Dual Photoredox/Nickel Catalysis Enables Diastereoselective Synthesis of Multisubstituted γ-Lactams Using Alkyl-GeMe3 as Radical Precursors.

Herein, we report a single-step, multicomponent approach to versatile γ-lactams through dual photoredox/nickel-catalyzed dicarbofunctionalization of α,ß-unsaturated γ-butyrolactam. This reaction utilized alkyl trimethylgermanium as a radical precursor and acyl chloride as the electrophile, demonstrating remarkable functional group compatibility.

Comparison of Short-Term Outcomes After Robotic Versus Laparoscopic Radical Gastrectomy for Advanced Gastric Cancer in Elderly Individuals: A Propensity Score-Matching Study.

BACKGROUND: Robotic gastrectomy (RG) has been widely used to treat gastric cancer. However, whether the short-term outcomes of robotic gastrectomy are superior to those of laparoscopic gastrectomy (LG) for elderly patients with advanced gastric cancer has not been reported. METHODS: The study enrolled of 594 elderly patients with advanced gastric cancer who underwent robotic or laparoscopic radical gastrectomy. The RG cohort was matched 1:3 with the LG cohort using propensity score-matching (PSM). RESULTS: After PSM, 121 patients were included in the robot group and 363 patients in the laparoscopic group. Excluding the docking and undocking times, the operation time of the two groups was similar (P = 0.617). The RG group had less intraoperative blood loss than the LG group (P < 0.001). The time to ambulation and first liquid food intake was significantly shorter in the RG group than in the LG group (P < 0.05). The incidence of postoperative complications did not differ significantly between the two groups (P = 0.14). Significantly more lymph nodes were dissected in the RG group than in the LG group (P = 0.001). Postoperative adjuvant chemotherapy was started earlier in the RG group than in the LG group (P = 0.02). CONCLUSIONS: For elderly patients with advanced gastric cancer, RG is safe and feasible. Compared with LG, RG is associated with less intraoperative blood loss; a faster postoperative recovery time, allowing a greater number of lymph nodes to be dissected; and earlier adjuvant chemotherapy.

Prevalence and genetic variation of the M, N, and S2 genes of feline coronavirus in Shandong Province, China.

Feline coronavirus (FCoV) is the causative agent of feline infectious peritonitis and diarrhoea in kittens worldwide. In this study, a total of 73 feline diarrhoeal faecal samples were collected from animal hospitals and pet markets in ShanDong province from 2017 to 2019. FCoV was detected in 58.23% (46/73) of the samples, using the RT-PCR method. The results showed that the detection rate of FCoV in healthy cats and sick cats was 41.7% (10/24) and 81.6% (40/49), respectively. Full gene amplification and sequencing of the N, M, and S2 genes of FCoV isolates were performed. An amino acid mutation (M1058L) in the S2 gene was found that can be used as a marker for distinguishing feline enteric coronavirus (FECV) from feline infectious peritonitis virus (FIPV). This study provides new epidemiological information about FCoV that will aid in the prevention of FCoV in China.

Using patient-derived organoids to predict locally advanced or metastatic lung cancer tumor response: A real-world study.

Predicting the clinical response to chemotherapeutic or targeted treatment in patients with locally advanced or metastatic lung cancer requires an accurate and affordable tool. Tumor organoids are a potential approach in precision medicine for predicting the clinical response to treatment. However, their clinical application in lung cancer has rarely been reported because of the difficulty in generating pure tumor organoids. In this study, we have generated 214 cancer organoids from 107 patients, of which 212 are lung cancer organoids (LCOs), primarily derived from malignant serous effusions. LCO-based drug sensitivity tests (LCO-DSTs) for chemotherapy and targeted therapy have been performed in a real-world study to predict the clinical response to the respective treatment. LCO-DSTs accurately predict the clinical response to treatment in this cohort of patients with advanced lung cancer. In conclusion, LCO-DST is a promising precision medicine tool in treating of advanced lung cancer.

Repurposing nitazoxanide as a novel anti-atherosclerotic drug based on mitochondrial uncoupling mechanisms.

