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.

BACKGROUND:Osteonecrosis due to drugs is a serious adverse reaction occurring after the application of such drugs.Increasing evidence suggests that the gut microbiota composition is associated with osteonecrosis due to drugs.However,the causal relationship of the gut microbiota to osteonecrosis due to drugs is still unclear. OBJECTIVE:To evaluate the potential causal relationship between the gut microbiota and the risk of osteonecrosis due to drugs using the Mendelian randomization method. METHODS:A two-sample Mendelian randomization study was performed using the summary statistics of gut microbiota from the largest available genome-wide association study meta-analysis(n=13 266)conducted by the MiBioGen consortium as well as the summary statistics of osteonecrosis due to drugs obtained from the FinnGen consortium R9 release data(264 cases and 377 013 controls).Inverse variance weighted,MR-Egger,weighted median,weighted model and simple model were used to examine the causal association between gut microbiota and osteonecrosis due to drugs.Sensitivity analysis was used to test whether the results of the Mendelian randomization analysis were reliable.Reverse Mendelian randomization analysis was performed on all the bacteria as an outcome for effect analysis and sensitivity analysis. RESULTS AND CONCLUSION:Inverse variance weighted estimates suggested that Lentisphaerae(phylum),Lentisphaeria(class),Melainabacteria(class),Gastranaerophilales(order),Rhodospirillales(order),Victivallales(order)and Bifidobacterium(genus)had protective causal effects on osteonecrosis due to drugs.Methanobacteria(class),Bacillales(order),Methanobacteriaceae(family),Lachnospiraceae(family),Methanobacteriales(order),Holdemania(genus),Holdemania(UCG010 group)(genus),Odoribacter(genus)and Tyzzerella3(genus)had negative causal effects on osteonecrosis due to drugs.According to the results of reverse Mendelian randomization analysis,Clostridiaceae1(family),Peptostreptococcaceae(family),Streptococcaceae(family),Clostridiumsensustricto1(genus)and Streptococcus(genus)showed negative causal effects on osteonecrosis due to drugs.However,Eisenbergiella(genus)showed protective causal effects on osteonecrosis due to drugs.None of the bidirectional sensitivity analysis revealed heterogeneity or horizontal pleiotropy.When gut microbiota were used as exposure and osteonecrosis due to drugs as the outcome,Mendelian randomization analysis found that seven bacterial traits were positively correlated to osteonecrosis due to drugs,nine bacterial traits were negatively related to osteonecrosis due to drugs.When osteonecrosis due to drugs were used as exposure and gut microbiota as the outcome,reverse Mendelian randomization analysis found a negative correlated relationship with five bacterial traits and a positive causal relationship with one bacterial trait.By changing the diversity and composition of gut microbiota,it is expected to improve the incidence and prognosis of osteonecrosis due to drugs,providing new ideas for the study of orthopedic diseases.

The pathogenesis of aplastic anemia(AA)is complex and associated with hematopoietic stem cell defect,abnormal bone marrow microenvironment,immune dysfunction,and somatic mutation,in which the immune mechanism plays an important role.This article reviews the pathogenesis of AA from the following aspects:regulatory T cell reduction,hematopoietic stem cell reduction caused by factor-related apoptosis/factor-related apoptosis ligand signaling pathway,aberrant target gene expression induced by inflammatory factor-stimulated microRNAs,and regulatory T cell dysfunction,so as to provide ideas and methods for clinical practice.

