OBJECTIVE: To elucidate the predictive value of norepinephrine equivalence (NEE) score on the 28-day death risk in patients with sepsis and provide evidence for its application in the diagnosis and treatment of sepsis and septic shock. METHODS: A retrospective cohort study was conducted based on the data of patients with sepsis from Medical Information Mart for Intensive Care-IV 2.2 (MIMIC-IV 2.2). The patients who received vasoactive agents within 6 hours after the diagnosis of sepsis or septic shock were enrolled, and they were divided into survival and non-survival groups based on their 28-day outcomes. The baseline characteristics, vital signs, and treatment data were collected. Multivariate Cox regression analysis was performed to identify factors influencing the 28-day death risk. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of various parameters on the 28-day death risk of septic patients. Kaplan-Meier survival curve was used to evaluate cumulative survival rate in patients classified by different quantitative parameters based on the cut-off values obtained from ROC curve analysis. RESULTS: A total of 7 744 patients who met the Sepsis-3 diagnostic criteria and received vasopressor treatment within 6 hours post-diagnosis were enrolled, of which 5 997 cases survived and 1 747 died, with the 28-day mortality of 22.6%. Significant differences were observed between the two groups regarding age, gender, height, body weight, race, type of intensive care unit (ICU), acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, Charlson comorbidity index (CCI) score, underlying comorbidities, and vital signs. Compared with the survival group, the non-survival group had poorer blood routine, liver and kidney function, coagulation function, blood gas analysis and other indicators. Multivariate Cox regression analysis revealed that age > 65 years old [hazard ratio (HR) = 0.892, 95% confidence interval (95%CI) was 0.801-0.994, P = 0.039] and male (HR = 0.735, 95%CI was 0.669-0.808, P < 0.001) were protective factors for 28-day death in patients with sepsis, and NEE score (HR = 1.040, 95%CI was 1.021-1.060, P < 0.001), shock index (HR = 1.840, 95%CI was 1.675-2.022, P < 0.001), APACHE II score (HR = 1.076, 95%CI was 1.069-1.083, P < 0.001), SOFA score (HR = 1.035, 95%CI was 1.015-1.056, P < 0.001), and CCI score (HR = 1.135, 95%CI was 1.115-1.155, P < 0.001) were independent risk factors for 28-day death in septic patients. ROC curve analysis showed that the area under the ROC curve (AUC) of NEE score for predicting the 28-day death risk of septic patients was 0.743 (95%CI was 0.730-0.756), which was comparable to the predictive value of APACHE II score (AUC = 0.742, 95%CI was 0.729-0.755) and ratio of mean arterial pressure (MAP)/NEE score (MAP/NEE; AUC = 0.738, 95%CI was 0.725-0.751, both P > 0.05), and better than SOFA score (AUC = 0.609, 95%CI was 0.594-0.624), CCI score (AUC = 0.658, 95%CI was 0.644-0.673), shock index (AUC = 0.613, 95%CI was 0.597-0.629) and ratio of diastolic blood pressure (DBP)/NEE score (DBP/NEE; AUC = 0.735, 95%CI was 0.721-0.748, all P < 0.05). According to the cut-off values of APACHE II and NEE scores obtained from ROC curve analysis, the patients were stratified for Kaplan-Meier survival curve analysis, and the results showed that the 28-day cumulative survival rate in the septic patients with an APACHE II score ≤ 22.5 was significantly higher than that in those with an APACHE II > 22.5 (Log-Rank test: χ² = 848.600, P < 0.001), and the 28-day cumulative survival rate in the septic patients with an NEE score ≤0.120 was significantly higher than that in those with an NEE score > 0.120 (Log-Rank test: χ² = 832.449, P < 0.001). CONCLUSIONS NEE score is an independent risk factor for 28-day death in septic patients who received vasoactive treatment within 6 hours of diagnosis and possesses significant predictive value. It can be used for severity stratification in sepsis management.
