Pirtobrutinib in Chinese patients with relapsed or refractory B-cell malignancies: A single-arm, open-label, phase 2, multicenter trial.

Pirtobrutinib, a highly selective, noncovalent (reversible) Bruton tyrosine kinase inhibitor (BTKi), demonstrated clinically meaningful antitumor responses in covalent BTKi pretreated mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in the global phase 1/2 BRUIN study. In this multi-center, open-label, phase 2 trial, we investigated the efficacy and safety of pirtobrutinib in Chinese patients with BTKi pretreated relapsed/refractory (R/R) MCL, CLL/SLL, or other B-cell malignancies. All patients received pirtobrutinib once daily in continuous 28-day cycles.

The cGAS-STING Pathway Is Essential in Acute Ischemia-Induced Neutropoiesis and Neutrophil Priming in the Bone Marrow.

Acute myocardial ischemia triggers a rapid mobilization of neutrophils from the bone marrow to peripheral blood, facilitating their infiltration into the infarcted myocardium. These cells are critical for inducing inflammation and contributing to myocardial repair. While neutrophils in infarcted tissue are better characterized, our understanding of whether and how ischemia regulates neutrophil production, differentiation, and functionality in the bone marrow remains limited.

Observation of Non-Hermitian Edge Burst Effect in One-Dimensional Photonic Quantum Walk.

Non-Hermitian systems can exhibit unique quantum phases without any Hermitian counterparts. For example, the latest theoretical studies predict a new surprising phenomenon that bulk bands can localize and dissipate prominently at the system boundary, which is dubbed the non-Hermitian edge burst effect. Here we realize a one-dimensional non-Hermitian Su-Schrieffer-Heeger lattice with bulk translation symmetry implemented with a photonic quantum walk.

Risk factors of postoperative nausea and vomiting following ambulatory surgery: A retrospective case-control study.

Objective: To explore potential risk factors of postoperative nausea and vomiting (PONV) following ambulatory surgery.

Method: Clinical data of 1670 cases receiving ambulatory surgery in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from September 2017 to December 2019 were retrospectively analyzed. They were categorized to PONV group and non-PONV group, and perioperative data in both groups were analyzed for assessing risk factors of PONV following ambulatory laparoscopy.

Ultra rapid lispro improves postprandial glucose control versus lispro in combination with insulin glargine/degludec in adults with type 2 diabetes: a prospective, randomized, double-blind, phase 3 trial.

Ultra rapid lispro (URLi) is a novel formulation of insulin lispro designed to more closely match the physiological insulin response to a meal, with the aim of improving postprandial glucose (PPG) control. We conducted a multinational, multicenter, randomized, double-blind, treat-to-target, 26-week, phase 3 trial to evaluate the efficacy and safety of URLi in adults with type 2 diabetes (T2D). After an 8-week lead-in period during which basal insulin glargine or degludec was optimized, adults with T2D were randomized (2:1) to prandial URLi (n = 395) or lispro (n = 200).

IL-2 delivery by engineered mesenchymal stem cells re-invigorates CD8 T cells to overcome immunotherapy resistance in cancer.

Immune checkpoint blockade (ICB)-based immunotherapy depends on functional tumour-infiltrating lymphocytes (TILs), but essential cytokines are less understood. Here we uncover an essential role of endogenous IL-2 for ICB responsiveness and the correlation between insufficient IL-2 signalling and T-cell exhaustion as tumours progress. To determine if exogenous IL-2 in the tumour microenvironment can overcome ICB resistance, we engineered mesenchymal stem cells (MSCs) to successfully deliver IL-2 mutein dimer (SIL2-EMSC) to TILs.

Three-dimensional versus two-dimensional laparoscopic surgery for rectal cancer: better promote postoperative sexual and urinary function of a propensity-matched study.

Laparoscopic total mesorectal excision (TME) with autonomic nerve preservation (ANP) is a common procedure for rectal cancer (RC), associated with a high prevalence of postoperative urogenital and anorectal dysfunctions. Compared to 2D laparoscopy, 3D laparoscopy provides better depth perception of the surgical field and hand-eye coordination to achieve better outcomes. We compared the performance of 2D and 3D laparoscopy on preserving urogenital and anorectal function in TME+ANP surgery for rectal cancer using propensity-score matching.

Magnetic resonance neuroimaging promotes the preservation of pelvic autonomic nerves in laparoscopic total mesorectal excision: a comparative study.

