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 expression of dermatopontin(DPT)in abdominal aortic aneurysm(AAA)and to explore the mechanism in promoting AAA progression.Methods Differential gene expression(DEG)and GO-KEGG pathway enrichment were used to assess DPT expression level and related pathways in AAA.AAA tissue samples were collected from patients undergoing open surgical repair at Beijing Hospital(experimental group,n=3),while control aortic tissues were collected from kidney transplant donors(n=3).Immun-ohistochemistry and immuno-fluorescence staining were performed to validate DPT protein expression differences in AAA tissues.Masson staining microscopy was used to evaluate fibrosis level.Human aortic smooth muscle cells(HASMCs)were divided into control(Ctrl)and lipopolysaccharide(LPS)-treated groups(n=3).RT-qPCR,ELISA,and immu-nocytochemistry(ICC)were used to measure DPT expression level.HASMCs were further divided into control(Ctrl)and recombinant human DPT-treated groups with 3 cases in each.RT-qPCR was performed to detect the ex-pression of interleukin-1α(IL-1α),interleukin-1β(IL-1β),collagen type Ⅰ alpha 1 chain(COL1A1),matrix metalloproteinase-2(MMP2),and matrix metalloproteinase-9(MMP9).Cell adhesion assays were conducted to ex-amine the role of integrin α3 and integrin β1 in HASMC adhesion.Results DPT was highly expressed in human AAA tissues(P＜0.01).LPS induced DPT expression and secretion in HASMCs(P＜0.05).DPT promoted IL-1α(P＜0.001)and IL-1β(P＜0.01)expression through a positive feedback mechanism while suppressed COL1A1(P＜0.001)production.DPT enhanced HASMC adhesion via the integrin α3β1 receptor(P＜0.001).Conclusions DPT promotes AAA progression by activating IL-1α/IL-1β inflammatory cytokines and inhibits COL1A1-mediated extra cellular matrix(ECM)remodeling.Integrin α3β1 is potentially involved in the regulation process.

Objective To explore the independent risk factors of bladder stones(BS)in patients with benign prostatic hyperplasia(BPH),and to construct a predictive model and an easy-to-use website.Methods The clinical data of 460 BPH patients treated during Jan.2022 and Jan.2025 in the First Affiliated Hospital of Shihezi University were retrospectively analyzed.The independent risk factors of BS in the training set were identified with univariate logistic regression and the Boruta algorithm,based on which a nomogram was constructed.The predictive performance of the model was evaluated with receiver operating characteristic(ROC)curve,sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV),F1 index,calibration curve and clinical decision curve analysis(DCA).The contribution of different variables to BS was evaluated with SHapley Additive exPlanations(SHAP)algorithm.A web page was established.Results Among the 460 BPH patients,144(31.3％)had BS,and 6 independent risk factors were identified,including neutrophil level,urine culture results,intravesical prostatic protrusion(IPP),urine nitrite test results,urine leukocytes test results,and urine occult blood results.In the test set,the area under the ROC curve(AUC)was 0.887(95％CI:0.816-0.947),sensitivity 0.705,specificity 0.968,PPV 0.912,NPV 0.876,and F1 score 0.795.Calibration and DCA indicated good discrimination and clinical applicability.SHAP results showed that the risk factors mentioned above were the most important for concurrent BS.The resulting website(https://wutiaowu2.shinyapps.io/bladderrrr/)was publicly accessible.Conclusion The neutrophil level,urine culture results,IPP,urinary nitrite test results,urinary leukocytes test results,and urinary occult blood test results were identified as the independent risk factors of BPH complicated with BS.The model and website developed based on these factors demonstrate high usability and accuracy,possessing significant clinical value.

Glaesserella parasuis is the causative agent of Gl?sser's disease in pigs.However,the pathogenic mechanisms underlying its virulence is not yet fully understood.The RuvB protein,a member of the AAA+superfamily,is implicated in various cellular processes,yet its specific role in the virulence of Glaesserella parasuis has not been fully characterized.In this study,we con-structed a RuvB gene deletion mutant,designated ΔRuvB,using the serotype 13 Glaesserella pa-rasuis strain ZJ1208 and a suicide plasmid-mediated natural transformation approach.To elucidate the functional role of the RuvB gene,we comprehensively evaluated the biological characteristics of the ΔRuvB strain through a series of assays,including growth kinetics,colony morphology,bac-terial staining,transmission electron microscopy(TEM),osmotic stress tolerance,high-tempera-ture tolerance,heat shock resistance,UV resistance,capsular polysaccharide quantification,serum bactericidal assays,and murine virulence experiments.Our findings revealed that the growth rate of ΔRuvB showed no significant difference compared to the parental strain.TEM revealed a notable increase in bacterial cell length;however,the number of outer membrane vesicles(OMVs)on the surface of ΔRuvB did not significantly increase.Notably,the ΔRuvB strain displayed a significant reduction in capsular polysaccharide production and serum resistance,as well as diminished toler-ance to UV radiation and high temperatures.Significant alterations were observed in its resistance to osmotic stress or oxidative stress.In the mouse toxicity challenge experiment,in com-parison with the parental strain ZJ1208,the mortality rate dropped by 20 percentage points,suggesting that the virulence of ΔRuvB has been weakened to some extent.Collectively,these results underscore the critical role of the RuvB gene in enhancing the environmental adaptability of Glaesserella parasuis.