Humans ; Retrospective Studies ; Sepsis/diagnosis* ; Male ; Female ; Norepinephrine/therapeutic use* ; Middle Aged ; Aged ; Prognosis ; Predictive Value of Tests ; Shock, Septic/mortality* ; Adult ; ROC Curve ; Risk Factors ; Survival Rate ; Aged, 80 and over

Disruption of normal secretion or mucociliary clearance can impair airway defense mechanisms and lung function, and increase the risk of infection. Airway clearance techniques are recommended as part of a comprehensive treatment plan for patients. Among these, vibratory expectoration is an important method of airway clearance, which loosens and liquefies mucus and metabolites on the surface of the respiratory tract through chest wall oscillation, promoting ciliary movement to facilitate sputum expulsion. However, commonly used handheld vibrating head devices and vest-type vibration expectorators have several limitations in clinical practice, such as inconvenience of operation, limited treatment time, poor adaptability, and difficulty in disinfection. To address these issues, the research team from the department of critical care medicine at Ruijin Hospital, Shanghai Jiao Tong University, has designed a novel belt-type vibration expectorator, which has been granted a national utility model patent (Patent No.: ZL 2023 2 1610983.1). The device is mainly composed of a chest strap assembly, a sputum clearance component, and a fixed shoulder strap component. Several pockets are placed on the outer surface of the chest strap, with corresponding inner-side openings that allow the percussion head of the percussive expectorator placed inside the pocket to make contact with the patient's chest wall. Each pocket has markings indicating the percussion position, enabling the placement of the percussive expectorator according to the location of infection, thereby achieving multi-point, precise percussive vibration expectoration in different body positions. On the inner side of the chest strap, there are diagrams illustrating postural drainage, providing guidance on the body positions patients should assume based on the location of infection. The hook-and-loop fasteners on both sides of the chest strap can be wrapped around and secured according to the patient's body shape, ensuring that the sputum clearance components adhere tightly to the chest wall, allowing the vibrations generated by percussion to be effectively transmitted to the patient's airways. Additionally, to prevent the chest strap from slipping due to changes in the patient's position, a Y-shaped fixing strap can be selectively attached to the chest strap for further stabilization. This innovation not only simplifies the operation process, improves convenience and flexibility of use, but also supports the principle of "disinfection after each use by one person," which helps to reduce the risk of nosocomial infections and improve the efficiency of patients' respiratory rehabilitation.
Humans ; Vibration ; Equipment Design ; Chest Wall Oscillation/instrumentation* ; Sputum ; Expectorants ; Mucociliary Clearance

OBJECTIVE: To investigate the incidence of sepsis in Xinjiang Uygur Autonomous Region and the compliance with sepsis diagnosis and treatment guidelines in intensive care unit (ICU) at different levels of hospitals, and to identify the risk factors associated with poor prognosis in patients with sepsis in this region. METHODS: A prospective cross-sectional survey was conducted in ICU of Xinjiang Uygur Autonomous Region Critical Care Medicine Alliance. The survey period was from 10:00 on January 31, 2024, to 09:59 on February 1, 2024. The patients diagnosed with sepsis admitted to the ICU during the study period were included in the analysis. Data on patient demographics, physiology, microbiology, and treatment protocols were collected, with follow-up until the 28th day after ICU admission or death. Baseline characteristics and treatment information of septic patients across different hospital levels were compared, as well as clinical data of septic patients with different 28-day outcomes. Multivariate Cox proportional hazards model was used to identify risk factors for 28-day death in septic patients. RESULTS: A total of 77 units of Xinjiang Uygur Autonomous Region Critical Care Medicine Alliance from 14 prefectures/cities in Xinjiang participated in the survey. On the survey day, 727 patients were admitted to ICU, of whom 179 (24.6%) were diagnosed with sepsis, and 64 (35.8%) died within 28 days, 115 (64.2%) survived. Among the participating institutions, 33 were tertiary hospitals (42.9%), managing 