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.

Background The impact of atmospheric fine particulate matter (PM_2.5) and ozone (O₃) on the mortality of circulatory system diseases cannot be ignored. However, whether the interaction between PM_2.5 and O₃ can affect population health is rarely reported and requires study. Objective To investigate the individual and interactive impacts of atmospheric PM_2.5 and O₃ on the mortality of circulatory system diseases in the population of Ningxia region. Methods The data of 119647 deaths due to circulatory system diseases, daily average concentrations of atmospheric pollutants, and meteorological data in Ningxia from 2013 to 2020 were retrieved. PM_2.5 was divided into low, medium, and high concentrations according to the primary and secondary national limits (35 and 75 μg·m⁻³) of the Ambient air quality standards. Similarly, O₃ was divided into low, medium, and high concentrations according to the national limits (100 and 160 μg·m⁻³). Using a generalized additive mixed model based on quasi Poisson distribution, the impacts of atmospheric PM_2.5 and O₃ as well as their interaction on the mortality of circulatory system diseases were analyzed using the population data of Ningxia region. Results During the target period, males and the ≥ 65 year group accounted for larger proportions of deaths due to circulatory system diseases (55.47% and 79.87% respectively). The daily average concentration of PM_2.5 (40.25 μg·m⁻³) exceeded the national primary limit. In the single pollution model, the highest cumulative lag effects for mortality from circulatory system diseases were PM_2.5 exposure over previous 1 d (lag01) and O₃ exposure for previous 2 d (lag02), and their excess risk (ER) values were 1.03% (95%CI: 0.67%, 1.40%) and 1.02% (95%CI: 0.57%, 1.50%), respectively. The results of concentration stratification analysis showed that the most significant risks of death from circulatory system diseases [ER (95%CI): 1.12% (0.32%, 1.92%) and 0.95% (0.13%, 1.79%) respectively] were found at medium PM_2.5 and O₃ concentrations. The interaction analysis revealed that under, a synergistic effect on the risk of death from circulatory system diseases was identified (relative excess risk due to interaction=3.08%, attributable proportion of interaction=2.90%, synergy index=1.89) when considering the coexistence of PM_2.5 and O₃ above the primary limit. As the concentrations of PM_2.5 and O₃ increased, the synergistic effect increased the risk of death from circulatory system diseases in the general population, men, women, and the ≥ 65 years group. Conclusion Both atmospheric PM_2.5 and O₃ can increase the risk of death from circulatory system diseases, and the two pollutants have a synergistic effect on the risk of death from circulatory system diseases.

Background Long-term exposure to ambient fine particulate matter (PM_2.5) may increase the risk of diabetes, and a healthy diet can effectively control fasting blood glucose levels. However, it is unclear whether dietary factors have a moderating effect on the risk of diabetes associated with atmospheric PM_2.5 exposure. Objective To investigate the association between long-term exposure to PM_2.5 and diabetes in rural areas of Ningxia, and potential interaction of long-term exposure to atmospheric PM_2.5 and diet on diabetes. Methods The study subjects were selected from the baseline survey data of the China Northwest Cohort-Ningxia (CNC-NX) , a natural population cohort. A total of 13917 subjects were included, excluding participants with missing covariate information. We utilized the annual average ambient PM_2.5 concentration from 2014 to 2018 as the long-term exposure level. Logistic regression and multiple linear regression were employed to analyze the associations of long-term atmospheric PM_2.5 exposure with diabetes and fasting blood glucose levels. Stratification by frequency of vegetable consumption, frequency of fruit consumption, and salty taste was used to examine moderating effects on the diabetes risk associated with atmospheric PM_2.5 exposure. Results The mean age of the 13917 subjects was (56.8±10.0) years, and the prevalence of diabetes was 9.8%. Between 2014 and 2018, the average annual concentration of PM_2.5 was (38.10±4.67) μg·m⁻³. The risk (OR) of diabetes was 1.018 (95%CI: 1.005, 1.032) and the fasting blood glucose was increased by 0.011 (95%CI: 0.004, 0.017) mmol·L⁻¹ for each 1 μg·m⁻³ increase in PM_2.5 concentration. Compared to those who consumed vegetables < 1 time per week, individuals who consume vegetables 1-3 times per week and ≥4 times per week had a reduced risk of developing diabetes by 27.1% (OR=0.729, 95%CI: 0.594, 0.893) and 16.8% (OR=0.832, 95%CI: 0.715, 0.971) respectively. Similarly, when compared to those who consumed fruits <1 time per week, individuals who consumed fruits 1-3 times per week and ≥4 times per week exhibited a reduced risk of diabetes by 16.4% (OR=0.836, 95%CI: 0.702, 0.998) and 18.2% (OR=0.818, 95%CI: 0.700, 0.959) respectively. Fasting blood glucose decreased by 0.202 (95%CI: -0.304, -0.101) mmol·L⁻¹ in participants who ate vegetables 1-3 times per week. The effect of salty taste on diabetes and fasting blood glucose was not significant. The results of stratified analysis by dietary factors and PM_2.5 concentration showed that the risks of diabetes were increased in the low PM_2.5 pollution-low vegetable intake frequency group and the high PM_2.5 pollution-low vegetable intake frequency group compared with the low PM_2.5 pollution-high vegetable intake frequency group, with OR values of 3.987 (95%CI: 2.943, 5.371) and 1.433 (95%CI: 1.143, 1.796) respectively. The risk of diabetes was 50.1% higher in participants with high PM_2.5 pollution and low fruit intake frequency than in participants with low PM_2.5 pollution and high fruit intake frequency (OR=1.501, 95%CI: 1.171, 1.926). No interaction was found between salty taste and PM_2.5 on diabetes. Conclusion Long-term exposure to ambient PM_2.5 is associated with an increased fasting blood glucose and an elevated risk of diabetes in rural Ningxia population. Increasing the frequency of weekly consumption of vegetables or fruits may have a certain protective effect against diabetes occurrence, as well as a moderating effect on diabetes and fasting blood glucose levels associated with long-term exposure to atmospheric PM_2.5.

