severity, and then examined the associations between oculomotor impairments and gait deficits. Methods: We included 7 patients with pre-HD, 30 patients with HD and 30 age-matched controls. We collected demographic data and assessed the Unified Huntington’s Disease Rating Scale (UHDRS) score. Examinations, including saccades, smooth pursuit tests, and optokinetic (OPK) tests, were performed to evaluate eye movement function. The parameters of gait include stride length, walking velocity, step deviation, step length, and gait phase. Results: HD patients have significant impairments in the latency and velocity of saccades, the gain of smooth pursuit, and the gain and slow phase velocities of OPK tests. Only the speed of saccades significantly differed between pre-HD patients and controls. There are significant impairments in stride length, walking velocity, step length, and gait phase in HD patients. The parameters of eye movement and gait variability in HD patients were consistent with the UHDRS scores. There were significant correlations between eye movement and gait parameters. Conclusion Our results show that eye movement and gait are impaired in HD patients and that the speed of saccades is impaired early in pre-HD. Eye movement and gait abnormalities in HD patients are significantly correlated with clinical disease severity.

OBJECTIVE To investigate the improvement effects and mechanism of Xiangsha yiwei tang on gastric mucosal injury in rats with chronic atrophic gastritis （CAG）. METHODS Rats were randomly assigned into normal control group， model group， Xiangsha yiwei tang low-， medium- and high-dose groups （6， 12， 18 g/kg， calculated by crude drug）， and high-dose group of Xiangsha yiwei tang+740 Y-P [Xiangsha yiwei tang 18 g/kg+transforming growth factor β1/phosphatidyl inositol 3 kinase/ protein kinase B（TGF-β1/PI3K/Akt） pathway activator group 740 Y-P 10 mg/kg]， with 18 rats in each group. Rats in each group were administered the corresponding drugs via oral gavage or injection， once daily， for 4 consecutive weeks. Gastric mucosal blood flow， the levels of serum gastrointestinal hormones [including motilin （MTL）， gastrin （GAS）， and pepsinogen （PP）]， as well as inflammatory cytokines [including tumor necrosis factor- α （TNF- α）， interleukin-1β （IL-1β）， IL-6] in rats were measured. Pathological damage to gastric mucosal tissue was observed in rats； the apoptotic rate of gastric mucosal cells was detected. The expressions of TGF-β1/PI3K/Akt signaling pathway-related proteins and apoptosis-related proteins [including B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax）] in the gastric mucosal tissues of rats were assessed. RESULTS Compared with normal control group， model group had abnormal gastric mucosal tissue structure， with shedding of gastric mucosal epithelial cells， and prominent infiltration of inflammatory cells. Gastric mucosal blood flow， the serum levels of MTL， GAS， PP， and Bcl-2 protein expression were lowered significantly， while serum levels of TNF-α， IL-1β and IL-6， apoptosis rate， protein expressions of Bax and TGF-β1， the phosphorylations of PI3K and Akt were increased significantly （P＜0.05）. Compared with model group， Xiangsha yiwei decoction groups exhibited attenuated histopathological injuries in gastric mucosal tissues， reduced inflammatory cell infiltration， and significant improvements in the aforementioned quantitative parameters （P＜0.05）. Compared with high-dose group of Xiangsha yiwei tang， high-dose group of Xiangsha yiwei decoction combined with 740 Y-P exhibited significantly aggravated histopathological injuries in gastric mucosal tissues， and the aforementioned quantitative parameters were markedly reversed （P＜0.05）. CONCLUSIONS Xiangsha yiwei tang can alleviate gastric mucosal damage in CAG rats， and its mechanism of action is related to the inhibition of TGF-β1/PI3K/Akt signaling pathway.

