Sensorineural hearing loss induced by gefitinib: A CARE-compliant case report and literature reviews.

RATIONALE: Gefitinib is a potent and selective orally active growth factor receptor (EGFR)-tyrosine kinase inhibitor that is commonly used to treat advanced non-small cell lung cancer patients with activating EGFR mutations. Hearing impairment with gefitinib was sparsely reported. In this report, we describe a case of sensorineural deafness associated with the administration of gefitinib, with a Naranjo score of 7. PATIENT CONCERNS: An 81-year-old female was diagnosed with lung adenocarcinoma with bone metastasis and an EGFR-activating mutation. The patient was prescribed gefitinib tablets at a daily dose of 250 mg for lung adenocarcinoma treatment. However, the patient experienced moderate to severe bilateral sensorineural deafness, primarily in her right ear, after taking gefitinib. Following the cessation of gefitinib administration, the patient exhibited partial restoration of auditory function. Upon resuming the medication, she experienced a worsening of deafness. DIAGNOSES: The otoscopic audiogram and hearing test indicated moderate to severe bilateral sensorineural deafness. INTERVENTIONS: The otolaryngologist recommended bilateral hearing aids to enhance hearing function. OUTCOMES: Throughout our follow-up period, the patient did not receive a hearing aid implant. LESSONS: This article first reported the ototoxicity caused by gefitinib. While rare, our report highlights that gefitinib-induced sensorineural deafness is possible and its mechanisms are still unclear. This adverse reaction should be monitored closely during clinical application of gefitinib to improve patient outcomes.

First Report of Tomato spotted wilt virus infecting Helichrysum bracteatum in China.

Strawflower (Helichrysum bracteatum, Asteraceae) , an annual or biennial herb, is one of the most popular flowers in the world because of the colorful flowers and the long flowering period. However, the ornamental plants belonging to Asteraceae are susceptible to numerous viruses such as cucumber mosaic virus (CMV) (Cucumovirus, Bromoviridae) , potato virus Y (Potyvirus, Potyviridae), tomato mosaic virus (ToMV) (Tobamovirus, Virgaviridae), tobacco mosaic virus (TMV) (Tobamovirus, Virgaviridae), chrysanthemum virus B (CVB) (Carlavirus, Betaflexiviridae), tomato aspermy virus (TAV) (Cucumovirus, Bromoviridae), tomato spotted wilt virus (TSWV) (Orthotospovirus tomatomaculae, Tospoviridae), and impatiens necrotic spot virus (INSV) (Orthotospovirus impatiensnecromaculae, Orthotospovirus) resulting in severe yield loss (Verma et al. 2003; Raj et al. 2007; Kondo et al. 2011; Liu et al. 2014; Marys et al. 2014; Min et al. 2020; Gautam et al. 2021; Read et al. 2022; Supakitthanakorn et al. 2022). Among these viruses, the TSWV, a thrips-transmitted negative-stranded RNA virus, is well known to cause viral disease in several plant species while is less reported in Helichrysum, especially in China. In April 2021, viral attack symptoms were detected on the leaves of H. bracteatum during our routine checks in the greenhouse located at Shunyi District, Beijing, China, such as wilting, shrinking, chlorotic blotches, chlorotic ring spots. To investigate the virus infecting H. bracteatum, in total of 25 symptomatic and 5 asymptomatic leaves were sampled and tested by the effective double antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) using antisera against CMV, PVY/PVX, ToMV, TMV, CVB, TAV, TSWV, INSV, separately (Agdia, USA). Only the TSWV showed positive in symptomatic samples, and asymptomatic samples were all negative, which implied TSWV infection. To further confirm the virus type of TSWV isolated from H. bracteatum samples, the genomic RNA of the virus was isolated using reverse transcription and polymerase chain reaction (RT-PCR), and then was cloned, sequenced and analyzed. Total RNA of five symptomatic leaves (ELISA-positive) were extracted using the FastPure Plant Total RNA Isolation Kit (Vazyme, China), and then were reverse transcribed by HiScript II Reverse Transcriptase (Vazyme, China). Each genome segments were amplified using Phanta Max Super-Fidelity DNA Polymerase (Vazyme, China) with TSWV-specific primers newly designed and listed in Table S1. The PCR setup was as follow: 95°C for 30 s, followed by 35 cycles at 95°C for 30 s, 55°C for 30 s, and 72°C for 1.5 min, with a final extension at 72°C for 10 min. All PCR products were cloned into the TA/Blunt-Zero vector (Vazyme, China) and sequenced (GENEWIZ, Inc.). We assembled and then analyzed the evolutionary relationship of three genomic fragments, that is, TSWV-BJFC-Hb S (2923 bp), M (4785 bp) and L (8971 bp) using the BLAST tools. The results showed high similarity with TSWV-henan isolated from pepper in China (99.6% to TSWV-S (MT799179.1), 99.8 % to TSWV-M (MT799178.1) and 99.8 % TSWV-L (MT799177.1)). These sequences have been submitted to the GenBank (OM982910, OM982911 and OM937131). Taking all of these evidences together, the viral disease observed in H. bracteatum was closely associated with TSWV. TSWV is currently widespread in China, infecting Nasturtium, Chrysanthemum and cowpea (Xiao et al. 2015; Hu et al. 2018; Yu et al. 2021). Epidemics of TSWV have also been reported in several other countries such as Korea, North Carolina, Turkey and India (Renukadevi et al. 2015; Koehler et al. 2016; Kwak et al. 2021; Erilmez, S. 2022). This is the first report of TSWV infection on H. bracteatum in China. Due to the fast spread and serious economic losses of TSWV, the rapid detection may be the essential way to prevent this viral disease among crops (Macharia et al. 2014).

