Objective:To explore the effects of passive distraction training modalities on aging skeletal muscle cells and its underlying mechanisms,and to provide experimental data on effective interventions for patients with severe loss of locomotor capacity in severe skeletal sarcopenia.Method:An in vitro skeletal muscle cell aging model by C2C12 differentiated skeletal muscle cells with D-ga-lactose stimulation were established.Aging skeletal muscle cells were subjected to cyclic stretch(0.5Hz,24h)using an FX-5000 Flex Cell Tension system.Senescence and oxidative stress levels were assessed through mito-chondrial membrane potential,antioxidant content,EdU assay,and β-galactosidase staining.The expression of AMPK/PGC-α/FOXO3 signaling molecules related to muscle cell protein synthesis and decomposition in the cells was analyzed by Western Blot.Result:Passive stretching significantly reduced the positive rate of aging in senescent skeletal muscle cells(18.03%±6.82%)compared with the aging group(42.86%±10.54%,P<0.05).The expression levels of intracellu-lar AMPK and PGC-1α significantly increased after passive stretching,while the expression of FOXO3 de-creased significantly compared to the aging group(P<0.05).In addition,passive stretching increased the mito-chondrial membrane potential but appeared to reduce the antioxidant content in aging skeletal muscle cells,po-tentially related to changes in PGC-1α expression levels.Conclusion:Passive stretching improved the aging state of skeletal muscle cells by modulating the AMPK/PGC-1α/FOXO3 signaling pathway and oxidative stress levels,revealing the great potential of passive stretch-ing as the treatment for severe sarcopenia.

Objective To explore the mechanism of Yizhu Wendan Decoction in treating eczema through GEO database combined with network pharmacology and experimental verification.Methods TCMSP,BATMAN-TCM and ETCM databases were used to screen the active components of Yizhu Wendan Decoction.Disease target information related to eczema was collected through GEO database.The drug-component-target network and PPI network were constructed by intersections of active component targets and disease targets.GO and KEGG pathway enrichment analyses were performed using DAVID database.CCK-8 method was used to screen out the optimal intervention concentration of freeze-dried powder of Yizhu Wendan Decoction.HaCaT cells were divided into control group,model group,Yizhu Wendan Decoction low concentration group,Yizhu Wendan Decoction high concentration group,si-IL-17RA group,si-IL-17RA+Yizhu Wendan Decoction low concentration group,si-IL-17RA+Yizhu Wendan Decoction high concentration group,Dexamethasone group,si-IL-17RA+Dexamethasone group.Each group was given relevant intervention.The expressions of chemokines and inflammatory factors were detected by qPCR.EdU and Annexin V-FITC/PI double staining were used to detect cell proliferation and apoptosis.Western blot was performed to detect the expressions of proteins related to apoptosis,skin barrier and IL-17 signaling pathway.Results By using databases,180 active components of Yizhu Wendan Decoction were obtained.Combined with GEO database microarrays related to eczema(GSE6012 and GSE57225),8 potential targets of Yizhu Wendan Decoction in the treatment of eczema were obtained.KEGG enrichment pathway mainly involved IL-17 signaling pathway,lipid and atherosclerotic,TNF signaling pathway,fluid shear stress and atherosclerotic,etc.When Yizhu Wendan Decoction freeze-dried powder concentration was 100 μg/mL,cell viability was the strongest.Yizhu Wendan Decoction could significantly inhibit the mRNA expressions of chemokines and inflammatory factors CCL17,CCL22,IL-1β,TNF-α,IL-6,IFN-γ,and increase the mRNA expression of IL-4 in eczema.It promoted the proliferation of HaCaT cells,increased the protein expression of Bcl-2,and reduced the protein expressions of Bad and Cleaved Caspase-3,thus inhibiting HaCaT cells apoptosis;promoted the protein expressions of FLG and LOR,and reduced the expression of MMP9,MMP1,CCL2,FOSL1,IL-17RA proteins in IL-17 signaling pathway.Conclusion Yizhu Wendan Decoction can treat eczema with multiple components,multiple pathways and multiple targets,promote the proliferation of HaCaT cells,inhibit their apoptosis,and restore the skin barrier.Its mechanism may be related to inhibiting the activation of IL-17 signaling pathway.

