OBJECTIVES:Optimal isavuconazole (ISA) dosing, trough concentrations (Cmin), and toxicity profiles in elderly patients with invasive pulmonary fungal disease (IFDs) remain unclear. METHODS:A multicenter retrospective study enrolled elderly IFDs inpatients treated with ISA at 5 tertiary hospitals in Beijing from October 2022 to June 2025. Serial Cmin monitoring and analysis of overexposure, toxicity, and efficacy were performed. RESULTS:140 Cmin values were assessed in 42 patients. Dose-reduction group maintained Cmin consistently >1 mg/L, with a higher target concentration achievement (98.1% vs 64.4%, P < 0.05) compared with conventional dosing. Conventional dosing showed 35.6% overexposure (daily Cmin increase is 0.033 mg/L, P = 0.009), linked to reduced eGFR within 21 days (OR = 0.955, P = 0.028) and BMI at 60 and 90 days post-treatment (OR = 0.788 and 0.780, both P < 0.05). Gastrointestinal toxicity (threshold: 4.693 mg/L) and hepatotoxicity were more frequent in conventional group compared with dose-reduction group. Mortality and efficacy did not differ significantly between groups. CONCLUSIONS:TDM-guided ISA dose reduction enhances target concentration attainment, reduces overexposure and toxicity without compromising efficacy, and is recommended for elderly patients, particularly those with renal impairment or lower BMI.

Both mesenchymal-epithelial transition factor (C-Met) and epidermal growth factor (EGFR) have been acknowledged as significant pan-tumor therapeutic targets. EGFR- and cMet-targeted autologous chimeric antigen receptor (CAR) T therapies have been tested in clinicals. However, the potential toxicity significantly limited their therapeutic outcomes. Compared to T cells, natural killer (NK) cells have a lower risk of inflammatory toxicity and graft-versus-host disease. CAR-NK therapies also can be produced as an off-the shelf product. To prevent antigen escape, we developed cMet targeted NK cells therapy in combination with EGFR targeted therapeutic antibody in treating solid tumors. Our preclinical results demonstrated cMet CAR-NK single treatment or combined with therapeutic antibodies showed better anti-tumor efficacy compared to EGFR/cMet dual-target CAR-NK cells. We verified EGFR and cMet expression in multiple tumor cell lines (HCT116-colon, NUGC4-gastric, and A549/NCI-1975-NSCLC), which were further engineered to express luciferase. EGFR targeted, cMet targeted, and cMet/EGFR dual-targeted CAR structures were designed and transduced with retroviral vectors into expanded NK cells. Flow cytometry was used to compare the transfection rates and phenotyping among different CAR structures. CAR-NK cell functionality was tested using in vitro cytotoxicity assays. In vivo study was performed in subcutaneously inoculated xenografts with intravenous delivery of cryopreserved CAR-NK cells. Flow cytometry analysis revealed efficient transduction in single targeted CARs and dual-targeted tandem CAR (∼80%), but low transduction level in dual-targeted parallel CAR (∼40%). All CAR constructs indicated in vitro specific cytotoxicity using luciferase- and RTCA-based assays. However, compared to dual-targeted CARs, EGFR and cMet single CARs demonstrated significant better tumor regression and NK cell persistence in peripheral blood in an NCI-H1975 s.c. xenograft mouse model. We demonstrated that combination of cMet CAR-NK with EGFR- or EGFR/cMet-targeted therapeutic antibodies resulted in both potent ADCC and CAR activity, whereas EGFR CAR-NK combo showed compromised in vitro tumor killing capacity. Furthermore, cMet CAR-NK solo or combo treatment showed excellent tumor control and survival prolong in different tumor cell line derived xenograft mouse models. These studies have a pivotal role in the evaluation of cMet CAR-NK cell combination therapies against solid tumors and reveal their therapeutic potential. Allogeneic cMet CAR-NK cell therapy and combo may provide safe and effective treatments for pan-tumor patients who have limited therapeutic options. Chao Wang, Tingting Liu, Qin Wang, Yanxue Gong, Fanxiang Gao, Feng Zhou, Zhuoxiao Cao. Combination of a novel allogeneic anti-cMet CAR-NK cell product with therapeutic antibodies in treating solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6120.