Lanthipeptides from the Same Core Sequence: Characterization of a Class II Lanthipeptide Synthetase from Microcystis aeruginosa NIES-88.

Class II lanthipeptide synthetases (LanMs) are relatively promiscuous to core peptide variations. Previous studies have shown that different LanMs catalyze identical reactions on the same core sequence fused to their respective cognate leaders. We characterized a new LanM enzyme from Microcystis aeruginosa NIES-88, MalM, and demonstrated that MalM and ProcM exhibited disparate dehydration and cyclization patterns on identical core peptides. Our study provided new insights into the regioselectivity of LanMs and showcased an appropriate strategy for lanthipeptide structural diversity engineering.

[Effect of Composite Leaching on Cadmium Removal Efficiency in Plow Layer Soil of Agricultural Land and Its Functional Regulation].

In order to explore the feasibility of soil leaching and the remediation of agricultural land polluted by medium (heavy) cadmium (Cd), the soil column was used to simulate in-situ leaching, and the citric acid (CA)+ferric chloride (FeCl3) composite leaching agent was selected. Under the optimal concentration combination and the addition amount of the composite leaching agent, the distribution characteristics of Cd in the plow-layer soil and below were investigated. The influence of the leaching process on soil health and the regulation effect of biochar were also investigated. The results showed that:① 0.1 mol·L-1 CA and 0.01 mol·L-1 FeCl3 were the best concentration combinations; under this concentration combination, when the eluent reached 9 pore volume, the content of Cd in the 20 cm soil column was lower than the risk screening value of 0.4 mg·kg-1 (GB 15618-2018) in the corresponding pH value of the tested soil after leaching. ② Under the optimal leaching conditions, the longitudinal distribution of Cd in the 60 cm soil column showed that the content of total Cd increased with the increase in soil depth after leaching, and the leachate of the soil column contained a certain amount of Cd, indicating that the leaching process promoted the downward migration of Cd. The content of available Cd in the soil after composite leaching also increased with the increase in soil depth, which was partly due to the change in exchangeable and carbonate-bound Cd in different soil layers. ③ A portion of the soil health indexes and enzyme activities decreased after CA+FeCl3 composite leaching. The addition of biochar can improve the health status of the soil after leaching; the soil health indexes and enzyme activities were restored significantly, and the risk of Cd reactivation also decreased after the addition of biochar. The results showed that part of Cd in the soil can be leached below the plow layer by CA+FeCl3 composite leaching; however, the leaching process may have a certain impact on soil health, and biochar has a significant effect on the recovery of soil after leaching.

