Activated partial thromboplastin time predicts mortality in patients with severe fever with thrombocytopenia syndrome: A multicenter study in north China.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high lethality. This study aimed to determine whether prolonged activated partial thromboplastin time (APTT) predicted SFTS mortality. Methods: SFTS patients were enrolled from 6 hospitals in the north China. Subjects were divided into training cohort and 5 externally validation cohorts. The least absolute shrinkage and selection operator Cox regression model was performed to screen potential prognostic factors. Risk factors were analyzed using multivariable regression models. Prognostic models were established by Cox regression and random survival forest (RSF) methods, and evaluated regarding discrimination, validity and clinical benefit. Time-dependent receiver operating characteristic (ROC) curve was used to evaluate the predictive effectiveness of variables. Results: 1332 SFTS cases were included, in which 211 patients died. Six potential prognostic factors were screened, and pulse, breath, APTT and aspartic transaminase (AST) were independently associated with mortality in both training cohort (Yantai, N = 791) and external validation cohort (N = 541). APTT was steadily correlated with the fatality (HR: 1.039-1.144; all P < 0.01) in each five sub-validation cohorts (Dandong, Dalian, Tai'an, Qingdao and Beijing). RSF model with variables of APTT, AST, pulse and breath had considerable prognostic effectiveness, which APTT showed the highest prognostic ability with the area under the curve of 0.848 and 0.787 for 7-day and 14-day survival, respectively. Survival differences were found between high and low levels of APTT for mortality using 50s as the optimal cut-off. Conclusions: SFTS patients have prolonged APTT, which is an independent risk factor for fatality. APTT≥50s was recommended as a biomarker to remind physicians to monitor and treat patients more aggressively to improve clinical prognosis.

Blending Aryl Ketone in Covalent Organic Frameworks to Promote Photoinduced Electron Transfer.

Aryl-ketone derivatives have been acknowledged as promising organic photocatalysts for photosynthesis. However, they are limited by their photostability and have been less explored for photoinduced electron transfer (PET) applications. Herein we demonstrate a novel strategy to cover the shortage of aryl-ketone photocatalysts and control the photoreactivity by implanting symmetric aryl ketones into the conjugated covalent organic frameworks (COFs). To prove the concept, three comparative materials with the same topology and varied electronic structures were built, adopting truxenone knot and functionalized terephthalaldehyde linkers. Spectroscopic investigation and excited carrier dynamics analysis disclosed improvements in the photostability and electronic transfer efficiency as well as the structure-performance relationships toward N-aryl tetrahydroisoquinoline oxidation. This system provides a robust rule of thumb for designing new-generation aryl-ketone photocatalysts.

High C-reactive protein to lymphocyte ratio predicts mortality outcomes of patients with severe fever with thrombocytopenia syndrome: A multicenter study in China.

Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening infectious disease caused by the SFTS virus (SFTSV). This study aimed to evaluate the predictive power of C-reactive protein to lymphocyte ratio (CLR) and establish an early-warning model for SFTS mortality. We retrospectively analyzed hospitalized SFTS patients in six clinical centers from May 2011 to 2022. The efficacy of CLR prediction was evaluated by the receiver operating characteristic (ROC) analysis. A nomogram was established and validated. Eight hundred and eighty-two SFTS patients (median age 64 years, 48.5% male) were enrolled in this study, with a mortality rate of 17.8%. The area under the ROC curve (AUC) of CLR was 0.878 (95% confidence interval [CI]: 0.850-0.903, p < 0.001), which demonstrates high predictive strength. The least absolute shrinkage and selection operator regression selected seven potential predictors. Multivariate logistic regression analysis determined three independent risk factors, including CLR, to construct the nomogram. The performance of the nomogram displayed excellent discrimination and calibration, with significant net benefits in clinical uses. CLR is a brand-new predictor for SFTS mortality. The nomogram based on CLR can serve as a convenient tool for physicians to identify critical SFTS cases in clinical practice.

