Construction of CD19 targeted dual- and enhanced dual-antibodies and their efficiency in the treatment of B cell malignancy.

BACKGROUND: T cell-redirecting bispecific antibodies establish a connection between endogenous T cells and tumor cells, activating T cells function to eliminate tumor cells without ex vivo genetic alteration or manipulation. Here, we developed a novel dual-specific antibody (DuAb) and an enhanced DuAb (EDuAb) with different stimulation signal to activate T cells, and evaluated their impact on the treatment of acute lymphoblastic leukemia (ALL). METHODS: The expression plasmids of the DuAb and EDuAb containing CD80 molecule were constructed by cloning heavy chain and light chain variable fragments from anti-human CD19 (HI19a) and CD3 (HIT3a) monoclonal antibody hybridomas, respectively. The activation and the anti-tumor efficacy of human T cells mediated by DuAb and EDuAb were evaluated in vitro. B-cell ALL xenograft NSG mouse model was established to investigate the therapeutic effect in vivo. RESULTS: EDuAb promoted the optimal expansion of primary human T cells with low expression of inhibitory markers in vitro than DuAb did. Both DuAb and EDuAb showed a similar capability in inducing healthy donor T cells to specifically eliminate B-ALL cell lines and primary blasts from patients. The similar ability was also observed in the patient-derived T cells. In vivo study showed that both DuAb and EDuAb significantly alleviated tumor burden and extended survival of B-ALL xenograft NSG mice. The median survival of PBS, DuAb and EDuAb treatment groups were 27, 38 and 45 days, respectively. The phenotype of T cells and cytokine release in peripheral blood (PB) of B-ALL xenograft NSG mice on day 24 were analyzed as well. The results showed that the proportion of CD8+ T cells and cytokine levels, including IL-2, IFN-γ and TNF-α, were higher in the EDuAb group than that of DuAb. Moreover, both DuAb and EDuAb significantly decreased the residual leukemia cells in PB of B-ALL xenograft NSG mice. CONCLUSIONS: Both DuAb and EDuAb showed great potential as novel treatments for B-ALL in clinical applications. However, compared to DuAb, EDuAb showed a significant advantage in promoting the proliferation and survival of T cells. Furthermore, EDuAb showed a better promising effect on eliminating tumor cells and extending survival in vivo, which provides new insights for the development of new multi-specific antibodies.

Efficacy and safety of Extrapleural block in patients with coronary artery disease after thoracoscopic surgery.

OBJECTIVE: This study aimed to investigate the efficacy and safety of extrapleural block (EPB) application in patients with coronary artery disease after thoracoscopic surgery. METHODS: Patients with typical symptoms of angina and myocardial ischemia who underwent thoracoscopic surgery at our institution between December 2018 and December 2020 were screened for eligibility and they received paravertebral blocking (PVB), EPB, and patient-controlled intravenous analgesia (PCIA). Visual analog scale (VAS) scores were used to assess the analgesic effect and safety outcomes included heart rate, incidence of postoperative rescue analgesics, cardiac complications, and adverse reactions such as nausea and vomiting. RESULTS: In total, 76 patients (age: 66.5 [61.3, 71] years; male: 63.2%) were eligible, including the PVB group (n = 22), EPB group (n = 25), and PVIA group (n = 29) with comparable baseline characteristics. There was a significantly higher proportion of patients with a VAS score of 1 in the EPB group compared with the other groups at 4 h (88.0% vs. 10.3% for PCIA and 45.5% for PVB; p < .001) and 6 h after the surgery (32.0% vs. 3.4% for PCIA and 13.6% for PVB; p = .012). The preoperative heart rate in the EPB group (81 [71, 94] beats/min) was slightly higher than those in the PVB (76 [70, 85] beats/min) and PCIA groups (76 [69, 84 beats/min]) but without significant difference (p = .193). There was no significant difference in the incidence of rescue analgesia, adverse events, and cardiac complications among the three groups (p = .296, .808, and .669, respectively.) CONCLUSION: Compared with PVB and PCIA, the EPB could more effectively relieve acute pain after thoracoscopic surgery in patients with coronary artery disease and offer comparable safety benefits in the management of postoperative heart rate, adverse events, and cardiac complications.

Self-Assembly of Mechanoluminochromic Ladder-Shaped Gold(I) Clusters Promoted Using Cooperative Aurophilicity.