Pepsin and Laryngeal and Hypopharyngeal Carcinomas.

Laryngeal and hypopharyngeal carcinomas are common malignant tumors of the head and neck, and the incidence of both is increasing. Laryngopharyngeal reflux refers to the retrograde flow of gastric contents into the larynx, oropharynx, and/or nasopharynx. It remains controversial whether laryngopharyngeal reflux is a risk factor for laryngeal and hypopharyngeal cancers. The refluxing substances mainly include hydrochloric acid, pepsin, and occasionally bile acids and bile salts, as well as bacteria that colonize the gastrointestinal tract. Loss of epithelium in the mucous membrane of the larynx and hypopharynx is thought to be caused by pepsin. Here, we review the relationships between laryngopharyngeal reflux and both laryngeal and hypopharyngeal carcinomas, as well as the significance of pepsin, methods of clinical detection, and the mechanism of carcinogenesis.

Efficacy of robotic radical hysterectomy for cervical cancer compared with that of open and laparoscopic surgery: A separate meta-analysis of high-quality studies.

BACKGROUND: To perform a meta-analysis of high-quality studies comparing robotic radical hysterectomy (RRH) vs laparoscopic radical hysterectomy (LRH), and open radical hysterectomy (ORH) for the treatment of cervical cancer. METHODS: A systematic search of PubMed, Embase, Cochrane Library, and Web of Science was performed to identify studies that compared RRH with LRH or ORH. The selection of high-quality, nonrandomized comparative studies was based on a validated tool (methodologic index for nonrandomized studies) since no randomized controlled trials have been published. Outcomes of interest included conversion rate, operation time, intraoperative estimated blood loss (EBL), length of hospital stay (LOS), morbidity, mortality, number of retrieved lymph nodes (RLNs), and long-term oncologic outcomes. RESULTS: Twelve studies assessing RRH vs LRH or ORH were included for this meta-analysis. In comparison with LRH, there was no difference in operation time, EBL, conversion rate, intraoperative or postoperative complications, LOS, and tumor recurrence (P > .05). Compared with ORH, patients underwent RRH had less EBL (weighted mean difference [WMD] = -322.59 mL; 95% confidence interval [CI]: -502.75 to -142.43, P < .01), a lower transfusion rate (odds ratio [OR] = 0.14, 95% CI: 0.06-0.34, P < .01), and shorter LOS (WMD = -2.71 days; 95% CI: -3.74 to -1.68, P < .01). There was no significant difference between RRH and LRH with respect to the operation time, intraoperative or postoperative complications, RLN, and tumor recurrence (P > .05). CONCLUSION: Our results indicate that RRH is safe and effective compared to its laparoscopic and open counterpart and provides favorable outcomes in postoperative recovery.

Analysis of the impact of extracellular acidity on the expression and activity of P-glycoprotein and on the P-glycoprotein-mediated cytotoxicity of daunorubicin in cancer cell by microfluidic chip technology.

