OBJECTIVE: To identify the underlying mechanism by which quercetin (Que) alleviates sepsis-related acute respiratory distress syndrome (ARDS). METHODS: In vivo, C57BL/6 mice were assigned to sham, cecal ligation and puncture (CLP), and CLP+Que (50 mg/kg) groups (n=15 per group) by using a random number table. The sepsisrelated ARDS mouse model was established using the CLP method. In vitro, the murine alveolar macrophages (MH-S) cells were classified into control, lipopolysaccharide (LPS), LPS+Que (10 μmol/L), and LPS+Que+acetylcysteine (NAC, 5 mmol/L) groups. The effect of Que on oxidative stress, inflammation, and apoptosis in mice lungs and MH-S cells was determined, and the mechanism with reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (MAPK) pathway was also explored both in vivo and in vitro. RESULTS: Que alleviated lung injury in mice, as reflected by a reversal of pulmonary histopathologic changes as well as a reduction in lung wet/dry weight ratio and neutrophil infiltration (P<0.05 or P<0.01). Additionally, Que improved the survival rate and relieved gas exchange impairment in mice (P<0.01). Que treatment also remarkedly reduced malondialdehyde formation, superoxide dismutase and catalase depletion, and cell apoptosis both in vivo and in vitro (P<0.05 or P<0.01). Moreover, Que treatment diminished the release of inflammatory factors interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 both in vivo and in vitro (P<0.05 or P<0.01). Mechanistic investigation clarifified that Que administration led to a decline in the phosphorylation of p38 MAPK in addition to the suppression of ROS expression (P<0.01). Furthermore, in LPS-induced MH-S cells, ROS inhibitor NAC further inhibited ROS/p38 MAPK pathway, as well as oxidative stress, inflammation, and cell apoptosis on the basis of Que treatment (P<0.05 or P<0.01). CONCLUSION Que was found to exert anti-oxidative, anti-inflammatory, and anti-apoptotic effects by suppressing the ROS/p38 MAPK pathway, thereby conferring protection for mice against sepsis-related ARDS.
Animals ; Sepsis/drug therapy* ; Quercetin/therapeutic use* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism* ; Apoptosis/drug effects* ; Male ; Oxidative Stress/drug effects* ; MAP Kinase Signaling System/drug effects* ; Lung/drug effects* ; Mice ; Lipopolysaccharides ; Macrophages, Alveolar/pathology* ; Inflammation/pathology* ; Protective Agents/therapeutic use*

Objective:To investigate the mechanisms of baicalin in treating septic acute liver injury through a combination of network pharmacology and animal experiments.Methods:Thirty male C57BL/6 mice (6 weeks old) were divided into five groups ( n=6): control group (normal saline), model group [lipopolysaccharide (LPS) 10 mg/kg, intraperitoneal injection], low-dose baicalin group (10 mg/kg), high-dose baicalin group (20 mg/kg), and baicalin-only group (20 mg/kg, without LPS). Baicalin was administered orally for 14 consecutive days prior to modeling. Mice were sacrificed 24 h after LPS injection. Alanine transaminase, aspartate transaminase liver tissue histopathology were measured; neutrophil infiltration was visualized using immunofluorescence; mRNA expression levels of interleukin (IL)-1β, IL-17, IL-6, and tumor necrosis factor (TNF)-α were detected by RT-qPCR; and the expression of Toll-like receptor 4 (TLR4) and phosphorylated nuclear factor (NF)-κB proteins were analyzed by Western blotting. Results:In the LPS model group, the ALT, AST, and histopathological injury score were (148.60±22.02) U/L, (81.58±11.59) U/L, and 8.50(7.75, 9.25), respectively. These indicators were significantly reduced in the high-dose baicalin group with (77.90±16.79) U/L, (49.92±14.89) U/L, and 1.00(1.00, 2.25) (all P<0.05). Compared with the LPS group, neutrophil infiltration in the liver of high-dose baicalin group was also significantly reduced [1.18%(0.98%, 1.22%) vs. 6.13%(5.41%, 8.69%), P<0.05]. RT-qPCR results showed that the relative mRNA expression levels of inflammatory cytokines IL-1β [(1.03±0.06) vs. (2.60±0.34)], IL-17 [(1.21±0.12) vs. (2.94 ± 0.39)], IL-6 [(1.37±0.26) vs. (2.73±0.18)], and TNF-α [(1.18±0.10) vs. (3.30±0.92)] were significantly decreased in the high-dose baicalin group compared with the LPS group (all P<0.05). Western blot analysis revealed that the relative protein expression levels of TLR4 [(1.25±0.13) vs. (1.73±0.06)] and phosphorylated NF-κB [(1.25±0.25) vs. (1.79±0.12)] were also significantly lower in the high-dose baicalin group (both P<0.05). Conclusion:Baicalin reduces liver injury in septic mice by downregula-ting the expression of pro-inflammatory cytokines IL-1β, IL-6, TNF-α, and IL-17, potentially through the inhibition of the TLR4/NF-κB signaling pathway.

