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 compare the characteristics of background mucosa, lesion features, and the efficiency of endoscopic submucosal dissection(ESD)between elderly and non-elderly patients with early gastric cancer(EGC).Methods:This study retrospectively collected data on patients with EGC who underwent ESD treatment at Beijing Hospital from April 2020 to December 2022.The clinical characteristics, background mucosa, lesion features, ESD outcomes, and pathological results of the patients were analyzed to compare the differences between elderly and non-elderly patients.Results:A total of 100 patients with EGC were selected, comprising 57 patients in the elderly group and 43 patients in the non-elderly group, with a total of 111 lesions identified(64 lesions in the elderly group and 47 lesions in the non-elderly group).The proportion of patients with a history of chronic atrophic gastritis was significantly higher in the elderly group(89.5%、51/57)compared to the non-elderly group(74.4%、32/43), with a statistically significant difference( P=0.047).Additionally, the difference in the extent of atrophy between elderly patients with EGC and their non-elderly counterparts was statistically significant( P=0.022).Among these patients, the proportion of those classified as Kimura-Takemoto C0 to C1 in the elderly group(15.6%、10/64)was lower than that in the non-elderly group(40.4%、19/47).In contrast, the proportion of patients classified as C2 to C3 in the elderly group(65.6%、42/64)was higher than that in the non-elderly group(51.1%、24/47), and the proportion of those classified as O1 to O3 in elderly patients(12.5%、8/64)was also higher than in the non-elderly group(4.3%、2/47).Furthermore, the difference in the extent of intestinal metaplasia between elderly and non-elderly patients with early gastric cancer was statistically significant( P=0.007).The overall proportion of total intestinal metaplasia in elderly patients(85.9%、55/64)was significantly higher than that in non-elderly patients(61.7%、29/47).Notably, the proportion of patients exhibiting extensive intestinal metaplasia(intestinal metaplasia present in both the gastric antrum and gastric body)was greater in the elderly group(43.8%、28/64)compared to the non-elderly group(23.4%、11/47).The Kyoto gastric cancer risk endoscopic score for elderly patients with EGC was(2.43±1.28)points, significantly higher than that of the non-elderly group(1.72±1.41)points, with a statistically significant difference observed( t=2.778, P=0.006).No statistically significant differences were observed in the proportions of total resection rates, R0 resections, curative resections, or postoperative complications following ESD when comparing elderly patients with EGC to their non-elderly counterparts. Conclusions:The proportion of extensive atrophy and intestinal metaplasia was higher in the background mucosa of elderly patients with EGC, and correspondingly, the Kyoto endoscopic gastric cancer risk score was elevated.Therefore, endoscopic examinations for elderly patients with chronic atrophic gastritis should be conducted with greater care and comprehensiveness.

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.

Background: The risk factors affecting the non ⁃ curative resection of endoscopic submucosal dissection (ESD) for early colorectal cancer and precancerous lesions were still lacking large scale studies in China. Aims: To analyze the efficacy of ESD for patients with early colorectal cancer and precancerous lesions, and explore the risk factors affecting the non⁃curative resection. Methods: A total of 229 patients with early colorectal cancer and precancerous lesions underwent ESD from September 2016 to September 2021 at Beijing Hospital were collected. The clinicopathological characteristics, efficacy of ESD were analyzed. Risk factors affecting the non ⁃ curative resection of ESD were analyzed by univariate analysis and Logistic multivariate regression analysis. Results: A total of 255 lesions were found. The en bloc resection rate was 90.2%, R0 resection rate was 87.8%, and curative resection rate was 83.5%. The total incidence of complications was 2.7%. Univariate analysis showed that detection rate of intraluminal protruding tumor (61.0% vs. 24.4%, P<0.05), rate of severe submucosal fibrosis (24.4% vs. 2.4%, P<0.05) were significantly increased in the non⁃curative resection group than in the curative resection group, and positive rate of lifting sign was significantly decreased (80.5% vs. 95.1%, P<0.05). Logistic multivariate regression analysis showed that intraluminal protruding tumor (OR=4.087, 95% CI: 1.523⁃10.968, P= 0.005) and severe submucosal fibrosis (OR=9.609, 95% CI: 1.107⁃83.439, P=0.04) were risk factors for ESD non⁃curative resection of early colorectal cancer and precancerous lesions. Conclusions: R0 resection rate and curative resection rate of ESD for early colorectal cancer and precancerous lesions are high, the incidence of surgical complications is low. Intraluminal protruding tumor, severe submucosal fibrosis are the independent risk factors of non⁃curative resection. Strict evaluation should be carried out before operation and reasonable treatment strategies should be formulated accordingly.

