Alzheimer's disease (AD), a prototypical neurodegenerative disorder, encompasses multifaceted pathological processes. As pivotal cellular structures within the central nervous system, ion channels play critical roles in regulating neuronal excitability, synaptic transmission, and neurotransmitter release. Extensive research has revealed significant alterations in the expression and function of ion channels in AD, implicating an important role of ion channels in the pathogenesis of abnormal Aβ deposition, neuroinflammation, oxidative stress, and disruptions in calcium homeostasis and neural network functionality. This review systematically summarizes the crucial roles and underlying mechanisms of ion channels in the onset and progression of AD, highlighting how these channel abnormalities contribute to AD pathophysiology. We also discuss the therapeutic potential of ion channel modulation in AD treatment, emphasizing the importance of addressing multifactorial nature and heterogeneity of AD. The development of multi-target drugs and precision therapies is proposed as a future direction of scientific research.
Alzheimer Disease/therapy* ; Humans ; Ion Channels/physiology* ; Oxidative Stress ; Animals ; Amyloid beta-Peptides/metabolism* ; Synaptic Transmission ; Calcium/metabolism*

OBJECTIVE: To assess the efficacy and safety of Erzhu Jiedu Decoction (EZJDD) Granules in treating mid-advanced hepatitis B virus-associated primary liver cancer (HBV-PLC) patients with Pi (Spleen)-deficiency and dampness-heat syndrome. METHODS: From January 2021 to June 2023, a cohort of 132 patients were enrolled and randomly assigned to a control group or a EZJDD group according to the random numbers, with 66 patients in each group. The patients in the control group received conventional treatment for 3 months, followed by a 3-month follow-up. In addition to the conventional treatment, patients in the EZJDD group were administered EZJDD Granules (10.9 g/pack, 2 packs twice per day) orally for same duration. Progression-free survival (PFS) as primary outcome was evaluated by Kaplan Meier method. Karnofsky performance status (KPS) scores were used to assess the quality of life in two groups before and after treatment, and survival rates were determined as well. The efficacy of Chinese medicine syndrome was calculated with Nimodipine method. Liver function, tumor indicators and T lymphocyte subsets were measured, respectively. Safety indicators were recorded and assessed. RESULTS: Of the 116 patients who completed the study, 57 were in the control group and 59 in the EZJDD group. The median PFS was 3.53 months (106 days) in the EZJDD group compared to 2.33 months (70 days) in the control group (P=0.005). Six-month survival rate was 52.63% (30/57) in the control group and 69.49% (41/59) in the EZJDD group (P=0.039). The median KPS score in the EZJDD group [70(63, 90)] was higher than that in the control group [70(60, 80)] (P=0.013). The total effective rate of CM syndrome was 52.63% (30/57) in the control group and 77.97% (46/59) in the EZJDD group (P=0.005). The levels of alpha fetoprotein, alpha fetoprotein-L3, alpha-L-fucosidase and protein induced by Vitamin K absence or antagonist- II in the EZJDD group increased less than the control group (P>0.05). CD8⁺ levels were decreased, while CD3⁺ and CD4⁺ levels, as well as CD4⁺/CD8⁺ ratio were significantly increased in the EZZJD group (P<0.05). No treatment-related adverse reactions were observed during the study. CONCLUSION EZJDD Granules significantly prolonged the median PFS and improved 6-month survival rate in patients with mid-advanced HBV-PLC (Registration No. ChiCTR2200056922).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Liver Neoplasms/complications* ; Hepatitis B virus/physiology* ; Hepatitis B/complications* ; Treatment Outcome ; Adult ; Spleen/drug effects* ; Quality of Life ; Medicine, Chinese Traditional ; Aged ; Syndrome

italic>Anoectochilus roxburghii liquid (spray, a hospital preparation of Wu Mengchao Hepatobiliary Hospital of Fujian Medical University) has shown a good clinical treatment effect during the COVID-19 pandemic, but its material basis and mechanism of action are still unclear. In this study, network pharmacology and molecular docking methods were used to predict the molecular mechanism of A. roxburghii liquid against COVID-19, and pharmacodynamic experiments in vitro were conducted to study the interaction between the current targets with clear preventive and therapeutic effects and the key components of A. roxburghii liquid. UPLC-MS and database were used to compare and analyze the active ingredients in the liquid, and 17 potential active ingredients with good drug-like properties were screened by in vivo pharmacokinetics process in SwissADME database. SwissTargetPrediction and GeneCards were searched to find 93 common targets. Cytoscape 3.8.2 software was used to construct the "component-target" network map, and the Metascape platform was used for gene function annotation and pathway enrichment analysis. It was found that the extract could regulate the positive response to external stimuli, inflammatory response, cytokine production and other biological processes by binding the active ingredients such as isorhamnetin, kaempferol, luteolin, quercetin and apigenin to the common targets (NOS3, MPO, MMP3, etc.), and play an anti-COVID-19 role. In the angiotensin-converting enzyme 2 (ACE2) activity inhibition assay, it was found that the stock solution of A. roxburghii liquid (for spray), and the supernatant after removing polysaccharides (mainly containing flavonoids) could to some extent inhibit the activity of ACE2. Crucially, in the experiment of 2019-nCOV-S pseudovirus infecting HEK-293T-ACE2 cells, we found that A. roxburghii liquid may exert anti-COVID-19 effects by blocking the binding of SARS-CoV-S protein to ACE2.