The self-assembly of mechanoluminochromic polynuclear gold(I) complexes has attracted more and more attention in the field of supramolecular gold(I) chemistry. In this work, we adopted a stepwise self-assembly strategy to precisely synthesize two polynuclear gold(I) supramolecular clusters. Through cooperative AuI···AuI and Au-N interactions, the gold(I) clusters 1+•BF4- and 24+•4BF4- with Au4 and Au16 cores, respectively, were successfully constructed. In these supramolecular clusters, (dppm)Au2Cl2 coordination motifs and trithiocyanuric linkers were stepwise assembled via sequential thiolate-chloride/phosphine coordination substitution and Au-S/Au-N coordination bond rearrangement. Two well-defined gold(I) supramolecular clusters displayed intense emission both in the solid state and in solution. Furthermore, the ladder-shaped cluster 24+•4BF4- exhibited reversible mechanochromic luminescence behavior in the solid state as well as aggregation-caused redshifted emission in solution. Upon mechanical grinding, the emission of the cluster 24+•4BF4- changed from yellow at 582 nm to red at 612 nm. The initial emission could be fully recovered by treatment with acetonitrile.

Effects of Multimodal Analgesia Combined with Auricular Point Therapy on Physical and Mental Stress and Rehabilitation Quality of Patients with Meniscus Injury during the Perioperative Period.

Objective: To investigate the effect of multimodal analgesia combined with auricular point therapy on physical and mental stress and rehabilitation quality of patients with meniscus injury during the perioperative period. Methods: 148 patients in our hospital from October 2019 to October 2021 who were scheduled to undergo meniscus surgery were selected and grouped according to the order of file establishment, with 74 cases in each. The control group was given routine analgesia, and the observation group was given multimodal analgesia combined with auricular point therapy. The pain level (visual analogue scale (VAS)), physical and mental stress (heart rate (HR), mean arterial pressure (MAP), depression scale (PHQ-9), and anxiety scale (GAD-7)), complications, rehabilitation quality, and analgesia satisfaction were observed. Results: The VAS scores of pain in the observation group were lower than those in the control group at 6 hours before operation and at 6 hours, 24 hours, and 72 hours after operation (P < 0.05). The MAP, HR, PHQ-9, and GAD-7 scores of the observation group were lower than those of the control group 6 hours before operation (P < 0.05). There was no significant difference in MAP, HR, PHQ-9, and GAD-7 scores between the two groups at 6 hours and 24 hours after operation (P > 0.05). The analgesic satisfaction of the observation group was better than that of the control group (P < 0.05). The incidence of complications in the observation group was 8.11% compared with 12.16% in the control group, which was not statistically significant (P > 0.05). The first exhaust, getting out of bed, and hospital stay in the observation group were shorter than those in the control group (P < 0.05). Conclusion: Multimodal analgesia combined with auricular acupuncture therapy is effective in perioperative patients with meniscus injury. It can reduce perioperative pain, reduce physical and mental stress, and promote early postoperative recovery through a variety of analgesic mechanisms.

Elevated monocytic myeloid-derived suppressor cells positively correlate with infection frequency in children with RRTIs.

In children with recurrent respiratory tract infections (RRTIs), the percentages and numbers of monocytic myeloid-derived suppressor cells (MDSCs) were elevated. The elevated MDSCs positively correlate with respiratory tract infection frequency in RRTIs children. The elevated MDSCs can inhibit CD8+ T-cells proliferation in RRTIs children.

Association of echocardiographic parameters with mortality in hospitalized patients with lupus nephritis.

AIM: Increasing evidence shows that the cardiac involvement attributes to the mortality of patients with lupus nephritis (LN) and echocardiography provides a valid measurement for cardiac disease. However, the association between echocardiographic parameters and mortality in LN patients without cardiac disease history remains unclear. The aim of this study was to explore the relationship between echocardiographic parameters and the mortality in hospitalized LN patients without cardiac disease history. METHODS: A total of 436 LN patients without cardiac disease history who underwent echocardiography at Sun Yat-sen Memorial Hospital, between 1 January 2000 and 31 December 2014, were enrolled into this study. The association between echocardiographic parameters and all-cause and cardiac mortality of LN patients was examined by the Cox proportional hazards model. RESULTS: In this cohort study, the median duration of follow-up was 18 months. Among 436 hospitalized LN patients, 88 patients (20.2%) died. Of them, 38 patients (43.2%) died of cardiac disease. Cardiac symptoms, high systolic blood pressure, high serum levels of C-reactive protein, low serum albumin, low estimated glomerular filtration rate (eGFR), and decreased left ventricular ejection fraction (LVEF) were found to be independently associated with increased all-cause mortality. Furthermore, the cardiac symptoms, low eGFR, increased left ventricular mass index (LVMI), and decreased LVEF were independently correlated with an increased cardiac mortality risk. CONCLUSIONS: Decreased LVEF was associated with increased all-cause and cardiac mortality and increased LVMI was an independent risk factor for cardiac mortality in hospitalized LN patients without cardiac disease history.