Erectile dysfunction (ED) is prevalent among men, but its relationship with dietary habits is uncertain. The aim of our study was to assess whether dietary patterns enhance erectile function by reviewing the literature published before August 1, 2022, via PubMed, Web of Science, and EMBASE databases. The data compiled included author details; publication dates, countries, treatments, patient numbers, ages, follow-ups, and clinical trial outcomes, such as ED cases, odds ratios (ORs), confidence intervals (CIs), and International Index of Erectile Function-5 (IIEF-5) scores with means and standard deviations. An analysis of 14 studies with 27 389 participants revealed that plant-based diets (OR = 0.71, 95% CI: 0.66-0.75; P < 0.00001), low-fat diets (OR = 0.27, 95% CI: 0.13-0.53; P = 0.0002), and alternative diets such as intermittent fasting and organic diets (OR = 0.54, 95% CI: 0.36-0.80; P = 0.002) significantly reduced ED risk. High-protein low-fat diets (hazard ratio [HR] = 1.38, 95% CI: 1.12-1.64; P < 0.00001) and high-carb low-fat diets (HR = 0.79, 95% CI: 0.55-1.04; P < 0.00001) improved IIEF-5 scores. Combined diet and exercise interventions decreased the likelihood of ED (OR = 0.49, 95% CI: 0.28-0.85; P = 0.01) and increased the IIEF-5 score (OR = 3.40, 95% CI: 1.69-5.11; P < 0.0001). Diets abundant in fruits and vegetables (OR = 0.97, 95% CI: 0.96-0.98; P < 0.00001) and nuts (OR = 0.54, 95% CI: 0.37-0.80; P = 0.002) were also correlated with lower ED risk. Our meta-analysis underscores a strong dietary-ED association, suggesting that low-fat/Mediterranean diets rich in produce and nuts could benefit ED management.
Humans ; Male ; Erectile Dysfunction/epidemiology* ; Diet ; Diet, Fat-Restricted ; Feeding Behavior ; Penile Erection/physiology* ; Diet, Vegetarian

OBJECTIVES: To assess the preliminary efficacy and safety of a dose-intensified C5VD regimen (cisplatin, 5-fluorouracil, vincristine, and doxorubicin) in children with locally advanced hepatoblastoma. METHODS: This prospective study enrolled 24 children with newly diagnosed, locally advanced hepatoblastoma who received the dose-intensified C5VD regimen at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children's Hospital between January 2020 and December 2023. Clinical characteristics, treatment outcomes, and chemotherapy-related toxicities were analyzed. RESULTS: Of the 24 patients, 13 were male and 11 were female, with a median age at diagnosis of 18.7 months (range: 3.5-79.4 months). All patients achieved complete macroscopic resection of hepatic lesions without liver transplantation. Serum alpha-fetoprotein levels decreased significantly after two chemotherapy cycles. During a median follow-up of 38.4 months (range: 15.8-50.7 months), all patients maintained continuous complete remission, with 3-year event-free survival and overall survival rates of 100%. Across 144 chemotherapy cycles, the incidence rates of grade 3-4 neutropenia, thrombocytopenia, and infections were 97%, 77%, and 71%, respectively; no treatment-related deaths occurred. Notably, 5 patients (21%) developed Brock grade ≥3 hearing loss, of whom 1 required a hearing aid. CONCLUSIONS The dose-intensified C5VD regimen demonstrates significant efficacy with an overall favorable safety profile in the treatment of newly diagnosed, locally advanced pediatric hepatoblastoma. Grade 3-4 myelosuppression and infection are the predominant toxicities. However, high‑dose cisplatin-induced ototoxicity remains a concern, highlighting the need for improved otoprotective strategies.
Humans ; Hepatoblastoma/pathology* ; Male ; Female ; Infant ; Liver Neoplasms/pathology* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child, Preschool ; Prospective Studies ; Doxorubicin/adverse effects* ; Child ; Cisplatin/adverse effects* ; Vincristine/adverse effects* ; Fluorouracil/adverse effects*

