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 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.

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.

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.

Objective:To investigate the clinical efficacy and prognostic influencing factors of open abdomen technique for acute pancreatitis with abdominal compartment syndrome (ACS).Methods:The retrospective cohort study was conducted. The clinical data of 186 patients of acute pancreatitis with ACS who were admitted to 6 hospitals, including 65 cases in the 910th Hospital of Joint Logistics Support Force of Chinese People′s Liberation Army, 46 cases in the First Affiliated Hospital of Wenzhou Medical University, 33 cases in the Fujian Provincial Hospital, 31 cases in the Second Affiliated Hospital of Fujian Medical University, 7 cases in the People′s Hospital Affiliated to Quanzhou Medical College, 4 cases in the Shishi General Hospital, from January 2013 to December 2020 were collected. There were 142 males and 44 females, aged (43±8)years. Observation indica-tors: (1) patients conditions after being treatment with open abdomen technique; (2) analysis of clinical characteristics in patients with different treatment outcomes; (3) changing trend of the volume of urine output, levels of lactic acid, levels of enteral nutrient intake and the sequential organ failure score in patients with different treatment outcomes; (4) influencing factors for prognosis of patients. Measurement data with normal distribution were represented as Mean± SD, and compari-son between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test or the continuity correction chi-square test. Repeated measurement data were analyzed using the repeated ANOVA. Spearman correlation analysis was used for correlation analyses. The COX regression model was used for univariate analysis and COX regression model with forward regression was used for multivariate analysis. Results:(1) Patients conditions after being treatment with open abdomen technique. Intra-abdominal pressure, oxygena-tion index, levels of lactic acid and sequential organ failure score of the 186 patients were (23.3±1.9)mmHg (1 mmHg=0.133 kPa), (121±24)mmHg, (5.0±3.4)mmol/L and 10.4±3.6 before the treatment with open abdomen technique and (11.2±2.9)mmHg, (222±38)mmHg, (3.2±2.1)mmol/L and 4.4±2.3 at postoperative 168 hours, showing significant differences in time effects before and after the treatment ( Ftime=855.26,208.50, 174.91,208.47, P<0.05). (2) Analysis of clinical characteristics in patients with different treatment outcomes. Of the 186 patients, 166 cases survived and were discharged, and 20 cases died during hospitalization. Age, sequential organ failure score, duration of ACS and levels of lactic acid during hospitalization before the treatment with open abdomen technique were (41±7)years, 9.4±3.4, 13(10,21)hours and (4.2±0.6)mmol/L in surviving patients, versus (45±6)years, 11.5±2.4, 65(39,84)hours and (5.2±0.5)mmol/L in dead patients, respectively, showing significant differences between them ( t=-2.10, -2.71, Z=-5.36, t=-7.16, P<0.05). Duration of postoperative acute gastro-intestinal injury, duration of continuous renal replacement therapy, time to liberation from mech-anical ventilation, duration of vasoactive drugs therapy, cases undergoing early abdominal closure, cases without intestinal fistula or with postoperative high-order intestinal fistula and low-order intestinal fistula during hospitalization after the treatment with open abdomen technique were 4(2,6)days, 4(3,7)days, 34(21,41)days, 3(2,6)days, 126, 131, 23, 12 in surviving patients, versus 13(10,17)days, 10(8,18)days, 0(0,3)days, 8(6,12)days, 1, 2, 15, 3 in dead patients, respectively, showing significant differences between them ( Z=-5.60, -3.75, -3.64, -3.06, χ2=41.43, 45.86, P<0.05). (3) Changing trend of the volume of urine output, levels of lactic acid, levels of enteral nutrient intake and the sequential organ failure score in patients with different treatment outcomes. The volume of urine output, levels of lactic acid, levels of enteral nutrient intake and the sequential organ failure score in surviving patients during hospitalization were (0.29±0.10)mL/(kg·h), (4.2±0.6)mmol/L, 0.0 kcal/(kg·d) and 9.4±3.4 before the treatment with open abdomen technique and (2.22±0.15)mL/(kg·h), (1.9±0.7)mmol/L, (20.7±2.9)kcal/(kg·d) and 3.7±2.2 at postoperative 168 hours. The above indicators in dead patients during hospitalization were (0.28±0.08)mL/(kg·h), (5.2±0.5)mmol/L, 0.0kcal/(kg·d) and 11.5±2.4 before the treatment with open abdomen technique and (0.28±0.09)mL/(kg·h), (7.7±0.8)mmol/L, (4.6±1.8)kcal/(kg·d) and 12.4±2.1 at postoperative 168 hours. There were significant differences in time effects in the above indicators in surviving patients and dead patients before and after the treatment with open abdomen technique ( Ftime=425.57, 188.59, 394.84, 37.52, P<0.05). There were interactive effects between the above indicators and the treatment outcome at different time points ( Finteraction=383.14, 233.04, 169.83, 36.61, P<0.05). There were signifi-cant differences in the change trends of the above indicators between the surviving patients and the dead patients during hospitalization ( Fgouprs=2 739.56, 877.98, 542.05, 240.85, P<0.05). (4) Influen-cing factors for prognosis of patients. Results of univariate analysis showed that age, sequential organ failure score, duration of ACS before surgery, procalcitonin, lactic acid, postoperative high-order intestinal fistula, abdominal hemorrhage, duration of postoperative acute gastrointestinal injury, duration of continuous renal replacement therapy, duration of vasoactive drugs therapy, early abdominal closure were related factors influencing prognosis of patients under-going treatment with open abdomen technique ( hazard ratio=1.07, 1.18, 1.39, 1.16, 8.25, 12.26, 2.83, 1.29, 1.56, 1.41, 0.02, 95% confidence interval as 1.00-1.15, 1.45-2.27, 1.22-1.57, 1.02-1.32, 1.75-38.90, 7.37-41.23, 1.16-6.93, 1.22-1.37, 1.23-1.99, 1.08-1.84, 0.00-0.16, P<0.05). Results of multivariate analysis showed that extended duration of ACS before surgery, postoperative high-order intestinal fistula and extended duration of postoperative acute gastrointestinal injury were independent risk factors influencing prognosis of patients undergoing treatment with open abdomen technique ( hazard ratio=1.05, 7.95, 1.17, 95% confidence interval as 1.01-1.32, 2.05-30.87, 1.13-1.95, P<0.05) and early abdominal closure was an independent protective factor ( hazard ratio=0.10, 95% confidence interval as 0.01-0.89, P<0.05). Results of Spearman correlation analysis showed that duration of ACS was positively correlated with sequential organ failure score before surgery ( r=0.71, P<0.05). Conclusions:Open abdomen technique is effective for acute pancreatitis with ACS. Extended duration of ACS before surgery, postoperative high-order intestinal fistula and extended duration of postoperative acute gastrointestinal injury are independent risk factors for prognosis of patients during hospitalization and early abdominal closure is an independent protective factor.