Acute respiratory distress syndrome (ARDS) is the leading cause of respiratory failure with high morbidity and mortality. Pulmonary surfactant (PS)-based complementary therapies have exhibited potential for ARDS healing and applied as an adjunctive therapy strategy. Coacervate (Coac) has the characteristics of softness, deformability and excellent molecular enrichment properties, and has attracted extensive attention in the biomedical field. Here PS and coacervate were combined for the potential ARDS treatment. The Coac, fabricated from polyallylamine hydrochloride (PAH) and adenosine triphosphate (ATP) by simple mixing, exhibited soft droplet property and high enrichment for dexamethasone sodium phosphate (DSP). To avoid the fusion effect of membraneless coacervate and endow it with biological functions of PS, liposomes with PS-biomimetic lipid components (PS-lipo) were further introduced to construct PS-biomimetic membranized coacervate (DSP@PS-Coac). The DSP@PS-Coac demonstrated high lung targeting effect and significant penetration efficiency after intravenous injection. Furthermore, PS-lipo replenished the endogenous PS pool and facilitated the distribution of DSP in inflammatory cells in the lung. In the ARDS mouse model, PS-Coac and DSP exerted synergetic anti-inflammatory functions, via reducing the recruitment of inflammatory neutrophils and modulating macrophages into anti-inflammatory phenotype. The overall results confirmed that DSP@PS-Coac may provide a promising delivery option for the treatment of ARDS.

Objective:To evaluate the clinical efficacy of the V-shaped bone tunnel technique at the base of the distal phalanx for treating tendinous mallet finger.Methods:A retrospective analysis was conducted on clinical data from patients with tendinous mallet finger treated in the Department of Hand and Foot Surgery at Linyi People’s Hospital between August 2022 and November 2023. Two oblique bone tunnels were created in a V-shaped configuration at the dorsal base of the distal phalanx, adjacent to the extensor tendon insertion, using a 0.8 mm Kirschner wire. A 4-0 double-needle monofilament tendon suture was passed through the tunnels to secure the ruptured extensor tendon to the base of the distal phalanx, followed by fixation of the distal interphalangeal (DIP) joint with a 1.0 mm Kirschner wire. The Kirschner wire was removed at 4 weeks postoperatively to initiate functional exercises. Regular follow-up was conducted to monitor wound healing and functional recovery of the DIP joint. At the final follow-up, the range of flexion and extension of the DIP joint was measured, and treatment outcomes were evaluated using Crawford’s mallet finger evaluation criteria, which classified results into four grades: excellent, good, fair, and poor.Results:Fifteen patients (16 fingers) were included, comprising 11 males and 4 females, with a mean age of 44.5 years (range: 17-65 years). The injured fingers included 2 index, 4 middle, 5 ring, and 5 little fingers, all presenting with DIP joint flexion deformity and limited active extension. Postoperative follow-up ranged from 6 to 28 months (mean: 17 months). All wounds healed primarily without complications such as infection or skin necrosis, and no cases of tendon re-rupture occurred. At the final follow-up, the measurement results of flexion and extension range of motion of the affected fingers at the DIP joint were as follows: the maximum flexion angle of all 16 fingers was 45°, among which 7 fingers had an extension angle of 0°, 8 fingers had limited extension ranging from 1° to 10°, and 1 finger had limited extension of 15°. Among the 16 fingers, 7 fingers were rated as excellent, 8 fingers as good and 1 finger as fair.Conclusion:The V-shaped bone tunnel technique for tendon-to-bone reattachment of the extensor tendon insertion is a simple and effective method for treating tendinous mallet finger. It provides satisfactory functional recovery, improves finger appearance, and is associated with minimal complications.