BACKGROUND AND PURPOSE: The anthelmintic drug nitazoxanide has a mitochondrial uncoupling effect. Mitochondrial uncouplers have been proven to inhibit smooth muscle cell proliferation and migration, inhibit NLRP3 inflammasome activation of macrophages and improve dyslipidaemia. Therefore, we aimed to demonstrate that nitazoxanide would protect against atherosclerosis. EXPERIMENTAL APPROACH: The mitochondrial oxygen consumption of cells was measured by using the high-resolution respirometry system, Oxygraph-2K. The proliferation and migration of A10 cells were measured by using Edu immunofluorescence staining, wound-induced migration and the Boyden chamber assay. Protein levels were measured by using the western blot technique. ApoE (-/-) mice were fed with a Western diet to establish an atherosclerotic model in vivo. KEY RESULTS: The in vitro experiments showed that nitazoxanide and tizoxanide had a mitochondrial uncoupling effect and activated cellular AMPK. Nitazoxanide and tizoxanide inhibited serum- and PDGF-induced proliferation and migration of A10 cells. Nitazoxanide and tizoxanide inhibited NLRP3 inflammasome activation in RAW264.7 macrophages, the mechanism by which involved the AMPK/IκBα/NF-κB pathway. Nitazoxanide and tizoxanide also induced autophagy in A10 cells and RAW264.7 macrophages. The in vivo experiments demonstrated that oral administration of nitazoxanide reduced the increase in serum IL-1ß and IL-6 levels and suppressed atherosclerosis in Western diet-fed ApoE (-/-) mice. CONCLUSION AND IMPLICATIONS: Nitazoxanide inhibits the formation of atherosclerotic plaques in ApoE (-/-) mice fed on a Western diet. In view of nitazoxanide being an antiprotozoal drug already approved by the FDA, we propose it as a novel anti-atherosclerotic drug with clinical translational potential.

Silencing of crustacean hyperglycemic hormone gene expression reveals the characteristic energy and metabolic changes in the gills and epidermis of crayfish Procambarus clarkii.

The crustacean hyperglycemic hormone (CHH) is a multifaceted neuropeptide instrumental in regulating carbohydrate and lipid metabolism, reproduction, osmoregulation, molting, and metamorphosis. Despite its significance, there is a dearth of research on its metabolic impact on the gills and epidermis-key organs in osmoregulation and molting processes. This study employed CHH dsRNA injections to silence CHH gene expression in Procambarus clarkii, followed by a metabolomic analysis of the gills and epidermis using nuclear magnetic resonance spectroscopy. Metabolic profiling through principal component analysis revealed the most pronounced changes at 24 h post-injection (hpi) in the epidermis and at 48 hpi in the gills. At 24 hpi, the epidermis exhibited significant modulation in 25 enrichment sets and 20 KEGG pathways, while at 48 hpi, 5 metabolite sets and 6 KEGG pathways were prominently regulated. Notably, pathways associated with amino acid metabolism, carbohydrate metabolism, and cofactor and vitamin metabolism were affected. A marked decrease in glucose and other carbohydrates suggested a compromised carbohydrate supply, whereas increased levels of citrate cycle intermediates implied a potential boost in energy provision. The silencing of CHH gene expression hampered the carbohydrate supply, which was possibly the main energy derived substrates. Conversely, the gills displayed significant alterations in 15 metabolite sets and 16 KEGG pathways at 48 hpi, with no significant changes at 24 hpi. These changes encompassed amino acid, carbohydrate, and lipid metabolism pathways. The decline in TCA cycle intermediates pointed to a potential downregulation of the cycle, whereas a decrease in ketone bodies indicated a shift towards lipid metabolism for energy production. Additionally, increased levels of nicotinate, nicotinamide, and quinolinate were observed in both organs. Overall, CHH's impact on the epidermis was prominent at 24 hpi and diminished thereafter, whereas its influence on metabolism in gills was delayed but intensified at 48 hpi. This differential CHH effect between gills and epidermis in P. clarkii provides new insights into the organ-specific regulatory mechanisms of CHH on energy metabolism and osmoregulation, warranting further comparative studies to elucidate the distinct roles of CHH in these organs.