Small cell lung cancer (SCLC) is an aggressively lethal malignancy with a high unmet medical need. Overexpression of Delta-like ligand 3 (DLL3) has been identified as a poor prognostic factor. Adoptive immunotherapy based on chimeric antigen receptor (CAR) T cells has been developed, however with significant adverse events. To address the critical need for an improved therapeutic intervention, we leveraged the ability of DLL3 targeted peripheral blood derived natural killer (PBNK) allogeneic cells therapy in treating SCLC. We describe preclinical in vitro and in vivo results demonstrating the antitumor efficacy of an off-the-shelf, cryopreserved DLL3 CAR-NK candidate. In addition, we make comprehensive comparison of PB units from different donors to establish criteria of starting materials selection for clinical and commercial supply of CAR-NK cells. PBNK cells were isolated from healthy donors with FcγRIIIA-158 (V/V, V/F) and propagated using feeder cells and cytokine cocktails. Various in vitro assays, including flow cytometry phenotyping, freeze-thaw viability/recovery, short-term and serial killing, cytokine releasing against tumor cells, were used for comprehensive function evaluation of PB units. DLL3 targeted CAR-NK cells were engineered by transducing donor-preselected NK cells with a retroviral vector encoding a DLL3 membrane-proximal epitope targeted scFv, a NK-optimized CAR backbone and a secreted IL15 armor. Activity of CAR-NK cells against target-expression SCLC cells was assessed in vitro and in vivo. PB Donors were selected with excellent NK expansion capacity and freeze/thaw recovery rate, stronger innate cytotoxicity and higher degranulation and intracellular IFN-γ buildup upon co-culturing with different tumor cells. The anti-DLL3 CAR was successfully transduced across all batches of CAR-NK cells derived from selected donors. NK-featured CAR backbone significantly enhanced expansion of NK cells and induced more activated NK phenotype compared to conventional CAR backbone. DLL3 CAR-NK cells was cytotoxic against DLL3+ tumor cells (SHP-77 and NCI-H2171 cells), and DLL3 CAR-NK cells combined with anti-PD-L1 antibodies could further enhance NK cells proliferation in response to tumor cells and could control multiple rounds of tumor cells re-challenge in vitro. Using a cell line derived xenograft mouse model, we showed that a single dose of cryopreserved DLL3 CAR-NK cells delayed tumor growth and prolonged mice survival. Synergistic in vivo antitumor efficacy and enhanced NK cell expansion in peripheral blood were observed when using CAR-NK combined with anti-PD-L1. Collectively, these results demonstrated the favorable manufacturability, potency, and safety of a DLL3 CAR-NK cells product and its potential as a novel allogeneic treatment option for patients with SCLC. Chao Wang, Tingting Liu, Qin Wang, Yanxue Gong, Ling Chen, Fanxiang Gao, Feng Zhou, Zhuoxiao Cao. A novel allogeneic anti-DLL3 CAR-NK cell therapy in treating small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6121.

Sensing temperature at the subcellular level is pivotal for gaining essential thermal insights into diverse biological processes. However, achieving sensitive and accurate sensing of the intracellular temperature remains a challenge. Herein, we develop a ratiometric organic fluorescent nanothermometer with reverse signal changes for the ultrasensitive mapping of intracellular temperature. The nanothermometer is fabricated from a binary mixture of saturated fatty acids with a noneutectic composition, a red-emissive aggregation-caused quenching luminogen, and a green-emissive aggregation-induced emission luminogen using a modified nanoprecipitation method. Different from the eutectic mixture with a single phase-transition point, the noneutectic mixture possesses two solid-liquid phase transitions, which not only allows for reversible regulation of the aggregation states of the encapsulated luminogens but also effectively broadens the temperature sensing range (25-48 degrees C) across the physiological temperature range. Remarkably, the nanothermometer exhibits reverse and sensitive signal changes, demonstrating maximum relative thermal sensitivities of up to 63.66% degrees C-1 in aqueous systems and 44.01% degrees C-1 in the intracellular environment, respectively. Taking advantage of these outstanding thermometric performances, the nanothermometer is further employed to intracellularly monitor minute temperature variations upon chemical stimulation. This study provides a powerful tool for the exploration of dynamic cellular thermal activities, holding great promise in unveiling intricate physiological processes.