Visible-Light-Induced Phenoxyl Radical-based Metal-Organic Framework for Selective Photooxidation of Sulfides.

Phenoxyl radicals originating from phenols through oxidation or photoinduction are relatively stable and exhibit mild oxidative activity, which endows them with the potential for photocatalysis. Herein, a stable and recyclable metal-organic framework Zr-MOF-OH constructed of a binaphthol derivative ligand has been synthesized and functions as an efficient heterogeneous photocatalyst. Zr-MOF-OH shows fairly good catalytic activity and substrate compatibility toward the selective oxidation of sulfides to sulfoxides under visible light irradiation. Such irradiation of Zr-MOF-OH converts the phenolic hydroxyl groups of the binaphthol derivative ligand to phenoxyl radicals through excited state intramolecular proton transfer, and the excited state photocatalyst triggers the single-electron oxidation of the sulfide. No reactive oxygen species are produced in the photocatalytic process, and triplet O2 directly participates in the reaction, endowing Zr-MOF-OH with wide substrate compatibility and high selectivity, which also proposes a promising pathway for the direct activation of substrates via phenoxyl radicals.

Zr-Based Metal-Organic Frameworks with Phosphoric Acids for the Photo-Oxidation of Sulfides.

Heterogeneous Brønsted acidic catalysts such as phosphoric acids are the conventional activators for organic transformations. However, the photocatalytic performance of these catalysts is still rarely explored. Herein, a novel Zr-based metal-organic framework Zr-MOF-P with phosphoric acids as a heterogeneous photocatalyst has been fabricated, which shows high selectivity and reactivity towards the photo-oxidation of sulfides under white light illumination. A mechanism study indicates that the selective oxygenation of sulfides occurs with triplet oxygen rather than common reactive oxygen species (ROS). When Zr-MOF-P is irradiated, the hydroxyl group of phosphoric acid is converted into oxygen radical, which takes an electron from the sulfides, and then the activated substrates react with the triplet oxygen to form sulfoxides, avoiding the destruction of the catalysts and endowing the reaction with high substrate compatibility and fine recyclability.

Natural killer cell dysfunction in cancer and new strategies to utilize NK cell potential for cancer immunotherapy.

The continuous, in-depth exploration of the occurrence and development of cancer has shown that immune cell dysfunction is closely associated with tumor progression and poor clinical prognosis. The inhibition of the effector functions of immune cells by numerous immunosuppressive factors in the tumor microenvironment (TME) promotes the progression and metastasis of malignant tumors. Natural killer (NK) cells are the main effector cells in the anti-tumor innate immune system. Dysfunctional NK cells, characterized as weakened proliferation capacity and reduced production of effector cytokines, have limited ability to kill malignant cells and inhibit tumor progression. The reversal of the dysfunctional state of NK cells and enhancement of their effector functions is a promising strategy that could improve the effectiveness of cancer immunotherapy. In order to fully use of the cytotoxic effects of NK cells and revitalize the anti-tumor potential of NK cells in tumor patients, it is necessary to learn more about the characteristics of NK cell dysfunction in TME. This will provide valuable information for the development of personalized strategies to restore anti-tumor immunity. Here, we reviewed the characteristics of dysfunctional NK cells in the TME and latest progress in research, and discussed promising immunotherapy strategies that could utilize NK cell potential for cancer immunotherapy.

Epidemiology of hemorrhagic fever with renal syndrome in Tai'an area.

