AIM: To delineate the specific mutation responsible for retinitis pigmentosa(RP)in a Yi pedigree, and to analyze the correlation of RHO gene mutation with clinical phenotype.METHODS:A comprehensive clinical evaluation was conducted on the proband diagnosed with RP and other familial members, complemented by a thorough ophthalmic examination. Peripheral blood samples were obtained from the proband and familial members, from which genomic DNA was extracte. Subsequent whole exome sequencing(WES)was employed to identify the variant genes in the proband. The identified variant gene was validated through Sanger sequencing, then an in-depth analysis of the mutation genes was carried out using genetic databases to ascertain the pathogenic mutation sites. Furthermore, an exhaustive analysis was performed to delineate the genotype and phenotype characteristics.RESULTS:The RP pedigree encompasses 5 generations with 42 members, including 19 males and 23 females. A total of 13 cases of RP were identified, consisting of 4 males and 9 females, which conforms to the autosomal dominant inheritance pattern. The clinical features of this family include an early onset age, rapid progression, and a more severe condition. The patients were found to have night blindness around 6 years old, representing the earliest reported case of night blindness in RP families. The retina was manifested by progressive osteocytoid pigmentation of the fundus, a reduced visual field, and significantly decreased or even vanished a and b amplitudes of ERG. The combined results of WES and Sanger sequencing indicated that the proband had a heterozygous missense mutation of the RHO gene c.1040C>T:p.P347L, where the 1 040 base C of cDNA was replaced by T, causing codon 347 to encode leucine instead of proline. Interestingly, this mutation has not been reported in the Chinese population.CONCLUSION:This study confirmed that the mutant gene of RP in a Yi nationality pedigree was RHO(c.1040C>T). This variant leads to the change of codon 347 from encoding proline to encoding leucine, resulting in a severe clinical phenotype among family members. This study provides a certain molecular, clinical, and genetic basis for genetic counseling and gene diagnosis of RHO.

AIM: To delineate the specific mutation responsible for retinitis pigmentosa(RP)in a Yi pedigree, and to analyze the correlation of RHO gene mutation with clinical phenotype.METHODS:A comprehensive clinical evaluation was conducted on the proband diagnosed with RP and other familial members, complemented by a thorough ophthalmic examination. Peripheral blood samples were obtained from the proband and familial members, from which genomic DNA was extracte. Subsequent whole exome sequencing(WES)was employed to identify the variant genes in the proband. The identified variant gene was validated through Sanger sequencing, then an in-depth analysis of the mutation genes was carried out using genetic databases to ascertain the pathogenic mutation sites. Furthermore, an exhaustive analysis was performed to delineate the genotype and phenotype characteristics.RESULTS:The RP pedigree encompasses 5 generations with 42 members, including 19 males and 23 females. A total of 13 cases of RP were identified, consisting of 4 males and 9 females, which conforms to the autosomal dominant inheritance pattern. The clinical features of this family include an early onset age, rapid progression, and a more severe condition. The patients were found to have night blindness around 6 years old, representing the earliest reported case of night blindness in RP families. The retina was manifested by progressive osteocytoid pigmentation of the fundus, a reduced visual field, and significantly decreased or even vanished a and b amplitudes of ERG. The combined results of WES and Sanger sequencing indicated that the proband had a heterozygous missense mutation of the RHO gene c.1040C>T:p.P347L, where the 1 040 base C of cDNA was replaced by T, causing codon 347 to encode leucine instead of proline. Interestingly, this mutation has not been reported in the Chinese population.CONCLUSION:This study confirmed that the mutant gene of RP in a Yi nationality pedigree was RHO(c.1040C>T). This variant leads to the change of codon 347 from encoding proline to encoding leucine, resulting in a severe clinical phenotype among family members. This study provides a certain molecular, clinical, and genetic basis for genetic counseling and gene diagnosis of RHO.