Objective:To summarize our experience in diagnosis and treatment of Budd-Chiari syndrome(BCS) accompanied with hepatic nodules.Methods:The clinical data of 33 patients with BCS accompanied with hepatic nodules who were treated at Henan Provincial People's Hospital from January 2012 to December 2018 were retrospectively analysed. A total of 33 patients were enrolled, including 17 males and 16 females, with an average age of 51 years. Analyze the treatment and prognosis of different types of nodules.Results:Of 33 patients, 27 were diagnosed to have hepatocellular carcinoma and 6 benign proliferative nodules. Treatment of patients with hepatocellular carcinoma included, transcatheter arterial chemoembolization ( n=1) and hepatectomy ( n=26). The survival time of these patients with hepatocellular carcinoma ranged from 10.0 to 78.0 months (mean 37.8 months). For the remaining 6 patients with benign nodules, the nodules were multiple and no malignant changes were observed on follow-up. Conclusion:For patients with BCS associated with benign nodules, no specific treatment was required. Hepatocellular carcinoma assocated with BCS had good prognosis. An aggressive surgical resectional approach is recommended to treat and to relieve the hepatic outflow obstruction.

Objective:To study the safety and efficacy of using entrapped duct-to-mucosa pancreaticojejunostomy for patients with small pancreatic ducts of less than 3 mm in diameter.Methods:The clinical data of patients who underwent entrapped duct-to-mucosa pancreaticojejunostomy at Henan Province People's Hospital from January 2017 to December 2019 were retrospectively analyzed. The incidences of complication including pancreatic fistula and abdominal hemorrhage were studied. The duration to carry out the pancreaticojejunostomy and postoperative hospital study were also analyzed.Results:Of 98 patients included in this study, there were 58 males and 40 females, with an average age of 62.3 (aged 24 to 73) years. The average time of completing the pancreaticoenterostomy was (10.2±3.1) min. There were 10 patients (10.2%) who developed grade A pancreatic fistulae. There were no grade B or C pancreatic fistulae, no portoperative bleeding and no perioperative deaths. The postoperative hospital stay was (13.4±4.6) days.Conclusion:Entrapped duct-to-mucosa pancreaticojejunostomy was simple, quick, safe and effective in patients with small pancreatic ducts.

Objective:Based on the current medical environment, to learn about cognition status of doctor-patient relationship among medical students and analyze causes of the tension between doctors and patients.Methods:Using the self-designed questionnaire "Clinical Medical Students' Cognition Survey on Occupational Status and Doctor-Patient Relationship", a cross-sectional survey was conducted on 527 medical students from 5-year and 7-year clinical program in Batch 2014 in a medical university in Heilongjiang Province. The survey mainly analyzed the causes of the tension between doctors and patients from the level of medical staff, patients and their families, hospitals and society. SPSS 22.0 was used for descriptive statistics and chi-square test.Results:The results showed that 93.7% of the medical students believed that the current doctor-patient relationship was not harmonious. There were cognitive differences among medical students in different gender ( P=0.029), first contact clinical grade ( P=0.003) and professional identity ( P<0.001). Conclusion:Medical students have a poor evaluation towards the current doctor-patient relationship. In order to construct harmonious doctor-patient relationship in the future, we can try to take measures such as carrying out relevant courses of doctor-patient communication, improving the medical students' communication skills and enhancing their professional identity.

Objective:To analyze the surgical method and clinical effect of modified anterolateral approach in the treatment of posterolateral tibial plateau fractures.Methods:From January 2014 to December 2017, 21 patients with posterolateral tibial plateau fractures were treated by the modified anterolateral approach in the second people's Hospital of Tangshan, Hebei Province were retrospectively analyzed.The outpatient department conducted regular reexaminations 1, 3, 6 and 12 months after the operation.Rasmussen radiology score, hospital for special surgery (HSS) score of knee function and Lysholm score were used to evaluate the postoperative knee function, and the score results were statistically analyzed.Results:The Rasmussen radiological score of 21 patients immediately after surgerywas (16.96±1.67), ranging from 15.00 to 18.00, with excellent in 15 cases, good in 6 cases, and the excellent and good rate was 100%.Rasmussen radiology score (16.57±1.51) in the last follow-up, ranging from 15.00 to 18.00, showed no significant difference between the last follow-up and the immediate postoperative ( t=0.935, P>0.05). At the last follow-up, the HSS score of knee joint function was (88.55±7.25), ranging from 80.00 to 9.00.At the last follow-up, Lysholm score (86.64±4.34), ranging from 82.00 to 90.00, was excellent in 15 cases, good in 6 cases, and excellent in 100%. Conclusion:The modified anterolateral approach for the treatment of posterolateral tibial plateau fractures is effective and simple, and can achieve good clinical results.