Tripterygium wilfordii multiglucoside,the primary active constituent of the Chinese materia medica of Tripterygium wilfordii,has anti-inflammatory and immune-regulation properties and is widely used to treat kidney and rheumatic and immunological diseases.However,the potential adverse effects of Tripterygium wilfordii multiglucoside on pediatric gonadal development have limited its clinical application in pediatrics.According to the traditional Chinese medicine theory,the reproductive toxicity of Tripterygium wilfordii is closely associated with deficiency in kidney essence and tian gui disorder.Based on the"kidney essence-tian gui"theory,this study elucidates the transformation of"kidney essence to tian gui"through the qi transformation of"original noumenon to supreme ultimate,"which is synergistically regulated by the accumulation of kidney qi,consolidation of spleen qi,and conveyance and dispersion of liver qi.It is channeled through the interconnected pathways of the thoroughfare channel,conception channel,and governor channel.The physiological process of"kidney essence to tian gui"is damaged by the bitter,cold,and toxicity of Tripterygium wilfordii,leading to kidney asthenia,spleen deficiency,liver depression,and meridian stagnation,causing tian gui dysregulation.Therefore,this study offers traditional Chinese medicine prevention and treatment strategies for pediatric medication safety,including nourishing the kidney essence to replenish the tian gui source,enhancing the middle jiao to strengthen the tian gui guard,regulating liver qi to promote the operation of tian gui,and unblocking the thoroughfare channel,conception channel,and governor channel to ensure the unobstructed pathway of tian gui.

ObjectiveTo investigate the role of 4-week high-intensity interval training (HIIT) in modulating the metabolic homeostasis of the pyruvate-lactate axis in the hippocampus of rats with chronic unpredictable mild stress (CUMS) to improve their depressive-like behavior. MethodsForty-eight SPF-grade 8-week-old male SD rats were randomly divided into 4 groups: the normal quiet group (C), the CUMS quiet group (M), the normal exercise group (HC), and the CUMS exercise group (HM). The M and HM groups received 8 weeks of CUMS modeling, while the HC and HM groups were exposed to 4 weeks of HIIT starting from the 5th week (3 min (85%-90%) S_max+1 min (50%-55%) S_max, 3-5 cycles, S_max is the maximum movement speed). A lactate analyzer was used to detect the blood lactate concentration in the quiet state of rats in the HC and HM groups at week 4 and in the 0, 2, 4, 8, 12, and 24 h after exercise, as well as in the quiet state of rats in each group at week 8. Behavioral indexes such as sucrose preference rate, number of times of uprightness and number of traversing frames in the absenteeism experiment, and other behavioral indexes were used to assess the depressive-like behavior of the rats at week 4 and week 8. The rats were anesthetized on the next day after the behavioral test in week 8, and hippocampal tissues were taken for assay. LC-MS non-targeted metabolomics, target quantification, ELISA and Western blot were used to detect the changes in metabolite content, lactate and pyruvate concentration, the content of key metabolic enzymes in the pyruvate-lactate axis, and the protein expression levels of monocarboxylate transporters (MCTs). Results4-week HIIT intervention significantly increased the sucrose preference rate, the number of uprights and the number of traversed frames in the absent field experiment in CUMS rats; non-targeted metabolomics assay found that 21 metabolites were significantly changed in group M compared to group C, and 14 and 11 differential metabolites were significantly dialed back in the HC and HM groups, respectively, after the 4-week HIIT intervention; the quantitative results of the targeting showed that, compared to group C, lactate concentration in the hippocampal tissues of M group, compared with group C, lactate concentration in hippocampal tissue was significantly reduced and pyruvate concentration was significantly increased, and 4-week HIIT intervention significantly increased the concentration of lactate and pyruvate in hippocampal tissue of HM group; the trend of changes in blood lactate concentration was consistent with the change in lactate concentration in hippocampal tissue; compared with group C, the LDHB content of group M was significantly increased, the content of PKM2 and PDH, as well as the protein expression level of MCT2 and MCT4 were significantly reduced. The 4-week HIIT intervention upregulated the PKM2 and PDH content as well as the protein expression levels of MCT2 and MCT4 in the HM group. ConclusionThe 4-week HIIT intervention upregulated blood lactate concentration and PKM2 and PDH metabolizing enzymes in hippocampal tissues of CUMS rats, and upregulated the expression of MCT2 and MCT4 transport carrier proteins to promote central lactate uptake and utilization, which regulated metabolic homeostasis of the pyruvate-lactate axis and improved depressive-like behaviors.