[Current Status and New Drugs Progress in the Treatment of Relapsed and Refractory Acute Myeloid Leukemia--Review].

The overall therapeutic outcome of acute myeloid leukemia (AML) is poor, and relapse and refractory are the main reasons for treatment failure. Leukemia cells of relapsed and refractory AML (R/R-AML) patients are usually resistant to conventional chemotherapy, and new treatment regimens are urgently needed to further improve the survival rate and prolong the survival time of these patients.There are no recommended unified treatment regimens other than entering clinical trials.At present,the main options are salvage chemotherapy and hematopoietic stem cell transplantation (HSCT), and HSCT is the only possible cure for R/R-AML, but the prognosis of most of these patients is still poor.In recent years,the treatment status of AML has progressed rapidly, and the new therapies are emerging, many new drugs have become the research focus. Some progress has been made in improving chemosensitivity and overcoming chemoresistance by combining the new drugs with the original chemotherapeutic drugs, which provide a new treatment option and improve the overall prognosis for R/R-AML patients. This article will review the current treatment status and the latest progress in new drug research of R/R-AML.

Clinical outcomes of EGFR+/METamp+ vs. EGFR+/METamp- untreated patients with advanced non-small cell lung cancer.

BACKGROUND: MET dysregulation has been implicated in the development of primary and secondary resistance to EGFR tyrosine kinase inhibitor (TKI) therapy. However, the clinicopathological characteristics and outcomes of patients harboring EGFR-sensitive mutations and de novo MET amplifications still need to be explored. METHODS: A total of 54 patients from our hospital with non-small cell lung cancer harboring EGFR-sensitive mutations and/or de novo MET amplifications were included in this study. Survival rates were estimated by the Kaplan-Meier method with log-rank statistics. Lung cancer organoids (LCOs) were generated from patient-derived malignant pleural effusion to perform drug sensitivity assays. RESULTS: Fifty-four patients with the appropriate clinicopathological characteristics were enrolled. MET FISH was performed in 40 patients who were stratified accordingly into two groups: EGFR+/METamp- (n = 22) and EGFR+/METamp + (n = 18). Survival rates for EGFR+/METamp- and EGFR+/METamp + patients respectively, were as follows: the median progression-free survival (PFS) was 12.1 and 1.9 months (p<0.001); the median post-progression overall survival (pOS) was 25.6 and 11.6 months (p = 0.023); the median overall survival (OS) was 33.2 and 12.7 months (p = 0.013). Drug testing conducted in LCOs derived from malignant pleural effusion from EGFR+/METamp + patients showed that dual targeted therapy was more effective than TKI monotherapy. CONCLUSION: EGFR+/METamp + patients treated with first-line TKI monotherapy had poor clinical outcomes. Dual targeted therapy showed potent anticancer activity in the LCO drug testing assay, suggesting that it is a promising first-line treatment for EGFR+/METamp + patients. Randomized controlled trials are needed to further validate these results.

Temperature effect on vibrational properties of crystalline Dibenz[a,h]anthracene.

Vibrational properties associated with the intra- and intermolecular bonding of the crystalline Dibenz[a,h]anthracene at low temperatures are investigated by Raman scattering. A complete characterization of phonon spectra is given for this material. In the 120-150 K temperature region, several lattice modes show abrupt changes of splitting and the discontinuities in the temperature shift, but no emergence of new modes. Moreover, the intensity ratio of I68/38 is greater than 1 below 130 K. Meanwhile, the aromatic C-C stretching modes exhibit anomalous behaviors in frequencies, widths, and intensities at about 130 K. These spectroscopic results demonstrate a disorder-order transition occurred at about 130 K. However, the modes, corresponding to C-H out-of-plane bending, C-H in-plane bending, and/or C-H rocking, have no significant change in the whole temperature range. It indicates that the transition mainly results from the change of the tilt angle between the molecules. Our work is of great significance to understand the internal vibrational properties of Dibenz[a,h]anthracene, and it also provides considerable supports for the further study of this material.