Objective:To explore the reliability of intraoperative fluoroscopy at lateral 10° and 30° Brodén views in addition to the standard lateral and axial calcaneal views in the lateral decubitus position to assess the quality of articular reduction in calcaneal fractures of Sanders types Ⅱ and Ⅲ.Methods:A retrospective study was conducted to analyze the clinical data of the 74 patients who had been treated at Department of Foot and Ankle Surgery, The People’s Hospital of Linyi for unilateral closed calcaneal fractures of Sanders type Ⅱ or Ⅲ from January 2024, to August 2024. According to the different methods of intraoperative fluoroscopy, the patients were divided into a precision group and a conventional group. In the precision group of 39 cases, intraoperative fluoroscopy was conducted at lateral 10° and 30° Brodén views in the surgery for calcaneal fractures in addition to the standard lateral and axial calcaneal views in the lateral decubitus position; in the conventional group of 35 cases, intraoperative fluoroscopy was conducted only in the standard lateral and axial calcaneal views in the surgery for calcaneal fractures. All patients were treated by traction assisted by external fixation, minimally invasive prying reduction through the tarsal sinus incision, and three-dimensional framework internal fixation. The 2 groups were compared in terms of frequency of intraoperative fluoroscopy; preoperative and postoperative B?hler angles, Gissane angles, and calcaneal varus angles; screw protrusions (more than 2 mm beyond the medial cortex) of the posterior articular surface screw, sustentaculum tali screw, and anterior tuberosity screw; skin irritation symptoms due to the main nail tail (protruding cortex > 1 mm); step-off of the posterior articular surface (more than 2 mm) and wide gap of the posterior articular surface (more than 2 mm).Results:There were no statistically significant differences in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). Both groups showed significant postoperative improvements in X-ray B?hler angle, Gissane angle, and calcaneal varus angle compared with the preoperative values ( P<0.05). There were no statistically significant differences in postoperative X-ray B?hler angle, Gissane angle, or calcaneal varus angle between the 2 groups ( P>0.05). There was no statistically significant difference in the frequency of intraoperative fluoroscopy between the 2 groups either ( P>0.05). The precision group had significantly fewer cases of screw protrusion (more than 2 mm beyond the medial cortex) of the posterior articular surface screw, sustentaculum tali screw, and anterior tuberosity screw, skin irritation symptoms due to the main screw tail (protruding cortex>1 mm), step-off of the posterior articular surface (more than 2 mm), and wide gap of the posterior articular surface (more than 2 mm) on the postoperative CT three-dimensional reconstruction compared with the conventional group ( P<0.05). Conclusion:In surgery for calcaneal fractures of Sanders types Ⅱ and Ⅲ, intraoperative fluoroscopy at lateral 10° and 30° Brodén views in addition to the standard lateral and axial calcaneal views in the lateral decubitus position provides stable and reliable intraoperative monitoring of B?hler angle, Gissane angle, calcaneal varus angle, reduction of the posterior articular surface of the calcaneus and the positions and lengths of implants.

Objective:To evaluate the clinical efficacy of the V-shaped bone tunnel technique at the base of the distal phalanx for treating tendinous mallet finger.Methods:A retrospective analysis was conducted on clinical data from patients with tendinous mallet finger treated in the Department of Hand and Foot Surgery at Linyi People’s Hospital between August 2022 and November 2023. Two oblique bone tunnels were created in a V-shaped configuration at the dorsal base of the distal phalanx, adjacent to the extensor tendon insertion, using a 0.8 mm Kirschner wire. A 4-0 double-needle monofilament tendon suture was passed through the tunnels to secure the ruptured extensor tendon to the base of the distal phalanx, followed by fixation of the distal interphalangeal (DIP) joint with a 1.0 mm Kirschner wire. The Kirschner wire was removed at 4 weeks postoperatively to initiate functional exercises. Regular follow-up was conducted to monitor wound healing and functional recovery of the DIP joint. At the final follow-up, the range of flexion and extension of the DIP joint was measured, and treatment outcomes were evaluated using Crawford’s mallet finger evaluation criteria, which classified results into four grades: excellent, good, fair, and poor.Results:Fifteen patients (16 fingers) were included, comprising 11 males and 4 females, with a mean age of 44.5 years (range: 17-65 years). The injured fingers included 2 index, 4 middle, 5 ring, and 5 little fingers, all presenting with DIP joint flexion deformity and limited active extension. Postoperative follow-up ranged from 6 to 28 months (mean: 17 months). All wounds healed primarily without complications such as infection or skin necrosis, and no cases of tendon re-rupture occurred. At the final follow-up, the measurement results of flexion and extension range of motion of the affected fingers at the DIP joint were as follows: the maximum flexion angle of all 16 fingers was 45°, among which 7 fingers had an extension angle of 0°, 8 fingers had limited extension ranging from 1° to 10°, and 1 finger had limited extension of 15°. Among the 16 fingers, 7 fingers were rated as excellent, 8 fingers as good and 1 finger as fair.Conclusion:The V-shaped bone tunnel technique for tendon-to-bone reattachment of the extensor tendon insertion is a simple and effective method for treating tendinous mallet finger. It provides satisfactory functional recovery, improves finger appearance, and is associated with minimal complications.