Herein we successfully utilize various directing groups to achieve a ligand-enabled nickel-catalyzed 1,2-borylalkylation of unactivated alkenes. A β-amino alcohol was employed as the ligand for non-asymmetric 1,2-borylalkylation of unactivated alkenes, while a bulky chiral diamine ligand was used to achieve the asymmetric 1,2-borylalkylation of allyl amides.

Primary myelofibrosis (PMF) is a severe myeloproliferative neoplasm that is characterized by low-differentiation megakaryoblasts and progressive bone marrow fibrosis. Although an Aurora kinase A (AURKA) targeting small -molecule inhibitor MLN8237 has been approved in clinical trials for differentiation therapy of high-risk PMF patients, its off-target side effects lead to a partial remission and serious complications. Here, we report a dual -targeting therapy agent (rLDL-MLN) with great clinical translation potential for differentiation therapy of PMF disease. In particular, the reconstituted low-density lipoprotein (rLDL) nanocarrier and the loaded MLN8237 can actively target malignant hematopoietic stem/progenitor cells (HSPCs) via LDL receptors and intracellular AURKA, respectively. In contrast to free MLN8237, rLDL-MLN effectively prohibits the proliferation of PMF cell lines and abnormal HSPCs and significantly induces their differentiation, as well as prevents the formation of erythrocyte and megakaryocyte colonies from abnormal HSPCs. Surprisingly, even at a 1500-fold lower dosage (0.01 mg/kg) than that of free MLN8237, rLDL-MLN still exhibits a much more effective therapeutic effect, with the PMF mice almost clear of blast cells. More importantly, rLDL-MLN promotes hematological recovery without any toxic side effects at the effective dosage, holding great promise in the targeted differentiation therapy of PMF patients.

Antimicrobial susceptibility testing plays a pivotal role in the discovery of new antibiotics. However, the development of simple, sensitive, and rapid assessment approaches remains challenging. Herein, we report an activated alkyne-based cascade signal amplification strategy for ultrafast and high-throughput antibiotic screening. First of all, a novel water-soluble aggregation-induced emission (AIE) luminogen is synthesized, which contains an activated alkyne group to enable fluorescence turn-on and metal-free click bioconjugation under physiological conditions. Taking advantage of the in-house established method for bacterial lysis, a number of clickable biological substances (i.e., bacterial solutes and debris) are released from the bacterial bodies, which remarkably increases the quantity of analytes. By means of the activated alkyne-mediated turn-on click bioconjugation, the system fluorescence signal is significantly amplified due to the increased labeling sites as well as the AIE effect. Such a cascade signal amplification strategy efficiently improves the detection sensitivity and thus enables ultrafast antimicrobial susceptibility assessment. By integration with a microplate reader, this approach is further applied to high-throughput antibiotic screening.

Photothermal therapy (PTT) systems typically do not possess intrinsic tumor-targeting capability, resulting in indiscriminate thermal damage to both cancer and normal cells. Herein, a low-density lipoprotein (LDL)-based nanosystem (denoted as MTTQ@LDL) is reported for targeted photothermal killing of cancer cells. Such a nanosystem is fabricated by reconstituting the lipophilic core of LDL with an organic photothermal agent MTTQ. The reconstitution process improves the supramolecular photothermal effects of MTTQ assemblies, which contributes to the significantly enhanced photothermal conversion efficiency (41.3% vs. 16.2%). MTTQ@LDL can actively target LDL receptor-overexpressed cancer cells via receptor-mediated endocytosis, enabling the selective killing of cancer cells over normal cells (98% vs. 7%) post-NIR irradiation. Reconstituted LDL can serve as a promising platform for targeted delivery of functional materials, holding great promise in tumor eradication in vivo. In this work, the lipophilic core of low-density lipoprotein (LDL) is reconstituted with a near-infrared (NIR)-absorbing organic photothermal agent. By virtue of the tumor-targeting capability of LDL, the reconstituted LDL particles can selectively kill LDL receptor-overexpressed cancer cells over normal cells via photothermal heating upon NIR irradiation, holding great promise in tumor eradication in vivo.image