ObjectiveThis study aimed to investigate the effects of 4-week high-intensity interval training (HIIT) on synaptic plasticity in the prefrontal cortex (PFC) of rats exposed to chronic unpredictable mild stress (CUMS), and to explore its potential mechanisms. MethodsA total of 48 male Sprague-Dawley rats were randomly divided into 4 groups: control (C), model (M), control plus HIIT (HC), and model plus HIIT (HM). Rats in groups M and HM underwent 8 weeks of CUMS to establish depression-like behaviors, while groups HC and HM received HIIT intervention beginning from the 5th week for 4 consecutive weeks. The HIIT protocol consisted of repeated intervals of 3 min at high speed (85%-90% maximal training speed, S_max) alternated with one minute at low speed (50%-55% S_max), with 3 to 5 sets per session, conducted 5 d per week. Behavioral assessments and tail-vein blood lactate levels were measured at the end of the 4th and 8th weeks. After the intervention, rat PFC tissues were collected for Golgi staining to analyze synaptic morphology. Enzyme-linked immunosorbent assays (ELISA) were employed to detect brain-derived neurotrophic factor (BDNF), monocarboxylate transporter 1 (MCT1), lactate, and glutamate levels in the PFC, as well as serotonin (5-HT) levels in serum. Additionally, Western blot analysis was conducted to quantify the expression of synaptic plasticity-related proteins, including c-Fos, activity-regulated cytoskeleton-associated protein (Arc), and N-methyl-D-aspartate receptor 1 (NMDAR1). ResultsCompared to the control group (C), the CUMS-exposed rats (group M) exhibited significant reductions in sucrose preference rates, number of grid crossings, frequency of upright postures, and entries into and duration spent in open arms of the elevated plus maze, indicating marked depressive-like behaviors. Additionally, the group M showed significantly reduced dendritic spine density in the PFC, along with elevated levels of c-Fos, Arc, NMDAR1 protein expression, and increased concentrations of lactate and glutamate. Conversely, BDNF and MCT1 contents in the PFC and 5-HT levels in serum were significantly decreased. Following HIIT intervention, rats in the group HM displayed considerable improvement in behavioral indicators compared with the group M, accompanied by significant elevations in PFC MCT1 and lactate concentrations. Furthermore, HIIT notably normalized the expression levels of c-Fos, Arc, NMDAR1, as well as glutamate and BDNF contents in the PFC. Synaptic spine density also exhibited significant recovery. ConclusionFour weeks of HIIT intervention may alleviate depressive-like behaviors in CUMS rats by increasing lactate levels and reducing glutamate concentration in the PFC, thereby downregulating the overexpression of NMDAR, attenuating excitotoxicity, and enhancing synaptic plasticity.

Tripterygium wilfordii multiglucoside,the primary active constituent of the Chinese materia medica of Tripterygium wilfordii,has anti-inflammatory and immune-regulation properties and is widely used to treat kidney and rheumatic and immunological diseases.However,the potential adverse effects of Tripterygium wilfordii multiglucoside on pediatric gonadal development have limited its clinical application in pediatrics.According to the traditional Chinese medicine theory,the reproductive toxicity of Tripterygium wilfordii is closely associated with deficiency in kidney essence and tian gui disorder.Based on the"kidney essence-tian gui"theory,this study elucidates the transformation of"kidney essence to tian gui"through the qi transformation of"original noumenon to supreme ultimate,"which is synergistically regulated by the accumulation of kidney qi,consolidation of spleen qi,and conveyance and dispersion of liver qi.It is channeled through the interconnected pathways of the thoroughfare channel,conception channel,and governor channel.The physiological process of"kidney essence to tian gui"is damaged by the bitter,cold,and toxicity of Tripterygium wilfordii,leading to kidney asthenia,spleen deficiency,liver depression,and meridian stagnation,causing tian gui dysregulation.Therefore,this study offers traditional Chinese medicine prevention and treatment strategies for pediatric medication safety,including nourishing the kidney essence to replenish the tian gui source,enhancing the middle jiao to strengthen the tian gui guard,regulating liver qi to promote the operation of tian gui,and unblocking the thoroughfare channel,conception channel,and governor channel to ensure the unobstructed pathway of tian gui.

