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 investigate the correlation of sperm aneuploidy with unexplained recurrent spontaneous abortion(URSA).Methods Thirty-four male partners of couples diagnosed with URSA in the Center of Reproductive Medicine of Northwest Women's and Children's Hospital from November 2021 to December 2023 were enrolled as the experimental group,after excluding chromosomal structural or numerical abnormalities in either partner of the couples,female age≥37 years,and other known female-related causes of miscarriage.Meanwhile,30 men,who had given birth to healthy children,or were infertile only due to female factors and had normal semen parameters,were selected as control group.Fluorescence in situ hybridization(FISH)was used to detect sperm aneuploidy after routine semen analysis for the males of the two groups.Results There were no significant differences in male age,semen volume,sperm concentration,percentage of progressively motile sperm,and percentage of sperm with normal morphology between the two groups(all P＞0.05).However,in the experimental group,the total nullisomy rate(2.10±1.93)％ versus(0.54±0.27)％,total dip-loidy rate(0.25±0.27)％ versus(0.05±0.05)％,and disomy rate of chromosome 18(0.77±1.15)％ versus(0.18±0.21)％,sex chromosomes(2.79±2.38)％ versus(0.78±0.52)％,chromosome 13(0.79±0.99)％ versus(0.21±0.22)％,and chromosome 21(1.24±1.68)％ versus(0.22±0.19)％ were significantly higher than those in the control group(P＜0.05).When the the mean aneu-ploidy rate in the control group(x+2s)was set as the upper limit of the normal reference value,the proportions of disomy rates of chro-mosomes 18,13,21 and sex chromosomes,as well as the total diploidy rate exceeding the threshold in the experimental group were 41.18％,35.29％,41.18％,55.88％,and 47.06％,respectively,with the proportion of abnormal disomy rate of sex chromosomes be-ing the highest.Conclusion The aneuploidy rate of sperm may be a related factor leading to unexplained recurrent spontaneous abor-tion in females,which has certain clinical significance for the assessment of male fertility and the diagnosis of male infertility.

Objective To investigate the effect of progressive muscle relaxation training intervention strategy in relieving fatigue of elderly patients with primary hepatocellular carcinoma(HCC)after receiving transcatheter arterial chemoembolization(T ACE),and to analyze its influencing factors.Methods Using convenience sampling method,a total of 150 elderly patients with HCC,who received TACE at a certain grade Ⅲ-A hospital at Peking of China from May 2021 to March 2023,were selected as the subjects of research.The patients were randomly divided into the study group and the control group,and progressive muscle relaxation training intervention strategy and conventional postoperative fatigue care method were employed respectively.The preoperative fatigue status and the postoperative fatigue recovery status were compared between the two groups,and the influencing factors were analyzed.Results In both groups,the postoperative one-day fatigue score was the highest,which was gradually decreased thereafter.The average recovery time of fatigue in the control group was 9.84 days,which in the study group was 6.16 days,the difference between the two groups was statistically significant(P=0.013).The body mass index(BMI),Child-Pugh classification,and preoperative grip strength index had an effect on the postoperative fatigue recovery time after intervention.A BMI of β=-0.953 and a preoperative grip strength index of β=-0.185 were negatively correlated with the postoperative fatigue recovery time after intervention,while a Child-Pugh classification of β=2.177 was positively correlated with the postoperative fatigue recovery time after intervention.Conclusion Progressive muscle relaxation training intervention strategy is helpful for shortening the postoperative fatigue recovery time in elderly patients with HCC after receiving TACE,and it is worth of promotion in clinical practice.The patient's nutrition and physical status such as BMI,hepatic reserve function and grip strength index,are the factors influencing the effectiveness of progressive muscle relaxation training intervention strategy.