97 septic cases (54.2%), and 44 were secondary hospitals (57.1%), managing 82 septic cases (45.8%). The lactic acid monitoring rate and continuous renal replacement therapy (CRRT) rate for septic patients in tertiary hospitals were significantly higher than those in secondary hospitals [lactic acid monitoring rate: 92.8% (90/97) vs. 82.9% (68/82), CRRT rate: 17.5% (17/97) vs. 3.7% (3/82), both P < 0.05]. No statistically significant differences were observed between tertiary and secondary hospitals in length of ICU stay or 28-day mortality [length of ICU stay (days): 11.0 (16.0) vs. 10.0 (22.0), 28-day mortality: 35.1% (34/97) vs. 36.6% (30/82), both P > 0.05]. Compared with survivors, non-survivors had higher acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, Charlson comorbidity index (CCI) score and lower Glasgow coma scale (GCS) score. Significant differences were noted in vital signs [heart rate, blood pressure, body temperature, pulse oxygen saturation (SpO₂)], laboratory markers [red blood cell count (RBC), white blood cell count (WBC), lymphocyte ratio (LYM%), blood urea nitrogen (BUN), total protein (TP), albumin (Alb), pH value, base excess (BE)], and monitoring, diagnosis and treatment information (invasive blood pressure monitoring, mechanical ventilation, CRRT, usage of norepinephrine). Multivariate Cox proportional hazards model indicated that body temperature [hazard ratio (HR) = 1.416, 95% confidence interval (95%CI) was 1.022-1.961, P = 0.037] and WBC (HR = 1.040, 95%CI was 1.010-1.071, P = 0.009) were independent risk factors for 28-day death in patients with sepsis. CONCLUSIONS Sepsis in Xinjiang Uygur Autonomous Region is characterized by a high mortality. In this region, tertiary hospitals demonstrate better compliance with bundled treatment strategies such as lactic acid monitoring and the usage of CRRT compared to secondary hospitals, yet they do not show significant advantages in clinical outcomes. Body temperature and WBC are independent risk factors for 28-day death in patients with sepsis in this region. However, clinicians should still consider the actual situation of patients, along with more optimal early warning indicators and comprehensive system assessments, to identify and prevent risk factors for adverse outcomes in patients.
Humans ; Sepsis/diagnosis* ; Cross-Sectional Studies ; Prospective Studies ; Risk Factors ; Intensive Care Units ; Prognosis ; China/epidemiology* ; Male ; Female ; Middle Aged ; Aged ; Proportional Hazards Models ; Incidence

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Objectives:To clarify the radiological anatomy features of adrenal arteries derived from digital subtraction angiography(DSA)in patients with primary aldosteronism(PA). Methods:The DSA images of 119 patients diagnosed with PA and underwent percutaneous selective adrenal artery embolization from January 2018 to December 2019 at the 2nd Affiliated Hospital of Nanchang University were retrospectively analyzed,and the number,origin,distribution,angle and diameter of adrenal arteries were analyzed. Results:The mean age of 119 PA patients was(49±11)years,with 71(59.7%)males,and at least one adrenal artery was successfully identified in all patients,a total of 192 adrenal arteries were analyzed.There were 20(10.4%)upper,40(20.8%)middle and 132(68.8%)lower adrenal arteries.Adrenal arteries originating from renal arteries accounted for 42.7%(82/192),adrenal arteries originating from the abdominal aorta accounted for 37.5%(72/192),and those from the inferior diaphragmatic arteries accounted for 19.8%(38/192).72.8%(83/114)of left adrenal arteries and 60.3%(47/78)of right adrenal arteries distributed at the level of the first lumbar vertebrae.28.1%(54/192)adrenal arteries distributed at the level of the second lumbar vertebrae,and 4.2%(8/192)adrenal arteries at the level of the 12th thoracic vertebrae.The angle range of left adrenal arteries intersecting with the origin arteries was 35.90° to 160.07°(renal artery),27.08° to 171.99°(accessory renal artery),0° to 158.70°(abdominal aorta);for right adrenal arteries,it was 18.43° to 172.53°(renal artery),69.26° to 114.62°(accessory renal artery),12.32° to 232.85°(abdominal aorta),respectively.The average diameters of left and right adrenal arteries were(0.98±0.45)mm and(1.27±0.42)mm,respectively. Conclusions:This study provides more detailed radiological anatomy data of adrenal arteries in PA patients.As a supplement to human anatomical features,the described data can provide practical guidance for adrenal artery interventional treatment.