The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has posed a global challenge to the control of the coronavirus disease 2019 (COVID-19) pandemic. Therefore, developing countermeasures that broadly protect against SARS-CoV-2 and related sarbecoviruses is essential. Herein, we have developed a lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) encoding the full-length Spike (S) glycoprotein of SARS-CoV-2 (termed RG001), which confers complete protection in a non-human primate model. Intramuscular immunization of two doses of RG001 in Rhesus monkey elicited robust neutralizing antibodies and cellular response against SARS-CoV-2 variants, resulting in significantly protected SARS-CoV-2-infected animals from acute lung lesions and complete inhibition of viral replication in all animals immunized with low or high doses of RG001. More importantly, the third dose of RG001 vaccination elicited effective neutralizing antibodies against current epidemic XBB and JN.1 strains and similar cellular response against SARS-CoV-2 Omicron variants (BA.1, XBB.1.16, and JN.1) were observed in immunized mice. All these results together strongly support the great potential of RG001 in preventing the infection of SARS-CoV-2 variants of concern (VOCs).

Objective:To continuously track the publishing budget of provincial Center for Disease Control and Prevention (CDC)in China and comprehend the management changes in the provincial CDCs based on the financial input.Methods:Publishing budget data for the period 2021—2024 of 31 provincial CDCs and provincial health administrations in China were collected and analyzed from the perspectives of time change and proportion relationship.Results:Statistical analysis revealed that the overall budget income of provincial CDCs in 2024 exceeded that of 2021.Most provincial CDCs in many provinces exhibited high-level growth(some with slight fluctuations),stable growth,and rapid growth in budget income changes.The proportion of provincial CDCs'budget income relative to provincial health administrations steadily increased,and the synergistic relationship mainly manifested as increase in the same direction,but there is a situation of changing from"strong benign"to"weak benign".Conclusion:The development of the budget income for provincial CDCs in China aligns with the imperative to establish a stable public health investment mechanism,reflecting more support towards provincial CDCs in recent years.Future efforts should continue focusing on the synergistic relationship between provincial CDCs and provincial health administrations,so as to provide guidance for the local provincial CDC budget management and provide references for CDCs in other provinces.

Objective To explore the mechanism of Yizhu Wendan Decoction in treating eczema through GEO database combined with network pharmacology and experimental verification.Methods TCMSP,BATMAN-TCM and ETCM databases were used to screen the active components of Yizhu Wendan Decoction.Disease target information related to eczema was collected through GEO database.The drug-component-target network and PPI network were constructed by intersections of active component targets and disease targets.GO and KEGG pathway enrichment analyses were performed using DAVID database.CCK-8 method was used to screen out the optimal intervention concentration of freeze-dried powder of Yizhu Wendan Decoction.HaCaT cells were divided into control group,model group,Yizhu Wendan Decoction low concentration group,Yizhu Wendan Decoction high concentration group,si-IL-17RA group,si-IL-17RA+Yizhu Wendan Decoction low concentration group,si-IL-17RA+Yizhu Wendan Decoction high concentration group,Dexamethasone group,si-IL-17RA+Dexamethasone group.Each group was given relevant intervention.The expressions of chemokines and inflammatory factors were detected by qPCR.EdU and Annexin V-FITC/PI double staining were used to detect cell proliferation and apoptosis.Western blot was performed to detect the expressions of proteins related to apoptosis,skin barrier and IL-17 signaling pathway.Results By using databases,180 active components of Yizhu Wendan Decoction were obtained.Combined with GEO database microarrays related to eczema(GSE6012 and GSE57225),8 potential targets of Yizhu Wendan Decoction in the treatment of eczema were obtained.KEGG enrichment pathway mainly involved IL-17 signaling pathway,lipid and atherosclerotic,TNF signaling pathway,fluid shear stress and atherosclerotic,etc.When Yizhu Wendan Decoction freeze-dried powder concentration was 100 μg/mL,cell viability was the strongest.Yizhu Wendan Decoction could significantly inhibit the mRNA expressions of chemokines and inflammatory factors CCL17,CCL22,IL-1β,TNF-α,IL-6,IFN-γ,and increase the mRNA expression of IL-4 in eczema.It promoted the proliferation of HaCaT cells,increased the protein expression of Bcl-2,and reduced the protein expressions of Bad and Cleaved Caspase-3,thus inhibiting HaCaT cells apoptosis;promoted the protein expressions of FLG and LOR,and reduced the expression of MMP9,MMP1,CCL2,FOSL1,IL-17RA proteins in IL-17 signaling pathway.Conclusion Yizhu Wendan Decoction can treat eczema with multiple components,multiple pathways and multiple targets,promote the proliferation of HaCaT cells,inhibit their apoptosis,and restore the skin barrier.Its mechanism may be related to inhibiting the activation of IL-17 signaling pathway.