Objective To systematically evaluate the efficacy and safety of proximal gastrectomy (PG) versus total gastrectomy (TG) for the treatment of Siewert type Ⅱ/Ⅲ adenocarcinoma of the esophagogastric junction (AEG). Methods PubMed, The Cochrane Library, Web of Science, EMbase, CNKI, Wanfang, and VIP databases were searched for literature comparing the efficacy and safety of PG and TG for the treatment of Siewert type Ⅱ/Ⅲ AEG. The search period was from database inception to March 2023. Meta-analysis was performed using Review Manager 5.4 software. Results A total of 23 articles were included, including 16 retrospective cohort studies, 5 prospective cohort studies, and 2 randomized controlled trials. The total sample size was 2 826 patients, with 1 389 patients undergoing PG and 1 437 patients undergoing TG. Meta-analysis results showed that compared with TG, PG had less intraoperative blood loss [MD=−19.85, 95%CI (−37.20, −2.51), P=0.02] and shorter postoperative hospital stay [MD=−1.23, 95%CI (−2.38, −0.08), P=0.04]. TG had a greater number of lymph nodes dissected [MD=−6.20, 95%CI (−7.68, −4.71), P<0.001] and a lower incidence of reflux esophagitis [MD=3.02, 95%CI (1.24, 7.34), P=0.01]. There were no statistically significant differences between the two surgical approaches in terms of operative time, postoperative survival rate (1-year, 3-year, 5-year), and postoperative overall complications (P>0.05). Conclusion PG has advantages in terms of intraoperative blood loss and postoperative hospital stay, while TG has advantages in terms of the number of lymph nodes dissected and the incidence of reflux esophagitis. There is no significant difference in long-term survival between the two surgical approaches.

Objective : To analyze the correlation between different laboratory biomarkers and disease activity in ankylosing spondylitis and to compare their specificity and sensitivity in assessing disease activity. Methods : Spearman correlation or Pearson correlation was used to analyze the correlation between disease activity and laboratory biomarkers. Receiver operating characteristic(ROC) was used to compare the sensitivity and specificity of each laboratory biomarker in evaluating disease activity. Results : Hypersensitive C-reactive protein, fibrinogen, D-dimer, erythrocyte sediment rate, C-reactive protein, immuno-inflammatory index(platelet count×neutrophil count/lymphocyte count), fibrinogen/albumin ratio, albumin and pro-albumin were correlated with disease activity. The ratio of fibrinogen to albumin, fibrinogen, erythrocyte sedimentation rate, immuno-inflammatory index, C-reactive protein and hypersensitive C-reactive protein had good values in determining the disease activity. Conclusion Different laboratory biomarkers are correlated with the disease activity of ankylosing spondylitis, and some of them have better discriminating values for the disease activity.

Objective:To investigate the clinical characteristics and the efficacy of thrombus aspiration in patients with early intrastent thrombosis (EST) following carotid artery stenting (CAS).Methods:This study is a retrospective case series, collecting clinical data of five patients who developed EST after CAS in the Department of Neurosurgery, Beijing Chaoyang Hospital, Capital Medical University from January 2021 to September 2023.All patients were male, with an age of (64.0±11.9) years (range:48 to 77 years), accounting for 2.0% (5/244) of CAS procedures during the same period.Among them, three patients did not receive standard dual antiplatelet therapy before the procedure, and one had an inadequate ADP inhibition rate (45.6%).Four patients received XACT carotid stents, while one received a Wallstent carotid stent.All five patients showed significant residual stenosis ranging from 43% to 55% after CAS.Emergency thrombus aspiration was performed in all cases, and data regarding perioperative conditions, vascular patency, and clinical outcomes were collected.Results:The interval between CAS and the occurrence of EST ranged from 3 hours to 14 days.The main clinical symptoms included sudden onset of consciousness disorders and contralateral limb weakness.None of the patients received preoperative intravenous thrombolysis, and thrombus aspiration was performed during the procedure to restore vascular patency.Four cases underwent balloon angioplasty during the procedure, and two cases utilized overlapping stents.Two patients experienced intraoperative embolization of thrombus to the C 2 segment.In one case, the embolized thrombus was retrieved using an intracranial thrombectomy stent, while in another case, it was aspirated using a guiding catheter.Postoperatively, all patients had a thrombolysis in cerebral infarction grade of 3, and symptoms improved in four cases.One patient showed no improvement in symptoms, and MRI revealed extensive new infarction in the right frontal and insular regions, adjacent to the right lateral ventricle.Regular follow-up examinations after discharge did not reveal restenosis or embolism within the stent.The follow-up period ranged from 7.6 to 21.2 months, with modified Rankin scale scores of 0 to 1 point in four cases and 2 points in one case, indicating good recovery in all patients. Conclusions:Acute intrastent thrombosis is a rare complication after carotid artery stenting.The combined use of percutaneous thrombus aspiration and endovascular techniques, such as balloon angioplasty and stent overlapping, can rapidly restore vessel patency with favorable outcomes.However, further large-scale clinical studies are needed to confirm the effectiveness of these treatments for acute intrastent thrombosis.