Objective:To establish a rapid pipeline for whole genome sequencing of Chikungunya virus (CHIKV) by combining imbricated multiplex-PCR amplification and Illumina high-throughput sequencing platform.Methods:The primary reference sequences of CHIKV were downloaded from the National Center for Biotechnology Information (NCBI) database, covering all genotypes of CHIKV. After multiple alignments using the Mafft software and phylogenetic analysis, the 20 CHIKV references were selected for primer design. The Primal Scheme tool and Geneious Prime software were used to design, evaluate and optimize the primer panel. Finally, seven CHIKV-positive samples were involved in the validation of the primer panel.Results:All the amplicons of the designed panel were generated successfully. The consensuses generated from the mapping results could cover 100.00% of the coding region of the CHIKV genome when the Ct-value of the sample was less than 33, as the percentage would decrease to 99.38% when the Ct-value reached 35. The mapping percentage could be increased by 5.70%-25.43% when using the stepwise correction mapping strategy.Conclusion:The multiplex-PCR amplification method for CHIKV whole genome sequencing is relatively simple and convenient, which only requires two tubes of PCR amplification and performs well on CHIKV-positive clinical samples with different concentration levels of virus.

Objective:To analyze the results of lymphocyte subsets and 12 plasma cytokines in patients with tuberculosis by flow cytometry and to evaluate their diagnostic efficacy in these patients.Methods:This is a retrospective case-control study. A total of 128 patients with evidence of tuberculosis disease or clinically confirmed tuberculosis who were admitted to the 8th Medical Center of PLA General Hospital from January 2022 to December 2023 were included. According to the location of mycobacterium tuberculosis infection, the patients were divided into the pulmonary tuberculosis group (83 cases) and the extrapulmonary tuberculosis group (45 cases), and 100 healthy age-and sex matched people who underwent health check up during the study period were selected as the control group. Flow cytometry was used to detect peripheral blood lymphocyte subsets and 12 plasma cytokines [including 10 pro-inflammatory factors: interleukin (IL)-5, interferon (IFN)-α, IL-2, IL-6, IL-1β, IFN-γ, IL-8, IL-17, IL-12P70, Tumor necrosis factor (TNF)-α, and two anti-inflammatory factors: IL-4, IL-10] in participants of all groups. Spearman correlation method was used to analyze the correlation between lymphocyte subsets and cytokines, binary Logistic regression was used to screen the TB related factors, and receiver operating curve (ROC) was used to evaluate the diagnostic efficacy of TB related factors.Results:Compared with the control group, the absolute number of CD3 +T lymphocytes, CD3 +CD8 +T lymphocytes, CD3 +CD4 +T lymphocytes, NK cells and B cells were lower in pulmonary tuberculosis group and extrapulmonary tuberculosis group (all P<0.05). Except for IL-1β, the levels of other 11 cytokines are all significantly higher in the pulmonary tuberculosis group (all P<0.01), and the levels of IL-6, IFN-γ, IL-17, TNF-α, IL-4 and IL-10 were significantly higher in extrapulmonary tuberculosis group (all P<0.05). Compared with extrapulmonary tuberculosis group, the level of IL-8 was higher in pulmonary tuberculosis group ( P=0.026). Spearman correlation analysis showed that IL-6, IFN-γ and IL-8 were negatively correlated with the absolute numbers of CD3 +T lymphocytes, CD3 +CD8 +T lymphocytes, CD3 +CD4 +T lymphocytes, NK cells and B cells (IL-6: R2=-0.30, -0.28, -0.32, -0.26, -0.28; IFN-γ: R2=-0.36, -0.31, -0.37, -0.25, -0.36; IL-8: R2=-0.14, -0.13, -0.16, -0.14, -0.22; all P<0.05), IL-10 was negatively correlated with the absolute number