Vascular cognitive impairment (VCI), caused by cerebrovascular dysfunction, severely impacts the quality of life in the elderly population, yet effective therapeutic approaches remain limited. Mitophagy, a selective mitochondrial quality-control mechanism, has emerged as a critical focus in neurological disease research. Accumulating evidence indicates that mitophagy modulates oxidative stress, neuroinflammation, and neuronal apoptosis. Key signaling pathways associated with mitophagy—including PINK1/Parkin, BNIP3/Nix, FUNDC1, PI3K/Akt/mTOR, and AMPK—have been identified as potential therapeutic targets for VCI. This review summarizes the mechanistic roles of mitophagy in VCI pathogenesis and explores emerging therapeutic strategies targeting these pathways, aiming to provide novel insights for clinical intervention and advance the development of effective treatments for VCI.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both Na_V1.7, Na_V1.8, and Na_V1.9 and K_V7 channels, a crucial regulator in controlling NP symptoms. The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP. Through an experimental design involving both in vitro and in vivo methods, E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury (CCI) mouse model. The results demonstrated that E0199 significantly inhibited Na_V1.7, Na_V1.8, and Na_V1.9 channels with a particularly low half maximal inhibitory concentration (IC₅₀) for Na_V1.9 by promoting sodium channel inactivation, and also effectively increased K_V7.2/7.3, K_V7.2, and K_V7.5 channels, excluding K_V7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses, indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically. The safety of E0199 was supported by neurobehavioral evaluations. Conclusively, E0199 represents a ground-breaking approach in NP treatment, showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

Increasing evidence showed that histone deacetylase 6 (HDAC6) dysfunction is directly associated with the onset and progression of various diseases, especially cancers, making the development of HDAC6-targeted anti-tumor agents a research hotspot. In this study, artificial intelligence (AI) technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline, which combined Voting strategy based on compound-protein interaction (CPI) prediction models, cascade molecular docking, and molecular dynamic (MD) simulations. The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays. Among the identified compounds, Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity (IC₅₀ = 5.41 nM) than that of tubastatin A (TubA) (IC₅₀ = 15.11 nM), along with a favorable subtype selectivity profile (selectivity index ≈ 117.23 for HDAC1), which was further verified by the Western blot analysis. Additionally, Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells, exerting desirable antiproliferative activity (IC₅₀ = 2.59 μM). Furthermore, based on long-term MD simulation trajectory, the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis, thereby elucidating its binding mechanism. Moreover, the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation, thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.

Objective:To investigate the effects of extracorporeal carbon dioxide removal (ECCO 2R) combined with continuous renal replacement therapy (CRRT) on respiratory efficiency and diaphragm function in patients with acute respiratory distress syndrome (ARDS) received mechanical ventilation. Methods:A prospective randomized controlled study was conducted. Sixty patients with mild to moderate ARDS admitted to the department of respiratory and critical care medicine of Henan Provincial People's Hospital from January 2019 to January 2021 were enrolled, and they were divided into observation group and control group according to the random number table method, with 30 cases in each group. All patients received antibiotics, anti-inflammatory, and mechanical ventilation therapy. On this basis, the observation group received ECCO 2R and CRRT, while the control group received bedside CRRT. Baseline data including gender, age, etiology, acute physiology and chronic health evaluationⅡ(APACHEⅡ), etc., were recorded. Arterial blood gas analysis [including arterial partial pressure of oxygen (PaO 2), arterial partial pressure of carbon dioxide (PaCO 2), and oxygenation index (PaO 2/FiO 2)] was performed at 12 hours and 24 hours during the treatment, and respiratory mechanics parameters [including tidal volume, respiratory rate, maximum expiratory pressure (MEP), and maximum inspiratory pressure (MIP)] were recorded, and rapid shallow breathing index (RSBI) was calculated. The levels of glutathione peroxidase (GSH-Px), malondialdehyde (MDA), and superoxide dismutase (SOD) in serum were detected by enzyme-linked immunosorbent assay (ELISA). Diaphragm thickness and diaphragm activity were measured by ultrasonography at 24 hours during the treatment. Results:There were no significantly differences in age, gender, etiology, and APACHEⅡ score between the two groups, indicating that the baseline data of the two groups were balanced and comparable. Compared with the 12 hours after treatment, the PaO 2 and PaO 2/FiO 2 in the observation group significantly increased, PaCO 2 significantly decreased, RSBI significantly decreased, MEP and MIP significantly increased, and serum GSH-Px and MDA significantly decreased, while SOD significantly increased at 24 hours during the treatment. In the control group, only PaCO 2 significantly decreased. Compared with the control group, the PaCO 2 significantly decreased in the observation group at 12 hours and 24 hours [mmHg (1 mmHg≈0.133 kPa): 55.05±7.57 vs. 59.49±6.95, 52.77±7.88 vs. 58.25±6.92, both P < 0.05], but no significantly differences in PaO 2 and PaO 2/FiO 2. Compared with the control group, the observation group showed significant decreases in RSBI at 12 hours and 24 hours (times·min -1·L -1: 85.92±8.83 vs. 90.38±3.78, 75.73±3.86 vs. 90.05±3.66, both P < 0.05), significant increases in MEP and MIP [MEP (mmH 2O, 1 mmH 2O≈0.01 kPa): 86.64±5.99 vs. 83.88±4.18, 93.70±5.59 vs. 85.04±3.73; MIP (mmH 2O): 44.19±6.66 vs. 41.17±3.13, 57.52±5.28 vs. 42.34±5.39, all P < 0.05], and significant decreases in serum GSH-Px and MDA [GSH-Px (mg/L): 78.52±8.72 vs. 82.10±3.37, 57.11±4.67 vs. 81.17±5.13; MDA (μmol/L): 7.84±1.97 vs. 8.71±0.83, 3.67±0.78 vs. 8.41±1.09, all P < 0.05], as well as a significant increase in SOD (U/L: 681.85±49.24 vs. 659.40±26.47, 782.32±40.56 vs. 676.65±51.97, both P < 0.05). Compared with the control group, the observation group showed significant increases in diaphragm thickness and diaphragm activity at 24 hours of treatment [diaphragm thickness (cm): 1.93±0.28 vs. 1.40±0.24, diaphragmatic thickening fraction: (0.22±0.04)% vs. (0.19±0.02)%, quiet breathing diaphragm displacement (cm): 1.42±0.13 vs. 1.36±0.06, deep breathing diaphragm displacement (cm): 5.11±0.75 vs. 2.64±0.59, all P < 0.05]. Conclusion:ECCO 2R combined with CRRT can reduce work of breathing and oxidative stress levels in ARDS patients receiving non-invasive ventilation, and protect diaphragm function.