New Cu(I) catalysts are effective in enantioselective Friedel-Crafts alkylation of a variety of indoles with different β,γ-unsaturated α-ketoesters. A control study shows that such a catalyst system is less sensitive to air, and the reactions can be carried out without special cares such as glovebox operation or moisture/oxygen-free conditions. Preliminary computation results suggest that there exists π-π stacking between the substrate and the catalyst, and such an interaction seems to play a role in stabilizing the reaction intermediate and enhancing the stereoselectivity of the reactions. The desired products can be obtained in up to 98% yield at 99% enantiomeric excess. The same high enantioselectivity can be observed when the reaction is carried in a gram scale, indicating a good scalability of the catalyst system in enantioselective Friedel-Crafts alkylation of different indoles with β,γ-unsaturated α-ketoesters.

Photodynamic therapy (PDT) has attracted much attention in disease treatments. However, the exploration of a novel method for the construction of outstanding photosensitizers (PSs) with stimuli-responsiveness remains challenging. In this study, we, for the first time, report a novel and effective strategy to boost reactive oxygen species (ROS) generation by bridging donor-acceptor (D-A) type PSs with the azo group. In contrast to the counterpart without azo-bridging, the azo-bridged PSs exhibit remarkably enhanced ROS generation via both type-I and type-II photochemical reactions. Theoretical calculations suggest that azo-bridging leads to a prominent reduction in ΔE ST, thereby enabling enhanced ROS generation via efficient intersystem crossing (ISC). The resulting azo-bridged PS (denoted as Azo-TPA-Th(+)) exhibits a particularly strong bactericidal effect against clinically relevant drug-resistant bacteria, with the killing efficiency up to 99.999999% upon white light irradiation. Since azo-bridging generates an azobenzene structure, Azo-TPA-Th(+) can undergo trans-to-cis isomerization upon UV irradiation to form emissive aggregates by shutting down the ISC channel. By virtue of the fluorescence turn-on property of unbound Azo-TPA-Th(+), we propose a straightforward method to directly discern the effective photodynamic bactericidal dose without performing the tedious plate-counting assay. This study opens a brand-new avenue for the design of advanced PSs with both strong ROS generation and stimuli-responsiveness, holding great potential in high-quality PDT with rapid prediction of the therapeutic outcome.

The maintenance of an intact membrane structure is of great importance for bacteria to execute various biological functions. However, chemical probes for monitoring the dynamic changes of bacterial membranes are barely reported. Herein, we, for the first time, report a novel polarity-sensitive probe for reflecting the packing degree of bacterial membrane lipids. Specifically, we synthesize a membrane-targeting fluorescent probe (TICT-lipid) that possesses both twist intramolecular charge transfer and aggregation-induced emission properties. TICT-lipid exhibits sensitive responses to the minute difference in the packing degree of membrane lipids, facilitating rapid differentiation of Gram-negative and Gram-positive bacteria. Interestingly, in the presence of membrane-disrupting antibiotics, the localization of TICT-lipid shifts from the outer membrane to the cell membrane by outputting blue-shifted and enhanced emission, making the mechanism of action of antibiotics clearly visible. TICT-lipid is a polarity-sensitive fluorescent probe, holding great promise in the study of membrane-related bacterial processes and antibiotic screening.

Chiral O-N-N tridentate ligands were designed from proline and BINOL. Their design strategy and performance were evaluated using a copper(II)-catalyzed asymmetric Henry reaction as a model. The desired β-nitroalcohols were obtained in up to 94% ee's. Preliminary results suggested that the stereofacial selection of the reactions was mainly controlled by the chiral diamine moiety derived from proline, and matching of the central and axial chiralities was essential for the high stereoselectivity of the reaction. Enantioswitching was observed when an appropriate substituent was introduced to the binaphthyl group. Si-selections were found in reactions using 2a without 3-substituents as chiral ligand, and Re-selections were found with the same high enantioselectivities when 2i bearing the 3-trifluoromethyl group was used as the chiral ligand.

