Meta-analysis on clinical efficacy of ringheaded thumbtack needle in the treatment of allergic rhinitis. / 揿针治疗变应性鼻炎临床疗效的Meta分析.

OBJECTIVES: To evaluate the efficacy and safety of ringheaded thrumbtack needle in the treatment of allergic rhinitis (AR). METHODS: Clinical studies about treatment of AR with ringheaded thrumbtack needle were searched from databases of CNKI, Wanfang, China Science and Technology Journal, China Biology Medicine disc, PubMed, Embase and Web of Science from their inception to November 2022. Two researchers independently screened the literature and collected related information. The total effective rate, visual analogue scale (VAS) for AR, rhinoconjunctivitis quality of life questionnaire (RQLQ), and recurrence rate were the main outcome indicators. Secondary outcome indicators included quantitative scores of symptoms and signs, 'quartering' symptom evaluation scale, etc. All the included studies were subjected to Meta-analysis using Stata software. RESULTS: A total of 22 clinical studies involving 1 491 participants were included. The results of Meta-analysis indicated that the total effective rate of ringheaded thrumbtack needle in the treatment of AR was higher than that of traditional Chinese and Western medicine ï¼»RR=1.20, 95%CI (1.14, 1.26), P<0.001ï¼½, and recurrence rate is lower than conventional therapy ï¼»OR=0.35, 95%CI (0.14, 0.89), P=0.027ï¼½. Moreover, The VAS score ï¼»WMD=-1.30, 95%CI (-1.85, -0.75), P<0.001ï¼½ and RQLQ score ï¼»WMD=-6.75, 95%CI (-12.74, -0.76), P=0.027ï¼½ of AR treated by ringheaded thrumbtack needle were lower than those of traditional Chinese and Western medicine. CONCLUSIONS: Ringheaded thrumbtack needle can improve the total effective rate, reduce the disease recurrence, and improve the symptoms of discomfort when AR outbreaks, and has no significant adverse reactions. However, the reliability is limited. Thus, it is still necessary to improve the level of evidence quality by including researches with large samples, rigorous design and international standards.

NDC1 promotes hepatocellular carcinoma tumorigenesis by targeting BCAP31 to activate PI3K/AKT signaling.

Hepatocellular carcinoma (HCC) is among the world's worst malignancies. Nuclear division cycle 1 (NDC1) is an essential membrane-integral nucleoporin, found in this study to be significantly increased in primary HCC. A multivariate analysis revealed that higher NDC1 expression was linked to worse outcome in HCC patients. Mouse xenograft tumors overexpressing NDC1 grew rapidly, and HCC cells overexpressing NDC1 showed enhanced proliferation, invasion, and migration in vitro. In contrast, knocking down NDC1 had the opposite effects in vitro. Furthermore, co-immunoprecipitation and liquid chromatograph mass spectrometer analyses revealed that NDC1 activated PI3K/AKT signaling by interacting with BCAP31. In summary, NDC1 and BCAP31 cooperate to promote the PI3K/AKT pathway, which is essential for HCC carcinogenesis. This suggests that NDC1 is predictive of prognosis in HCC.

No evidence of coronary plaque stabilization by allopurinol in patients with acute coronary syndrome.