of CD3 +CD4 +T lymphocytes, NK cells and B cells ( R 2=-0.14, -0.19, -0.21, all P<0.05); Binary Logistic regression analysis showed that IL-6, IFN-γ, IL-8 and IL-10 were the related factors of tuberculosis ( OR=1.809, 1.136, 0.910, 2.218, all P<0.05), ROC curve analysis showed that the AUC of IL-6, IFN-γ, IL-8 and IL-10 in the joint diagnosis of tuberculosis was 0.845, the sensitivity was 0.766, and the specificity was 0.820. Conclusion:The lower absolute number of lymphocyte subsets and cytokine levels in patients with pulmonary tuberculosis and extrapulmonary tuberculosis indicate that their immune function is in a low state, and the higher levels of pro-inflammatory factors (IL-6, IFN-γ, IL-8) and anti-inflammatory factor (IL-10) indicates the higher inflammatory status, and evaluation of these 4 cytokines has satisfactory diagnostic efficacy for tuberculosis.

Objective:To investigate the therapeutic effect of methotrexate loaded vesicles on experimental periodontitis in mice.Methods:Extracellular vesicles (EVs) were isolated from human umbilical cord mesenchymal stem cells (hUC-MSC). Methotrexate loaded vesicles (MTX-EVs) were constructed, whose morphology and size were analyzed by using scanning electron microscopy and particle size analyzer. Western blotting was used to identify their surface specific proteins. C57BL/6J male mice of 4-5 weeks (provided by Experimental Animal Center of The Fourth Military Medical University) were selected, among which 8 were randomly selected by blind grasp method without treatment and fed normally as normal group, and others were induced to periodontitis models by local injection of lipopolysaccharide (LPS) into the periodontium. The LPS was injected once every day with a concentration of 2 g/L and a volume of 5 μl, lasting for two weeks. The mice with successfully induced periodontitis were randomly divided into 4 groups by blind grasping method, with 8 mice in each group. The LPS group was with no treatment, and the other three groups were treated with periodontal local injection of MTX, EVs or MTX-EVs, respectively. Two weeks later, enzyme-linked immunosorbent assay (ELISA) was used to detect the expressions of inflammatory cytokine interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in gingival tissue. The amount of alveolar bone resorption of four groups was detected by using micro-CT scanning and HE staining. The expression proportion of the inflammatory factor in gingival tissue was analyzed by using flow cytometry.Results:The scanning electron microscopy results showed that EVs and MTX-EVs were circular or elliptical in shape. Dynamic light scattering (DLS) particle size analysis showed that the particle size of EVs was around 200 nm, while that of MTX-EVs was around 300 nm. The ELISA results showed IL-1β levels in the normal group, LPS group, LPS+MTX group, LPS+EVs group and LPS+MTX-EVs group were (28.86±2.76), (51.50±2.04), (35.26±2.40), (45.49±2.04) and (35.77±3.49) ng/L. That is, the IL-1β concentrations in the LPS+MTX group, LPS+EVs group and LPS+MTX-EVs group were significantly lower than that in the LPS group ( P<0.05); the mass concentration of IL-1β in the LPS +MTX-EVs group was significantly lower than that in the LPS+EVs group ( P<0.05). The concentrations of IL-6 in the normal group, LPS group, LPS+MTX group, LPS+EVs group and LPS+MTX-EVs group were (125.44±4.12), (221.64±10.59), (178.16±16.90), (181.09±18.22) and (170.15±9.04) ng/L, among which the concentration of IL-6 in the last three groups were significantly lower than that in the LPS group ( P<0.05). The mass concentration of IL-6 in the LPS+MTX-EVs group was significantly lower than those in the LPS+MTX group and LPS+EVs group ( P<0.05). The concentrations of TNF-α in the normal group, LPS group, LPS+MTX group, LPS+EVs group and LPS+MTX-EVs group were (320.27±38.68), (479.62±40.94), (342.18±25.89), (415.88±12.01) and (325.75±30.83) ng/L, among which the concentrations of last three groups were significantly lower than the LPS group ( P<0.05); the mass concentration of TNF-α in the LPS+MTX-EVs group was significantly lower than those in the LPS+EVs group and LPS+MTX group ( P<0.05). The micro-CT results showed that the distance of cement-enamel junction-alveolar bone crest (CEJ-ABC) of the first molar and root (M1R1) in the normal group, LPS group, LPS+MTX group, LPS+EVs group and LPS+MTX-EVs group of mice were (0.11±0.03), (0.28±0.02), (0.23±0.03), (0.20±0.04), and (0.18±0.03) mm, respectively. Compared with the LPS group, the CEJ-ABC of the M1R1 in the LPS+MTX group, LPS+EVs group and LPS+MTX-EVs group were inhibited to varied degrees with statistically significant differences ( P<0.05). Among them, LPS+MTX-EVs group had the best bone resorption inhibitioin effect compared to LPS+MTX group and LPS+EVs group, and the differences were statistically significant ( P<0.05). The flow cytometry results indicated that the proportion of interferon-γ (IFN-γ) positive cells was (11.77±1.02)% in the LPS group, (6.87±0.65)% in the LPS+EVs group, and (4.15±0.92)% in the LPS+MTX-EVs group, respectively. The proportions of IFN-γ positive cells in the LPS+EVs group and LPS+MTX-EVs group were significantly lower than that in the LPS group ( P<0.05), while the ratio of IFN-γ positive cells in the LPS+MTX-EVs group was found significantly lower than that in the LPS+EVs group ( P<0.05). Conclusions:MTX-EVs can effectively alleviate the periodontal local inflammatory environment and reduce bone resorption of alveolar bone in periodontitis model mice.

Objective:To establish a rapid pipeline for whole genome sequencing of Chikungunya virus (CHIKV) by combining imbricated multiplex-PCR amplification and Illumina high-throughput sequencing platform.Methods:The primary reference sequences of CHIKV were downloaded from the National Center for Biotechnology Information (NCBI) database, covering all genotypes of CHIKV. After multiple alignments using the Mafft software and phylogenetic analysis, the 20 CHIKV references were selected for primer design. The Primal Scheme tool and Geneious Prime software were used to design, evaluate and optimize the primer panel. Finally, seven CHIKV-positive samples were involved in the validation of the primer panel.Results:All the amplicons of the designed panel were generated successfully. The consensuses generated from the mapping results could cover 100.00% of the coding region of the CHIKV genome when the Ct-value of the sample was less than 33, as the percentage would decrease to 99.38% when the Ct-value reached 35. The mapping percentage could be increased by 5.70%-25.43% when using the stepwise correction mapping strategy.Conclusion:The multiplex-PCR amplification method for CHIKV whole genome sequencing is relatively simple and convenient, which only requires two tubes of PCR amplification and performs well on CHIKV-positive clinical samples with different concentration levels of virus.

Perimenopausal period is a period with high incidence of female depression, which shows the symptoms of depressed mood and disturbed mind. The pathogenesis of the disease is not clear and it is urgent to search for efficient treatment. Leptin is a hormone secreted by fat cells and plays a role in both metabolism and neuroprotection. In recent years, leptin has been reported to ameliorate perimenopausal depression, and leptin is closely related to estrogen synthesis and secretion. Therefore, leptin may be used as a potential molecular target for the treatment of perimenopausal depression. In this paper, the research on the relationship between leptin and perimenopausal depression is reviewed.
Depression ; Leptin ; Estrogens