Low-density lipoproteins (LDLs) are an endogenous nanocarrier to transport lipids in vivo. Owing to their biocompatibility and biodegradability, reduced immunogenicity, and natural tumor-targeting capability, we, for the first time, report the reconstitution of native LDL particles with saturated fatty acids and a mitochondrion-targeting aggregation-induced emission (AIE) photosensitizer for fluorescence-feedback photodynamic therapy (PDT). In particular, a novel AIE photosensitizer (TPA-DPPy) with a donor-acceptor (D-A) structure and a pyridinium salt is designed and synthesized, which possesses typical AIE and twisted intramolecular charge transfer (TICT) characteristics as well as reactive oxygen species (ROS)-sensitizing capability. In view of its prominent photophysical and photochemical properties, TPA-DPPy is encapsulated into LDL particles for photodynamic killing of cancer cells that overexpress LDL receptors (LDLRs). The resultant LDL (rLDL) particles maintain a similar morphology and size distribution to native LDL particles, and are efficiently ingested by cancer cells via LDLR-mediated endocytosis, followed by the release of TPA-DPPy for mitochondrion-targeting. Upon light irradiation, the produced ROS surrounding mitochondria lead to efficient and irreversible cell apoptosis. Interestingly, this process can be fluorescently monitored in a real-time fashion, as reflected by the remarkably enhanced luminescence and blue-shifted emission, indicating the increased mechanical stress during apoptosis. Quantitative cell viability analysis suggests that TPA-DPPy exhibits an outstanding phototoxicity toward LDLR-overexpressing A549 cancer cells, with a killing efficiency of ca. 88%. The rLDL particles are a class of safe and multifunctional nanophototheranostic agents, holding great promise in high-quality PDT by providing real-time fluorescence feedback on the therapeutic outcome.

Background The difficulty of early diagnosis of bloodstream infection in the elderly patients leads to high mortality. Therefore, it is essential to determine some new methods of early warning of bloodstream infection in the elderly patients for timely adjustment of treatment and improvement of prognosis. Methods Patients aged over 65 years with suspected bloodstream infections were included and divided into bloodstream infection (BSI) and non-bloodstream infection (non-BSI) groups based on blood culture results. The morphology of microparticles (MPs) was observed by using transmission electron microscopy, and the number of MPs was dynamically monitored by flow cytometry. Results A total of 140 patients were included in the study: 54 in the BSI group and 86 in the non-BSI group. Total MPs (T-MPs) ≥ 6000 events/µL (OR, 7.693; 95% CI 2.944–20.103, P < 0.0001), neutrophil-derived MPs (NMPs) ≥ 500 events/µL (OR, 12.049; 95% CI 3.574–40.623, P < 0.0001), and monocyte counts ≤ 0.4 × 10 9 /L (OR, 3.637; 95% CI 1.415–9.348, P = 0.007) within 6 h of fever were independently associated with bloodstream infection in the elderly patients. We also developed an early warning model for bloodstream infection in the elderly patients with an area under the curve of 0.884 (95% CI 0.826–0.942, P < 0.0001), sensitivity of 86.8%, specificity of 76.5%, positive predictive value of 70.8%, and negative predictive value of 89.8%. Conclusion The early warning model of bloodstream infection based on circulating T-MPs, NMPs, and monocyte counts within 6 h of fever in the elderly patients was helpful in early detection of bloodstream infection and therefore promptly adjustment of treatment plan.

在对细胞、生物大分子等柔软样品进行纳米操作时,原子力显微镜（atomic force microscope,AFM）面临缺乏实时视觉反馈的问题.为此,搭建了一套面向柔软样品的AFM纳米操作可视化系统.具体而言,首先建立了AFM形貌图像坐标系到虚拟场景坐标系之间的映射关系,从而得到虚拟场景中样品的顶点信息,进而通过3维图形引擎渲染样品的虚拟形貌.在此基础上,提出了一种基于接触力学理论的样品形变估计和仿真方法,对探针按压导致的样品形变进行了虚拟视觉反馈,从而使得刻画的虚拟形貌能够和样品的真实形貌保持一致,并准确地还原按压过程中样品表面的形貌变化.仿真和实验结果表明,所设计的纳米操作可视化系统能够在虚拟场景中实时呈现AFM纳米操作过程.