BACKGROUND: Allopurinol, a xanthine inhibitor that lowers uric acid concentration, has been proven to reduce inflammation and oxidative stress in patients with cardiovascular disease. However, it is unknown whether these beneficial effects translate into favorable plaque modification in acute coronary syndromes (ACS). This study aimed to investigate whether allopurinol could improve coronary plaque stabilization using coronary computed tomography angiography (CCTA). METHODS: This was a prospective, single-center, randomized, double-blind clinical trial began in March 2019. A total of 162 ACS patients aged 18-80 years with a blood level of high-sensitivity C-reactive protein (hsCRP) â€‹> â€‹2 â€‹mg/L were included. The subjects were randomly assigned in a 1:1 ratio to receive either allopurinol sustained-release capsules (at a dose of 0.25 â€‹g once daily) or placebo for 12 months. The plaque analysis was performed at CCTA. The primary efficacy endpoint was the change in low-attenuation plaque volume (LAPV) from baseline to the 12-month follow-up. RESULTS: Among 162 patients, 54 in allopurinol group and 51 in placebo group completed the study. The median follow-up duration was 14 months in both groups. Compared with placebo, allopurinol therapy did not significantly alter LAPV (-13.4 â€‹± â€‹3.7 â€‹% vs. -17.8 â€‹± â€‹3.6 â€‹%, p â€‹= â€‹0.390), intermediate attenuation plaque volume (-16.1 â€‹± â€‹3.0 â€‹% vs. -16.2 â€‹± â€‹2.9 â€‹%, p â€‹= â€‹0.992), dense calcified plaque volume (12.2 â€‹± â€‹13.7 â€‹% vs. 9.7 â€‹± â€‹13.0 â€‹%, p â€‹= â€‹0.894), total atheroma volume (-15.2 â€‹± â€‹3.2 â€‹% vs. -16.4 â€‹± â€‹3.1 â€‹%, p â€‹= â€‹0.785), remodeling index (2.0 â€‹± â€‹3.9 â€‹% vs. 5.4 â€‹± â€‹3.8 â€‹%, p â€‹= â€‹0.536) or hsCRP levels (-73.6 [-91.6-17.9] % vs. -81.2 [-95.4-47.7] %, p â€‹= â€‹0.286). CONCLUSIONS: Our findings suggest that allopurinol does not improve atherosclerotic plaque stability or inflammation in ACS.

Global burden of inflammatory bowel disease 1990-2019: A systematic examination of the disease burden and twenty-year forecast.

BACKGROUND: Inflammatory bowel disease (IBD) is an idiopathic intestinal disease with various levels and trends in different countries and regions. Understanding the current burden and trends of IBD in various geographical locations is essential to establish effective strategies for prevention and treatment. We report the average annual percentage change (AAPC) and estimated annual percentage change (EAPC) in age-standardized rates (ASR) of IBD in different regions based on the Global Burden of Disease (GBD) study from 1990-2019, and the relationships between IBD and the human development index (HDI) and socio-demographic index (SDI). The prevalence trends of IBD were predicted by gender from 2019-2039. AIM: To comprehensively investigate IBD data, providing further insights into the management of this chronic disease. METHODS: We collected the information on the incidence of IBD from the GBD study from 1990-2019 to calculate the AAPC and EAPC in ASR of IBD in different regions. The relationships between IBD, HDI, and SDI were analyzed. The Nordpred and Bayesian age-period-cohort models were used to predict the prevalence trends of IBD by gender from 2019-2039, and the reliability of the results was validated. Statistics of all the data in this study were performed using R software (version 4.2.1). RESULTS: North America consistently had the highest IBD ASR, while Oceania consistently had the lowest. East Asia had the fastest average annual growth in ASR (2.54%), whereas Central Europe had the fastest decline (1.38%). Countries with a low age-standardized incidence rates in 1990 showed faster growth in IBD while there was no significant correlation in 2019. Additionally, IBD increased faster in countries with a low age-standardized death rates in 1990, whereas the opposite was true in 2019. Analysis of SDI and IBD ASR showed that countries with a high SDI generally had a higher IBD ASR. Finally, the projections showed a declining trend in the incidence of IBD from 2019-2039, but a gradual increase in the number of cases. CONCLUSION: As the global population increases and ages, early monitoring and prevention of IBD is important to reduce the disease burden, especially in countries with a high incidence of IBD.

A potential therapeutic approach for gastric cancer: inhibition of LACTB transcript 1.