Objective:To explore the reliability of intraoperative fluoroscopy at lateral 10° and 30° Brodén views in addition to the standard lateral and axial calcaneal views in the lateral decubitus position to assess the quality of articular reduction in calcaneal fractures of Sanders types Ⅱ and Ⅲ.Methods:A retrospective study was conducted to analyze the clinical data of the 74 patients who had been treated at Department of Foot and Ankle Surgery, The People’s Hospital of Linyi for unilateral closed calcaneal fractures of Sanders type Ⅱ or Ⅲ from January 2024, to August 2024. According to the different methods of intraoperative fluoroscopy, the patients were divided into a precision group and a conventional group. In the precision group of 39 cases, intraoperative fluoroscopy was conducted at lateral 10° and 30° Brodén views in the surgery for calcaneal fractures in addition to the standard lateral and axial calcaneal views in the lateral decubitus position; in the conventional group of 35 cases, intraoperative fluoroscopy was conducted only in the standard lateral and axial calcaneal views in the surgery for calcaneal fractures. All patients were treated by traction assisted by external fixation, minimally invasive prying reduction through the tarsal sinus incision, and three-dimensional framework internal fixation. The 2 groups were compared in terms of frequency of intraoperative fluoroscopy; preoperative and postoperative B?hler angles, Gissane angles, and calcaneal varus angles; screw protrusions (more than 2 mm beyond the medial cortex) of the posterior articular surface screw, sustentaculum tali screw, and anterior tuberosity screw; skin irritation symptoms due to the main nail tail (protruding cortex > 1 mm); step-off of the posterior articular surface (more than 2 mm) and wide gap of the posterior articular surface (more than 2 mm).Results:There were no statistically significant differences in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). Both groups showed significant postoperative improvements in X-ray B?hler angle, Gissane angle, and calcaneal varus angle compared with the preoperative values ( P<0.05). There were no statistically significant differences in postoperative X-ray B?hler angle, Gissane angle, or calcaneal varus angle between the 2 groups ( P>0.05). There was no statistically significant difference in the frequency of intraoperative fluoroscopy between the 2 groups either ( P>0.05). The precision group had significantly fewer cases of screw protrusion (more than 2 mm beyond the medial cortex) of the posterior articular surface screw, sustentaculum tali screw, and anterior tuberosity screw, skin irritation symptoms due to the main screw tail (protruding cortex>1 mm), step-off of the posterior articular surface (more than 2 mm), and wide gap of the posterior articular surface (more than 2 mm) on the postoperative CT three-dimensional reconstruction compared with the conventional group ( P<0.05). Conclusion:In surgery for calcaneal fractures of Sanders types Ⅱ and Ⅲ, intraoperative fluoroscopy at lateral 10° and 30° Brodén views in addition to the standard lateral and axial calcaneal views in the lateral decubitus position provides stable and reliable intraoperative monitoring of B?hler angle, Gissane angle, calcaneal varus angle, reduction of the posterior articular surface of the calcaneus and the positions and lengths of implants.

