Objective To investigate the genetic causes of auditory neuropathy with optic atrophy in a family.Methods The proband's medical history and family history were inquired in detail,and relevant clinical examina-tions were performed to confirm the diagnosis of auditory neuropathy with optic atrophy,and the genetic pedigree of the family was drawn.Peripheral blood of proband(Ⅲ-7)was collected for whole exome sequencing,and the patho-genicity of the detected mutations were interpreted.Blood samples of proband's wife(Ⅲ-8),eldest daughter(Ⅳ-7),second daughter(Ⅳ-9)and son(Ⅳ-10)were tested for mutation sites by Sanger sequencing.Combined with clinical manifestations and examination results,the family was studied.Results The genetic pattern of this family was autosomal dominant.The proband showed decreased visual acuity at the age of 19,bilateral sensorineural deaf-ness at the age of 30,and decreased speech recognition rate.Among 20 members of the family of 5 generations,10(2 deceased)showed similar symptoms of hearing and visual impairment.Proband(Ⅲ-7),eldest daughter(Ⅳ-7)and son(Ⅳ-10)underwent relevant examination.Pure tone audiometry showed bilateral sensorineural deafness.ABR showed no response bilaterally.The 40 Hz AERP showed no response in both ears.OAE showed responses in some or all of the frequencies.No stapedial reflex was detected.The eye movement of Ⅲ-7 and Ⅳ-10 were reasona-ble in all directions,and color vision was normal.Ocular papilla atrophy was observed in different degrees in fundus examination.OCT showed thinning of optic disc nerve fibers in both eyes,and visual evoked potential showed pro-longed P100 wave peak.They were diagnosed as hereditary auditory neuropathy with optic atrophy.A mutation of the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)at a pathogenic locus on chromosome 3 was detected by whole exon detection in Ⅲ-7.The results of generation sequencing analysis showed that the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)mutation of chromosome 3 was also found in Ⅳ-7 and Ⅳ-10.Meanwhile,the gen-otypes of Ⅲ-8 and Ⅳ-9 were wild homozygous,that is,no mutation occurred.Conclusion The OPA1 c.1334G＞A(p.Arg445His,NM_015560.2)mutation site might be the pathogenic mutation in this family.

Objective To analyze the epidemiological characteristics of hand-foot-mouth disease(HFMD)in Gan-zhou.Methods The epidemiological data of HFMD reported by the Infectious Disease Surveillance System,a sub-system of China Disease Prevention and Control Information System,from 2017 to 2020 were analyzed by descriptive methods.Enterovirus(EV)nucleic acid and typing detections via throat swabs,anal swabs or herpes fluid of patients was detected by real-time fluo-rescent polymerase chain reaction.The change in HFMD epidemic characteristics was compared between 2020 and 2017-2019.Results The incidence of HFMD in Ganzhou in 2020 was significantly lower than that from 2017 to 2019(x2=50.587,P＜0.05).In 2020,the incidence of HFMD in counties and districts of Ganzhou(except Huichang County)signifi-cantly decreased compared with that in 2017-2019(P＜0.05).From 2017 to 2019,the incidence of HFMD was obviously seasonal,with a high incidence in summer and autumn,and two significant incidence peaks were formed in June and September in 2017 and 2018,respectively.In 2019,there was a summer peak in June.The epidemic trend in 2020 was different,with a very low epidemic trend in summer and autumn,and a peak in winter.The incidence of HFMD in men,women and all ages in 2020 significantly decreased compared with that in 2017-2019(P＜0.05),and the age of onset was mainly distributed in 1-5 years,especially in children aged 1 to 3 years.There was a significant difference in the incidence of HFMD among different ages(P＜0.05).The positive rate of EV in Ganzhou in 2020 was lower than that from 2017 to 2019(x2=47.273,P＜0.05).The positive rate of EV in January,March to September in 2020 was significantly lower,and the positive rate of EV in November,December 2020 was significantly higher than that in the same period in 2017 to 2019(P＜0.05).Strain CA16 showed an increasing trend year by year from 2017 to 2019,and became the dominant strain in 2019.The proportion of patients infected with CA6 strain was on the fise from 2018 to 2020,and CA6 became the dominant strain in 2020.Conclusion The HFMD in Ganzhou has obvious population characteristics and seasonality,and the pathogen spectrum is constantly changing.