BACKGROUND: This study sought to investigate the role of LACTB transcript 1 in regulating adaptive immune resistance and stemness in gastric cancer and its potential as a therapeutic target for precision medicine. METHODS: Bioinformatics analysis and RT-qPCR were used to analyze the expression level of LACTB and its transcripts in gastric cancer cells. The effects of LACTB transcript 1 on adaptive immune resistance and stemness were evaluated using in vitro cell experiments and western blotting experiments. RESULTS: Our study findings revealed that LACTB transcript 1 modulated adaptive immune resistance and inhibited the stemness of gastric cancer cells. Knocking down the expression level of LACTB transcript 1 activated autophagy and inhibited EMT. As expected, overexpression of LACTB transcript 1 yielded the opposite findings. The expression level of LACTB transcript 1 in the peripheral blood of gastric cancer patients was consistent with the bioinformatics analysis, suggesting its potential as a biomarker of gastric cancer. CONCLUSIONS: LACTB transcript 1 is a promising therapeutic target for precision medicine in gastric cancer by modulating immune evasion mechanisms and stemness. These findings provide insights into leveraging long non-coding RNAs (lncRNAs) in immunotherapy, radiotherapy, and chemotherapy to enhance cancer therapy efficacy, particularly in the context of targeting tumor heterogeneity and stemness.

Multiple heart-cutting two-dimensional liquid chromatography/charged aerosol detector assay of ginsenosides for quality evaluation of ginseng from diverse Chinese patent medicines.

For quality control of Chinese patent medicines (CPMs) containing the same herbal medicine or different herbal medicines that have similar chemical composition, current ″one standard for one species″ research mode leads to poor universality of the analytical approaches unfavorable to discriminate easily confused species. Herein, we were aimed to elaborate a multiple heart-cutting two-dimensional liquid chromatography/charged aerosol detector (MHC-2DLC/CAD) approach to quantitatively assess ginseng from multiple CPMs. Targeting baseline resolution of 16 ginsenosides (noto-R1/Rg1/Re/Rf/Ra2/Rb1/Rc/Ro/Rb2/Rb3/Rd/Rh1/Rg2/Rg3/Rg3(R)/24(R)-p-F11), experiments were conducted to optimize key parameters and validate its performance. A Poroshell 120 EC-C18 column and an XBridge Shield RP18 column were separately utilized in the first-dimensional (1D) and the second-dimensional (2D) chromatography. Eight consecutive cuttings could achieve good separation of 16 ginsenosides within 85 min. The developed MHC-2DLC/CAD method showed good linearity (R2 > 0.999), repeatability (RSD < 6.73%), stability (RSD < 5.63%), inter- and intra-day precision (RSD < 5.57%), recovery (93.76-111.14%), and the limit of detection (LOD) and limit of quantification (LOQ) varied between 0.45-2.37 ng and 0.96-4.71 ng, respectively. We applied it to the content determination of 16 ginsenosides simultaneously from 28 different ginseng-containing CPMs, which unveiled the ginsenoside content difference among the tested CPMs, and gave useful information to discriminate ginseng in the preparation samples, as well. The MHC-2DLC/CAD approach exhibited advantages of high specificity, good separation ability, and relative high analysis efficiency, which also justified the feasibility of our proposed ″Monomethod Characterization of Structure Analogs″ strategy in quality evaluation of diverse CPMs that contained different ginseng.

Clinical guideline on magnetically controlled capsule gastroscopy (2021 edition).

With the development and generalization of endoscopic technology and screening, clinical application of magnetically controlled capsule gastroscopy (MCCG) has been increasing. In recent years, various types of MCCG are used globally. Therefore, establishing relevant guidelines on MCCG is of great significance. The current guidelines containing 23 statements were established based on clinical evidence and expert opinions, mainly focus on aspects including definition and diagnostic accuracy, application population, technical optimization, inspection process, and quality control of MCCG. The level of evidence and strength of recommendations were evaluated. The guidelines are expected to guide the standardized application and scientific innovation of MCCG for the reference of clinicians.

Alphaherpesvirus upregulates NDRG1 expression to facilitate the nuclear import of viral UL31 and UL34 proteins.