OBJECTIVE: To establish an in vitro cell model simulating acute graft-versus-host disease (aGVHD) bone marrow microenvironment injury with the advantage of mouse serum of aGVHD model and explore the effect of serum of aGVHD mouse on the adipogenic differentiation ability of mesenchymal stem cells (MSCs). METHODS: The 6-8-week-old C57BL/6N female mice and BALB/c female mice were used as the donor and recipient mice of the aGVHD model, respectively. Bone marrow transplantation (BMT) mouse model (n=20) was established by being injected with bone marrow cells (1×10⁷ per mouse) from donor mice within 4-6 hours after receiving a lethal dose (8.0 Gy, 72.76 cGy/min) of γ ray general irradiation. A mouse model of aGVHD (n=20) was established by infusing a total of 0.4 ml of a mixture of donor mouse-derived bone marrow cells (1×10⁷ per mouse) and spleen lymphocytes (2×10⁶ per mouse). The blood was removed from the eyeballs and the mouse serum was aspirated on the 7^th day after modeling. Bone marrow-derived MSCs were isolated from 1-week-old C57BL/6N male mice and incubated with 2%, 5% and 10% BMT mouse serum and aGVHD mouse serum in the medium, respectively. The effect of serum in the two groups on the in vitro adipogenic differentiation ability of mouse MSCs was detected by Oil Red O staining. The expression levels of related proteins PPARγ and CEBPα were detected by Western blot. The expression differences of key adipogenic transcription factors including PPARγ, CEBPα, FABP4 and LPL were determined by real-time quantitative PCR (RT-qPCR). RESULTS: An in vitro cell model simulating the damage of bone marrow microenvironment in mice with aGVHD was successfully established. Oil Red O staining showed that the number of orange-red fatty droplets was significantly reduced and the adipogenic differentiation ability of MSC was impaired at aGVHD serum concentration of 10% compared with BMT serum. Western blot experiments showed that adipogenesis-related proteins PPARγ and CEBPα expressed in MSCs were down-regulated. Further RT-qPCR assay showed that the production of PPARγ, CEBPα, FABP4 and LPL, the key transcription factors for adipogenic differentiation of MSC, were significantly reduced. CONCLUSION The adipogenic differentiation capacity of MSCs is inhibited by aGVHD mouse serum.
Animals ; Mesenchymal Stem Cells/cytology* ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Adipogenesis ; Female ; Cell Differentiation ; Graft vs Host Disease/blood* ; Bone Marrow Cells/cytology* ; PPAR gamma/metabolism* ; Disease Models, Animal ; CCAAT-Enhancer-Binding Protein-alpha/metabolism*

OBJECTIVE: To analyze the efficacy and safety of decitabine-based myeloablative preconditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML). METHODS: The clinical characteristics and efficacy of 115 AML patients who underwent allo-HSCT at the First Medical Center of Chinese PLA General Hospital from August 2018 to August 2022 were retrospectively analyzed, including 37 patients treated with decitabine conditioning regimen (decitabine group) and 78 patients without decitabine conditioning regimen (non-decitabine group). The cumulative incidence of relapse (CIR), overall survival (OS), leukemia-free survival (LFS), non-relapse mortality (NRM) and graft versus host disease (GVHD) were analyzed. RESULTS: For the patients in first complete remission (CR1) state before allo-HSCT, the 1-year relapse rates of decitabine group(22 cases) and non-decitabine group(69 cases) were 9.1% and 29.6%, respectively, the difference was statistically significant(P =0.042). The 1-year cumulative incidence of acute graft-versus-host disease (aGVHD) in decitabine group and non-decitabine group was 62.2% and 70.5%, respectively, and the 1-year cumulative incidence of chronic inhibitor-versus-host disease (cGVHD) was 18.9% and 14.1%, respectively, there were no significant differences in the incidence of aGVHD and cGVHD between the two groups (P >0.05). Of the 115 patients, there were no significantly differences in the 1-year CIR(21.7% vs 28.8%, P =0.866), NRM(10.9% vs 3.9%, P =0.203), OS(75.2% vs 83.8%, P =0.131) and LFS(74.6% vs 69.1%, P =0.912) between the decitabine group(37 cases) and the non-decitabine group(78 cases). CONCLUSION Decitabine-based conditioning regimen could reduce the relapse rate of AML CR1 patients with good safety.
Humans ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation/methods* ; Decitabine/therapeutic use* ; Transplantation Conditioning/methods* ; Retrospective Studies ; Graft vs Host Disease ; Transplantation, Homologous ; Male ; Female ; Adult ; Middle Aged ; Adolescent ; Young Adult