Anthelmintic niclosamide attenuates pressure-overload induced heart failure in mice.

The heart is a high energy demand organ and enhancing mitochondrial function is proposed as the next-generation therapeutics for heart failure. Our previous study found that anthelmintic drug niclosamide enhanced mitochondrial respiration and increased adenosine triphosphate (ATP) production in cardiomyocytes, therefore, this study aimed to determine the effect of niclosamide on heart failure in mice and the potential molecular mechanisms. The heart failure model was induced by transverse aortic constriction (TAC) in mice. Oral administration of niclosamide improved TAC-induced cardiac hypertrophy, cardiac fibrosis, and cardiac dysfunction in mice. Oral administration of niclosamide reduced TAC-induced increase of serum IL-6 in heart failure mice. In vitro, niclosamide within 0.1 µM increased mitochondrial respiration and ATP production in mice heart tissues. At the concentrations more than 0.1 µM, niclosamide reduced the increased interleukin- 6 (IL-6) mRNA expression in lipopolysaccharide (LPS)-stimulated RAW264.7 and THP-1 derived macrophages. In cultured primary cardiomyocytes and cardiac fibroblasts, niclosamide (more than 0.1 µM) suppressed IL-6- and phenylephrine-induced cardiomyocyte hypertrophy, and inhibited collagen secretion from cardiac fibroblasts. In conclusion, niclosamide attenuates heart failure in mice and the underlying mechanisms include enhancing mitochondrial respiration of cardiomyocytes, inhibiting collagen secretion from cardiac fibroblasts, and reducing the elevated serum inflammatory mediator IL-6. The present study suggests that niclosamide might be therapeutic for heart failure.

[Comparative study of femoral head replacement and internal fixation in the treatment of unstable intertrochanteric fractures in the elderly].

OBJECTIVE: To compare the clinical efficacy of femoral head replacement and internal fixation in the treatment of unstable intertrochanteric fractures in the elderly. METHODS: Retrospective analysis of 70 cases of unstable intertrochanteric fractures treated from January 2016 to January 2019 and meeting the inclusion and exclusion criteria, 39 cases were fixed with closed reduction and new proximal femoral intramedullary nail(InterTAN), and 31 cases were treated with open trochanter reconstruction and artificial femoral head replacement. The operation time, intraoperative bleeding, hospital stay, weight bearing time, postoperative complication rate and hip function recovery (Harris score) were compared between two groups. RESULTS: All cases were followed up for 12 to 24 months. There were no significant differences in intraoperative bleeding and hospital stay between the two groups (P>0.05). The operation time in replacement group was longer than that in internal fixation group (P< 0.05). The postoperative weight-bearing time in replacement group was significantly earlier than that in internal fixation group (P<0.05). In the replacement group, there were 1 case of pulmonary infection, 1 case of deep venous thrombosis and 1 case of periprosthetic fracture;in the internal fixation group, there were 4 cases of pulmonary infection, 3 cases of internal fixation failure, 3 cases of cerebral infarction and 2 cases of urinary infection;there was significant difference between two groups (P< 0.05). The Harris score in replacement group was higher than that in internal fixation group one month after operation (P< 0.05), but there was no significant difference between two groups at 12 months after operation(P>0.05). CONCLUSION: InterTAN and femoral head replacement can treat unstable intertrochanteric fractures in the elderly, but femoral head replacement can move down early, improve the quality of life at the end of life, reduce postoperative complications and facilitate the treatment of coexisting diseases in internal medicine.

Vital Carbohydrate and Lipid Metabolites in Serum Involved in Energy Metabolism during Pubertal Molt of Mud Crab (Scylla paramamosain).