Proteins UL31 and UL34 encoded by alphaherpesvirus are critical for viral primary envelopment and nuclear egress. We report here that pseudorabies virus (PRV), a useful model for research on herpesvirus pathogenesis, uses N-myc downstream regulated 1 (NDRG1) to assist the nuclear import of UL31 and UL34. PRV promoted NDRG1 expression through DNA damage-induced P53 activation, which was beneficial to viral proliferation. PRV induced the nuclear translocation of NDRG1, and its deficiency resulted in the cytosolic retention of UL31 and UL34. Therefore, NDRG1 assisted the nuclear import of UL31 and UL34. Furthermore, in the absence of the nuclear localization signal (NLS), UL31 could still translocate to the nucleus, and NDRG1 lacked an NLS, thus suggesting the existence of other mediators for the nuclear import of UL31 and UL34. We demonstrated that heat shock cognate protein 70 (HSC70) was the key factor in this process. UL31 and UL34 interacted with the N-terminal domain of NDRG1 and the C-terminal domain of NDRG1 bound to HSC70. Replenishment of HSC70ΔNLS in HSC70-knockdown cells, or interference in importin α expression, abolished the nuclear translocation of UL31, UL34, and NDRG1. These results indicated that NDRG1 employs HSC70 to facilitate viral proliferation in the nuclear import of PRV UL31 and UL34.

Acute transcriptomic changes in murine RAW 264.7 cells following pseudorabies virus infection.

Next-generation sequencing enables the evaluation of gene expression changes resulting from virus-host interactions at the RNA level. Pseudorabies virus (PRV) causes substantial economic loss in the swine industry. Recent research has revealed that PRV can be transmitted to and infect humans as well. To identify physiopathological and pathological responses post-PRV infection, we characterized transcriptomic changes in the murine RAW 264.7 cell line over the course of 36 h. In total, 156, 153, and 190 differentially expressed genes were identified at 2 h, 12 h, and 36 h, respectively. Seven differentially expressed genes (Trim27, Ccdc117, Mrps12, Ccl4, Cerkl, Ubald1, and Hmga1-rs1) were present across all treatment groups. Our findings expand our knowledge of gene regulation and immune response following PRV infection. These differentially expressed genes can subsequently improve our understanding of PRV pathogenesis.

Green Tea Polyphenols Prevent Early Vascular Aging Induced by High-Fat Diet via Promoting Autophagy in Young Adult Rats.

OBJECTIVE: Epidemiology studies indicate that green tea polyphenols (GTP) perform a protective effect on cardiovascular diseases, but the underlying mechanisms are complex. The present study aimed to investigate the effect of GTP on high-fat diets (HFD) induced-early vascular aging. METHODS: Six-week young adult Wistar rats were fed with standard chow or HFD in the presence and absence of GTP (200 mg/kg body weight) for 18 weeks. In vitro experiment, human umbilical vascular endothelial cells (HUVECs) were treated with palmitic acid (PA) and GTP. RESULTS: The results showed that GTP alleviated the disorganized arterial wall and the increased intima-media thickness induced by HFD. In addition, the vascular oxidative injury was suppressed following GTP treatment. Furthermore, GTP elevated the ratio of LC3-II/LC3-I and suppressed expression of p62/SQSTM1, and restored SIRT3 expression in the aorta of HFD rats. Consistently, in cultured HUVECs, GTP inhibited cell senescence indicated by SA-ß-gal and promoted endothelial autophagy compared with the PA treatment group. The activity of SIRT3 was specifically inhibited by 3-TYP, and the protective effect of GTP was consequently abolished. CONCLUSION: The findings indicated that GTP protected against early vascular senescence in young HFD rats via ameliorating oxidative injury and promoting autophagy which was partially regulated by the SIRT3 pathway.

Multi-level fingerprinting and cardiomyocyte protection evaluation for comparing polysaccharides from six Panax herbal medicines.

The role of polysaccharides in quality control of ginseng is underestimated. Large-scale comparison on the polysaccharides of Panax ginseng (PG), P. quinquefolius (PQ), P. notoginseng (PN), Red ginseng (RG), P. japonicus (ZJS), and P. japonicus var. major (ZZS), was performed by both chemical and biological approaches. Holistic fingerprinting at polysaccharide and the hydrolyzed oligosaccharide and monosaccharide levels utilized various chromatography methods, while OGD and OGD/R models on H9c2 cells were introduced to evaluate the protective effects on cell viability and mitochondrial function. Polysaccharides from six ginseng species exhibited remarkable content difference (RG > PG/ZZS/ZJS/PQ > PN), but weak differentiations in molecular weight distribution and oligosaccharide profiles, while Glc and GalA were richer for monosaccharide compositions of PG and RG polysaccharides, respectively. RG polysaccharides (25/50/100 µg/mL) showed significant cardiomyocyte protection by regulating mitochondrial functions. These new evidences may provide support for the supplementary role of polysaccharides in quality control of ginseng.

