COMPERA 2.0 risk stratification has been demonstrated to be useful in patients with precapillary pulmonary hypertension (PH). However, its suitability for patients at risk for post-capillary PH or PH associated with left heart disease (PH-LHD) is unclear. To investigate the use of COMPERA 2.0 in patients with severe aortic stenosis (SAS) undergoing transcatheter aortic valve replacement (TAVR), who are at risk for post-capillary PH, a total of 327 eligible SAS patients undergoing TAVR at our institution between September 2015 and November 2020 were included in the study. Patients were classified into four strata before and after TAVR using the COMPERA 2.0 risk score. The primary endpoint was all-cause mortality. Survival analysis was performed using Kaplan-Meier curves, log-rank test, and Cox proportional hazards regression model. The study cohort had a median (interquartile range) age of 76 (70‒80) years and a pulmonary arterial systolic pressure of 33 (27‒43) mmHg (1 mmHg=0.133 kPa) before TAVR. The overall mortality was 11.9% during 26 (15‒47) months of follow-up. Before TAVR, cumulative mortality was higher with an increase in the risk stratum level (log-rank, both P<0.001); each increase in the risk stratum level resulted in an increased risk of death (hazard ratio (HR) 2.53, 95% confidential interval (CI) 1.54‒4.18, P<0.001), which was independent of age, sex, estimated glomerular filtration rate (eGFR), hemoglobin, albumin, and valve type (HR 1.76, 95% CI 1.01‒3.07, P=0.047). Similar results were observed at 30 d after TAVR. COMPERA 2.0 can serve as a useful tool for risk stratification in patients with SAS undergoing TAVR, indicating its potential application in the management of PH-LHD. Further validation is needed in patients with confirmed post-capillary PH by right heart catheterization.
Humans ; Aortic Valve Stenosis/complications* ; Aged ; Hypertension, Pulmonary/mortality* ; Male ; Female ; Transcatheter Aortic Valve Replacement ; Aged, 80 and over ; Risk Assessment/methods* ; Proportional Hazards Models ; Kaplan-Meier Estimate ; Retrospective Studies

Background Occupational stress is an important public health problem in the military. At present, there are few studies about occupational stress of officers and soldiers of the armed forces in China, especially the effects of plateau related environmental factors on occupational stress. Objective To understand current status and identify influencing factors of occupational stress among officers and soldiers stationed in plateaus, and provide a scientific basis for managing occupational stress. Methods In April 2023, stratified cluster sampling was used to recruit troops by deployed altitudes ranging from 500 to 3000 m into two strata of low altitude (＜2500 m) and high altitude (≥2500 m) based on the medical definition of plateau. Two regimental units were randomly selected from each stratum respectively, and one battalion unit was randomly selected from each regimental unit with all the officers and soldiers. Four selected battalion units were surveyed with a total of 2284 officers and soldiers. We designed a general questionnaire to collect their basic information, and distributed effort-reward imbalance questionnaires to evaluate occupational stress. We used logistic regression to identify potential influencing factors of occupational stress. Results Positive occupational stress was reported in 508 plateau-stationed officers and soldiers, with a prevalence rate of 22.2%. The total effort-reward imbalance score and the dimensional scores of effort, reward, and overcommitment in M (P₂₅, P₇₅) were 0.9 (0.7, 1.0), 16.0 (13.0, 19.0), 36.0 (33.0, 39.0), and 18.0 (15.0, 19.0), respectively. There were significant differences in the positive rate of occupational stress by gender, age, military service length, marital status, only child or not, physical fitness condition, reporting underlying diseases or not, exercise frequency before conscription, psychological changes after entering the plateaus, and having altitude sickness or not (P <0.05). The results of logistic regression showed that being female (OR=1.532, 95%CI: 1.061, 2.213), only child (OR=1.281, 95%CI: 1.038, 1.581), and with underlying diseases (OR=1.950, 95%CI: 1.340, 2.839) were associated with a higher risk of occupational stress. While setting 0 to <3 years of military service as the control group, the risk of occupational stress was higher in subgroups of 3 to 9 years (OR=1.380, 95%CI: 1.113, 1.710) and ≥9 years (OR=2.141, 95%CI: 1.461, 3.137). The participants reporting nervousness or fear (OR=1.728, 95%CI: 1.133, 2.635) and agitation or euphoria (OR=1.380, 95%CI: 1.113, 1.710) had a higher risk of reporting occupational stress than those with no psychological changes after entering the plateaus. Meanwhile, those who had regular exercise (OR=0.670, 95%CI: 0.492, 0.913) before enlistment, good physical fitness condition (OR=0.572, 95%CI: 0.426, 0.767) and excellent physical fitness condition (OR=0.502, 95%CI: 0.366, 0.688) had a lower risk of occupational stress. Conclusion Officers and soldiers in plateaus generally report a high rate of occupational stress. Female, military service length ≥3 years, being only child, with underlying diseases, nervousness/ fear or agitation/ euphoria after entering plateaus are risk factors for elevated occupational stress in this group; while good or excellent physical fitness condition and frequent exercise before enlistment are protective factors for occupational stress. Therefore, it is necessary to pay attention to the occupational stress problems in officers and soldiers stationed in plateaus and provide targeted intervention measures.