Interactions between brain-resident and peripheral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia. However, conventional bulk sequencing makes it challenging to depict this complex immune network. Using single-cell RNA sequencing, we mapped compositional and transcriptional features of peri-infarct immune cells. Microglia were the predominant cell type in the peri-infarct region, displaying a more diverse activation pattern than the typical pro- and anti-inflammatory state, with axon tract-associated microglia (ATMs) being associated with neuronal regeneration. Trajectory inference suggested that infiltrated monocyte-derived macrophages (MDMs) exhibited a gradual fate trajectory transition to activated MDMs. Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis, with SOX2 and related Akt/CREB signaling as the underlying mechanisms. This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.
Humans ; Ischemic Stroke ; Brain/metabolism* ; Macrophages ; Brain Ischemia/metabolism* ; Microglia/metabolism* ; Gene Expression Profiling ; Anti-Inflammatory Agents ; Neuronal Plasticity/physiology* ; Infarction/metabolism*

The mesencephalic astrocyte-derived neurotrophic factor (MANF) has been recently identified as a neurotrophic factor, but its role in hepatic fibrosis is unknown. Here, we found that MANF was upregulated in the fibrotic liver tissues of the patients with chronic liver diseases and of mice treated with CCl₄. MANF deficiency in either hepatocytes or hepatic mono-macrophages, particularly in hepatic mono-macrophages, clearly exacerbated hepatic fibrosis. Myeloid-specific MANF knockout increased the population of hepatic Ly6C^high macrophages and promoted HSCs activation. Furthermore, MANF-sufficient macrophages (from WT mice) transfusion ameliorated CCl₄-induced hepatic fibrosis in myeloid cells-specific MANF knockout (MKO) mice. Mechanistically, MANF interacted with S100A8 to competitively block S100A8/A9 heterodimer formation and inhibited S100A8/A9-mediated TLR4-NF-κB signal activation. Pharmacologically, systemic administration of recombinant human MANF significantly alleviated CCl₄-induced hepatic fibrosis in both WT and hepatocytes-specific MANF knockout (HKO) mice. This study reveals a mechanism by which MANF targets S100A8/A9-TLR4 as a "brake" on the upstream of NF-κB pathway, which exerts an impact on macrophage differentiation and shed light on hepatic fibrosis treatment.

Objective:This study aims to explore the event-related potentials (ERPs) response to alcohol visual cues and their correlations with subjective craving in patients with alcohol dependence (AD) and to search for brain source regions associated with alcohol craving.Methods:Twenty male inpatients with AD were recruited as alcohol-dependent group and 18 healthy men as the control group. ERPs evoked by visual Oddball paradigm containing alcohol cues were tested in both groups and standardized low-resolution brain electromagnetic tomography (sLORETA) was used for brain source localization of ERPs-P300.Visual Analogue Scale (VAS) and Penn Alcohol Craving Scale (PACS) were used for subjective craving assessment. Difference analysis of ERPs data in two groups was performed by mixed-design analysis of variance. The permutation test was used to analyze the difference between two groups of brain source localization. Spearman correlation analysis was conducted between ERPs data, drinking habits, and scale data.Results:Compared with the control group, the alcohol-dependent group showed significantly longer P300 peak latency ( F=9.32, P=0.004) and higher P300 amplitude ( F=20.59, P<0.01; F=14.74, P<0.01) of Fz/Cz when viewing alcohol cues images, and P300 brain source regions were significantly more active in the bilateral dorsolateral prefrontal cortex and right superior parietal lobule ( P<0.01). In the alcohol-dependent group, alcohol cues images evoked significantly longer P300 peak latency ( F=33.82, P<0.01) and higher P300 amplitude ( F=12.56, P=0.001; F=10.92, P=0.002) of Fz/Cz than fruit images, and P300 brain source regions were significantly more active in the left insular cortex and right parahippocampal gyrus ( P<0.01). The P300 amplitude evoked by alcohol cues was positively correlated with VAS and PACS scores ( r s=0.590, P=0.048; r s=0.780, P<0.01). Conclusion:ERPs evoked by visual alcohol cues may help to objectively evaluate craving-related psychology in patients with AD. The bilateral dorsolateral prefrontal cortex, right inferior parietal lobule, left insular cortex, and right parahippocampal gyrus may be related to alcohol craving.