Inhibition of USP14 influences alphaherpesvirus proliferation by degrading viral VP16 protein via ER stress-triggered selective autophagy.

Alphaherpesvirus infection results in severe health consequences in a wide range of hosts. USPs are the largest subfamily of deubiquitinating enzymes that play critical roles in immunity and other cellular functions. To investigate the role of USPs in alphaherpesvirus replication, we assessed 13 USP inhibitors for PRV replication. Our data showed that all the tested compounds inhibited PRV replication, with the USP14 inhibitor b-AP15 exhibiting the most dramatic effect. Ablation of USP14 also influenced PRV replication, whereas replenishment of USP14 in USP14 null cells restored viral replication. Although inhibition of USP14 induced the K63-linked ubiquitination of PRV VP16 protein, its degradation was not dependent on the proteasome. USP14 directly bound to ubiquitin chains on VP16 through its UBL domain during the early stage of viral infection. Moreover, USP14 inactivation stimulated EIF2AK3/PERK- and ERN1/IRE1-mediated signaling pathways, which were responsible for VP16 degradation through SQSTM1/p62-mediated selective macroautophagy/autophagy. Ectopic expression of non-ubiquitinated VP16 fully rescued PRV replication. Challenge of mice with b-AP15 activated ER stress and autophagy and inhibited PRV infection in vivo. Our results suggested that USP14 was a potential therapeutic target to treat alphaherpesvirus-induced infectious diseases.Abbreviations ATF4: activating transcription factor 4; ATF6: activating transcription factor 6; ATG5: autophagy related 5; ATG12: autophagy related 12; CCK-8: cell counting kit-8; Co-IP: co-immunoprecipitation; CRISPR: clustered regulatory interspaced short palindromic repeat; Cas9: CRISPR associated system 9; DDIT3/CHOP: DNA-damage inducible transcript 3; DNAJB9/ERdj4: DnaJ heat shock protein family (Hsp40) member B9; DUBs: deubiquitinases; EIF2A/eIF2α: eukaryotic translation initiation factor 2A; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; EP0: ubiquitin E3 ligase ICP0; ER: endoplasmic reticulum; ERN1/IRE1: endoplasmic reticulum (ER) to nucleus signaling 1; FOXO1: forkhead box O1; FRET: Förster resonance energy transfer; HSPA5/BiP: heat shock protein 5; HSV: herpes simplex virus; IE180: transcriptional regulator ICP4; MAP1LC3/LC3: microtube-associated protein 1 light chain 3; MOI: multiplicity of infection; MTOR: mechanistic target of rapamycin kinase; PPP1R15A/GADD34: protein phosphatase 1, regulatory subunit 15A; PRV: pseudorabies virus; PRV gB: PRV glycoprotein B; PRV gE: PRV glycoprotein E; qRT-PCR: quantitative real-time polymerase chain reaction; sgRNA: single guide RNA; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; TCID50: tissue culture infective dose; UB: ubiquitin; UBA: ubiquitin-associated domain; UBL: ubiquitin-like domain; UL9: DNA replication origin-binding helicase; UPR: unfolded protein response; USPs: ubiquitin-specific proteases; VHS: virion host shutoff; VP16: viral protein 16; XBP1: X-box binding protein 1; XBP1s: small XBP1; XBP1(t): XBP1-total.

Endoscopic submucosal dissection treatment of metachronous early gastric adenocarcinoma in a case with diffuse large B-cell lymphoma.

Cases of primary gastric lymphoma complicated with gastric adenocarcinoma are rare in clinical practice. We report a case of metachronous early gastric adenocarcinoma diagnosed eight years after the onset of gastric diffuse large B-cell lymphoma (DLBCL) and treated with endoscopic submucosal dissection (ESD).