Background: There are limited methods to predict the therapeutic effect of immune checkpoint inhibitors (ICIs). The purpose of this study was to explore the value of circulating microparticles (MPs) in predicting thetherapeutic effects of immunotherapy. Methods: A prospective study was conducted at the cancer center of PLA general hospital, including all patients with advanced non-small cell lung cancer (NSCLC) who were treated with pembrolizumab or nivolumab from December 2018 to December 2019. The patients were divided into an immune-related objective response (iOR) group and an immune-related disease progression (iPD) group.The numbers of total MPs, platelet-derived microparticles (PMPs) and T-lymphocyte-derived microparticles (T-LyMPs) at baseline and after immunotherapy were detected using a flow cytometer. Univariate analysis and multivariate logistic regression analysis were used to determine the independent influencing factors. Results: We identified 32 patients in the iOR group and 18 patients in the iPD group. No significant difference were found intotal MPs, PMPs and T-LyMPs at the baseline between the 2 groups. While total MPs, PMPs and T-LyMPs in the iPD group were significantly higher than those in the iOR group after immunotherapy(P < 0.05). In the multivariate logistic regression analysis, PMPs ≥80 events/µL after immunotherapy(OR, 7.270; 95% CI, 1.092-48.404, P = 0.04) were associated with disease progression in advanced NSCLC and could independently predict the therapeutic effect of immunotherapy. Conclusions: PMPs after immunotherapy independently predicted the therapeutic effects of ICIs, making it possible to monitor the therapeutic effect in real time and rapidly adjust treatment regimens. In addition, this study found for the first time that elevated circulating T-LyMPs were associated with disease progression in advanced NSCLC.

Sensing temperature at the subcellular level is of great importance for the understanding of miscellaneous biological processes. However, the development of sensitive and reliable organic fluorescent nanothermometers remains challenging. In this study, we report the fabrication of a novel organic fluorescent nanothermometer and study its application in temperature sensing. First of all, we synthesize a dual-responsive organic luminogen that can respond to the molecular state of aggregation and environmental polarity. Next, natural saturated fatty acids with sharp melting points as well as reversible and rapid phase transition are employed as the encapsulation matrix to correlate external heat information with the fluorescence properties of the luminogen. To apply the composite materials for biological application, we formulate them into colloidally dispersed nanoparticles by a technique that combines in situ surface polymerization and nanoprecipitation. As anticipated, the resultant zwitterionic nanothermometer exhibits sensitive, reversible, reliable, and multiparametric responses to temperature variation within a narrow range around the physiological temperature (i.e., 37 °C). Taking spectral position, fluorescence intensity, and fluorescence lifetime as the correlation parameters, the maximum relative thermal sensitivities are determined to be 2.15% °C-1, 17.06% °C-1, and 17.72% °C-1, respectively, which are much higher than most fluorescent nanothermometers. Furthermore, we achieve the multimodal temperature sensing of bacterial biofilms using these three complementary fluorescence parameters. Besides, we also fabricate a cationic form of the nanothermometer to facilitate efficient cellular uptake, holding great promise for studying thermal behaviors in biological systems.

Binaphthyl-prolinol ligands were designed and applied in enantioselective arylation of aromatic aldehydes and sequential arylation-lactonization of methyl 2-formylbenzoate. Under optimized conditions, the reactions provided the desired diarylmethanols and 3-aryl phthalides in up to 96% yields with up to 99% ee and up to 89% yields with up to 99% ee, respectively. In particular, essentially optically pure 3-aryl phthalides (over 99% ee) were obtained in large quantities through recrystallization.