Hemorrhagic fever with renal syndrome (HFRS), a serious threat to human health, is mainly transmitted by rodents in Eurasia. The risk of disease differs according to sex, age, and occupation. Further, temperature and rainfall have some lagging effects on the occurrence of the disease. The quantitative data for these factors in the Tai'an region of China are still unknown. We used a forest map to calculate the risk of HFRS in different populations and used four different mathematical models to explain the relationship between time factors, meteorological factors, and the disease. The results showed that compared with the whole population, the relative risk in rural medical staff and farmers was 5.05 and 2.00, respectively (p < 0.05). Joinpoint models showed that the number of cases decreased by 33.32% per year from 2005 to 2008 (p < 0.05). The generalized additive model showed that air temperature was positively correlated with disease risk from January to June, and that relative humidity was negatively correlated with risk from July to December. From January to June, with an increase in temperature, after 15 lags, the cumulative risk of disease increased at low temperatures. From July to December, the cumulative risk decreased with an increase in the relative humidity. Rural medical staff, farmers, men, and middle-aged individuals were at a high risk of HFRS. Moreover, air temperature and relative humidity are important factors that affect disease occurrence. These associations show lagged and differing effects according to the season.

Effects of Full Inhalation of Sevoflurane and Total Intravenous Anesthesia on Hemodynamics, Serum Myocardial Enzymes, and Myocardial Markers in Elderly Patients Undergoing Hysterectomy.

OBJECTIVE: To compare the effects of sevoflurane inhalation and intravenous anesthesia on hemodynamics, serum myocardial enzymes, and myocardial markers in elderly patients undergoing hysterectomy. METHODS: Group A and group B were established randomly regarding a total of 126 elderly patients who underwent an elective hysterectomy. Patients in group A were given full anesthesia with sevoflurane, and patients in group B were given anesthesia with intravenous anesthesia. The operation time, anesthesia time, and recovery time in Postanesthesia Care Unit (PACU) were compared; plasma cortisol concentration, hemodynamics, serum myocardial enzymes, and myocardial markers were detected and compared between the two groups of patients before anesthesia (T 0), after anesthesia (T 1), and after surgery (T 2). RESULTS: Group A observed a longer extubation time and recovery time in PACU than group B (P < 0.05). Results show a lower systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and plasma cortisol concentration of T 1 by comparison with those of T 0 (P < 0.05), but no significant difference remains in terms of intergroup SBP, DBP, and HR (P > 0.05), and there was no interaction effect of groups and time (P > 0.05). The two groups showed no great disparity in the levels of lactate dehydrogenase (LDH), aspartate transaminase (AST), creatine kinase (CK), and CK-MB as a subtype of CK before surgery between the two groups of patients (P > 0.05). After surgery, LDH, AST, CK, and CK-MB levels in both groups were witnessed a surge, in which group A obtained higher levels of LDH, AST, CK, and CK-MB (all P < 0.05). CONCLUSION: Total intravenous anesthesia will not increase the hemodynamic fluctuation of elderly patients undergoing hysterectomy and can reduce the damage to the myocardium of patients with surgical trauma, which can protect the myocardium of elderly patients to a certain extent, so it can be adopted as the optimal anesthesia protocol for surgery.

Propeller Configuration Flipping of the Trivalent Boron-Inducing Substituent Dependence of the Circularly Polarized Luminescence Sign in Triarylborane-Based [7]Helicenes.

We here disclose two triarylborane-based [7]helicenes, which contain a dimesitylboryl or a 2-(dimesitylboryl)phenyl at position 9 of the [7]helicene skeleton. The change in the peripheral substituent from dimesitylboryl to 2-(dimesitylboryl)phenyl induced doubling of |glum| and sign inversion of the circularly polarized luminescence (CPL). The substituent dependence of the CPL sign is reasonably explained by the propeller configuration flipping of boron, which has a significant influence on the chiroptical properties.

The predictive effect of the platelet-to-lymphocyte ratio (PLR) and the neutrophil-to-lymphocyte ratio (NLR) on the risk of death in patients with severe fever with thrombocytopenia syndrome (SFTS): a multi-center study in China.