Objective:To investigate the mechanisms of baicalin in treating septic acute liver injury through a combination of network pharmacology and animal experiments.Methods:Thirty male C57BL/6 mice (6 weeks old) were divided into five groups ( n=6): control group (normal saline), model group [lipopolysaccharide (LPS) 10 mg/kg, intraperitoneal injection], low-dose baicalin group (10 mg/kg), high-dose baicalin group (20 mg/kg), and baicalin-only group (20 mg/kg, without LPS). Baicalin was administered orally for 14 consecutive days prior to modeling. Mice were sacrificed 24 h after LPS injection. Alanine transaminase, aspartate transaminase liver tissue histopathology were measured; neutrophil infiltration was visualized using immunofluorescence; mRNA expression levels of interleukin (IL)-1β, IL-17, IL-6, and tumor necrosis factor (TNF)-α were detected by RT-qPCR; and the expression of Toll-like receptor 4 (TLR4) and phosphorylated nuclear factor (NF)-κB proteins were analyzed by Western blotting. Results:In the LPS model group, the ALT, AST, and histopathological injury score were (148.60±22.02) U/L, (81.58±11.59) U/L, and 8.50(7.75, 9.25), respectively. These indicators were significantly reduced in the high-dose baicalin group with (77.90±16.79) U/L, (49.92±14.89) U/L, and 1.00(1.00, 2.25) (all P<0.05). Compared with the LPS group, neutrophil infiltration in the liver of high-dose baicalin group was also significantly reduced [1.18%(0.98%, 1.22%) vs. 6.13%(5.41%, 8.69%), P<0.05]. RT-qPCR results showed that the relative mRNA expression levels of inflammatory cytokines IL-1β [(1.03±0.06) vs. (2.60±0.34)], IL-17 [(1.21±0.12) vs. (2.94 ± 0.39)], IL-6 [(1.37±0.26) vs. (2.73±0.18)], and TNF-α [(1.18±0.10) vs. (3.30±0.92)] were significantly decreased in the high-dose baicalin group compared with the LPS group (all P<0.05). Western blot analysis revealed that the relative protein expression levels of TLR4 [(1.25±0.13) vs. (1.73±0.06)] and phosphorylated NF-κB [(1.25±0.25) vs. (1.79±0.12)] were also significantly lower in the high-dose baicalin group (both P<0.05). Conclusion:Baicalin reduces liver injury in septic mice by downregula-ting the expression of pro-inflammatory cytokines IL-1β, IL-6, TNF-α, and IL-17, potentially through the inhibition of the TLR4/NF-κB signaling pathway.

This umbrella review aimed to summarize and provide a general evaluation of the effectiveness of current treatments for male infertility and assess the quality of evidence and possible biases. An umbrella review of systematic reviews and meta-analyses available in PubMed, Web of Science, and Scopus, covering studies published up to October 2023, was conducted. Sperm concentration, morphology, and motility were used as endpoints to evaluate the effectiveness of the treatments. Of 2998 studies, 18 published meta-analyses were extracted, yielding 90 summary effects on sperm concentration ( n = 36), sperm morphology ( n = 26), and sperm motility ( n = 28) on 28 interventions. None of the meta-analyses were classified as having low methodological quality, whereas 12 (66.7%) and 6 (33.3%) had high and moderate quality, respectively. Of the 90 summary effects, none were rated high-evidence quality, whereas 53.3% ( n = 48), 25.6% ( n = 23), and 21.1% ( n = 19) were rated moderate, low, and very low, respectively. Significant improvements in sperm concentration, morphology, and motility were observed with pharmacological interventions (N-acetyl-cysteine, antioxidant therapy, aromatase inhibitors, selective estrogen receptor modulators, hormones, supplements, and alpha-lipoic acid) and nonpharmacological interventions (varicocele repair and redo varicocelectomy). In addition, vitamin supplementation had no significant positive effects on sperm concentration, motility, or morphology. Treatments for male infertility are increasingly diverse; however, the current evidence is poor because of the limited number of patients. Further well-designed studies on single treatment and high-quality meta-analysis of intertreatment comparisons are recommended.
Humans ; Male ; Antioxidants/therapeutic use* ; Infertility, Male/therapy* ; Meta-Analysis as Topic ; Sperm Count ; Sperm Motility ; Systematic Reviews as Topic

Hepatohilar cholangiocarcinoma is a common malignant tumor of the biliary system,and radical surgery is one of the important treatment methods.Due to the narrow space at the hi-lum and the high rate of anatomical variation,radical surgery is challenging.By using medical imag-ing technology and 3D reconstruction,surgeons can accurately determine the stage and classifica-tion of hilar cholangiocarcinoma preoperatively.They can assess the tumor's resectability by Ac-cording to the bile duct separation limit points(U point,P point)and anticipate the impact of portal vein,bile duct,and arterial variations on the surgical plan,thereby improving the rate of radical re-section and reducing complication rates.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.