Background: How to preserve pelvic autonomic nerves system (PANS) in total mesorectal excision (TME) is still a technical challenge for gastrointestinal surgeons, and nerve preservation according to preoperative magnetic resonance imaging (MRI) is a hot topic in pelvic surgery. The purpose of this study was to assess the postoperative urogenital function of patients with rectal cancer (RC) who underwent preoperative and postoperative neuroimaging of PANS vs. patients who did not.

Next generation of tumor-activating type I IFN enhances anti-tumor immune responses to overcome therapy resistance.

Type I interferon is promising in treating different kinds of tumors, but has been limited by its toxicity, lack of tumor targeting, and very short half-life. To target tumors, reduce systemic toxicity, and increase half-life, here we engineer a masked type I IFN-Fc (ProIFN) with its natural receptor connected by a cleavable linker that can be targeted by tumor-associated proteases. ProIFN has a prolonged serum half-life and shows an improved tumor-targeting effect.

Identification and characteristics of a novel gland-forming gene in cotton.

The cotton (Gossypium hirsutum) pigment gland is a distinctive structure that functions as the main deposit organ of gossypol and its derivatives. It is also an ideal system in which to study cell differentiation and organogenesis. However, only a few genes that determine the process of gland formation have been reported, including GoPGF, CGP1, and CGFs; the molecular mechanisms underlying gland initiation are still largely unclear.

Pancreatic Safety of Once-Weekly Dulaglutide in Chinese Patients with Type 2 Diabetes Mellitus: Subgroup Analysis by Potential Influencing Factors.

Introduction: In the randomized, open-label, parallel-arm, active-controlled phase III AWARD-CHN2 trial, once-weekly dulaglutide plus concomitant oral antihyperglycemic medications (OAMs) improved HbA1c over 26 weeks compared with once-daily insulin glargine in patients with type 2 diabetes mellitus (T2DM). This post-hoc subgroup analysis of AWARD-CHN2 investigated the pancreatic safety of dulaglutide in Chinese patients with T2DM, stratified by potential influencing factors.

Methods: Changes in pancreatic enzyme (pancreatic amylase, total amylase, and lipase) levels over 26 weeks were assessed and stratified by patient age (< 60, ≥ 60 years), sex (female, male), duration of diabetes (< 10, ≥ 10 years), baseline weight (< 70, ≥ 70 kg), BMI (< 25, ≥ 25 kg/m), HbA1c (< 8.

Tumor-conditional IL-15 pro-cytokine reactivates anti-tumor immunity with limited toxicity.

IL-15 is a promising cytokine to expand NK and CD8 T cells for cancer immunotherapy, but its application is limited by dose-limiting, on-target off-tumor toxicity. Here, we have developed a next-generation IL-15 that is activated inside the tumor microenvironment (TME). This pro-IL-15 has the extracellular domain of IL-15Rβ fused to the N-terminus of sIL-15-Fc through a tumor-enriched Matrix Metalloproteinase (MMP) cleavable peptide linker to block its activity.

A Pragmatic Study of Basal and Mid-Mixture Insulins as Starter Insulins in Chinese Patients With Type 2 Diabetes: Observations From Long-Term, Real-World Experience.

Introduction: According to Chinese guidelines, basal insulin (BI) or premixed insulins are recommended insulin starters following the failure of oral antihyperglycemic medication (OAM) in Chinese patients with type 2 diabetes (T2D). This pragmatic study investigated the long-term effectiveness, safety, and cost of add-on BI and mid-mixture insulin analog (MMI) regimens in Chinese patients with T2D.

Methods: This multicenter, open-label, pragmatic study randomized patients 1:1 to receive either BI or MMI with OAMs adjusted according to current standards of care.

DNA Sensing in Mismatch Repair-Deficient Tumor Cells Is Essential for Anti-tumor Immunity.

Increased neoantigens in hypermutated cancers with DNA mismatch repair deficiency (dMMR) are proposed as the major contributor to the high objective response rate in anti-PD-1 therapy. However, the mechanism of drug resistance is not fully understood. Using tumor models defective in the MMR gene Mlh1 (dMLH1), we show that dMLH1 tumor cells accumulate cytosolic DNA and produce IFN-β in a cGAS-STING-dependent manner, which renders dMLH1 tumors slowly progressive and highly sensitive to checkpoint blockade.

Efficacy and safety of once-weekly dulaglutide in adult Chinese patients with type 2 diabetes and lower baseline body mass index.