Objective:To discuss the clinical curative effect of the treatment of bundling bone fragment with figure-of-eight suture through double bone tunnels in the chronic bony mallet finger.Methods:A retrospective analysis was performed on patients with chronic bony mallet fingers who underwent surgery in the Department of Hand and Foot Microsurgery of Nanjing Jiangbei Hospital from May 2021 to February 2023. During the procedure, made into transverse double bone tunnels on the base of the distal phalanx with 0.8 mm Kirschner wire, bundling bone fragment with figure-of-eight suture through double bone tunnels, then fixed with Kirschner wire elastic compression. Removal of the Kirschner wire 3 weeks after the procedure, the active flexion and extension range of the joints of the affected finger and the corresponding finger were measured at the last follow-up, then the range of motion (ROM) of the distal interphalangeal joint (DIPJ) and total action movement (TAM) of the fingers (affected and healthy finger) were recorded. The curative effects were evaluated according to the TAM system of the American Association of Hand Surgeons, including 4 grades: excellent, good, fair, and poor. SPSS 13.0 software was used for statistical analysis of the data, and the measurement data conforming to normal distribution were expressed as Mean±SD. The ROM of DIPJ and TAM of the affected finger were compared with the corresponding healthy finger 6 months after surgery by a paired sample t-test. P<0.05 indicated that the difference was statistically significant. Results:A total of 30 patients (30 digits) were enrolled, including 19 males and 11 females, and the age ranged from 18 to 62 years old, with an average age of 31 years old. The time from injury to operation was 24 to 65 days (mean of 35 days). According to Wehbe and Schneider classification, there were 8 cases of type Ⅰa, 6 cases of type Ⅰb, 7 cases of type Ⅱa, 5 cases of type Ⅱb, 2 cases of type Ⅲa and 2 cases of type Ⅲb. All incisions healed well, the intraoperative blood loss was minimal, with no infection. All 30 cases were followed up for 6 to 7 months. All fractures were well aligned and healed, malformed fingers were completely corrected, and no needle tunnel infection or needle breakage were observed. At the last follow-up, the differences of the ROM of the DIPJ [(30.2±3.5)° vs. (30.4±3.3)°, t=2.57, P=0.463] and the TAM [(235.3±3.6)° vs. (237.7±4.2)°, t=1.78, P=0.247] between the affected and healthy fingers were not statistically significant. Finger function assessment: 27 cases were excellent, and 3 cases were good, and the excellent and good rate was 100%. Conclusion:Satisfactory therapeutic outcome for the treatment of chronic bony mallet finger deformity can be achieved by bundling bone fragment with figure-of-eight suture through double bone tunnels. It is an effective and practical method.

Objective To develop a matrix metalloproteinase(MMP)-responsive hyaluronic acid(HA)-based controlled-release material for brain-derived neurotrophic factor(BDNF)to provide a novel therapeutic strategy for intervention and repair of traumatic brain injury(TBI).Methods HA was modified with amination,followed by condensation with Suflo-SMCC carboxyl group to form amide,and then linked with glutathione(GSH)to synthesize HA-GSH.The recombinant glutathione S-transferase(GST)-tissue inhibitor of metalloproteinase(TIMP)-BDNF(GST-TIMP-BDNF)expression plasmid was constructed using molecular cloning technique with double enzyme digestion by Bam H Ⅰ and Eco R Ⅰ.The recombinant GST-TIMP-BDNF protein was expressed in the Escherichia coli prokaryotic expression system,and purified by ion exchange chromatography,confirmed by Western blotting.MMP diluents were supplemented with PBS,MMP inhibitor marimastat,and varing concentrations(0.4,0.6,0.8 mg/ml)of GST-TIMP-BDNF or GST-BDNF.MMP-2 activity was analyzed using an MMP activity detection kit to evaluate the inhibitory effect of the recombinant protein on MMP.Primary rat neurons were extracted and cultured to establish an iron death model induced by RSL3.The effect of recombinant protein GST-TIMP-BDNF on neuronal injury was detected by immunofluorescence staining.Results MRI hydrogen spectrum identification confirmed the successful synthesis of HA-GSH.Western blotting results showed the successful expression of the recombinant protein GST-TIMP-BDNF containing the GST tag using the E.coli prokaryotic expression system.MMP activity detection results indicated that the recombinant protein GST-TIMP-BDNF had a superior inhibitory effect on MMP-2 activity compared to GST-BDNF(P<0.05).Immunofluorescence staining results showed a significant increase in fluorescence intensity in rat neurons treated with GST-TIMP-BDNF after RSL3 induction(P<0.05).Conclusion A MMP-responsive HA-based BDNF controlled-release material has been successfully developed,exhibiting a protective effect on neuron damage.