OBJECTIVE: To explore the impact of extracellular acidic environment on the expression and activity of P-glycoprotein (P-gp) and on the P-gp-mediated cytotoxicity of daunomycin in cancer cells by using microfluidic chip technology. METHODS: The A549 cells cultured on a microfluidic chip were divided into experiment group and control group. The experiment group was exposed to an acidic cell culture medium (pH 6.6), while the control group was treated with a neutral cell culture medium (pH 7.4). The expression of P-gp was detected by cell immunofluorescense analysis and the activity of P-gp was evaluated by Rhodamine 123 efflux experiment. Meanwhile, the cytotoxicity of daunomycin was analyzed by cell live/dead fluorescence staining method. RESULTS: Microfluidic chip designed in this study could provide a suitable microenvironment for the growth of A549 cells and the A549 cells reached the confluence of 90% after inoculation for 72 h. Treatment of the acidic cell culture media on A549 cells did not make a significant difference on the expression level of P-gp. However, the activity of P-gp was significantly enhancement and peaked at 6 h after treatment with acidic cell culture media. Meanwhile, the cytotoxicity of daunomycin reduced significantly after treatment with acidic cell culture medium for 6 h,and a reversal effect was obtained when synergy with verapamil. CONCLUSIONS: Microfluidic chip technology can shorten the analysis time and reduce the reagent consumption. It can be used as a new technology platform for understanding the mechanisms of multi-drug resistance and for screening highly efficient multi-drug resistance reversal agents.

Effect of lithium salts addition on the ionic liquid based extraction of essential oil from Farfarae Flos.

In this study, an ionic liquids (ILs) based extraction approach has been successfully applied to the extraction of essential oil from Farfarae Flos, and the effect of lithium chloride was also investigated. The results indicated that the oil yields can be increased by the ILs, and the extraction time can be reduced significantly (from 4h to 2h), compared with the conventional water distillation. The addition of lithium chloride showed different effect according to the structures of ILs, and the oil yields may be related with the structure of cation, while the chemical compositions of essential oil may be related with the anion. The reduction of extraction time and remarkable higher efficiency (5.41-62.17% improved) by combination of lithium salt and proper ILs supports the suitability of the proposed approach.

[Expression and significance of LMP2 and PPM1A in gestational trophoblastic disease].

OBJECTIVE: To investigate the expression of low molecular mass polypeptide-2 (LMP2) and protein phosphatase 1A (PPM1A) in gestational trophoblastic disease and elucidate their predictive value in malignant transformation of hydatidiform mole. METHODS: The expressions of LMP2 and PPM1A protein in 196 complete hydatidiform moles (in which 28 cases with malignant transformation), 7 invasive moles, 5 choriocarcinomas and 20 normal chorionic villus were detected with the method of EnVision immunohistochemistry. Their clinicopathologic data were retrospectively analyzed. RESULTS: LMP2 and PPM1A protein expressed in cytotrophocytes, syncytiotrophoblast and extravillous trophoblast. The level of LMP2 expression in deteriorative hydatidiform mole was significantly higher than that in non-deteriorative hydatidiform mole or normal chorionic villus (6.79±2.38, 5.26±2.63 and 3.10±1.65, all P<0.01), while there were no difference compared with gestational trophoblastic neoplasms (6.42±2.68, P=0.113). The level of PPM1A expression was highest in normal chorionic villus, and decreased gradually in hydatidiform mole (non-deteriorative and deteriorative) and gestational trophoblastic neoplasms (6.30±2.98, 4.93±2.50, 4.43±2.04 and 3.33±2.06, all P<0.01); the level of PPM1A expression in deteriorative hydatidiform mole was significantly lower than that in non-deteriorative hydatidiform mole (P=0.001). The expression of LMP2 protein was correlated to theca lutein ovarian cyst, the expression of PPM1A protein was related with uterine size (P<0.05). While, there was no correlation between the expressions of the two proteins (P>0.05). CONCLUSIONS: High expression of LMP2 and low expression of PPM1A might play an important role in the motility and invasiveness of trophoblast cells and malignant transformation of hydatidiform mole. Testing the expression of LMP2 and PPM1A in hydatidiform mole tissues of initial uterine evacuation might be have some reference significance in judging outcomes of hydatidiform mole.