Efficacy and safety of lubiprostone for the treatment of functional constipation in Chinese adult patients: A multicenter, randomized, double-blind, placebo-controlled trial.

OBJECTIVES: Functional constipation is a gastrointestinal disorder prevalent around the world. Lubiprostone is the first locally acting type-2 chloride channel activator to be used for treating constipation. This study aimed to evaluate the efficacy and safety of lubiprostone in Chinese adults with functional constipation. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study. Patients with functional constipation were randomized to receive either lubiprostone (24 mcg twice daily) or placebo for 4 weeks. The primary end-point was the frequency of spontaneous bowel movements (SBMs) during the first week of treatment. The secondary end-points included the median time of the first SBM, SBM frequency at weeks 2, 3 and 4, weekly response rate of SBMs, the stool consistency score and average number of complete spontaneous bowel movements (CSBMs) per week. RESULTS: In total, 259 patients were randomized, with 130 in the lubiprostone group and 129 in the placebo group. SBM frequency was higher in the lubiprostone group (4.88 ± 4.09/wk) than that in the placebo group (3.22 ± 2.01/wk) at week 1 (P < 0.0001). SBM frequency was also higher in the lubiprostone group at weeks 2, 3 and 4. The average number of CSBMs and the stool consistency score in the lubiprostone group were significantly higher than that in the placebo group at each week. No drug-related serious adverse events (AEs) occurred. The most commonly reported AE was nausea. CONCLUSION: Lubiprostone was superior to placebo in treating Chinese patients with functional constipation, together with good safety profile.

Analysis of Cucurbita ficifolia (Cucurbitaceae) chloroplast genome and its phylogenetic implications.

The figleaf gourd (Cucurbita ficifolia Bouché), is a member of the Cucurbitaceae. Figleaf gourd genotypes are exclusively used as a rootstock for cucumber owing to their high physiological compatibility with cucumber. In this study, the complete chloroplast (cp) genome of C. ficifolia was assembled. The cp genome of C. ficifolia was 157,631 bp in length, it consists of a pair of inverted repeats (IRa and IRb) regions (25,638 bp) separated by the large single-copy (LSC, 88,211 bp) and small single-copy (SSC, 18,144 bp) regions. The cp genome encodes 111 unique genes, including 80 protein-coding genes, 27 transfer RNA genes, and four ribosomal RNA genes. The overall GC content of C. ficifolia cp genome was 37.2%. The phylogenetic tree of Cucurbitaceae showed that C. ficifolia was clustered into genus Cucurbita and the bootstrap value is 100%.

Establishment and validation of a computer-assisted colonic polyp localization system based on deep learning.

BACKGROUND: Artificial intelligence in colonoscopy is an emerging field, and its application may help colonoscopists improve inspection quality and reduce the rate of missed polyps and adenomas. Several deep learning-based computer-assisted detection (CADe) techniques were established from small single-center datasets, and unrepresentative learning materials might confine their application and generalization in wide practice. Although CADes have been reported to identify polyps in colonoscopic images and videos in real time, their diagnostic performance deserves to be further validated in clinical practice. AIM: To train and test a CADe based on multicenter high-quality images of polyps and preliminarily validate it in clinical colonoscopies. METHODS: With high-quality screening and labeling from 55 qualified colonoscopists, a dataset consisting of over 71000 images from 20 centers was used to train and test a deep learning-based CADe. In addition, the real-time diagnostic performance of CADe was tested frame by frame in 47 unaltered full-ranged videos that contained 86 histologically confirmed polyps. Finally, we conducted a self-controlled observational study to validate the diagnostic performance of CADe in real-world colonoscopy with the main outcome measure of polyps per colonoscopy in Changhai Hospital. RESULTS: The CADe was able to identify polyps in the test dataset with 95.0% sensitivity and 99.1% specificity. For colonoscopy videos, all 86 polyps were detected with 92.2% sensitivity and 93.6% specificity in frame-by-frame analysis. In the prospective validation, the sensitivity of CAD in identifying polyps was 98.4% (185/188). Folds, reflections of light and fecal fluid were the main causes of false positives in both the test dataset and clinical colonoscopies. Colonoscopists can detect more polyps (0.90 vs 0.82, P < 0.001) and adenomas (0.32 vs 0.30, P = 0.045) with the aid of CADe, particularly polyps < 5 mm and flat polyps (0.65 vs 0.57, P < 0.001; 0.74 vs 0.67, P = 0.001, respectively). However, high efficacy is not realized in colonoscopies with inadequate bowel preparation and withdrawal time (P = 0.32; P = 0.16, respectively). CONCLUSION: CADe is feasible in the clinical setting and might help endoscopists detect more polyps and adenomas, and further confirmation is warranted.

