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.

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 investigate the impacts of andrographolide on sciatic nerve function injury in diabetic peripheral neuropathy （DPN） rats by regulating high-mobility group protein box 1 （HMGB1）/receptor for advanced glycation end products （RAGE） signal pathway. METHODS A total of 84 rats were randomly divided into the control group （normal saline）， DPN group （normal saline）， low-dose andrographolide group （0.833 mg/kg）， high-dose andrographolide group （3.332 mg/kg）， lipoic acid group （positive control， 0.1 g/kg）， recombinant rat HMGB1 protein （rHMGB1） group （8 μg/kg）， and high-dose andrographolide+ rHMGB1 group， with 12 rats in each group. All rats except those in the control group were fed with high glucose and high fat diet combined with intraperitoneal injections of streptozotocin to establish the DPN rat model. After 24 hours of successful modeling， medication was administered daily for 8 weeks. The changes in fasting blood glucose， mechanical pain threshold， heat pain threshold and sciatic nerve conduction velocity were detected. Pathological changes in the sciatic nerve of rats and the activity of superoxide dismutase （SOD） and the content of malondialdehyde （MDA） in the sciatic nerve of rats were also detected. Besides， the expressions of HMGB1， RAGE proteins and phosphorylation level of nuclear factor κB p65（NF-κB p65） protein in rat sciatic nerves were found. RESULTS Compared with the control group， the pathological damage of the sciatic nerve of rats in the DPN group was strengthened， the fasting blood glucose， heat pain threshold， MDA content and the 诊治。E-mail：dqiaur@163.com expressions of HMGB1， RAGE proteins and phosphorylation level of NF-κB p65 protein were increased （P＜0.05）， while the mechanical pain threshold， sensory nerve conduction velocity， motor nerve conduction velocity， and SOD activity were decreased/slowed down （P＜0.05）. Compared with the DPN group， the above indexes were significantly potentiated in the andrographolide low- and high-dose groups and lipoic acid group （P＜0.05）， and the corresponding trends in the rHMGB1 group were opposite to those in the above three administration groups （P＜0.05）. Moreover， rHMGB1 attenuated the hypoglycemic effect of high-dose andrographolide on blood glucose and the improvement of oxidative stress injury in the sciatic nerve of DPN rats （P＜0.05）. CONCLUSIONS Andrographolide may reduce blood glucose by inhibiting the HMGB1/RAGE pathway and oxidative stress， thus ameliorating sciatic nerve injury in DPN rats.

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.

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.

Objective:To investigate the clinicopathological characteristics of rashes in monkeypox patients through a series of skin biopsies, and examine their pathological features and the most effective tests.Methods:Patients with monkeypox virus infection admitted to Beijing Ditan Hospital from June to August 2023 were identified. Among them, 24 patients underwent skin biopsies for clinical pathological study that were included in this study. Clinical information, rash pictures, and nucleic acid test results were analyzed using histopathology, immunohistochemistry, RNAscope ? hybridization and electron microscopy. Results:All 24 patients were male, including 14 patients with concurrent human immunodeficiency virus infection. Their average age was (32.3±5.4) years. The nucleic acid test confirmed monkeypox virus infection. The clinical feature of monkeypox rashes was solitary rather than clustered distribution, with rashes occurring in similar phase, distinguishing it from herpesvirus. The rashes in these patients were mostly scattered, with an average of (13.0±11.8) rashes, and most commonly present in the perineum, face, limbs, and trunk. The three main pathological features of these rashes were ballooning degeneration of the epidermal spinous cell layer, the characteristic intra-cytoplasmic Guarnieri′s bodies and significant infiltration of inflammatory cells in whole dermal layer. Immunohistochemistry, RNAscope ? hybridization, and electron microscopy can all effectively detect the monkeypox virus. Electron microscopy showed viral replication in various types of skin cells. Conclusions:The study describes the pathological features of monkeypox virus rashes. Pathological examination of skin biopsy samples is helpful to diagnose these rashes. The study suggests that the monkeypox virus has a unique epitheliotropic affinity and can infect various types of cells in the skin.

Wound microenvironment is directly related to the speed and quality of wound healing, and it is composed of various physical, chemical, and biological factors, and these factors are in a dynamic balance under normal conditions. In order to understand the effects of various physical, chemical, and biological factors on wound healing and to create microenvironment that can promote wound healing, this paper reviewed several wound external microenvironment factors including temperature, humidity, pH values, oxygen, microorganism, and biomechanics.

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.