Objective:To determine the erythromycin resistance of Bordetella pertussis isolates and their ptxP1 and ptxP3 phenotypic composition and compare clinical manifestations of children with pertussis caused by the two types of strains. Methods:This was a cross-sectional study, the pertussis cases diagnosed using bacterial culture from January 2019 to December 2022 in Beijing Children′s Hospital and the First People′s Hospital of Wuhu were collected.Any suspected Bordetella pertussis colonies were identified by the slide agglutination test.The susceptibility of isolates to erythromycin was detected by the E-test and K-B test.The ptxP gene was amplified by polymerase chain reaction and sequenced to determine its genotype. t-test, Mann-Whitney U-test, Chi-square test and Fisher′s exact test were use to statistical analysis. Results:A total of 192 strains of Bordetella pertussis were identified, including 188 (97.9%) erythromycin-resistant strains.Among the 188 strains, 30.3%(57/188) belonged to the ptxP1 genotype and 69.7%(131/188) belonged to the ptxP3 genotype.In children aged below 1 year old, the incidence of paroxysmal cough caused by infection with the ptxP3 strain was higher than that with the ptxP1 strain (57.1% vs.29.4%, P<0.05), and children infected with the ptxP3 strain were more likely to develop apnea or asphyxia (23.8% vs.17.6%), post-tussive vomiting (44.4% vs.32.4%), whooping cough (72.0% vs.50.0%) and pneumonia or bronchitis (85.7% vs.73.5%) compared to those infected with the ptxP1 strain, but the differences were not statistically significant(all P>0.05). In children aged 1 year old and above, the white blood cell count of children infected with the ptxP1 strain was higher than that of infections with the ptxP3 strain [13.5(9.9, 24.5)×10 9/L, 10.3 (7.0, 16.4)×10 9/L, P<0.05], and children infected with the ptxP1 strain were more likely to contract other pathogen infections than those infected with the ptxP3 strain (17.4% vs.4.4%, P>0.05). Conclusions:ptxP3 erythromycin-resistant Bordetella pertussis has become the main pathogen of pertussis.Infants with pertussis caused by the ptxP3 erythromycin-resistant strain show more significant manifestations and a higher possibility of severe symptoms than those infected with the ptxP1 erythromycin-resistant strain.