BACKGROUND: Severe fever with thrombocytopenia syndrome is caused by infection with the severe fever with thrombocytopenia syndrome virus. METHODS: Between April 2011 and December 2019, data on consecutive patients who were diagnosed with severe fever with thrombocytopenia syndrome were prospectively collected from five medical centers in China. The score of the death risk model was correlated with the platelet-to-lymphocyte ratio and the neutrophil-to-lymphocyte ratio. Multivariable Cox analyses were used to identify the independent factors associated with mortality. RESULTS: During the study period, 763 patients were diagnosed with severe fever with thrombocytopenia syndrome; 415 of these patients were enrolled in our study. We found that the neutrophil-to-lymphocyte ratio of the group that died was significantly higher on admission (P=0.007) than that of the group that survived, and the neutrophil-to-lymphocyte ratio showed a positive correlation with the score of the death risk model. Multivariate Cox regression suggested that a neutrophil-to-lymphocyte ratio greater than 5.4 was an independent risk factor for survival time (HR=6.767, P=0.011). Platelet-to-lymphocyte ratio did not show a special role in this study. CONCLUSIONS: A neutrophil-to-lymphocyte ratio greater than 5.4 can increase the risk of death and decrease the survival time of patients. In summary, the neutrophil-to-lymphocyte ratio provides a supplementary means for effectively managing severe fever with thrombocytopenia syndrome (SFTS).

Predictive Value of Triglyceride-Glucose Index for In-hospital Mortality in Patients With Severe Fever With Thrombocytopenia Syndrome: A Multi-Center Observational Study.

Background: Triglyceride-glucose (TyG) index has been proposed as a reliable indicator for insulin resistance and proved to be closely associated with the severity and mortality risk of infectious diseases. It remains indistinct whether TyG index performs an important role in predicting in-hospital mortality in patients with severe fever with thrombocytopenia syndrome (SFTS). Methods: The current study retrospectively recruited patients who were admitted for SFTS from January to December 2019 at five medical centers. TyG index was calculated in accordance with the description of previous study: Ln [fasting triglyceride (TG) (mg/dl) × fasting blood glucose (FBG) (mg/dl)/2]. The observational endpoint of the present study was defined as the in-hospital death. Results: In total, 79 patients (64.9 ± 10.5 years, 39.2% female) who met the enrollment criteria were enrolled in the current study. During the hospitalization period, 17 (21.5%) patients died in the hospital. TyG index remained a significant and independent predictor for in-hospital death despite being fully adjusted for confounders, either being taken as a nominal [hazard ratio (HR) 5.923, 95% CI 1.208-29.036, P = 0.028] or continuous (HR 7.309, 95% CI 1.854-28.818, P = 0.004) variate. TyG index exhibited a moderate-to-high strength in predicting in-hospital death, with an area under the receiver operating characteristic curve (AUC) of 0.821 (95% CI 0.712-0.929, P < 0.001). The addition of TyG index displayed significant enhancement on the predictive value for in-hospital death beyond a baseline model, manifested as increased AUC (baseline model: 0.788, 95% CI 0.676-0.901 vs. + TyG index 0.866, 95% CI 0.783-0.950, P for comparison = 0.041), increased Harrell's C-index (baseline model: 0.762, 95% CI 0.645-0.880 vs. + TyG index 0.813, 95% CI 0.724-0.903, P for comparison = 0.035), significant continuous net reclassification improvement (NRI) (0.310, 95% CI 0.092-0.714, P = 0.013), and significant integrated discrimination improvement (0.111, 95% CI 0.008-0.254, P = 0.040). Conclusion: Triglyceride-glucose index, a novel indicator simply calculated from fasting TG and FBG, is strongly and independently associated with the risk of in-hospital death in patients with SFTS.

Role of Anesthesia Nurses in the Treatment and Management of Patients With COVID-19.