Objective:To evaluate the epidemiological characteristics and explore the associated factors of breakthrough cases (BC) from Public Health Emergency Events (PHEEs) of varicella in Zhejiang Province from 2019 to 2022.Methods:Data on cases were obtained from the China Information System for Disease Control and Prevention and the PHEEs Reporting Information Database of Varicella in Zhejiang Province. History records were matched through the Zhejiang Provincial Immunization Information System. Descriptive analysis and multiple logistic regression model with a bidirectional stepwise selection method were performed to explore associated factors for BC during 2019-2022.Results:A total of 144 276 varicella cases were reported from 2019 to 2022, with the annual reported incidence of 47.35-82.80 cases per 100 000 population. Among these cases, 109 172 were non-breakthrough cases (NBC, accounting for 75.67%), 34 517 were BC (23.92%), and the rest 587 cases had unclear vaccination history on varicella (0.41%). A total of 214 PHEEs of varicella were reported, of which 99.07% occurred in school settings. The proportion of PHEEs that occurred in high school increased significantly as time went on ( χ2trend=5.742, P=0.017). Multiple logistic regression model which focused on "BC vs. NBC (as the reference)" indicated that the year of onset ( OR=1.585, 95% CI:1.343-1.878), the month of onset (taking January as the reference, OR=2.311-15.652), city (taking Hangzhou as the reference, Jiaxing OR=2.370, Jinhua OR=2.197, Lishui OR=0.134), age ( OR=0.887, 95% CI: 0.826-0.944), PHEEs setting (taking "primary school and below" as the reference, "high school and above" OR=0.516, 95% CI: 0.305-0.897), and the number of rashes ( OR=0.569, 95% CI: 0.458-0.703) were associated factors. Multiple logistic regression model which focused on "two-dose BC vs. one-dose BC (as the reference)" showed that the age of initial vaccination ( OR=0.045, 95% CI: 0.014-0.107), the time interval from onset to the last dose ( OR=0.037, 95% CI: 0.011-0.087) and the age of onset ( OR=20.724, 95% CI: 8.383-72.485) were associated factors. Conclusion:During 2019-2022, the reported high-risk group of varicella in Zhejiang Province has shifted to adolescents and young adults. Although vaccination could not completely prevent the onset of VZV, it could relieve clinical symptoms and delay the age of onset.