Objective:To explore the factors influencing the supportive communication ability of medical undergraduates, and to propose strategies to improve supportive communication.Methods:By cluster sampling, we selected 388 medical undergraduates of grades 2017 and 2018 from Harbin Medical University for a questionnaire survey on supportive communication, general self-efficacy, and health education abilities. SPSS 22.0 was used for descriptive statistical analysis. AMOS 22.0 was used to construct a structural equation model to verify the relationship between the three variables. Mediating effects were also tested.Results:The students showed good supportive communication ability, with a total score of (74.28±10.84) points. The general self-efficacy score was (27.81±5.58) points, and the total score of health education ability was (25.50±4.76) points. General self-efficacy had direct positive effects on supportive communication and health education abilities ( β=0.75, 0.31, both P<0.001). Health education ability had a direct positive effect on supportive communication ability ( β=0.14, P<0.001). Health education ability played a significant mediating role in the influence of general self-efficacy on supportive communication ability (standardized mediating effect value=0.042, P<0.01), with the mediating effect accounting for 5.1%. Conclusions:The health education competency of medical undergraduates can mediate the effect of general self-efficacy on supportive communication ability. By strengthening medical humanities education to increase general self-efficacy and also emphasizing the cultivation of health education competency, the supportive communication ability of students can be improved.

【Objective】 To investigate the safety and effectiveness of suctioning flexible ureteroscopy with intelligent pressure-control at different times after drainage for patients with urogenic sepsis complicated with upper urinary tract stones. 【Methods】 Clinical data of 59 patients treated in the Department of Urology, Affiliated Hospital of Nantong University during May 2022 and May 2023 were collected.The patients were divided into early lithotripsy (≤1 week) group (n=27) and late lithotripsy (>1 week) group (n=32).Baseline data, imaging data and postoperative data of the two groups were compared. 【Results】 There were no significant differences between the two groups in the stone-free rate, total incidence of complications, incidence of high-grade complications, length of stay after lithotripsy, hospitalization costs after lithotripsy and total hospitalization costs (P>0.05). 【Conclusion】 Both early lithotripsy (<1 week) and late lithotripsy (>1 week) are safe and effective in the treatment of urogenic sepsis after drainage.

Exosomes are extracellular vesicles that are released from the cell into the extracellular microenvironment,and are a carrier of biological information transmitted over long distances,which have a dual regulatory effect on the immune system.Studies have shown that viruses can hold the endosomal-exosomal pathway hostage to spread.This review describes the role played by exosomes in viral infections.On the one hand,exosomes can transmit antiviral substances and trigger im-mune responses against viral infections,and on the other hand,exosomes can serve as potential mediators of viral transmis-sion,which have been shown to be closely related to the transmission and immune escape of a variety of viruses.Understand-ing the role of exosomes in viral infections is essential for the detection of viruses in the blood,for improving blood safety,and for the search and development of antiviral drugs.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Objective: To analyze the influencing factors of psychological flexibility for cancer-related pain patients, so as to provide insights for improving their psychological flexibility. Methods: Cancer-related pain patients hospitalized in the Oncology Department of Anhui Cancer Hospital were selected as the subjects of the survey. Demographic information and disease information were collected through questionnaires. Pain belief was assessed using the Pain Beliefs and Perceptions Inventory. Alexithymia was assessed using the Twenty-Item Toronto Alexithymia Scale-Ⅱ. Psychological flexibility was assessed using the Psychological Inflexibility in Pain Scale. The influencing factors of psychological flexibility among cancer-related pain patients was analyzed by using a multiple linear regression model. Results: A total of 202 cancer-related pain patients were surveyed, including 114 males (56.44%) and 88 females (43.56%). The mean age was (59.99±11.53) years. The primary tumor type was digestive system cancer, with 121 cases (59.90%). The average pain intensity in the past 24 hours was mainly mild, with 150 cases (74.26%). The median pain beliefs score was -0.19 (interquartile range, 0.39) points. The total score of alexithymia was (66.86±5.60) points. The total score of psychological flexibility in cancer-related pain patients was (66.35±7.23) points. Multiple linear regression analysis showed that pain belief (β'=0.321), alexithymia (β'=0.222), and average pain intensity in the past 24 hours (β'=-0.481) were influencing factors for psychological flexibility in cancer-related pain patients. Conclusion The psychological flexibility of cancer-related pain patients is related to pain beliefs, alexithymia and average pain intensity in the past 24 hours.