Objective:To investigate the temporal expression of Growth Differentiation Factor-15 (GDF15) in the serum of patients with Acute Coronary Syndrome (ACS) and explore the clinical significance of GDF15 in protecting cardiomyocytes in ACS.Methods:A retrospective study was conducted on 289 ACS patients admitted to the emergency departments from February to October 2023. Data on gender, age, troponin T (TnT), creatine kinase isoenzyme (CK-MB), GDF15, and B-type natriuretic peptide (BNP) within 30 minutes of admission were recorded. Differences in these indicators among different groups were compared. Receiver Operating Characteristic (ROC) curves were plotted to evaluate the diagnostic value of GDF15, TnT, and BNP for ACS. Among the patients, 15 exhibited a temporal expression pattern of GDF15, and their blood samples were re-measured using a GDF15 fluorescent quantitative immunochromatographic assay kit. Fifteen patients without temporal expression were randomly selected as controls, and their samples were also re-measured to exclude detection errors. Fifteen patients with temporal expression were included in the temporal expression group, and 15 without temporal expression were included in the non-temporal expression group. Laboratory indicators such as fasting blood glucose, glycated hemoglobin, triglycerides, creatinine, and uric acid were compared between the groups. Additionally, patient age, gender, body mass index (BMI), coronary angiography results, echocardiography, Gensini score, left ventricular ejection fraction (LVEF), and GRACE risk score were recorded to assess their correlation with GDF15 temporal expression. Statistical analysis was performed using SPSS 27 software, with continuous data expressed as mean ± standard deviation (Mean ± SD) and compared using t-tests and χ2 tests. Results:The overall trend in ACS patients showed a higher proportion of males than females (73.36% vs. 26.64%). The oldest group was the Unstable Angina (UA) group, with a mean age of (63.98 ± 15.19) years, while the youngest group was the non-ACS chest pain group, with a mean age of (54.29 ± 16.39) years. A higher proportion of patients in the UA, ST-segment elevation myocardial infarction (STEMI), and non-ST-segment elevation myocardial infarction (NSTEMI) groups had a history of smoking. The combination of GDF15 and TnT showed high diagnostic value for ACS, with an area under the ROC curve (AUC) of 0.843, consistent with previous studies. Among all ACS patients, 15 exhibited a temporal expression pattern of GDF15, where GDF15 levels peaked at 4 hours, gradually decreased, and peaked again at 24 hours. Patients in the temporal expression group had higher LVEF and left ventricular end-systolic diameter compared to the non-temporal expression group. The Gensini score was lower in the temporal expression group, and the GRACE risk score was significantly lower in the temporal expression group (00.7±14.72) compared to the non-temporal expression group (116.1±23.46), with a statistically significant difference ( P = 0.0115). There were no significant differences in general characteristics (age, gender, BMI) or clinical biochemical indicators (fasting blood glucose, glycated hemoglobin, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, creatinine, uric acid) between the temporal and non-temporal expression groups ( P > 0.05). Conclusions:GDF15 demonstrates significant diagnostic and prognostic predictive value in ACS. Patients with temporally dynamic expression of serum GDF15 exhibit milder myocardial injury and a lower probability of mortality. These findings provide novel therapeutic targets and research directions for further exploring the role of GDF15 in ACS management.

Objective To explore the mechanism by which T cell immunoglobulin and mucin domain-3(TIM-3)promotes the Hippo signaling pathway in the pathogenesis of preeclampsia.Methods HTR-8/Svneo cells were divided into a control group(Con),a recombinant human Tim-3 protein(Tim-3 Fc)group,a YAP1 inhibitor CA3 group and a Tim-3 Fc+CA3 group.Cell proliferation was analyzed by 5-ethynyl-2 '-deoxyuridine(EdU).Cell invasion and migration were evaluated by Transwell assay,and cell apoptosis was analyzed by terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assay.Protein expression levels of TIM-3 and Hippo pathway components in HTR-8/SVneo cells were detected by Western Blot.Results Compared to the Con group,protein expression levels of TIM-3,YAP1 and TAZ were up-regulated in HTR-8/SVneo trophoblast cells of the TIM-3 Fc group(P<0.05).Compared to the TIM-3 Fc group,protein expression levels of YAP1 and TAZ were down-regulated in trophoblast cells of the TIM-3 Fc+CA3 group(P<0.05).Compared to the Con group,the rate of EdU positive cells in HTR-8/SVneo trophoblast cells in TIM-3 Fc group was increased significantly(P<0.05).Compared to the TIM-3 Fc group,the rate of EdU positive cells and the number of apoptotic cells in HTR-8/SVneo trophoblast cells of the TIM-3 Fc+CA3 group were decreased significantly(P<0.05).Compared to the Con group,the number of HTR-8/SVneo trophoblast cells in TIM-3 Fc group was increased significantly(P<0.05).Compared to the TIM-3 Fc group,the number of HTR-8/SVneo trophoblast cells in TIM-3 Fc+CA3 group was decreased significantly(P<0.05).Conclusions Tim-3 activates the Hippo pathway by interacting with YAP1 in trophoblast cells,thus promoting cell proliferation,invasion and migration.