Value of preoperative gastroscopic carbon nanoparticles labeling in patients undergoing laparoscopic radical gastric cancer surgery.

BACKGROUND AND OBJECTIVES: Lymph node metastasis is crucial for gastric cancer. We aim to explore the value of preoperative gastroscopic carbon nanoparticles labeling in patients undergoing laparoscopic radical gastric cancer surgery. METHODS: 1199 cases undergoing laparoscopic radical gastric cancer surgery were retrospectively analyzed. 214 cases received preoperative gastroscopic carbon nanoparticles labeling. The number of total lymph nodes detected, positive lymph nodes, N staging, and operation time were analyzed. RESULTS: The patients received carbon nanoparticles labeling had more total lymph nodes detected (27.9 ± 6.5 vs 22.2 ± 4.0; P ＜ 0.001) and shorter operation time (185.9 ± 27.8min vs 218.7 ± 69.2min; P ＜ 0.001) compared with the control group. In addition, preoperative endoscopic carbon nanoparticles labeling improved the diagnosis rate of synchronous multiple gastric cancer (2.8% vs 0.4%; P ＜ 0.001). CONCLUSIONS: Preoperative endoscopic carbon nanoparticles tracer labeling is of great value in patients undergoing laparoscopic radical gastric cancer surgery. It shortens the operation time, increases the number of total lymph nodes detected for more accurate pathological TNM staging, and finds some cases of synchronous multiple gastric cancer.

Echolocation in soft-furred tree mice.

Echolocation is the use of reflected sound to sense features of the environment. Here, we show that soft-furred tree mice (Typhlomys) echolocate based on multiple independent lines of evidence. Behavioral experiments show that these mice can locate and avoid obstacles in darkness using hearing and ultrasonic pulses. The proximal portion of their stylohyal bone fuses with the tympanic bone, a form previously only seen in laryngeally echolocating bats. Further, we found convergence of hearing-related genes across the genome and of the echolocation-related gene prestin between soft-furred tree mice and echolocating mammals. Together, our findings suggest that soft-furred tree mice are capable of echolocation, and thus are a new lineage of echolocating mammals.

Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial.

BACKGROUND: Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who do not respond to or who have progressive disease after salvage therapies have a poor prognosis. Loncastuximab tesirine is a CD19-directed antibody-drug conjugate with encouraging phase 1 single-agent antitumour activity and acceptable safety in non-Hodgkin lymphoma. We aimed to evaluate the antitumour activity and safety of loncastuximab tesirine in patients with relapsed or refractory DLBCL. METHODS: We did a multicentre (28 hospital sites in the USA, UK, Italy, and Switzerland), open-label, single-arm, phase 2 trial (LOTIS-2) in patients aged 18 years or older with relapsed or refractory DLBCL after two or more multiagent systemic treatments, who had measurable disease and Eastern Cooperative Oncology Group performance status 0-2. Eligible patients received loncastuximab tesirine intravenously on day 1 of each 21-day cycle, at 150 µg/kg for two cycles, then 75 µg/kg thereafter, for up to 1 year or until disease relapse or progression, unacceptable toxicity, death, major protocol deviation, pregnancy, or patient, investigator, or sponsor decision. The primary endpoint was overall response rate assessed by central review. Primary antitumour activity and safety analyses were done in the as-treated population (patients who received at least one dose of loncastuximab tesirine), when all responding patients had at least 6 months of follow-up after initial documented response. Enrolment is complete. This trial is registered with ClinicalTrials.gov, NCT03589469. FINDINGS: Between Aug 1, 2018, and Sept 24, 2019, 184 patients were assessed for eligibility and 145 (79%) were enrolled and received at least one dose of loncastuximab tesirine, including patients with high-risk characteristics for poor prognosis, such as double-hit, triple-hit, transformed, or primary refractory DLBCL. 70 of 145 patients had complete or partial response (overall response rate 48·3% [95% CI 39·9-56·7]); 35 had complete response and 35 had partial response. The most common grade 3 or higher treatment-emergent adverse events were neutropenia (37 [26%] of 145 patients), thrombocytopenia (26 [18%]), and increased gamma-glutamyltransferase (24 [17%]). Serious adverse events were reported in 57 (39%) of 145 patients. Treatment-emergent adverse events with a fatal outcome occurred in eight (6%) of 145 patients; none were considered related to loncastuximab tesirine. INTERPRETATION: Loncastuximab tesirine has substantial single-agent antitumour activity and produces durable responses with an acceptable safety profile, potentially offering a new therapeutic option for heavily pretreated patients with relapsed or refractory DLBCL. FUNDING: ADC Therapeutics.