As the backbone for the treatment of patients with coronavirus disease 2019 (COVID-19), nurses have been playing key roles in cabin hospitals, isolation wards, and intensive care units for critical cases. Anesthesia nurses have their own professional specialties, such as airway management, the use and maintenance of life support equipment, including ventilators, and the use of high-flow oxygen equipment. With rich experience in emergency responses and nursing, anesthesia nurses, along with emergency nurses and critical care nurses, play important roles during the treatment of patients with COVID-19. In our hospital, 27 of 34 anesthesia nurses participated in the front-line fight against COVID-19 and did an excellent job. Anesthesia care by nurses is relatively new in China, and the role of anesthesia nurses during a disaster response has not been fully appreciated. Given their specialty, anesthesia nurses have played important roles in the treatment of patients with COVID-19. We hope that authorities will consider including anesthesia nurses in national disaster response medical rescue teams.

High Levels of Circulating Cell-free DNA Are Associated With a Poor Prognosis in Patients With Severe Fever With Thrombocytopenia Syndrome.

BACKGROUND: The extensive geographical distribution and high mortality rate of severe fever with thrombocytopenia syndrome (SFTS) have made it an important threat to public health. Neutrophil extracellular traps (NETs) can be activated by a variety of pathogens and are associated with thrombocytopenia in viral infections. We aimed to identify NET production and its predictive value for disease progression and prognosis in patients with SFTS. METHODS: A prospective study was performed with a multicenter cohort of patients with SFTS (n = 112) to quantify serum NET levels. Three markers of NETs-namely, cell-free DNA (cfDNA), myeloperoxidase-DNA complexes, and lactoferrin-DNA complexes-were measured with PicoGreen double-stranded DNA assays and enzyme-linked immunosorbent assays. Receiver operating characteristic curves and multivariate regression analyses were performed to calculate the predictive value of cfDNA levels. RESULTS: SFTS was characterized by pronounced NET formation. The serum levels of NETs changed dynamically during disease progression, with an inverse pattern of the trends of platelet and neutrophil levels. High cfDNA levels were strongly associated with multiple pathological processes, including coagulopathy, myocardial damage, liver dysfunction, and the development of encephalopathy. A high level of cfDNA (>711.7 ng/mL) at the time of the initial diagnosis predicted severe illness in patients with SFTS (odds ratio, 8.285 [95% confidence interval, 2.049-33.503]; P = .003). CONCLUSIONS: This study has a high degree of clinical impact for identification of cfDNA as a useful predictive biomarker of clinical outcomes of SFTS.

Triarylborane-based [5]Helicenes with Full-Color Circularly Polarized Luminescence.

The efficient synthetic route was disclosed to prepare optically active triarylborane-based [5]helicenes, 7B-PhHC and 7B5N-PhHC. Their emission wavelengths are tunable by both the chemical structure modification and the tuning of excited state charge transfer dynamics via selection of appropriate solvents or addition of external F-, enabling the full-color circularly polarized luminescence with moderate to good quantum yields (0.07-0.51) and high luminescence dissymmetry factors (glum > 5 × 10-3).

A nomogram to predict mortality in patients with severe fever with thrombocytopenia syndrome at the early stage-A multicenter study in China.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) caused by the SFTS virus is an emerging infectious disease that was first identified in the rural areas of China in 2011. Severe cases often result in death due to multiple organ failure. To date, there are still numerous problems remain unresolved in SFTS, including unclear pathogenesis, lack of specific treatment, and no effective vaccines available. AIM: To analyze the clinical information of patients with early-stage SFTS and to establish a nomogram for the mortality risk. METHODS: Between April 2011 and December 2018, data on consecutive patients who were diagnosed with SFTS were prospectively collected from five medical centers distributed in central and northeastern China. Multivariable Cox analyses were used to identify the factors independently associated with mortality. A nomogram for mortality was established using those factors. RESULTS: During the study period, 429 consecutive patients were diagnosed with SFTS at the early stage of the disease (within 7 days of fever), among whom 69 (16.1%) died within 28 days. The multivariable Cox proportional hazard regression analysis showed that low lymphocyte percentage, early-stage encephalopathy, and elevated concentration of serum LDH and BUN were independent risk factors for fatal outcomes. Received-operating characteristic curves for 7-, 14-, and 28-days survival had AUCs of 0.944 (95% CI: 0.920-0.968), 0.924 (95% CI: 0.896-0.953), and 0.924 (95% CI: 0.895-0.952), respectively. Among low-risk patients, 6 patients died (2.2%). Among moderate-risk patients, 25 patients died (24.0%, hazard ratio (HR) = 11.957). Among high-risk patients, the mortality rate was 69.1% (HR = 57.768). CONCLUSION: We established a simple and practical clinical scoring system, through which we can identify critically ill patients and provide intensive medical intervention for patients as soon as possible to reduce mortality.