Objective To investigate the diagnostic value of immunophenotype in distinguishing acute promyelocytic leukemia(APL)from HLA-DR negative acute myeloid leukemia(AML)using flow cytometry.Methods A retrospective observational study was con-ducted including 42 APL patients and 28 newly diagnosed or relapsed HLA-DR negative AML patients admitted to our hospital from 2014 to 2024.Immunophenotype analysis was performed on bone marrow aspirate samples using flow cytometry.The positive expression rates of CD64,MPO,CD7,CD11c,CD9,CD123 and other antigens were compared between the two groups using the Chi-square test.The diagnostic efficiency of the CD9/123 and CD64+MPO+CD7 CD11c-models for APL was evaluated using receiver operating charac-teristic(ROC)curves.Results The HLA-DR negative AML group exhibited significantly lower positive rates of CD64,CD9 and MPO(P＜0.05),and higher positive rates of CD11c and CD7(P＜0.05)compared to APL group.The CD64+MPO+CD7-CD11c-model had an area under the curve(AUCROC)of 0.859,sensitivity of 93.8％and specificity of 75.0％for distinguishing APL.The CD9/CD123 expression pattern had AUCROC of 0.919,sensitivity of 83.3％and specificity of 84.0％for APL diagnosis.The combined CD9/123 and CD64+MPO+CD7-CD11c-model had AUCROC of 0.955,sensitivity of 83.3％and specificity of 100％.Conclusion The combined CD9/123 and CD64+MPO+CD7-CD11c-expression pattern may serve as a helpful tool for differentiating APL from HLA-DR negative AML.

Objective:To evaluate the epidemiological characteristics and explore the associated factors of breakthrough cases (BC) from Public Health Emergency Events (PHEEs) of varicella in Zhejiang Province from 2019 to 2022.Methods:Data on cases were obtained from the China Information System for Disease Control and Prevention and the PHEEs Reporting Information Database of Varicella in Zhejiang Province. History records were matched through the Zhejiang Provincial Immunization Information System. Descriptive analysis and multiple logistic regression model with a bidirectional stepwise selection method were performed to explore associated factors for BC during 2019-2022.Results:A total of 144 276 varicella cases were reported from 2019 to 2022, with the annual reported incidence of 47.35-82.80 cases per 100 000 population. Among these cases, 109 172 were non-breakthrough cases (NBC, accounting for 75.67%), 34 517 were BC (23.92%), and the rest 587 cases had unclear vaccination history on varicella (0.41%). A total of 214 PHEEs of varicella were reported, of which 99.07% occurred in school settings. The proportion of PHEEs that occurred in high school increased significantly as time went on ( χ2trend=5.742, P=0.017). Multiple logistic regression model which focused on "BC vs. NBC (as the reference)" indicated that the year of onset ( OR=1.585, 95% CI:1.343-1.878), the month of onset (taking January as the reference, OR=2.311-15.652), city (taking Hangzhou as the reference, Jiaxing OR=2.370, Jinhua OR=2.197, Lishui OR=0.134), age ( OR=0.887, 95% CI: 0.826-0.944), PHEEs setting (taking "primary school and below" as the reference, "high school and above" OR=0.516, 95% CI: 0.305-0.897), and the number of rashes ( OR=0.569, 95% CI: 0.458-0.703) were associated factors. Multiple logistic regression model which focused on "two-dose BC vs. one-dose BC (as the reference)" showed that the age of initial vaccination ( OR=0.045, 95% CI: 0.014-0.107), the time interval from onset to the last dose ( OR=0.037, 95% CI: 0.011-0.087) and the age of onset ( OR=20.724, 95% CI: 8.383-72.485) were associated factors. Conclusion:During 2019-2022, the reported high-risk group of varicella in Zhejiang Province has shifted to adolescents and young adults. Although vaccination could not completely prevent the onset of VZV, it could relieve clinical symptoms and delay the age of onset.