Objective:To develop and evaluate the efficacy and safety of a three-dimensional (3D) digestive endoscope for gastric endoscopic submucosal dissection (ESD) through animal experiments.Methods:Two Dutch pigs were utilized from the Zhengzhou University Animal Experiment Center for the study. ESD procedures were performed by two senior endoscopists, one using 3D glasses and the other utilizing a 3D high-definition head display. The success of ESD was assessed based on predefined criteria, including completion of surgical steps, complete detachment of the presumptive lesion, and effective bleeding control during and after the surgery. The number of successful procedures and incidences of perforation were recorded. The stereoscopic experience of the endoscopists, including both the primary endoscopist and the assistant, was also evaluated. Furthermore, the assessment encompassed any reported symptoms of eye discomfort, such as eye fatigue, ocular pain, and blurred vision. Additionally, the confidence level of the endoscopists in the mechanical aspects of the operation, as well as encountered issues during the endoscopic procedures, were documented.Results:Two ESD were successful and no perforation occurred. Feedback from endoscopists suggested that 3D digestive endoscopy offered clear images with enhanced three-dimensionality during surgery, clear sense of distance and layering, allowing for a precise judgment of bleeding points, which surpassed 2D capabilities. No eye discomfort was experienced by endoscopists or assistants during or after the procedures. While endoscopists exhibited high confidence in 3D digestive endoscopy, they noted issues with image blurring when the camera was positioned less than 10 mm from the gastrointestinal tract wall.Conclusion:Preliminary results show that 3D digestive endoscopes can provide excellent stereo imaging, improved positioning accuracy, and safety during live animal stomach ESD procedures, without significantly increasing endoscopists' eye discomfort. Nevertheless, efforts are needed to address image blurring concerns when the camera is close to the gastrointestinal tract wall.

Objective:To compare the influence of dronedarone and amiodarone on the bleeding risk of patients with atrial fibrillation treated with rivaroxaban anticoagulation.Methods:Clinical data of 81 patients with atrial fibrillation treated with rivaroxaban anticoagulation at Xi'an International Medical Center Hospital from January 2020 to July 2023, including 36 patients treated with dronedarone and 45 patients treated with amiodarone, were retrospectively analyzed. The effects of dronedarone and amiodarone on the anticoagulation of rivaroxaban were compared using the incidence of bleeding events, thrombosis events, and adverse reactions as outcome measures.Results:The total bleeding in the dronedarone group [22.22% (8/36)] was significantly higher than that in the amiodarone group [6.67% (3/45)] ( χ2 = 4.12, P < 0.05). The total bleeding of conventional-dose rivaroxaban in the dronedarone group was 30.00% (6/20), while the total bleeding of low-dose rivaroxaban was 12.50% (2/16), with no statistical significance ( χ2 = 1.58, P > 0.05). No thrombotic events or adverse reactions to dronedarone or amiodarone were observed in all patients. Conclusion:Compared with amiodarone, dronedarone significantly increases the bleeding risk of rivaroxaban anticoagulation in patients with non-valvular atrial fibrillation, and reducing the dose of rivaroxaban in patients using dronedarone does not reduce the bleeding risk.

Objective To establish a rapid and sensitive liquid chromatography-tandem mass spectrometry(LC-MS/MS)analysis method for determination of unsymmetrical dimethylhydrazine(UDMH)contents in rat plasma and investigate the toxicokinetic characteristics of UDMH in rats.Methods Twenty-two SD rats were divided into the intravenous injection of 10 mg/kg dose group(4 females)and intragastric administration groups(low,medium and high dose,with 6 rats in each group,half males and half females).The rats were given 10mg/kg by intravenous administration and 10 mg/kg,30 mg/kg,and 90 mg/kg single dose of UDMH by gavage.Blood samples were collected from the orbital venous plexus at 0 hour before administration and at different time points after administration.The plasma samples were extracted with protein precipitation and derivatization before being analyzed using the LC-MS/MS method.Separation was carried out on a ZORBAX column(4.6mm×75mm,3.5 μm),with a mobile phase composed of 0.3％acetonitrile/formic acid at a flow rate of 1 mL/min.Propranolol was used as the internal standard.An electrospray ionization(Turbo Ionspray)source was applied and the mass spectrometer was operated in a positive MRM mode.Quantitative analysis showed that the ionization source unsymmetrical dimethylhydrazine and propranolol was at m/z:192.0→148.1,m/z:260.2→116.1,respectively.The toxicokinetic parameters were analyzed with the DAS 2.1 software.Results Quantification of UDMH exhibited a good linearity within the concentration range of 50-50000 ng/mL,with a linear correlation coefficient greater than 0.9900 and a lower limit of quantification of 50 ng/mL.The average recovery rate of UDMH was 98.1％,compared with 100.5％for the internal standard propranolol hydrochloride.The inter batch precision of standard curve samples ranged from 0.7％to 6.3％,and the relative error was between-7.1％and 6.2％.The inter batch and intra batch precision of quality control samples ranged from1.8％to 19.8％,and the relative error from-9.8％to 0.2％.The main pharmacokinetic parameters of UDMH in rats exposed to 10 mg/kg,30 mg/kg,and 90 mg/kg gavage were UC(0-t):(7624.99±2569.31),(34284.04±6657.15),(84720.88±22354.80)μg/L·h,t1/2:(0.07±0.15),(2.24±1.45),(3.04±0.90)h,Tmax:(0.75±0.27),(0.51±0.29),(0.29±0.10)h,Cmax:(4454.14±1329.45),(19442.45±9121.07),(32334.35±9882.41)μg/L,F:(77.34±26.06)％,(115.92±22.51)％,(95.48±25.19)％.Conclusion The LC-MS/MS method is highly accurate and specific,and is suitable for the toxicokinetic study of UDMH in rats.Single gavage administration of UDMH results in absorption and elimination saturation at a high dose.This study provides data for toxicological studies related to UDMH.