As the global population continues to age,the incidence of neurodegenerative diseases has seen a constant increase in the elderly.Research indicates that neuroinflammation is a significant pathological mechanism in neurodegenerative diseases such as Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,multiple sclerosis and Huntington's disease.Astrocytes are key glial cells involved in the regulation of neuroinflammation.More studies have revealed that astrocytes closely interact with other glial cells,neurons and peripheral immune cells to regulate synaptic plasticity,neuronal function,glutamate cycling and energy metabolism in the central nervous system,which shows notable therapeutic effects on neurodegenerative diseases.This paper aims to further explore specific manifestations and potential molecular mechanisms of astrocyte-mediated inflammatory processes in neurodegenerative diseases through interactions of astrocytes and other cells,therefore to identify new therapeutic targets from the perspective of astrocytes and then improve the symptoms.

The human immune system plays a key role in maintaining tissue homeostasis and disease progression. The development of biomaterials that can regulate the innate immune system and adapt to the immune system has great application prospects in the field of tissue engineering. This paper discusses how to design the surface interface topographies or the physicochemical properties of biomaterials, to regulate the fate of macrophages, such as activation, polarization, adhesion, migration, proliferation, and secretion. At the same time, the application of these biomaterials with immunoregulation function in the field of wound healing is discussed. In addition, this paper also put forward the limitations of biomaterials in immunoregulation applications and prospected the future development directions.

Objective:To explore the abnormalities of functional brain networks and their relationship with behavioral scale scores in patients with spinal cerebellar ataxia (SCA) type 3 using MRI.Methods:The study was a cross-sectional study. Clinical and imaging data of 52 patients with SCA type 3 (SCA type 3 group) and 55 normal control group admitted to the First Affiliated Hospital of Army Medical University from May 2017 to May 2023 were prospectively analyzed. All participants underwent structural and resting-state functional MRI. Graph theory analysis assessed global and nodal properties of brain network connectivity, including clustering coefficient (Cp), characteristic path length (Lp), normalized clustering coefficient (γ), normalized characteristic path length (λ), small-world index (σ), global efficiency (Eglob), local efficiency (Eloc), assortativity, and nodal efficiency. The area under the curve (AUC) for global attribute parameters was calculated and a two-sample t-test was used to compare the AUC values of the global attribute parameters between the 2 groups, and corrected for false discovery rate correction (FDR). A two-sample t-test was used to compare the node efficiencies of the 2 groups, corrected for network-based statistics (NBS), and the brain regions with significant differences in node efficiencies between the 2 groups were selected as the brain regions of interest, and a two-sample t-test was used to compare the differences in resting state functional connectivity (rsFC) values between the brain regions of interest and other brain regions in the SCA type 3 group and the normal control group, corrected for NBS. Spearman test was used to correlate significantly different rsFC values ( P<0.01) between the 2 groups and their clinical behavioral scores. Results:Compared with the normal control group, the AUC value of Cp for brain network connectivity was significantly increased in the SCA type 3 group ( Z=2.05, P=0.043), whereas the differences in γ, λ, σ, Eglob, Eloc, Lp, and homozygosity were not statistically significant between the 2 groups (all P>0.05). The SCA type 3 group had significantly lower nodal efficiency in the left precuneus ( t=-2.16, NBS corrected P=0.033) and left inferotemporal gyrus ( t=-2.25, NBS corrected P=0.027), and significantly higher nodal efficiency in the right lentiform nucleus ( t=2.05, NBS corrected P=0.043) and left middle temporal gyrus ( t=2.25, NBS corrected P=0.027) compared to normal control group. Significant alterations in rsFC values were found between multiple brain regions in SCA type 3 patients, correlating with clinical data and behavioral assessment scores. Conclusions:SCA type 3 patients exhibit specific alterations in brain functional networks, including changes in clustering coefficient and nodal efficiency. Furthermore, rsFC between brain regions correlates with behavioral abnormalities.