Objective:To explore the effects of passive distraction training modalities on aging skeletal muscle cells and its underlying mechanisms,and to provide experimental data on effective interventions for patients with severe loss of locomotor capacity in severe skeletal sarcopenia.Method:An in vitro skeletal muscle cell aging model by C2C12 differentiated skeletal muscle cells with D-ga-lactose stimulation were established.Aging skeletal muscle cells were subjected to cyclic stretch(0.5Hz,24h)using an FX-5000 Flex Cell Tension system.Senescence and oxidative stress levels were assessed through mito-chondrial membrane potential,antioxidant content,EdU assay,and β-galactosidase staining.The expression of AMPK/PGC-α/FOXO3 signaling molecules related to muscle cell protein synthesis and decomposition in the cells was analyzed by Western Blot.Result:Passive stretching significantly reduced the positive rate of aging in senescent skeletal muscle cells(18.03%±6.82%)compared with the aging group(42.86%±10.54%,P<0.05).The expression levels of intracellu-lar AMPK and PGC-1α significantly increased after passive stretching,while the expression of FOXO3 de-creased significantly compared to the aging group(P<0.05).In addition,passive stretching increased the mito-chondrial membrane potential but appeared to reduce the antioxidant content in aging skeletal muscle cells,po-tentially related to changes in PGC-1α expression levels.Conclusion:Passive stretching improved the aging state of skeletal muscle cells by modulating the AMPK/PGC-1α/FOXO3 signaling pathway and oxidative stress levels,revealing the great potential of passive stretch-ing as the treatment for severe sarcopenia.

Objective:To continuously track the publishing budget of provincial Center for Disease Control and Prevention (CDC)in China and comprehend the management changes in the provincial CDCs based on the financial input.Methods:Publishing budget data for the period 2021—2024 of 31 provincial CDCs and provincial health administrations in China were collected and analyzed from the perspectives of time change and proportion relationship.Results:Statistical analysis revealed that the overall budget income of provincial CDCs in 2024 exceeded that of 2021.Most provincial CDCs in many provinces exhibited high-level growth(some with slight fluctuations),stable growth,and rapid growth in budget income changes.The proportion of provincial CDCs'budget income relative to provincial health administrations steadily increased,and the synergistic relationship mainly manifested as increase in the same direction,but there is a situation of changing from"strong benign"to"weak benign".Conclusion:The development of the budget income for provincial CDCs in China aligns with the imperative to establish a stable public health investment mechanism,reflecting more support towards provincial CDCs in recent years.Future efforts should continue focusing on the synergistic relationship between provincial CDCs and provincial health administrations,so as to provide guidance for the local provincial CDC budget management and provide references for CDCs in other provinces.