Allergic diseases are immune disorders caused by allergens, leading to inflammation or organ dysfunction. In the past decade, the prevalence of allergic diseases in China has increased dramatically, imposing a heavy economic burden on the health care system and society. In vitro diagnosis of allergic diseases plays a crucial role in the diagnosis, treatment, and prevention of such diseases. This article enumerates the in vitro tests and diagnostic techniques of allergic diseases, gives an advocacy for quality management of IgE-related tests, summarizes the clinical interpretation and relevant research progress, aiming to provide a reference for improving laboratory diagnosis of allergic diseases.

Objective:To investigate the value of implantable cardiac monitor (ICM) in the diagnosis and treatment of patients over 60 years old with unexplained syncope.Methods:This was a multi-center, prospective cohort study. Between June 2018 and April 2021, patients over the age of 60 with unexplained syncope at Beijing Hospital, Fuwai Hospital, Beijing Anzhen Hospital and Puren Hospital were enrolled. Patients were divided into 2 groups based on their decision to receive ICM implantation (implantation group and conventional follow-up group). The endpoint was the recurrence of syncope and cardiogenic syncope as determined by positive cardiac arrhythmia events recorded at the ICM or diagnosed during routine follow-up. Kaplan‐Meier survival analysis was used to compare the differences of cumulative diagnostic rate between the 2 groups. A multivariate Cox regression analysis was performed to determine independent predictors of diagnosis of cardiogenic syncope in patients with unexplained syncope.Results:A total of 198 patients with unexplained syncope, aged (72.9±8.25) years, were followed for 558.0 (296.0,877.0) d, including 98 males (49.5%). There were 100 (50.5%) patients in the implantation group and 98 (49.5%) in the conventional follow-up group. Compared with conventional follow-up group, patients in the implantation group were older, more likely to have comorbidities, had a higher proportion of first degree atrioventricular block indicated by baseline electrocardiogram, and had a lower body mass index (all P<0.05). During the follow-up period, positive cardiac arrhythmia events were recorded in 58 (58.0%) patients in the ICM group. The diagnosis rate (42.0% (42/100) vs. 4.1% (4/98), P<0.001) and the intervention rate (37.0% (37/100) vs. 2.0% (2/98), P<0.001) of cardiogenic syncope in the implantation group were higher than those in the conventional follow-up group (all P<0.001). Kaplan-Meier survival analysis showed that the cumulative diagnostic rate of cardiogenic syncope was significantly higher in the implantation group than in the traditional follow-up group ( HR=11.66, 95% CI 6.49-20.98, log-rank P<0.001). Multivariate analysis indicated that ICM implantation, previous atrial fibrillation, diabetes mellitus or first degree atrioventricular block in baseline electrocardiogram were independent predictors for cardiogenic syncope (all P<0.05). Conclusions:ICM implantation improves the diagnosis and intervention rates in patients with unexplained syncope, and increases diagnostic efficiency in patients with unexplained syncope.