Objective:To investigate the value of systemic inflammatory response syndrome (SIRS), pediatric sequential organ failure assessment (pSOFA) and pediatric critical illness score (PCIS) in predicting mortality of pediatric sepsis in pediatric intensive care units (PICU) from Southwest China.Methods:This was a prospective multicenter observational study. A total of 447 children with sepsis admitted to 12 PICU in Southwest China from April 2022 to March 2023 were enrolled. Based on the prognosis, the patients were divided into survival group and non-survival group. The physiological parameters of SIRS, pSOFA and PCIS were recorded and scored within 24 h after PICU admission. The general clinical data and some laboratory results were recorded. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare the predictive value of SIRS, pSOFA and PCIS in mortality of pediatric sepsis.Results:Amongst 447 children with sepsis, 260 patients were male and 187 patients were female, aged 2.5 (0.8, 7.0) years, 405 patients were in the survival group and 42 patients were in the non-survival group. 418 patients (93.5%) met the criteria of SIRS, and 440 patients (98.4%) met the criteria of pSOFA≥2. There was no significant difference in the number of items meeting the SIRS criteria between the survival group and the non-survival group (3(2, 4) vs. 3(3, 4) points, Z=1.30, P=0.192). The pSOFA score of the non-survival group was significantly higher than that of the survival group (9(6, 12) vs. 4(3, 7) points, Z=6.56, P<0.001), and the PCIS score was significantly lower than that of the survival group (72(68, 81) vs. 82(76, 88) points, Z=5.90, P<0.001). The predictive value of pSOFA (AUC=0.82) and PCIS (AUC=0.78) for sepsis mortality was significantly higher than that of SIRS (AUC=0.56) ( Z=6.59, 4.23, both P<0.001). There was no significant difference between pSOFA and PCIS ( Z=1.35, P=0.176). Platelet count, procalcitonin, lactic acid, albumin, creatinine, total bilirubin, activated partial thromboplastin time, prothrombin time and international normalized ratio were all able to predict mortality of sepsis to a certain degree (AUC=0.64, 0.68, 0.80, 0.64, 0.68, 0.60, 0.77, 0.75, 0.76, all P<0.05). Conclusion:Compared with SIRS, both pSOFA and PCIS had better predictive value in the mortality of pediatric sepsis in PICU.

OBJECTIVE To study the chemical composition and analgesia molecular mechanism of Shuanghu Zhongtongning tincture by UPLC-Q-TOF-MS/MS and network pharmacology. METHODS By comparing the chromatogram and blank chromatogram of Shuanghu Zhongtongning tincture, combined with PubChem, HMDB, MassBank database spectrum and the lysis information of reference substance, the chemical composition of Shuanghu Zhongtongning tincture was analyzed and identified. Protein-protein interaction network was constructed by using STRING database, and potential targets of analgesic effect of Shuanghu Zhongtongning tincture were screened. And GO and KEGG enrichment analysis were performed to analyze the core pathways related to analgesia. The network of "chemical composition-disease-target" was constructed by Cytoscape software to analyze the key compounds related to analgesia. RESULTS Seventeen core components of neochlorogenic acid, chlorogenic acid, hesperidin, neohesperidin, ferulic acid, berberine, ursolic acid, deoxyaconitine, mesaconitine, hypaconitine, benzoylmesaconine, benzoylhypacoitine, caffeic acid, quercetin, oleanolic acid, 4-hydroxycinnamic acid and mefenamic acid were identified, 3 core targets of STAT3, MAPK3 and MAPK1 were found, and 4 key signaling pathways of IL-17, TNF, PI3K-Akt and arachidonic metabolism were revealed. CONCLUSION This study preliminarily clarifies the chemical composition of Shuanghu Zhongtongning tincture and potential mechanism of analgesic effect, and provides a scientific theoretical basis for the study on the material basis and mechanism of Shuanghu Zhongtongning tincture.

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease. At present, no definite ALS biomarkers are available. In this study, exosomes from the plasma of patients with ALS and healthy controls were extracted, and differentially expressed exosomal proteins were compared. Among them, the expression of exosomal coronin-1a (CORO1A) was 5.3-fold higher than that in the controls. CORO1A increased with disease progression at a certain proportion in the plasma of patients with ALS and in the spinal cord of ALS mice. CORO1A was also overexpressed in NSC-34 motor neuron-like cells, and apoptosis, oxidative stress, and autophagic protein expression were evaluated. CORO1A overexpression resulted in increased apoptosis and oxidative stress, overactivated autophagy, and hindered the formation of autolysosomes. Moreover, CORO1A activated Ca²⁺-dependent phosphatase calcineurin, thereby blocking the fusion of autophagosomes and lysosomes. The inhibition of calcineurin activation by cyclosporin A reversed the damaged autolysosomes. In conclusion, the role of CORO1A in ALS pathogenesis was discovered, potentially affecting the disease onset and progression by blocking autophagic flux. Therefore, CORO1A might be a potential biomarker and therapeutic target for ALS.
Mice ; Animals ; Amyotrophic Lateral Sclerosis/pathology* ; Calcineurin/metabolism* ; Motor Neurons/pathology* ; Microfilament Proteins/metabolism* ; Cytoskeletal Proteins/metabolism*