Objective:To study the application effect of the Benner's theory stratified training based on the "Protect the World" platform for nurses specialized in neurological rehabilitation.Methods:A total of 70 nurses who underwent on-the-job training for neurorehabilitation nursing specialists in 2023 were divided into control group ( n=35) and observation group ( n=35) based on random odd and even numbers to receive different training methods. The control group received routine nursing training, while the observation group received Benner's theory stratified training based on the "Protect the World" platform. The theoretical and skill assessment scores, job competency, and satisfaction scores of two groups of nurses were compared before and after training. SPSS 25.0 was used for t-test and chi-square test. Results:Before training, there were no significant differences between the two groups of nurses in terms of theory scores [(88.35±4.41) vs. (89.43±4.07)] and skill assessment scores [(89.22±3.27) vs. (88.43±3.16)]. After training, the theoretical and skill assessment scores were significantly higher in the observation group as compared with the control group [(95.51±5.01) vs. (90.24±4.99) and (95.15±4.24) vs. (91.13±4.33), both P<0.05]. After training, the competency scores and total scores of education guidance, management function, diagnostic function, assistance role, and intervention treatment were significantly higher in the observation group than in the control group ( P<0.05). The satisfaction survey scores were significantly higher in the observation group than in the control group ( P<0.05). Conclusions:The Benner's theory stratified training based on the "Protect the World" platform can improve the theoretical and skill assessment scores of nurses specialized in neurological rehabilitation. This approach significantly boosts their overall professional competence and holds considerable potential for broader adoption.

BACKGROUND: Cutaneous wound healing represents a common fundamental phenomenon requiring the participation of cells of distinct types and a major concern for the public. Evidence has confirmed that photobiomodulation (PBM) using near-infrared (NIR) can promote wound healing, but the cells involved and the precise molecular mechanisms remain elusive. METHODS: Full-thickness skin defects with a diameter of 1.0 cm were made on the back of rats and randomly divided into the control group, 10 J, 15 J, and 30 J groups. The wound healing rate at days 4, 8, and 12 postoperatively was measured. HE and Masson staining was conducted to reveal the histological characteristics. Immunofluorescence staining was performed to label the epidermal stem cells (ESCs) and hair follicle stem cells (HFSCs). Western blot was performed to detect the expressions of proteins associated with ESCs and HFSCs. Cutaneous wound tissues were collected for RNA sequencing. Gene ontology and the Kyoto Encyclopedia of Genes and Genomes analysis was performed, and the hub genes were identified using CytoHubba and validated by qRT-PCR. RESULTS: PBM can promote reepithelialization, extracellular matrix deposition, and wound healing, increase the number of KRT14+/PCNA+ ESCs and KRT15+/PCNA+ HFSCs, and upregulate the protein expression of P63, Krt14, and PCNA. Three hundred and sixty-six differentially expressed genes (DEGs) and 7 hub genes including Sox9, Krt5, Epcam, Cdh1, Cdh3, Dsp, and Pkp3 were identified. These DEGs are enriched in skin development, cell junction, and cadherin binding involved in cell–cell adhesion etc., while these hub genes are related to skin derived stem cells and cell adhesion. CONCLUSION PBM accelerates wound healing by enhancing reepithelialization through promoting ESCs and HFSCs proliferation and elevating the expression of genes associated with stem cells and cell adhesion. This may provide a valuable alternative strategy to promote wound healing and reepithelialization by modulating the proliferation of skin derived stem cells and regulating genes related to cell adhesion.