Highlights In Chinese patients with type 2 diabetes (T2D) and body mass index (BMI) <25 kg/m , dulaglutide demonstrated great improvements in glycemic control with mild body weight reduction and low hypoglycemia risk. The results indicate that dulaglutide is effective and safe in patients with T2D and lower BMI; therefore, BMI should not be a consideration when dulaglutide is prescribed to Chinese patients with T2D.

Efficacy and Safety of Once-Weekly Dulaglutide in Elderly Chinese Patients with Type 2 Diabetes: A Post Hoc Analysis of AWARD-CHN Studies.

Introduction: This analysis evaluated the efficacy and safety of dulaglutide in Chinese patients with type 2 diabetes (T2D) aged ≥ 60 and < 60 years.

Methods: This post hoc analysis included patients with T2D enrolled in two phase 3 clinical trials AWARD-CHN1 (NCT01644500) and AWARD-CHN2 (NCT01648582) of dulaglutide 0.75 and 1.

Telomere Stress Potentiates STING-Dependent Anti-tumor Immunity.

Telomerase is an attractive target for anti-tumor therapy as it is almost universally expressed in cancer cells. Here, we show that treatment with a telomere-targeting drug, 6-thio-2'-deoxyguanosine (6-thio-dG), leads to tumor regression through innate and adaptive immune-dependent responses in syngeneic and humanized mouse models of telomerase-expressing cancers. 6-thio-dG treatment causes telomere-associated DNA damages that are sensed by dendritic cells (DCs) and activates the host cytosolic DNA sensing STING/interferon I pathway, resulting in enhanced cross-priming capacity of DCs and tumor-specific CD8 T cell activation.

Curcumin Attenuates Both Acute and Chronic Immune Nephritis.

Curcumin is known to have immunomodulatory potential in addition to anti-oxidant, anti-inflammatory and anti-carcinogenic effects. The aim of the present study is to investigate the therapeutic effects of curcumin on immune-mediated renal disease in an anti-glomerular basement membrane (GBM) model (representing acute kidney Injury, AKI) and murine lupus model (representing chronic kidney disease, CKD). In the AKI model, female anti-GBM 129/svj mice were administered with curcumin right before disease induction.

Mutation of SELF-PRUNING homologs in cotton promotes short-branching plant architecture.

In cotton, the formation of fruiting branches affects both plant architecture and fiber yield. Here, we report map-based cloning of the axillary flowering mutation gene (GbAF) that causes bolls to be borne directly on the main plant stem in Gossypium barbadense, and of the clustered boll mutation gene (cl1) in G. hirsutum.

Rapid mapping and cloning of the virescent-1 gene in cotton by bulked segregant analysis-next generation sequencing and virus-induced gene silencing strategies.

Map-based gene cloning is a vital strategy for the identification of the quantitative trait loci or genes underlying important agronomic traits. The conventional map-based cloning method is powerful but generally time-consuming and labor-intensive. In this context, we introduce an improved bulked segregant analysis method in combination with a virus-induced gene silencing (VIGS) strategy for rapid and reliable gene mapping, identification and functional verification.

Prevention of murine lupus nephritis by targeting multiple signaling axes and oxidative stress using a synthetic triterpenoid.

Objective: Current treatment options for lupus are far from optimal. Previously, we reported that phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin, MEK-1/ERK-1,2, p38, STAT-3, STAT-5, NF-κB, multiple Bcl-2 family members, and various cell cycle molecules were overexpressed in splenic B cells in an age-dependent and gene dose-dependent manner in mouse strains with spontaneous lupus. Since the synthetic triterpenoid methyl-2-cyano-3,12-dioxooleana-1,9-dien-28-oate (CDDO-Me) has been shown to inhibit AKT, MEK-1/2, and NF-κB, and to induce caspase-mediated apoptosis, we tested the therapeutic potential of this agent in murine lupus nephritis.

Logical thinking in pattern differentiation of traditional Chinese medicine.

Objective: To discuss the application of logic to pattern differentiation for treatment in Traditional Chinese Medicine (TCM).

Methods: Comparing logic reasoning of syllogism with the logical thinking of TCM pattern differentiation for treatment.

Results: TCM logical thinking depends on symbolic and intuitive judgment with abstractive reasoning integrated into the process.

Peritoneal catheter implantation elicits IL-10-producing immune-suppressor macrophages through a MyD88-dependent pathway.

Catheters are implanted into the peritoneal cavity during the process of peritoneal dialysis. Though these catheters may be effective and beneficial, the impact of catheters on the immune system is poorly understood. Catheters and other devices implanted in the peritoneal cavity elicit a foreign body reaction.