Objective:To discuss the clinical curative effect of the treatment of bundling bone fragment with figure-of-eight suture through double bone tunnels in the chronic bong mallet finger.Methods:A retrospective analysis was performed on patients with chronic bong mallet fingers who underwent surgery in the Department of Hand and Foot Microsurgery of Nanjing Jiangbei Hospital from May 2021 to February 2023. During the procedure, made into transverse double bone tunnels on the base of the distal phalanx with 0. 8 mm Kirschner wire, bundling bone fragment with figure-of-eight suture through double bone tunnels, then fixed with Kirschner wire elastic compression. Removal of the Kirschner wire 3 weeks after the procedure, the active flexion and extension range of the joints of the affected finger and the corresponding finger were measured at the last follow-up, then the range of motion (ROM) of the distal interphalangeal joint (DIPJ) and total action movement (TAM) of the fingers (affected and healthy finger) were recorded. The curative effects were evaluated according to the TAM system of the American Association of Hand Surgeons, including 4 grades: excellent, good, fair, and poor. SPSS 13. 0 software was used for statistical analysis of the data, and the measurement data conforming to normal distribution were expressed as Mean ± SD. The ROM of DIPJ and TAM of the affected finger were compared with the corresponding healthy finger 6 months after surgery by a paired sample t test. P<0. 05 indicates that the difference is statistically significant. Results:A total of 30 patients (30 digits) were enrolled, including 19 males and 11 females, and the age ranged from 18 to 62 years old, with an average age of 31 years old. The time from injury to operation was 24 to 65 days (mean of 35 days) . According to Wehbe and Schneider classification, there were 8 cases of type Ⅰa, 6 cases of type Ⅰb, 7 cases of type Ⅱa, 5 cases of type Ⅱb, 2 cases of type Ⅲa and 2 cases of type Ⅲb. All incisions healed well, the intraoperative blood loss was minimal, with no infection. All 30 cases were followed up for 6 to 7 months. All fractures were well aligned and healed, malformed fingers were completely corrected, and no needle tunnel infection or needle breakage were observed. At the last follow-up, the differences of the ROM of the DIPJ [ (30. 2±3. 5) °vs. (30. 4±3. 3) °, t=2. 57, P=0. 463] and the TAM [ (235. 3± 3. 6) ° vs. (237. 7± 4. 2) °, t=1. 78, P= 0. 247 ] between the affected and healthy fingers were not statistically significant. Finger function assessment: 27 cases were excellent, and 3 cases were good, and the excellent and good rate was 100%. Conclusion:Satisfactory therapeutic outcome for the treatment of chronic bong mallet finger deformity can be achieved by bundling bone fragment with figure-of-eight suture through double bone tunnels. It is an effective and practical method.