Objective:This study aims to explore the event-related potentials (ERPs) response to alcohol visual cues and their correlations with subjective craving in patients with alcohol dependence (AD) and to search for brain source regions associated with alcohol craving.Methods:Twenty male inpatients with AD were recruited as alcohol-dependent group and 18 healthy men as the control group. ERPs evoked by visual Oddball paradigm containing alcohol cues were tested in both groups and standardized low-resolution brain electromagnetic tomography (sLORETA) was used for brain source localization of ERPs-P300.Visual Analogue Scale (VAS) and Penn Alcohol Craving Scale (PACS) were used for subjective craving assessment. Difference analysis of ERPs data in two groups was performed by mixed-design analysis of variance. The permutation test was used to analyze the difference between two groups of brain source localization. Spearman correlation analysis was conducted between ERPs data, drinking habits, and scale data.Results:Compared with the control group, the alcohol-dependent group showed significantly longer P300 peak latency ( F=9.32, P=0.004) and higher P300 amplitude ( F=20.59, P<0.01; F=14.74, P<0.01) of Fz/Cz when viewing alcohol cues images, and P300 brain source regions were significantly more active in the bilateral dorsolateral prefrontal cortex and right superior parietal lobule ( P<0.01). In the alcohol-dependent group, alcohol cues images evoked significantly longer P300 peak latency ( F=33.82, P<0.01) and higher P300 amplitude ( F=12.56, P=0.001; F=10.92, P=0.002) of Fz/Cz than fruit images, and P300 brain source regions were significantly more active in the left insular cortex and right parahippocampal gyrus ( P<0.01). The P300 amplitude evoked by alcohol cues was positively correlated with VAS and PACS scores ( r s=0.590, P=0.048; r s=0.780, P<0.01). Conclusion:ERPs evoked by visual alcohol cues may help to objectively evaluate craving-related psychology in patients with AD. The bilateral dorsolateral prefrontal cortex, right inferior parietal lobule, left insular cortex, and right parahippocampal gyrus may be related to alcohol craving.

Objective:Diffusion tensor imaging (DTI) was used to explore the structural integrity of white matter fibers in male alcohol-dependent patients.Methods:DTI scans were performed on 33 male alcohol dependent patients (alcohol dependence group) and 30 healthy adult males (control group). The image data was analyzed by using FSL (Funtional MRI Software Library) software on the Matlab platform, and the two groups were compared based on the TBSS (tract based spatial statistics) method. White matter fiber anisotropy fractional anisotropy (FA) and mean diffusivity (MD) between the two groups were investigated by t test. Results:Compared with the control group, the FA value of the corpus callosum knees decreased (0.55±0.03 vs. 0.58±0.02； t=-3.26, P<0.05), the FA value of the left hippocampus decreased (0.42±0.06 vs. 0.46±0.06； t=-2.69, P<0.05), and the MD value of the left hippocampus increased (122±9 vs. 115±12； t=2.58, P<0.05), the MD value of the left frontal lobe area increased (121±7 vs. 116±11； t=2.50, P<0.05), the MD value of the left frontal bridge bundle increased (122±8 vs. 115±10； t=2.79, P<0.05). Conclusion:Alcohol-dependent patients have abnormal DTI signals representing a damaged structural integrity of white matter fibers in the corpus callosum, hippocampus, and frontal lobe.