Pubertal molt is a vital stage in the cultivation of mature female crabs in the aquacultural industry of Scylla paramamosain. Since fasting occurs during molting, which requires a large supply of energy, internal energy reserves are critical. However, the dynamics of energy supply during pubertal molt is not clear. This study focuses on the variations of carbohydrates and lipids in serum during the pubertal molt of S. paramamosain via a metabolomics approach. Eleven lipid or carbohydrate metabolic pathways were significantly influenced postmolt. A remarkable decrease in carbohydrates in serum suggested that free sugars were consumed for energy. A significant decrease in glucose and alpha-d-glucosamine 1-phosphate showed that chitin synthesis exhausted glycogen, resulting in insufficient glucose supply. An increase in l-carnitine and acetylcarnitine, and a significant decrease in 15 fatty acyls and 8 glycerophosphocholines in serum indicated that carnitine shuttle was stimulated, and ß-oxidation was upregulated postmolt. In addition, astaxanthin, ponasterone A, and riboflavin in serum were significantly decreased postmolt. Eleven potential metabolite biomarkers were identified for pubertal molt. Taken together, carbohydrates and lipids were possibly major energy reserves in pubertal molt. This study suggests that an increase in carbohydrate and lipid levels in crab feed may alleviate the effects of fasting during molt and improve farm productivity in mature female crabs.

Genome and Evolutionary Analysis of Nosema ceranae: A Microsporidian Parasite of Honey Bees.

Microsporidia comprise a phylum of single cell, intracellular parasites and represent the earliest diverging branch in the fungal kingdom. The microsporidian parasite Nosema ceranae primarily infects honey bee gut epithelial cells, leading to impaired memory, suppressed host immune responses and colony collapse under certain circumstances. As the genome of N. ceranae is challenging to assembly due to very high genetic diversity and repetitive region, the genome was re-sequenced using long reads. We present a robust 8.8 Mbp genome assembly of 2,280 protein coding genes, including a high number of genes involved in transporting nutrients and energy, as well as drug resistance when compared with sister species Nosema apis. We also describe the loss of the critical protein Dicer in approximately half of the microsporidian species, giving new insights into the availability of RNA interference pathway in this group. Our results provided new insights into the pathogenesis of N. ceranae and a blueprint for treatment strategies that target this parasite without harming honey bees. The unique infectious apparatus polar filament and transportation pathway members can help to identify treatments to control this parasite.

Ultrasound-Based Multimodal Imaging Predicting Ischemic-Type Biliary Lesions After Living-Donor Liver Transplantation.

BACKGROUND: Ischemic-type biliary lesions (ITBL) are accepted as the most incomprehensible biliary complications after living-donor liver transplantation (LDLT). Early predicting the development of ITBL in pediatric patients permits more preventive strategies. However, few studies have focused on the early prediction of ITBL. OBJECTIVE: This study aimed to establish a nomogram including ultrasound-based multimodal imaging to predict ITBL in children with biliary atresia (BA) within 2 years after receiving LDLT. METHODS: The records of 94 BA children with at least one year of follow-up after LDLT were reviewed retrospectively. They were randomly divided into a training cohort for constructing a nomogram (n=64) and a validation cohort (n=30). In the training cohort, patients diagnosed as ITBL were included in the ITBL group and those without any vascular and biliary complication were included in the non-ITBL group. Multivariate Cox regression was used for the establishment of the nomogram in predicting the risk of ITBL within 2 years post-LDLT. The discrimination and calibration of the nomogram were internally and externally validated. The performances of the nomogram and the individual components were compared by the area under the curve (AUC) of receiver operating characteristic (ROC) curve. RESULTS: In the training cohort, 18 BA children were included in the ITBL group and 46 were in the non-ITBL group. Last pediatric end-stage liver disease (PELD) score, gamma-glutamyl transpeptidase (GGT), resistive index (RI), and liver stiffness measurement (LSM) were the independent predictors for the development of ITBL within 2 years post-LDLT. The nomogram incorporating these independent predictors showed good discrimination and calibration by the internal and external validation. Its performance was better than any individual component in predicting the prognosis (P < 0.05). CONCLUSION: The established nomogram may be used to predict the risk of ITBL within 2 years post-LDLT in BA children.

A Nomogram Predicting the Prognosis of Children With Biliary Atresia After Hepatoportoenterostomy.