Objective To analyze the efficacy of different intracavitary operations for calyceal diverticulum calculi,so as to provide reference for the diagnosis and treatment of such disease.Methods A retrospective analysis of the data of 21 patients with calyceal diverticulum calculi was conducted during Jan.2015 and Dec.2021.The patients were divided into the retrograde intrarenal surgery(RIRS,n=14)group and percutaneous nephrolithotomy(PCNL,n=7)group.The perioperative data were compared.Results There was no significant difference in stone load between the RIRS group and PCNL group[(11.56±4.79)mm vs.(13.06±6.27)mm,P=0.609].There were significant differences in the thickness of renal parenchyma at the top of the diverticulum[(10.08±4.81)mm vs.(5.24±2.23)mm,P=0.005],operation time[(58.57±19.23)min vs.(88.29±25.28)min,P=0.007],hospitalization time[3(1,5)vs.12(5,7),P=0.023]days.After operation,there were no significant differences in stone-clearance rate,decrease of hemoglobin,and postoperative complications between the two groups(P＞0.05).Conclusion Both RIRS and PCNL are viable options for treating renal calyceal diverticulum calculi.RIRS has advantages of shorter operation time and hospital stay.PCNL can be an alternative treatment when RIRS is unsuccessful.

OBJECTIVE: To explore the effect of auricular point pressure on anesthetic recovery in the patients undergoing laparoscopic cholecystectomy. METHODS: One hundred and forty patients undergoing laparoscopic cholecystectomy were randomized into a trial group (52 cases, 2 cases dropped out) and a control group (52 cases, 2 cases were eliminated). In the control group, the conventional anesthesia program and recovery intervention were adopted. In the trial group, on the basis of the regimen as the control group, the intervention of auricular point pressure was supplemented. The auricular points on the right side were selected, including sympathetic (AH_6a), brain (subcortex, AT₄), thalamus, exciting point, heart and sore center. One day before operation, the auricular point pressure started; and the auricular points were stimulated specially before anesthesia (T0), at the moment of operation ending (T1), when entering the recovery room, at the moment of the tube removal (T2) and in 10 min of the tube removal (T3), respectively; each auricular point was pressed for 1 min a time. The recovery time of spontaneous breathing, the time of eye opening, the removal time of endotracheal tube, the recovery time of orientation, and the time of exiting recovery room were compared between the two groups. The score of pain visual analogue scale (VAS) and that of Richmond agitation-sedation scale (RASS) at T2, T3 and when exiting recovery room (T4), and the relevant circulatory indexes (heart rate [HR], systolic blood pressure [SBP], diastolic blood pressure [DBP] and mean arterial pressure [MAP]) at T0, T1, T2 and T3 were observed in the two groups. RESULTS: In the trial group, the recovery time of spontaneous breathing, the time of eye opening, the removal time of endotracheal tube, the recovery time of orientation, the time of exiting recovery room were shorter than those of the control group (P<0.01, P<0.05). The pain VAS and RASS scores at T2, T3 and T4, as well as HR, SBP, DBP and MAP at T0, T1, T2 and T3 were not different statistically between the two groups (P>0.05). CONCLUSION Auricular point pressure can shorten the recovery time from anesthesia in the patients undergoing laparoscopic cholecystectomy.
Humans ; Cholecystectomy, Laparoscopic ; Male ; Female ; Middle Aged ; Adult ; Anesthesia Recovery Period ; Acupuncture Points ; Aged ; Young Adult

Objective:To establish the first Mini-Formative Evaluation of Radiation Oncology (Mini-FERO) scale in China and evaluate its preliminary application value in the standardized training for radiation oncology resident physicians.Methods:Based on the educational curriculum and examination requirements for the standardized training for radiation oncology resident physicians, as well as the standardized Mini-Clinical Evaluation Exercise (Mini-CEX) scale commonly used in clinical practice, the Mini-Formative Evaluation of Radiation Oncology (Mini-FERO) scale was developed to facilitate the standardized training for resident physicians in the field of radiation oncology. In this prospective study, a randomization method using a random number table was employed to select a cohort of 26 resident physicians who completed their rotations in Department of Radiation Oncology at the Cancer Hospital, Chinese Academy of Medical Sciences from March 1, 2021 to December 31, 2021. The Mini-FERO scale was administered in the initial, middle, and final stages during the rotation period. The differences in evaluation scores before and after the assessments were analyzed by paired t-test. Furthermore, participating resident physicians and supervising teachers provided satisfaction ratings, and a comprehensive evaluation of the Mini-FERO scale was conducted. Results:The average scores of the three examinations of 26 resident physicians demonstrated a successive improvement, with individual performance in each assessed category also showing progressive enhancement. The second evaluation exhibited a more pronounced score increase compared to the first evaluation, with a mean improvement of (1.43±1.02) points ( t=7.13, P<0.001); while the third evaluation had a mean improvement of (0.41±0.50) points ( t=4.07, P<0.001) compaired to the second evaluation, with a mean difference of (1.02±1.15) points between the two ( t=4.53, P<0.001). The average time required for the assessments was (34.31±24.46) min. Overall satisfaction ratings from the evaluated resident physicians for the Mini-FERO scale were (8.42±0.85) points, and supervising teachers reported an overall satisfaction rating of (8.45±0.85) points. The satisfaction rate was 96% (25/26). Conclusions:In this study, the Mini-FERO scale was successfully developed and validated in the context of clinical teaching practice for radiation oncology resident physicians. The Mini-FERO scale is proven to be a feasible tool for assessing the gradual improvement of resident physicians throughout their learning process in the field of radiation oncology. Importantly, it offers the advantages of short assessment time, thereby avoiding additional burden on supervising teachers. The adoption of the Mini-FERO scale addresses current limitations of lacking of formative evaluation in the standardized training for radiation oncology resident physicians.