Camidanlumab tesirine in patients with relapsed or refractory lymphoma: a phase 1, open-label, multicentre, dose-escalation, dose-expansion study.

BACKGROUND: Novel approaches are required to improve outcomes in relapsed or refractory classical Hodgkin lymphoma and non-Hodgkin lymphoma. We aimed to evaluate camidanlumab tesirine, an anti-CD25 antibody-drug conjugate, in this patient population. METHODS: This was a phase 1, dose-escalation (part 1), dose-expansion (part 2), multicentre trial done in 12 hospital sites (seven in the USA and five in the UK). Adults (≥18 years old) with pathologically confirmed relapsed or refractory classical Hodgkin lymphoma or non-Hodgkin lymphoma, an Eastern Cooperative Oncology Group performance status 0-2, who had no therapies available to them with established clinical benefit for their disease stage were enrolled. Camidanlumab tesirine was administered intravenously (3-150 µg/kg) once every 3 weeks. Primary objectives were to assess dose-limiting toxicity, determine maximum tolerated dose and recommended expansion dose(s), and assess safety of camidanlumab tesirine. Safety was assessed in all treated patients; antitumour activity was assessed in patients with one or more valid baseline and post-baseline disease assessment and in those who had disease progression or died after first study-drug dose. This trial was registered with ClinicalTrials.gov, NCT02432235. FINDINGS: Between Oct 5, 2015, and Jun 30, 2019, 133 patients were enrolled (77 [58%] had classical Hodgkin lymphoma and 56 (42%) had non-Hodgkin lymphoma). Median follow-up was 9·2 months (IQR 4·2-14·3). Eight dose-limiting toxicities were reported in five (6%) of 86 patients who were evaluable; the maximum tolerated dose was not reached. The recommended doses for expansion were 30 µg/kg and 45 µg/kg for patients with classical Hodgkin lymphoma and 80 µg/kg for patients with T-cell non-Hodgkin lymphomas. No recommended doses for expansion were defined for B-cell non-Hodgkin lymphomas. Grade 3 or worse treatment-emergent adverse events (reported by ≥10% of the 133 patients) included increased γ-glutamyltransferase (20 [15%] patients), maculopapular rash (16 [12%]), and anaemia (15 [11%]); 74 (56%) patients had serious treatment-emergent adverse events, most commonly pyrexia (16 [12%]). One (1%) fatal treatment-emergent adverse event and two (2%) deaths outside the reporting period were considered at least possibly study-drug related. Antitumoural activity was seen in classical Hodgkin and non-Hodgkin lymphomas; notably in all patients with classical Hodgkin lymphoma, the overall response was 71% (95% CI 60-81). INTERPRETATION: These results warrant evaluation of camidanlumab tesirine as a potential treatment option for relapsed or refractory lymphoma, particularly in patients with classical Hodgkin lymphoma. FUNDING: ADC Therapeutics.