Myocardial dysfunction is the most serious complication of sepsis. Sepsis-induced myocardial dysfunction (SMD) is often associated with gastrointestinal dysfunction, but its pathophysiological significance remains unclear. The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD. In mice, knockdown of the gastrin receptor, cholecystokinin B receptor (Cckbr), aggravated lipopolysaccharide (LPS)-induced cardiac dysfunction and increased inflammation in the heart, whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury. Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes, 48 h prior to LPS administration, alleviated LPS-induced cardiac injury in Cckbr-deficient mice. The intravenous injection of bone marrow macrophages (BMMs) overexpressing Cckbr reduced LPS-induced myocardial dysfunction. Furthermore, gastrin treatment inhibited toll-like receptor 4 (TLR4) expression through the peroxisome proliferator-activated receptor α (PPAR-α) signaling pathway in BMMs. Thus, our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD, which could be used to develop new treatment modalities for SMD.

Focal cortical dysplasia (FCD) is one of the most common causes of drug-resistant epilepsy. Dysmorphic neurons are the major histopathological feature of type II FCD, but their role in seizure genesis in FCD is unclear. Here we performed whole-cell patch-clamp recording and morphological reconstruction of cortical principal neurons in postsurgical brain tissue from drug-resistant epilepsy patients. Quantitative analyses revealed distinct morphological and electrophysiological characteristics of the upper layer dysmorphic neurons in type II FCD, including an enlarged soma, aberrant dendritic arbors, increased current injection for rheobase action potential firing, and reduced action potential firing frequency. Intriguingly, the upper layer dysmorphic neurons received decreased glutamatergic and increased GABAergic synaptic inputs that were coupled with upregulation of the Na⁺-K⁺-Cl^- cotransporter. In addition, we found a depolarizing shift of the GABA reversal potential in the CamKII-cre::PTEN^flox/flox mouse model of drug-resistant epilepsy, suggesting that enhanced GABAergic inputs might depolarize dysmorphic neurons. Thus, imbalance of synaptic excitation and inhibition of dysmorphic neurons may contribute to seizure genesis in type II FCD.
Animals ; Drug Resistant Epilepsy/surgery* ; Epilepsy/pathology* ; Malformations of Cortical Development/pathology* ; Malformations of Cortical Development, Group I ; Mice ; Neurons/pathology* ; Seizures/pathology*

Background:In the clinical setting, the effect of intra-abdominal hypertension on the human body is dependent on time, but its role is not yet clear.Objective:To investigate the effect of the duration of intra-abdominal hypertension (IAH) on the prognosis of critically ill patients.Methods:This prospective cohort study enrolled 256 IAH patients who were admitted to the Surgical ICU of 10 Grade A hospitals in Fujian Province from January 2018 to December 2020. The duration of IAH (DIAH) was obtained after monitoring IAP, and ICU length of stay, duration of mechanical ventilation, duration of continuous renal replacement therapy (CRRT) and average daily energy intake from enteral nutrition during ICU stay were observed and recorded. The correlation was analyzed by Spearman rank correlation. The patients were divided into the survival group and the death group according to their survival state at 60 days after enrollment. Thereafter, clinical characteristics between the two groups were compared. Multivariable logistic regression was used to study and validate the relationship between DIAH and 60-day mortality. The receiver operating characteristics (ROC) curve was established to evaluate the predictive abilities of DIAH on the mortality risk.Results:In critically ill patients, DIAH was positively correlated with duration of mechanical ventilation ( r=0.679, P<0.001), duration of CRRT ( r=0.541, P<0.001) and ICU length of stay ( r=0.794, P<0.001), respectively. In addition, there was a negative correlation between DIAH and average daily energy intake from enteral nutrition ( r=-0.669, P<0.001). After multivariable adjustment, DIAH was an independent risk factor for 60-day mortality in critically patients with IAH ( OR=1.05, 95% CI: 1.01-1.12; P = 0.012), and exhibited a linearity change trend relationship with mortality risk. The ROC curve analysis of DIAH showed that the area under ROC curve (AUC) was 0.825 (95% CI: 0.763~0.886, P<0.01). When the cut-off value was 16.5 days, the sensitivity was 78.4% and the specificity was 75.4%. Conclusions:DIAH is an important risk factor for prognosis in critically ill patients. Early identification and rapid intervention for the etiology of IAH should be performed to shorten DIAH.