Objective·To investigate the pathological and physiological changes underlying noise-induced cochlear nucleus damage and the regulating function of astrocytes on the damage,using a combination of morphological analysis,and molecular biology techniques.Methods·Forty-eight male C57BL/6J mice were randomly divided into two groups and exposed to 110 dB SPL(sound pressure level)broadband noise for 2 hours.Auditory brainstem response(ABR)tests were performed on the mice on days 1,7,14,30,and 90 after the noise exposure.Immunofluorescence staining of cochlear nuclear tissue was conducted to observe cochlear nuclear neurons and auditory synapses,as well as astrocyte activation levels.In addition,the damage to the cochlear nuclear neurons and synapses caused by noise was verified through Western blotting.Results·A significant decrease in cochlear nuclear Bushy cells after noise exposure was observed.The Western blotting results showed that there was severe loss of nerve fibers in cochlear nuclear neurons,indicating that noise caused significant damage to cochlear nucleus neurons.Moreover,a significant loss of auditory synapses labeled with vesicular glutamate transporter 1(Vglutl)was observed,which was the severest on day 14 after noise exposure and slowly recovered on day 90.Interestingly,astrocytes in the cochlear nucleus displayed obvious clustering and activation after noise exposure.By staining with glial fibrillary acidic protein(GFAP),most astrocytes were distributed around the cochlear nucleus,granule cell area,and auditory nerve root before noise exposure,and they had a small size.However,on day 14 after noise exposure,a large number of activated astrocytes aggregated in the ventral cochlear nucleus,and they all showed a pattern of growth around the synapses.Conclusion·Noise exposure leads to significant damage in the cochlear nucleus,and it is possible that astrocytes are involved in its damage and repair processes.These findings will provide a crucial foundation for further understanding the mechanisms of sound signal analysis,integration,and neural plasticity in the cochlear nucleus.

Objective To explore the gene expression profile in paraspinal muscle degeneration(PMD)and identify key ferroptosis genes.Methods RNA sequencing was performed on paraspinal muscle tissue of 3 normal and 3 PMD patients respectively to obtain differentially expressed genes.Through protein-protein interaction(PPI)and gene functional enrichment analysis,the intersection of ferroptosis genes was identified to identify key hub genes associated with ferroptosis.The diagnostic value for PMD disease was analyzed by receiver operating characteristic(ROC)curves.Results A total of 292 differentially expressed genes were identified in PMD.Among them,125 genes were significantly downregulated and 167 genes were significantly upregulated.Bioinformatics analysis revealed that 14 differentially expressed genes were associated with ferroptosis.Among them,ferroptosis genes MUC1,ATF3 and CDKN1A were key hub genes with good specificity and sensitivity for diagnosing PMD.Functional enrichment analysis revealed that they may mediate the occurrence and progression of PMD by regulating cell apoptosis,ferroptosis and skeletal muscle tissue development and differentiation.Conclusion Ferroptosis genes MUC1,ATF3 and CDKN1A can serve as biomarkers for diagnosing PMD,providing theoretical basis for decoding the pathological mechanism of PMD and developing new drugs.

Objective To investigate the related factor underlying the differential vulnerability of inner hair cell(IHC)ribbon synapses to noise exposure.Methods Twenty-eight C57BL/6J mice were randomly divided into the noise exposure group(NED1)and the control group(CTR)with 14 mice in each group.The noise exposure group was exposed to bandpass noise of 2～20 kHz at 103 dB SPL for two hours while the control group was bred in a quiet environment.Before and after noise exposure,auditory brainstem response was conducted to detect the audi-tory function,whole-mount immunofluorescence staining was used to observe the number of inner hair cell ribbon synapses in different turns.The calcium influx of inner hair cells in the apical and middle turn using whole-cell patch clamp recording was analyzed.Furthermore,the immunofluorescence intensity of calpain in inner hair cells from dif-ferent mouse cochlear turns using whole-mount immunofluorescence staining was compared.Western blotting was used to verify that CtBP2 was degraded by calpain.Results After noise exposure,the ABR threshold of 11.3,16.0,22.6,32.0 kHz increased significantly and the number of ribbon synapses of inner hair cells at the middle turn and basal turn of the cochlea decreased significantly.However,whole-cell patch clamp recordings showed that calcium ion channels were fewer but single-channel current was higher at the apical turn of the cochlea.The open probability of calcium ion channels in IHCs showed no significant difference between the apical turn and the middle turn of the cochlea.But the expression level of calpain of the inner hair cells at the middle and basal turn of the basi-lar membrane was significantly higher than that at the apical turn after noise exposure.The western blotting results also showed that CtBP2 was cleaved in a Ca2+-dependent manner by calpain.Conclusion Calpain may be the main related factor that accounts for the vulnerability of ribbon synapses in inner hair cells in the high frequency region of basal membrane.