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15% of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.‍T260A, p.‍R422W, and p.‍R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5%‍‒‍49.7% of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3%‍‒‍17.9%, which was significantly higher than that (6.9%‍‒‍7.4%) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.
Humans ; Apoptosis Inducing Factor/metabolism* ; NAD/metabolism* ; Dimerization ; Apoptosis

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15％ of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.T260A, p.R422W, and p.R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5％?49.7％ of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3％?17.9％, which was significantly higher than that (6.9％?7.4％) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.

Intensity-modulated radiation therapy(IMRT) is currently the main treatment method for nasopharyngeal carcinoma. During radiotherapy for nasopharyngeal carcinoma, factors such as body mass reduction, tumor regression, and organ displacement at risk can affect the precise implementation of radiation therapy. Applying adaptive radiotherapy (ART) technology to optimize the treatment plan at the appropriate timing can reduce the adverse effects caused by the above factors and enhance the accuracy of radiotherapy. There are no uniform standards for the necessity, timing, and case selection of ART. In this review, the research progress of ART in the radiotherapy of nasopharyngeal carcinoma in recent years was reviewed to provide a reference for further clinical application of ART in nasopharyngeal carcinoma.

In order to better evaluate the transport effect of nanoparticles through the nasal mucosa, an nasal cavity-mimic model was designed based on M cells. The differentiation of M cells was induced by co-culture of Calu-3 and Raji cells in invert model. The ZO-1 protein staining and the transport of fluorescein sodium and dexamethasone showed that the inverted co-culture model formed a dense monolayer and possessed the transport ability. The differentiation of M cells was observed by up-regulated expression of Sialyl Lewis A antigen (SLAA) and integrin 1, and down-regulated activity of alkaline phosphatase. After targeting M cells with iRGD peptide (cRGDKGPDC), the transport of nanoparticles increased. , the co-administration of iRGD could result in the increase of nanoparticles transported to the brain through the nasal cavity after intranasal administration. In the evaluation of immune effect , the nasal administration of OVA-PLGA/iRGD led to more release of IgG, IFN-, IL-2 and secretory IgA (sIgA) compared with OVA@PLGA group. Collectively, the study constructed M cell model, and proved the enhanced effect of targeting towards M cell with iRGD on improving nasal immunity.

: Objective: To investigate the effects of ezrin enhancer knockout on ezrin gene expression, cell proliferation and migration of human esophageal carcinoma Eca-109 cells. : Methods: The CRISPR/Cas9 recombinant plasmids targeting upstream/downstream of human ezrin enhancer were co-transfected into human esophageal carcinoma Eca-109 cells, and the cell line Eca-C2 with ezrin enhancer knockout was screened by purinomycin. Then the expression levels of ezrin mRNAand protein in Eca-C2 cells were detected by Real-time quantitative PCR (qPCR) and Western blotting, respectively; The expression levels of MAPK-pathway-related proteins were detected by protein array technology; and the effects of ezrin enhancer knockout on the proliferation and migration of Eca-C2 cells were analyzed by WST-1 method and wound-healing assay, respectively. : Results:The human esophageal carcinoma cell line Eca-C2 with stable ezrin enhancer knockout was established successfully. Compared with control cells, the mRNA and protein expressions of ezrin in Eca-C2 cells were significantly reduced (all P<0.05).Among the 17 detected MAPK pathway related proteins in Eca-C2 cells, 9 proteins (AKT, CREB, GSK3b, MKK6, mTOR, P38, P53, P70S6K and RSK1) were down-regulated, and the cell proliferation and migration were significantly inhibited (all P<0.05). Conclusion: ezrin enhancer knockout can significantly inhibit the cell proliferation and migration of human esophageal carcinoma Eca-109 cells.