Objective To explore the clinical characteristics of myelodysplastic syndrome(MDS)with U2 small nuclear RNA cofactor 1(U2AF1)mutation in different age groups,as well as the efficacy and prognosis of an arsenic-containing traditional Chinese medicine(TCM)compound prescription(Qinghuang Capsules combined with Bushen Yijing Formula).Methods A retrospective analysis was conducted on the clinical data of patients with MDS who were hospitalized in the Hematology Department Ward of Xiyuan Hospital,China Academy of Chinese Medical Sciences,and received arsenic-containing TCM compound treatment from November 30,2020,to September 30,2023.Stratified by age,the U2AF1 mutation and wild-type groups aged＜65 years and≥65 years were compared in terms of sex,TCM syndrome,World Health Organization classification,MDS Revised International Prognostic Score System(IPSS-R)score,blood routine indicators,serum lactate dehydrogenase content,nephroblastoma 1(WT1)expression level,bone marrow puncture and biopsy indicators,and chromosomal prognostic grades,et al.Furthermore,the efficacy of arsenic-containing TCM compound were compared in the U2AF1 mutation and wild-type groups among different age groups,as well as the influence of age on the survival prognosis of MDS patients with U2AF1 mutation.Results A total of 201 patients with MDS were included.104 patients were under 65 years old,among whom 20 had U2AF1 mutation,and 84 had wild-type.Ninety-seven patients were aged 65 years or older,among whom 19 patients had the U2AF1 mutation and 78 had the wild-type.Among patients aged＜65 years,the U2AF1 mutation group had a higher proportion of male patients and very low-risk/low-risk patients with an IPSS-R score≤3(P＜0.05),a lower mean corpuscular volume(MCV)(P＜0.05),and a relatively higher proportion of peripheral blood cell line 1 reduction than the wild-type group(P＜0.05).Among patients aged≥65 years,the MCV in the U2AF1 mutation group was lower(P＜0.05),and the expression level of the bone marrow WT1 gene and the proportion of patients with reticular fiber grade 4 were relatively higher than in the wild-type group(P＜0.05).The total effective rate of the arsenic-containing TCM compound for patients with U2AF1 mutation was 61.5％(24/39),and the total response rate was 30.8％(12/39).The total effective rate for the wild-type patients was 67.9％(110/162),and the total response rate was 29.6％(48/162).No significant difference was observed in the total effective and response rates.Kaplan-Meier survival analysis of 39 patients with U2AF1 mutation revealed that the median overall survival(mOS)of patients older than 65 years had not been reached.The 1-,2-,and 3-year survival rates were 93.8％,84.4％,and 84.4％,respectively.The mOS of the patients aged≥65 years was 35 months(95％confidence interval[CI]:7.559-62.441),and the 1-,2-,and 3-year survival rates were 66.2％,58.9％,and 29.4％,respectively.The mOS of patients in the aged≥65 years group was significantly lower than that in the aged＜65 years group(P＜0.05),and no significant difference was observed in median progression-free survival between the two groups.Conclusion The U2AF1 mutation is closely associated with the clinical characteristics of MDS.However,age and the presence of U2AF1 mutation have no significant effect on the total effective and response rates of arsenic-containing TCM compound.Age is a significant factor influencing the prognosis of patients with MDS with U2AF1 mutation.Patients aged 65 years or older have a shorter survival time than those younger than 65 years.

Objective The study attempted to establish a less invasive model for dissecting and monitoring the sympathetic nerve in rats via a dorsal approach for subarachnoid block-related studies.Methods A traditional abdominal approach model and a new dorsal approach model were established in SD rats,and the modeling time of the two models was observed.The stability of the new model was evaluated by measuring blood pressure(BP),heart rate(HR),percentage change in lumbar sympathetic nerve activity(LSNA change％),norepinephrine(NE),and nitric oxide(NO)content after subarachnoid injection of bupivacaine.Results(1)Building a new model:the time required to create new models for the dorsal approach(DA)group was shorter than that for the traditional abdominal approach(VA)group,as shown by the result(P＜0.0001).(2)Evaluation of the new model:compared with the NS group,the MAP and SBP were lower at T2(5 min after injection of bupivacaine into the subarachnoid space)and T3(10 min)(P＜0.05);the LSNA change％was significantly different(P＜0.05);the concentration of NE was lower at T3(P＜0.05).Conclusions The study presents a novel lumbar sympathetic anatomy model using the dorsal approach for subarachnoid-related investigations,which was effectively employed to examine the impact of subarachnoid block anesthesia on lumbar sympathetic nerve activity.

