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 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.

Clinical cases of necrotizing fasciitis and complete urethral defects in the scrotal region are rare. The diagnosis and treatment are very challenging. This article reports one case. The patient was admitted to the hospital after 1 week of poor urination and 2 days of scrotal swelling, and then underwent bladder diversion, surgical debridement, vacuum-sealing drainage, and wound closure. After four weeks, the wound healed and the patient was discharged. Six months later after surgery, scrotal urethral reconstruction was performed using a circular phimosis pedicled skin flap graft to repair the 12 cm urethral defect. The urethral catheter was removed after three weeks. The bladder fistula tube was removed after 5 weeks. During the follow-up of one year, there was no occurrence of urinary fistula and urinary obstruction.

Objective To study the effect of curcumin on wound healing in diabetic mice.Methods The effect of curcumin on fibroblast activity was examined by the MTT assay,and the ROS detection kit was used to detect the effect of curcumin on the hydrogen peroxide-induced scavenging effect of reactive oxygen species(ROS)in fibroblasts.Q-PCR was used to detect the effects of curcumin on the mRNA expression of inflammatory factors CD86,CD206,IL-6 and ARG1 in lipopolysaccharide-induced RAW 264.7macrophage.The wound model of diabetes was established by intraperitoneal injection of streptozotocin.Hematoxylin-eosin(HE)and Masson staining were used to evaluate wound healing and histomorphological changes,and immunofluorescence staining was used to determine skin tissue α-smooth muscle actin,CD86 and CD206 expression.Results Curcumin had no significant effect on fibroblast activity at concentrations less than 20 mol·L-1;curcumin scavenged hydrogen peroxide-induced intracellular ROS in fibroblasts;curcumin decreased the mRNA expression of CD86 and IL-6 while increasing CD206 and ARG1 in lipopolysaccharide-induced RAW 264.7 macrophages.After in vivo administration,compared with the control group,wound healing was significantly faster in the curcumin(15,30 mg·mL-1)group after 7 d and 14 d of wound perforation(P＜0.01).Hematoxylin-eosin(HE)and Masson staining results confirmed a significant increase in granulation tissue and a significant increase in collagen deposition in the curcumin(15,30 mg·mL-1)group.Immunofluorescence assay showed significantly higher expression of CD206(P＜0.01)and significantly reduced expression of CD86(P＜0.01)in the skin wounds of curcumin(15,30 mg·mL-1)for 14 d.In addition,the expression of α-SMA in the wound of the high-dose curcumin(30 mg·mL-1)group was significantly higher than that of the low-dose curcumin group(P＜0.01).Conclusion Curcumin accelerates diabetic wound healing by promoting granulation tissue proliferation and collagen deposition in refractory diabetic wounds in mice through its anti-inflammatory and antioxidant effects.

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.

Objectives:To evaluate the clinical value of the Paris system for reporting urinary cytology (TPS) in the diagnosis of urothelial carcinoma (UC).Methods:A total of 1 744 cytological diagnostic records (from 751 cases) were collected retrospectively. All specimens were voided urines and histopathology as the gold standard. The sensitivity and specificity of urinary cytological diagnosis of UC and risk of high grade malignant (ROHM) in each diagnostic category were compared.Results:There were 360 cases with histopathology. The percentage of negative for high-grade urothelial carcinoma (NHGUC) was 30.1% (226/751), atypical urothelial cells (AUC) was 29.8% (224/751), suspicious for high-grade urothelial carcinoma (SHGUC) was 16.8% (126/751), high grade urothelial carcinoma (HGUC) was 21.2% (159/751), and non-urothelial malignancy (NUM) was 2.1% (16/751). The histpathologic ROHM corresponding to each cytological diagnosis category were 27.3% for NHGUC, 32.7% for AUC, 74.7% for SHGUC, 96.6% for HGUC and 100.0% for NUM, respectively. ROHM of SHGUC was significantly higher than that of AUC group, and the difference between the two groups was statistically significant ( P＜0.001). ROHM of HGUC group was significantly higher than that of SHGUC group, and the difference was statistically significant ( P＜0.001). With SHGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 76.7% (165/215) and 85.7% (18/21), and with HGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 53.0% (114/215) and 100.0% (21/21), respectively. Conclusions:Urine cytology has high sensitivity and specificity in the diagnosis of HGUC. The malignant risk of TPS varies with different diagnosis category. The high malignant risk population in cancer hospital leads to the relatively high malignant proportion and ROHM in each diagnosis category. Urinary cytology TPS reporting system is helpful to clinical management and has good clinical application value.

Objective:To study the clinicopathological features of Sjogren′s syndrome (SS) with liver injury and to improve the understanding of this disease.Methods:Forty-nine patients with SS complicated with liver injury were collected from Beijing Ditan Hospital, Capital Medical University from October 2008 to January 2022. All patients underwent ultrasound-guided liver biopsy, and all specimens were stained with HE. The histopathologic characteristics were observed and the pathologic indexes were graded. Immunohistochemical stains for CK7, CK19, CD38, MUM1 and CD10 were performed by EnVision method; and special histochemical stains for reticulin, Masson′s trichrome, Rhodanine, Prussian blue, periodic acid Schiff (PAS) and D-PAS stains were conducted .Results:The age of patients ranged from 31 to 66 years, including 3 males and 46 females. SS combined with drug-induced liver injury was the most common (22 cases, 44.9%), followed by autoimmune liver disease (13 cases, 26.5%, including primary biliary cholangitis in eight cases, autoimmune hepatitis in 3 cases, and PBC-AIH overlap syndrome in 2 cases), non-alcoholic fatty liver disease (NAFLD, 9 cases, 18.4%) and other lesions (5 cases, 10.2%; including 3 cases of nonspecific liver inflammation, 1 case of liver amyloidosis, and 1 case of porto-sinusoidal vascular disease). Among them, 28 cases (57.1%) were associated with obvious interlobular bile duct injury, mainly in SS combined with PBC group and drug-induced liver injury group. Twenty-three cases (46.9%) were associated with hepatocyte steatosis of varying degrees. In SS with autoimmune liver disease group, ISHAK score, degree of fibrosis bile duct injury, bile duct remodeling, lymphocyte infiltration of portal area, and plasma cell infiltration, MUM1 and CD38 expression; serum ALP and GGT, IgM; elevated globulin; positive AMA, proportion of AMA-M2 positive and IgM positive were all significantly higher than those in other groups(all P<0.05). Serum ALT, direct bilirubin and SSA positive ratio in SS combined with drug liver group were significantly higher than those in other groups(all P<0.05). The serum total cholesterol level in SS combined with PBC group ( P=0.006) and NALFD group ( P=0.011) were significantly higher than those in other groups ( P<0.05). Conclusions:The pathologic manifestations of SS patients with liver injury are varied. The inflammatory lesions of SS patients with autoimmune liver disease are the most serious, and the inflammatory lesions of SS patients with non-alcoholic fatty liver disease and non-specific inflammation are mild. Comprehensive analysis of liver histopathologic changes and laboratory findings is helpful for the diagnosis of SS complicated with different types of liver injury.