1,1'-Binaphthyl Consisting of Two Donor-π-Acceptor Subunits: A General Skeleton for Temperature-Dependent Dual Fluorescence.

Temperature-dependent dual fluorescence with the anti-Kasha's rule is of great interest, but is a very challenging property to achieve in small organic molecules. The highly sensitive temperature-dependent dual fluorescence of 2,2'-bis(dimethylamino)-6,6'-bis(dimesitylboryl)-1,1'-binaphthyl (BNMe2 -BNaph), which essentially consists of two donor-π-acceptor (D-π-A) subunits, inspired the exploration of the importance of its structural features and the general utility of this molecular design. The reference compound MBNMe2 -BNaph, which lacks one electron-accepting Mes2 B, is found to show less sensitive temperature-dependent dual fluorescence, suggesting that the structure of BNMe2 -Bnaph, consisting of two symmetrical D-π-A subunits, is very important for achieving highly sensitive temperature-dependent dual fluorescence. In addition, it is found that another two 1,1'-binaphthyls, CHONMe2 -BNaph and CNNMe2 -BNaph, which also consist of two D-π-A subunits with Mes2 B groups replaced by CHO and CN, respectively, also show temperature-dependent dual fluorescence, with the fluorescence changing in a similar manner to BNMe2 -BNaph, indicating the general utility of the current molecular design for temperature-dependent dual fluorescence. Furthermore, the temperature-dependent dual fluorescence behaviors, such as the relative intensities of the two emission bands, the separation of the two emissions bands, and the sensitivity of the fluorescence intensity ratio to temperature, are greatly influence by the electron acceptors.

2,2'-Diamino-6,6'-diboryl-1,1'-binaphthyl: A Versatile Building Block for Temperature-Dependent Dual Fluorescence and Switchable Circularly Polarized Luminescence.

Temperature-dependent dual fluorescence and switchable circularly polarized luminescence (CPL) are two highly pursued but challenging properties for small organic molecules (SOMs). We herein disclose a triarylborane π-system based on a 2,2'-diamino-6,6'-diboryl-1,1'-binaphthyl scaffold that can serve as a versatile building block for achieving these two properties by simply choosing different amino groups. BNMe2 -BNaph with less bulky dimethylamino groups displays temperature-dependent dual fluorescence, and can thus be used as a highly sensitive ratiometric fluorescence thermometer. On the other hand, BNPh2 -BNaph with bulky diphenylamino groups exhibits intense fluorescence in both solution and in the solid state. A change of solvent from nonpolar cyclohexane to highly polar MeCN not only shifts the CPL position to much longer wavelength but also inverts the CPL sign. In addition, the complexation of BNPh2 -BNaph with fluoride greatly enhances the CPL intensity.

Modification of [5]Helicene with Dimesitylboryl: One Way To Enhance the Fluorescence Efficiency.

The efficient synthetic route was disclosed to prepare structurally asymmetric [5]helicenes, which are substituted with either BMes2 (7B-HC) or both BMes2 and NMe2 (8B5NMe2-HC, 7B5NMe2-HC). Compared with the parent [5]helicene, these compounds show greatly enhanced fluorescence. In addition, they still retain fairly strong fluorescence in the solid state. Moreover, the complexation of 8B5NMe2-HC and 7B5NMe2-HC with fluoride can induce significant blue shift in fluorescence and the formed complexes are also highly fluorescent.