Objective To explore the clinical characteristics of myelodysplastic syndrome(MDS)with U2 small nuclear RNA cofactor 1(U2AF1)mutation in different age groups,as well as the efficacy and prognosis of an arsenic-containing traditional Chinese medicine(TCM)compound prescription(Qinghuang Capsules combined with Bushen Yijing Formula).Methods A retrospective analysis was conducted on the clinical data of patients with MDS who were hospitalized in the Hematology Department Ward of Xiyuan Hospital,China Academy of Chinese Medical Sciences,and received arsenic-containing TCM compound treatment from November 30,2020,to September 30,2023.Stratified by age,the U2AF1 mutation and wild-type groups aged＜65 years and≥65 years were compared in terms of sex,TCM syndrome,World Health Organization classification,MDS Revised International Prognostic Score System(IPSS-R)score,blood routine indicators,serum lactate dehydrogenase content,nephroblastoma 1(WT1)expression level,bone marrow puncture and biopsy indicators,and chromosomal prognostic grades,et al.Furthermore,the efficacy of arsenic-containing TCM compound were compared in the U2AF1 mutation and wild-type groups among different age groups,as well as the influence of age on the survival prognosis of MDS patients with U2AF1 mutation.Results A total of 201 patients with MDS were included.104 patients were under 65 years old,among whom 20 had U2AF1 mutation,and 84 had wild-type.Ninety-seven patients were aged 65 years or older,among whom 19 patients had the U2AF1 mutation and 78 had the wild-type.Among patients aged＜65 years,the U2AF1 mutation group had a higher proportion of male patients and very low-risk/low-risk patients with an IPSS-R score≤3(P＜0.05),a lower mean corpuscular volume(MCV)(P＜0.05),and a relatively higher proportion of peripheral blood cell line 1 reduction than the wild-type group(P＜0.05).Among patients aged≥65 years,the MCV in the U2AF1 mutation group was lower(P＜0.05),and the expression level of the bone marrow WT1 gene and the proportion of patients with reticular fiber grade 4 were relatively higher than in the wild-type group(P＜0.05).The total effective rate of the arsenic-containing TCM compound for patients with U2AF1 mutation was 61.5％(24/39),and the total response rate was 30.8％(12/39).The total effective rate for the wild-type patients was 67.9％(110/162),and the total response rate was 29.6％(48/162).No significant difference was observed in the total effective and response rates.Kaplan-Meier survival analysis of 39 patients with U2AF1 mutation revealed that the median overall survival(mOS)of patients older than 65 years had not been reached.The 1-,2-,and 3-year survival rates were 93.8％,84.4％,and 84.4％,respectively.The mOS of the patients aged≥65 years was 35 months(95％confidence interval[CI]:7.559-62.441),and the 1-,2-,and 3-year survival rates were 66.2％,58.9％,and 29.4％,respectively.The mOS of patients in the aged≥65 years group was significantly lower than that in the aged＜65 years group(P＜0.05),and no significant difference was observed in median progression-free survival between the two groups.Conclusion The U2AF1 mutation is closely associated with the clinical characteristics of MDS.However,age and the presence of U2AF1 mutation have no significant effect on the total effective and response rates of arsenic-containing TCM compound.Age is a significant factor influencing the prognosis of patients with MDS with U2AF1 mutation.Patients aged 65 years or older have a shorter survival time than those younger than 65 years.

Objective The study attempted to establish a less invasive model for dissecting and monitoring the sympathetic nerve in rats via a dorsal approach for subarachnoid block-related studies.Methods A traditional abdominal approach model and a new dorsal approach model were established in SD rats,and the modeling time of the two models was observed.The stability of the new model was evaluated by measuring blood pressure(BP),heart rate(HR),percentage change in lumbar sympathetic nerve activity(LSNA change％),norepinephrine(NE),and nitric oxide(NO)content after subarachnoid injection of bupivacaine.Results(1)Building a new model:the time required to create new models for the dorsal approach(DA)group was shorter than that for the traditional abdominal approach(VA)group,as shown by the result(P＜0.0001).(2)Evaluation of the new model:compared with the NS group,the MAP and SBP were lower at T2(5 min after injection of bupivacaine into the subarachnoid space)and T3(10 min)(P＜0.05);the LSNA change％was significantly different(P＜0.05);the concentration of NE was lower at T3(P＜0.05).Conclusions The study presents a novel lumbar sympathetic anatomy model using the dorsal approach for subarachnoid-related investigations,which was effectively employed to examine the impact of subarachnoid block anesthesia on lumbar sympathetic nerve activity.