Objective:To evaluate the relationship between the mechanism by which aucubin improved attention deficit hyperactivity disorder (ADHD) induced by maternal exposure to S-ketamine and GABAergic neurons in the habenular nucleus of offspring mice.Methods:SPF healthy C57BL/6 wild-type pregnant mice were used in this study, and an ADHD model in offspring mice was established by intraperitoneally injecting S-ketamine in the middle and late pregnancy. Twenty-four offspring of pregnant mice exposed to S-ketamine were divided into 2 groups ( n=12 each) at 14 days after birth using a random number table method: ADHD + normal saline group (AN group) and ADHD + aucubin group (AA group). Twenty-four offspring of pregnant mice exposed to normal saline were divided into 2 groups ( n=12 each) at 14 days after birth by a random number table method: control + normal saline group (CN group) and control + aucubin group (CA group). Aucubin 40 mg/kg was intraperitoneally injected once a day for 7 consecutive days in CA group and AA group, and the equal volume of normal saline was given instead in CN group and AN group. At 14 days after birth, the 16-channel microfilament array electrode was placed in the habenular nucleus, and the ratio of excitatory neurons to inhibitory neurons in the habenular nucleus was recorded when the mice buried beads in the marble burying test. At 21 days after birth (after the end of peritoneal administration), the impulsive and stereotypical behaviors of offspring mice were evaluated by elevated zero maze and marble burying test, respectively, and then the expression of glutamate decarboxylase 2 (GAD2) in habenular nucleus was detected by the immunofluorescence method. Results:Compared with CN group, the ratio of excitatory neurons to inhibitory neurons in the habenular nucleus was significantly increased, the expression of GAD2 was down-regulated, the time spent in the open arm was prolonged, the number of entries into the open arm and the number of buried beads were increased in AN group ( P<0.05), and no statistically significant differences were found in the above indexes in CA group ( P>0.05). Compared with AN group, the ratio of excitatory neurons to inhibitory neurons in the habenular nucleus was significantly decreased, the expression of GAD2 was up-regulated, the time spent in the open arm was shortened, and the number of entries into the open arm and the number of buried beads were decreased in AA group ( P<0.05). Conclusions:The mechanism by which aucubin alleviates prenatal S-ketamine exposure-induced ADHD may be related to increasing the number of GABAergic neurons in the habenular nucleus of offspring mice.

Objective To determine the chemical constituents in BSLYT by ultra-high performance liquid chromatography-mass spectrometry(UHPLC-MS/MS),and to establish a high-performance liquid chromatographic fingerprint of the material basis of BSLYT and the content determination of its six main constituents,mononoside,loganin,oroxin A,oroxin B,baicalein and astilbin,providing a reference for the quality control.Methods The mass spectrometry data were used to establish the fingerprints.The content of the main components in the BSLYT samples was calculated by using the external method,and the discrepency between different batches of samples were analyzed by combining with chemometric methods.Results A total of 69 compounds were identified by mass spectrometry,and 13 compounds were identified after comparison with high-performance liquid chromatography(HPLC).The similarity of the baseline characterization profiles of the 15 batches of BSLYT substances was above 0.90,and a total of 27 common peaks were identified.Cluster analysis(CA)classified the substance benchmarks into 2 classes,S1,S2,S5,S8,S9,S13,and S15 were clustered into one class,and S3,S4,S6,S7,S10-S12,and S16 were clustered into one class.By combining PCA and OPLS-DA,the chemical components affecting the baseline classification of the substances were screened and attributed to wood butterfly,cornelian cherry and cocos nigra,respectively.The contents of six components were determined by MICS,which ranged from 0.31%-0.51%,0.12%-0.22%,0.09%-0.19%,0.09%-0.24%,0.07%-0.18%,and 0.08%-0.29%for mononoside,loganin,oroxin A,oroxin B,baicalein and astilbin respectively.Conclusion The fingerprint and multi-indicator content determination method established in this paper are accurate and stable,which provide a basis for the quality control of the material benchmark of Kidney and Pharynx Formula and its related preparations.