OBJECTIVE: To retrospectively analyze the clinical characteristics, co-mutated genes in newly diagnosed acute myeloid leukemia (AML) patients with NRAS and KRAS gene mutations, and the impact of NRAS and KRAS mutations on prognosis. METHODS: The clinical data and next-generation sequencing results of 80 newly diagnosed AML patients treated at our hospital from December 2018 to December 2023 were collected. The clinical characteristics, co-mutated genes of NRAS and KRAS , and the impact of NRAS and KRAS mutations on prognosis in newly diagnosed AML patients were analyzed. RESULTS: Among 80 newly diagnosed AML patients, NRAS mutations were detected in 20 cases(25.0%), and KRAS mutations were detected in 9 cases(11.3%). NRAS mutations predominantly occurred at codons 12 and 13 of exon 2, as well as codon 61 of exon 3, while KRAS mutations were most commonly occurred at codons 12 and 13 of exon 2, all of which were missense mutations. There were no statistically significant differences observed in terms of age, sex, white blood cell count(WBC), hemoglobin(Hb), platelet count(PLT), bone marrow blasts, first induction chemotherapy regimen, CR1/CRi1 rates, chromosome karyotype, 2022 ELN risk classification and allogeneic hematopoietic stem cell transplantation(allo-HSCT) among the NRAS mutation group, KRAS mutation group and NRAS/KRAS wild-type group (P >0.05). KRAS mutations were significantly correlated with PTPN11 mutations (r =0.344), whereas no genes significantly associated with NRAS mutations were found. Survival analysis showed that compared to the NRAS/KRAS wild-type group, patients with NRAS mutation had a relatively higher 5-year overall survival (OS) rate and relapse-free survival (RFS) rate, though the differences were not statistically significant (P =0.097, P =0.249). Compared to the NRAS/KRAS wild-type group, patients with KRAS mutation had a lower 5-year OS rate and RFS rate, with no significant differences observed (P =0.275, P =0.442). There was no significant difference in the 5-year RFS rate between the KRAS mutation group and NRAS mutation group (P =0.157), but the 5-year OS rate of patients with KRAS mutation was significantly lower than that of patients with NRAS mutation (P =0.037). CONCLUSION In newly diagnosed AML patients, KRAS mutation was significantly correlated with PTPN11 mutation. Compared to patients with NRAS/KRAS wild-type, those with NRAS mutation showed a more favorable prognosis, while patients with KRAS mutation showed a poorer prognosis; however, these differences did not reach statistical significance. Notably, the prognosis of AML patients with KRAS mutation was significantly inferior compared to those with NRAS mutation.
Humans ; Leukemia, Myeloid, Acute/diagnosis* ; Mutation ; Prognosis ; Proto-Oncogene Proteins p21(ras)/genetics* ; GTP Phosphohydrolases/genetics* ; Retrospective Studies ; Membrane Proteins/genetics* ; Female ; Male ; Middle Aged ; Adult ; Aged

OBJECTIVE: To explore the efficacy and adverse reactions of CAG regimen combined with venetoclax, chidamide, and azacitidine in the treatment of elderly patients with acute myeloid leukemia (AML). METHODS: 15 elderly AML patients aged≥60 years old who were admitted to the Hematology Department of our hospital from May 2022 to October 2023 were treated with the CAG regimen combined with venetoclax, chidamide and azacitidine, and the efficacy, treatment-related adverse events, overall survival (OS) and event-free survival (EFS) were analyzed. RESULTS: After one course of treatment, 11 out of 15 patients achieved complete response (CR), 3 patients achieved CR with incomplete hematologic recovery (CRi), and 1 patient died due to prior infection before efficacy evaluation, and the overall response rate (ORR) was 93.3% (14/15). The median follow-up time was 131 (19-275) days, with median OS and EFS both remaining unreached. Next-generation sequencing (NGS) analysis showed that among the 15 patients, 13 were detected with gene mutations, and there were 7 genes with mutation frequencies of more than 10%, including ASXL1 (4 cases), RUNX1 (4 cases), BCOR (3 cases), DNMT3A (3 cases), STAG2 (2 cases), IDH1/2 (2 cases), and TET (2 cases). Among the 13 patients with detectable mutations, 12 patients achieved composite response (CR+CRi). The average recovery time of white blood cell count was 14.6 days after chemotherapy, and the average recovery time of platelets was 7.7 days after chemotherapy. The main adverse event was myelosuppression, with 10 patients accompanied by infection. Except for 1 patient who died due to septic shock during chemotherapy, no patients experienced serious complications such as heart, liver, or kidney damage during the treatment process. CONCLUSION The CACAG+V regimen, which combines the CAG regimen with venetoclax, chidamide, and azacitidine, can be applied in the treatment of elderly AML patients, demonstrating good safety and induction remission rate.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Sulfonamides/therapeutic use* ; Aminopyridines/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Azacitidine/therapeutic use* ; Aged ; Benzamides/therapeutic use* ; Male ; Female ; Treatment Outcome ; Middle Aged ; Cytarabine ; Aclarubicin ; Granulocyte Colony-Stimulating Factor