Background: Although Kasai portoenterostomy (KPE) is performed timely for most children with biliary atresia (BA), the native liver survival (NLS) is still poor due to the progressive liver fibrosis. Many children have to receive liver transplantation (LT) within 2 years after KPE. Early prediction of the prognosis permits the implementation of prophylactic treatments for BA children. However, studies about the prediction are limited. Objective: The purpose of this study is to establish a nomogram to predict the prognosis of BA children within 2 years after KPE. Methods: The follow-up data of 151 BA children were retrospectively reviewed, and were randomly divided into a training cohort for constructing a nomogram (n = 103) and a validation cohort (n = 48). In the training cohort, patients were divided into Group A and Group B according to whether death or LT were observed within 2 years post-KPE. Multivariate Cox regression based on the baseline characteristics, liver function indicators and LSM (liver stiffness measurement) values at KPE and 3 months after KPE was utilized for the establishment of the nomogram in predicting the prognosis of BA within 2 years after KPE. The discrimination and calibration of the nomogram were internally and externally validated. Results: Fifty-six BA children were included in Group A and 47 were included in group B. Age at KPE, METAVIR score F4, LSM at 3 months, first onset of cholangitis within 3 months, and jaundice clearance time were the independent predictors for the prognosis of BA children within 2 years after KPE (all P < 0.05). The developed nomogram based on these independent predictors showed good discrimination and calibration by the internal and external validation. Its performance was better than each predictor in predicting the prognosis (all P < 0.05). Conclusions: The established nomogram based on the indicators from the first 3 months after KPE may be useful for predicting the prognosis of BA children within 2 years post-KPE and helpful for the consideration of LT.

Chemical mitochondrial uncouplers share common inhibitory effect on NLRP3 inflammasome activation through inhibiting NFκB nuclear translocation.

Activation of NLRP3 inflammasome is implicated in varieties of pathologies, the aim of the present study is to characterize the effect and mechanism of mitochondrial uncouplers on NLRP3 inflammasome activation by using three types of uncouplers, niclosamide, CCCP and BAM15. Niclosamide, CCCP and BAM15 inhibited LPS plus ATP-induced increases of NLRP3 protein and IL-1ß mRNA levels in RAW264.7 macrophages and THP-1 derived macrophages. Niclosamide, CCCP and BAM15 inhibited LPS plus ATP-induced increase of NFκB (P65) phosphorylation, and inhibited NFκB (P65) nuclear translocation in RAW264.7 macrophages. Niclosamide and BAM15 inhibited LPS-induced increase of IκBα phosphorylation in RAW264.7 macrophages, and the inhibitory effect was dependent on increased intracellular [Ca2+]i; however, CCCP showed no significant effect on IκBα phosphorylation in RAW264.7 macrophages stimulated with LPS. In conclusion, chemical mitochondrial uncouplers niclosamide, CCCP and BAM15 share common inhibitory effect on NLRP3 inflammasome activation through inhibiting NFκB nuclear translocation.

Predictive and Prognostic Potential of TP53 in Patients With Advanced Non-Small-Cell Lung Cancer Treated With EGFR-TKI: Analysis of a Phase III Randomized Clinical Trial (CTONG 0901).

BACKGROUND: Mutations in TP53 are commonly found in patients with epidermal growth factor receptor (EGFR) mutant advanced non-small-cell lung cancer (NSCLC). In this study, we determined the predictive and prognostic potential of different subtypes of TP53 using data from a phase III randomized trial (CTONG 0901). PATIENTS AND METHODS: The trial enrolled 195 patients who had undergone next-generation sequencing of 168 genes before treatment with EGFR tyrosine kinase inhibitors. Mutations in TP53 (exon 4 or 7, other mutations, and wild-type) were analyzed based on the therapeutic response and survival. A Cox proportional hazards model was used to determine the potential of the predictive and prognostic factors. RESULTS: All 195 patients harbored activating EGFR mutations: the most common concomitant mutations were TP53 (134/195, 68.7%), CTNNB1 (20/195, 10.3%), and RB1 (16/195, 8.2%). The genetic profiles between patient subgroups administered first-line (132, 67.7%) or later-line (63, 32.3%) treatments did not significantly differ. The median progression-free survival in patients with mutations in exon 4 or 7 of TP53, other TP53 mutations, and wild-type TP53 were 9.4, 11.0, and 14.5 months (P = .009), respectively. Overall survival times were 15.8, 20.0, and 26.1 months (P = .004), respectively. Mutations in exon 4 or 7 of TP53 served as independent prognostic factors for progression-free (P = .001) and overall survival (P = .004) in patients. CONCLUSION: Mutations in exon 4 and/or 7 in TP53 are promising predictive and prognostic indicators in EGFR-mutated NSCLC.