OBJECTIVE:To investigate the level and changing trend of microparticles (MPs) in super-elderly infected patients, and explore its early warning effect on infection.METHODS:The infected patients ≥ 85 years old admitted to the Second Medical Center of Chinese PLA General Hospital from December 2018 to March 2019 were selected as the observation group, and the healthy volunteers ≥ 85 years old in the same period were selected as the control group. Venous blood samples were collected at the 2nd hour, the 2nd day and the 7th day after fever, and the inflammatory markers such as white blood cell count (WBC), neutrophil percentage (NEUT), C-reactive protein (CRP) and procalcitonin (PCT) were measured. The levels of MPs were determined by flow cytometry. Annexin V labeled CD11b positive MPs (Annexin V+/CD11b+ MPs) represented leukocyte microparticles (LMPs), and Annexin V labeled CD66b positive MPs (Annexin V+/CD66b+ MPs) represented neutrophil microparticle (NMPs). The differences of each index at different time points between the two groups were compared, and the predictive value of each index to the infection of elderly patients was analyzed by receiver operating characteristic (ROC) curve.RESULTS:A total of 38 subjects were enrolled, including 28 cases in the observation group and 10 cases in the control group. The levels of LMPs and NMPs in the observation group increased to the peak at the 2nd hour after fever, and were significantly higher than those in the control group [LMPs (cells/μL): 55.0 (28.8, 197.2) vs. 19.0 (13.5, 28.3), NMPs (cells/μL): 226.5 (123.3, 516.5) vs. 26.5 (22.0, 48.8), both P < 0.01]. With the control of the disease, LMPs and NMPs decreased gradually. The NMPs on the 2nd day was significantly lower than that at the 2nd hour of fever [cells/μL: 106.0 (40.0, 309.0) vs. 226.5 (123.3, 516.5), P < 0.05], and the LMPs and NMPs on the 7th day were significantly lower than those on the 2nd day [LMPs (cells/μL): 17.0 (12.5, 43.8) vs. 42.0 (13.0, 117.0), NMPs (cells/μL): 30.0 (15.8, 62.0) vs. 106.0 (40.0, 309.0), both P < 0.05]. There was no significant difference in the levels of LMPs and NMPs between the two groups on the 7th day. Among the inflammatory markers, the NEUT in the observation group was significantly higher than that in the control group at the 2nd hour of fever (0.70±0.09 vs. 0.59±0.04, P < 0.01), but there was no significant difference in WBC, CRP and PCT between the two groups. On the 2nd day, the inflammatory markers in the observation group reached the peak and were significantly higher than those in the control group [WBC (×109/L): 9.33±2.44 vs. 6.37±1.28, NEUT: 0.78±0.08 vs. 0.57±0.04, CRP (mg/L): 5.67±2.99 vs. 0.33±0.18, PCT (μg/L): 0.80±0.67 vs. 0.07±0.03, all P < 0.01]. On the 7th day, the inflammatory markers in the observation group decreased significantly, and there was no significant difference between the observation group and the control group. ROC curve analysis showed that the area under ROC curve (AUC) and 95% confidence interval (95%CI) of LMPs and NMPs on the day of fever were higher than those of WBC, NEUT, CRP and PCT [0.888 (0.763-1.000), 0.973 (0.931-1.000) vs. 0.679 (0.346-0.811), 0.829 (0.700-0.958), 0.607 (0.404-0.811), 0.554 (0.358-0.749)].CONCLUSIONS:LMPs and NMPs are significantly increased in the early stage of fever, which can predict the incidence of infection in the super-elderly patients.

Objective To compare the efficacy and safety of polymyxin B and tigecycline in treatment of carbapenemresistant pneumonia in elderly patients. Methods This retrospective review involved 44 patients (≥85 years old) from January 2017 to December 2019. All the patients received meropenem in combination with polymyxin B or tigecycline divided into two groups. Group-wise general conditions, clinical efficacy, prognosis and adverse events were analyzed and compared, accordingly. Results A total of 20 patients in the polymyxin B group and 24 patients in the tigecycline group were included. The effective rate, bacterial clearance rate and thirty-day mortality of polymyxin B group were 65.0%, 30.0% and 25.0% respectively, with no significant difference from tigecycline group (58.3%, 20.8% and 20.8%)(P>0.05). Compared with tigecycline group, the elevated bilirubin incidence in polymyxin B group was significantly lower (10.0% vs. 41.7%, P 0.05). Conclusion We found no significant difference in efficacy and thirty-day mortality between two groups. This study found for the first time that light may play a role in promoting skin pigmentation induced by polymyxin B. DOI: 10.11855/j.issn.0577-7402.2020.12.11