Objective:To discuss the clinical curative effect of the treatment of bundling bone fragment with figure-of-eight suture through double bone tunnels in the chronic bong mallet finger.Methods:A retrospective analysis was performed on patients with chronic bong mallet fingers who underwent surgery in the Department of Hand and Foot Microsurgery of Nanjing Jiangbei Hospital from May 2021 to February 2023. During the procedure, made into transverse double bone tunnels on the base of the distal phalanx with 0. 8 mm Kirschner wire, bundling bone fragment with figure-of-eight suture through double bone tunnels, then fixed with Kirschner wire elastic compression. Removal of the Kirschner wire 3 weeks after the procedure, the active flexion and extension range of the joints of the affected finger and the corresponding finger were measured at the last follow-up, then the range of motion (ROM) of the distal interphalangeal joint (DIPJ) and total action movement (TAM) of the fingers (affected and healthy finger) were recorded. The curative effects were evaluated according to the TAM system of the American Association of Hand Surgeons, including 4 grades: excellent, good, fair, and poor. SPSS 13. 0 software was used for statistical analysis of the data, and the measurement data conforming to normal distribution were expressed as Mean ± SD. The ROM of DIPJ and TAM of the affected finger were compared with the corresponding healthy finger 6 months after surgery by a paired sample t test. P<0. 05 indicates that the difference is statistically significant. Results:A total of 30 patients (30 digits) were enrolled, including 19 males and 11 females, and the age ranged from 18 to 62 years old, with an average age of 31 years old. The time from injury to operation was 24 to 65 days (mean of 35 days) . According to Wehbe and Schneider classification, there were 8 cases of type Ⅰa, 6 cases of type Ⅰb, 7 cases of type Ⅱa, 5 cases of type Ⅱb, 2 cases of type Ⅲa and 2 cases of type Ⅲb. All incisions healed well, the intraoperative blood loss was minimal, with no infection. All 30 cases were followed up for 6 to 7 months. All fractures were well aligned and healed, malformed fingers were completely corrected, and no needle tunnel infection or needle breakage were observed. At the last follow-up, the differences of the ROM of the DIPJ [ (30. 2±3. 5) °vs. (30. 4±3. 3) °, t=2. 57, P=0. 463] and the TAM [ (235. 3± 3. 6) ° vs. (237. 7± 4. 2) °, t=1. 78, P= 0. 247 ] between the affected and healthy fingers were not statistically significant. Finger function assessment: 27 cases were excellent, and 3 cases were good, and the excellent and good rate was 100%. Conclusion:Satisfactory therapeutic outcome for the treatment of chronic bong mallet finger deformity can be achieved by bundling bone fragment with figure-of-eight suture through double bone tunnels. It is an effective and practical method.

Objective:To discuss the clinical curative effect of the treatment of bundling bone fragment with figure-of-eight suture through double bone tunnels in the chronic bony mallet finger.Methods:A retrospective analysis was performed on patients with chronic bony mallet fingers who underwent surgery in the Department of Hand and Foot Microsurgery of Nanjing Jiangbei Hospital from May 2021 to February 2023. During the procedure, made into transverse double bone tunnels on the base of the distal phalanx with 0.8 mm Kirschner wire, bundling bone fragment with figure-of-eight suture through double bone tunnels, then fixed with Kirschner wire elastic compression. Removal of the Kirschner wire 3 weeks after the procedure, the active flexion and extension range of the joints of the affected finger and the corresponding finger were measured at the last follow-up, then the range of motion (ROM) of the distal interphalangeal joint (DIPJ) and total action movement (TAM) of the fingers (affected and healthy finger) were recorded. The curative effects were evaluated according to the TAM system of the American Association of Hand Surgeons, including 4 grades: excellent, good, fair, and poor. SPSS 13.0 software was used for statistical analysis of the data, and the measurement data conforming to normal distribution were expressed as Mean±SD. The ROM of DIPJ and TAM of the affected finger were compared with the corresponding healthy finger 6 months after surgery by a paired sample t-test. P<0.05 indicated that the difference was statistically significant. Results:A total of 30 patients (30 digits) were enrolled, including 19 males and 11 females, and the age ranged from 18 to 62 years old, with an average age of 31 years old. The time from injury to operation was 24 to 65 days (mean of 35 days). According to Wehbe and Schneider classification, there were 8 cases of type Ⅰa, 6 cases of type Ⅰb, 7 cases of type Ⅱa, 5 cases of type Ⅱb, 2 cases of type Ⅲa and 2 cases of type Ⅲb. All incisions healed well, the intraoperative blood loss was minimal, with no infection. All 30 cases were followed up for 6 to 7 months. All fractures were well aligned and healed, malformed fingers were completely corrected, and no needle tunnel infection or needle breakage were observed. At the last follow-up, the differences of the ROM of the DIPJ [(30.2±3.5)° vs. (30.4±3.3)°, t=2.57, P=0.463] and the TAM [(235.3±3.6)° vs. (237.7±4.2)°, t=1.78, P=0.247] between the affected and healthy fingers were not statistically significant. Finger function assessment: 27 cases were excellent, and 3 cases were good, and the excellent and good rate was 100%. Conclusion:Satisfactory therapeutic outcome for the treatment of chronic bony mallet finger deformity can be achieved by bundling bone fragment with figure-of-eight suture through double bone tunnels. It is an effective and practical method.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*