Survey of Incidence and Nested PCR Detection of Sugarcane White Leaf in Different Varieties.

Sugarcane white leaf (SCWL) is a devastating sugarcane (Saccharum officinarum) disease caused by a 16SrXI group phytoplasma, which is extremely harmful to sugarcane production. To determine the occurrence of SCWL in different varieties in 2018, we conducted a field survey and performed nested PCR detection of SCWL phytoplasma in cane-planting areas of Mangweng and Hepai in Gengma, Yunnan province, which are the areas most severely affected by SCWL in China. The results of the field survey showed that the symptomatic incidence of SCWL differed among varieties. The mean symptomatic incidence of SCWL on variety Yuetang60 was the highest (73.50%), and it was the lowest on Liucheng05-136 (13.67%). Using nested PCR, the SCWL phytoplasma was detected in symptomatic plants of all varieties more than 90% of the time; the SCWL phytoplasma was detected in 91 and 97% of symptomatic plants of Yingyu91-59 and Liucheng05-136 varieties, respectively. The SCWL phytoplasma was detected by PCR in 82% of the asymptomatic plant samples. The results of this study showed that field survey based on white leaf symptoms did not accurately reflect the actual occurrence of the SCWL phytoplasma.

Concomitant genetic alterations having greater impact on the clinical benefit of EGFR-TKIs in EGFR-mutant advanced NSCLC than BIM deletion polymorphism.

BACKGROUND: In previous studies, the predictive role of BIM deletion polymorphism with respect to responses to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has been controversial. The potential reasons for these inconsistent findings were unknown. METHODS: Data from CTONG0901 clinical trial and medical records of Guangdong Lung Cancer Institute (GLCI) were retrospectively pooled. A total of 194 and 141 EGFR-mutant non-small cell lung cancer (NSCLC) patients treated with first- and second-generation EGFR-TKIs were examined in the CTONG0901 and GLCI cohorts, respectively. Sixty-eight patients were treated with third-generation EGFR-TKIs in the GLCI cohort. The BIM gene status was examined by next-generation sequencing. RESULTS: The frequency of BIM deletion polymorphism was 11.3% and 17.0% in CTONG0901 and GLCI cohorts, respectively. For first- and second-generation EGFR-TKIs in CTONG0901 cohort, objective response (ORR) was 54.5% in BIM deletion group versus 56.4% in wild-type BIM group (P = .87); disease control rate (DCR) was 90.9% versus 88.4% (P = 1.00); progression-free survival (PFS) was 10.5 versus 11.2 months (P = .59); and overall survival (OS) was 20.5 versus 20.5 months (P = .73). In GLCI cohort, ORR was 54.2% versus 60.7% (P = .55); DCR was 91.7% versus 96.6% (P = .27); PFS was 10.1 versus 11.6 months (P = .63); and OS was 58.5 versus 45.0 months (P = .93). For third-generation EGFR-TKIs, ORR was 18.2% versus 63.2% (P = .02); DCR was 81.8% versus 96.5%, (P = .12); PFS was 5.8 versus 9.0 months (P = .13); and OS was 30.0 versus 24.8 months (P = .85). Cox regression analysis showed that concomitant genetic alterations could adversely affect the response to EGFR-TKIs, but not BIM deletion. CONCLUSIONS: The presence of BIM deletion showed no relation to an impaired response to first-, second-, and third-generation EGFR-TKIs in NSCLC patients. The factors influencing the response of EGFR-TKIs were concomitant genetic alterations, but not BIM deletion.