Objective:To analyze the characteristics of eyes with congenital optic disc pits (ODPs) through multimodal imaging.Methods:A cross-sectional study was conducted.Thirty-eight patients (38 eyes) diagnosed with congenital ODPs in the Second Hospital of Hebei Medical University from January 2009 to January 2020 were enrolled.A comprehensive summary analysis of the imaging results including fundus photography, spectral domain-optical coherence tomography (SD-OCT), infrared imaging, fundus autofluorescence (FAF), fluorescein fundus angiography (FFA) and indocyanine green angiography (ICGA) was performed.This study protocol adhered to the Declaration of Helsinki and was approved by an Ethics Committee of The Second Hospital of Hebei Medical University (No.2021-P011). Written informed consent was obtained from each subject prior to any medical examination.Results:Among the 38 eyes, there were 32 eyes with ODPs located in or below the temporal side of optic disc, 4 eyes with ODPs located above the temporal side of optic disc, and 2 eyes with ODPs located at the center of optic disc, which were round or quasi-circular pale depression, and dark red eminences with clear or unclear boundaries between milk spots were found in 29 eyes with optical-disc macular degeneration (ODP-M) by fundus photography.SD-OCT examination showed that the structure of lamina cribrosa in the lesion area in all ODPs patients was incomplete, which presented a dark area with no tissue reflection, and the fissure led to the deep optic nerve.Fluid was found in the outer nuclear layer in all ODP-M patients, and there were 27 eyes with fluid in the inner nuclear layer, 13 eyes in the ganglion cell layer, and 4 eyes under the inner limiting membrane.Among the 29 eyes with ODP-M, there were 21 eyes with retinoschisis in outer layer, 27 eyes with neuroepithelial detachment.In the 27 eyes with neuroepithelial detachment, spot-like high reflection and reduced or disappeared ellipsoid band reflectance were seen above the neuroepithelium in 18 eyes.In infrared images, there were circular or quasi-circular low-reflection areas in the temporal side of the optic disc, and the lesion of ODP-M eyes presented low-reflection areas.FAF examination showed that in 27 eyes with ODP-M, there was a hypofluorescent region at the posterior pole consistent with the lesion range, among which, there was a granular or sheet-like hyperfluorescence at the center of the hypofluorescent region in 18 eyes.FFA showed that the optic disc depression in the arterial phase of patients was in a localized hypofluorescence state.During the venous phase, fluorescein dye extravasation along the temporal side of the optic disc could be found.A strong fluorescent arc with unclear boundaries at the temporal edge of the optic disc was formed in the late stage of angiography.Among the 29 eyes with ODP-M, the area of the macular lesion showed hyperfluorescence during the late stage of angiography in 27 eyes with neuroepithelial detachment, and no extension of dye toward the macula was found.ICGA showed that the optic disc depression of ODPs patients presented a localized hypofluorescence, and the lesion showed hyperfluorescence in 27 of the 29 ODP-M eyes with neuroepithelial detachment.Conclusions:Multimodal imaging can be helpful to realize the early diagnosis, etiology analysis of ODPs and make treatment plan.

As one of the top 10 breakthrough and emerging technologies in the world in 2018, cultured meat has attracted extensive attention due to its advantages of traceable origin, food safety and green sustainable development. Europe and the United States have invested a lot of resources to focus on research about cultured meat, which will affect our domestic meat and food market in the future. At present, the challenge of cultured meat production is how to efficiently simulate the growth environment of animal muscle tissue and realize large-scale production in bioreactor. Although cell tissue engineering has been deeply studied and achieved varying successful application, it is still difficult to obtain large-scale cultured meat production due to the high cost and technical requirements. Therefore, the development of efficient and safe cell culture technology is an urgent problem for large-scale cultured meat production, which can effectively reduce costs and achieve industrial application. In this review, we summarize the research progress of animal cell tissue culture technology used for cultured meat, and highlighted the current challenges and possible strategies in further applications.
Animals ; Bioreactors ; Cell Culture Techniques ; Meat ; Tissue Engineering ; United States