Femoral head fracture combined with posterior hip dislocation is a serious traumatic condition. Conservative treatment has a long time of bed rest, and may cause muscle apraxia atrophy, hypostatic pneumonia, deep vein thrombosis of the lower limbs, or pulmonary embolism, which has poor clinical efficacy. Therefore, surgical treatment is the first choice for femoral head fracture combined with posterior hip dislocation. The direct anterior approach of the hip can better expose Pipkin type I and type II femoral head fractures without the need to dislocate the hip completely. However, the disadvantage is that it destroys the structural integrity of the anterior hip joint, which increases the risk of femoral head necrosis and heterotopic ossification to a certain extent. The medial approach can also be chosen for Pipkin type I and II fractures, but it is important to avoid damaging the integrity of the fascial layer, some small vascular branches can be ligated, and injury to the medial rotary femoral artery should be avoided. The lateral approach is considered to be an effective treatment for Pipkin type III fractures, but there is limited exposure of the posterior acetabular injury and a risk of injury to the superior gluteal vessels and nerves, which may be secondary to adductor weakness postoperatively. The posterior approach is the main surgical approach for type IV Pipkin fracture. The classic posterior lateral approaches mainly include the Kocher - Langenbeck approach and the Ganz surgical dislocation approach. The Kocher - Langenbeck approach does not destroy the abductors and is particularly suitable for patients with posterior hip dislocation and difficult to reposition. Ganz surgical approach protects the blood supply of the medial femoral circumcator artery, so the incidence of femoral head necrosis is low. It can achieve all-round visualization of the femoral head and acetabulum, comprehensively evaluate the lesions of the femoral head and acetabulum, and find the occult injuries missed in imaging examinations..

Objective:To explore the application and research progress of lasers in the treatment of kidney neoplasms through an integrated bibliometric and Meta-analysis study.Methods:On June 7th, 2024, an online search of the Web of Science Core Collection (WoSCC) and China National Knowledge Infrastructure (CNKI) databases for all relevant literature on lasers in kidney neoplasms was conducted. The retrieved results were subjected to a comprehensive bibliometric analysis. The high-quality studies were then screened to further describe the clinical characteristics of patients who underwent laser-assisted laparoscopic partial nephrectomy (LLPN). Subsequently, a Meta-analysis was performed using RevMan 5.4.1 software on further selected high-quality studies to compare the changes in renal function before and after LLPN treatment, and the differences in efficacy between LLPN and traditional laparoscopic partial nephrectomy (LPN).Results:Our study obtained a total of 549 publications on lasers in kidney neoplasms, including 513 in English and 36 in Chinese. Bibliometric analysis revealed an overall upward trend in the annual publications and citations in this field. China was found to be a leading contributor ranking second in total publications ( n=100, 18.2%). The primary application of laser treatment was in nephron-sparing surgery for kidney neoplasms, especially in LPN. We further screened 11 high-quality studies comprising 284 patients who underwent LLPN for kidney neoplasms. Comprehensive descriptive statistical analysis was performed on clinical characteristics of the 284 patients. All patients had T 1a stage tumors with a mean tumor length of 2.6 cm (range: 0.8-4.0 cm), all being local, solitary, and exophytic tumors. Further Meta-analysis indicated that there were no significant differences in renal function indicators including both serum creatinine levels ( MD=4.52, 95% CI-9.73-0.69, P = 0.09) and estimated glomerular filtration rate ( MD=3.05, 95% CI-1.03-7.13, P= 0.14) before and after LLPN. Additionally, compared to traditional LPN, LLPN showed significantly reduced operative time ( MD=-10.58, 95% CI= -13.11-8.06, P<0.001), but no significant differences in estimated blood loss ( MD= -27.09, 95% CI-67.38-13.21, P=0.19) and hospital stay ( MD=-1.59, 95% CI-3.42-0.25, P=0.09). Conclusions:The application of lasers in managing of kidney neoplasms is arousing increasing attention among urologists. LLPN offers several advantages, including precise cutting and effective hemostasis. This technique demonstrates considerable clinical value for patients with exophytic T 1a kidney neoplasms undergoing "zero-ischemia" nephron-sparing surgery.