Objective To explore the independent risk factors of bladder stones(BS)in patients with benign prostatic hyperplasia(BPH),and to construct a predictive model and an easy-to-use website.Methods The clinical data of 460 BPH patients treated during Jan.2022 and Jan.2025 in the First Affiliated Hospital of Shihezi University were retrospectively analyzed.The independent risk factors of BS in the training set were identified with univariate logistic regression and the Boruta algorithm,based on which a nomogram was constructed.The predictive performance of the model was evaluated with receiver operating characteristic(ROC)curve,sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV),F1 index,calibration curve and clinical decision curve analysis(DCA).The contribution of different variables to BS was evaluated with SHapley Additive exPlanations(SHAP)algorithm.A web page was established.Results Among the 460 BPH patients,144(31.3％)had BS,and 6 independent risk factors were identified,including neutrophil level,urine culture results,intravesical prostatic protrusion(IPP),urine nitrite test results,urine leukocytes test results,and urine occult blood results.In the test set,the area under the ROC curve(AUC)was 0.887(95％CI:0.816-0.947),sensitivity 0.705,specificity 0.968,PPV 0.912,NPV 0.876,and F1 score 0.795.Calibration and DCA indicated good discrimination and clinical applicability.SHAP results showed that the risk factors mentioned above were the most important for concurrent BS.The resulting website(https://wutiaowu2.shinyapps.io/bladderrrr/)was publicly accessible.Conclusion The neutrophil level,urine culture results,IPP,urinary nitrite test results,urinary leukocytes test results,and urinary occult blood test results were identified as the independent risk factors of BPH complicated with BS.The model and website developed based on these factors demonstrate high usability and accuracy,possessing significant clinical value.

Glaesserella parasuis is the causative agent of Gl?sser's disease in pigs.However,the pathogenic mechanisms underlying its virulence is not yet fully understood.The RuvB protein,a member of the AAA+superfamily,is implicated in various cellular processes,yet its specific role in the virulence of Glaesserella parasuis has not been fully characterized.In this study,we con-structed a RuvB gene deletion mutant,designated ΔRuvB,using the serotype 13 Glaesserella pa-rasuis strain ZJ1208 and a suicide plasmid-mediated natural transformation approach.To elucidate the functional role of the RuvB gene,we comprehensively evaluated the biological characteristics of the ΔRuvB strain through a series of assays,including growth kinetics,colony morphology,bac-terial staining,transmission electron microscopy(TEM),osmotic stress tolerance,high-tempera-ture tolerance,heat shock resistance,UV resistance,capsular polysaccharide quantification,serum bactericidal assays,and murine virulence experiments.Our findings revealed that the growth rate of ΔRuvB showed no significant difference compared to the parental strain.TEM revealed a notable increase in bacterial cell length;however,the number of outer membrane vesicles(OMVs)on the surface of ΔRuvB did not significantly increase.Notably,the ΔRuvB strain displayed a significant reduction in capsular polysaccharide production and serum resistance,as well as diminished toler-ance to UV radiation and high temperatures.Significant alterations were observed in its resistance to osmotic stress or oxidative stress.In the mouse toxicity challenge experiment,in com-parison with the parental strain ZJ1208,the mortality rate dropped by 20 percentage points,suggesting that the virulence of ΔRuvB has been weakened to some extent.Collectively,these results underscore the critical role of the RuvB gene in enhancing the environmental adaptability of Glaesserella parasuis.

Objective:To investigate the correlation between miR-137 gene polymorphism and genetic susceptibility to gestational diabetes mellitus.Methods:A total of 500 pregnant women with gestational diabetes who were admitted to Shunde Women and Childrens Hospital of Guangdong Medical University from January 2023 to September 2023 were selected as the observation group, and 500 healthy pregnant women with normal glucose metabolism and no pregnancy complications were selected as the control group. Polymerase chain reaction (PCR) was used to detect rs1625579 polymorphisms of miR-137 gene between the two groups, and the clinical data of the two groups were compared to analyze the influencing factors of the occurrence of gestational diabetes mellitus.Results:The frequencies of GT+ GG genotype and allele G at rs1625579 site of miR-137 gene in observation group were 13.20% and 7.00%, respectively, which were significantly higher than those in control group (all P<0.05). Fasting blood glucose (FPG), fasting insulin (FINS) and insulin resistance index (HOMA-IR) of miR-137 genotype GT+ GG pregnant women in the observation group were (7.92±0.81)mmol/L, (19.92±3.10)mmol/L and 6.60±1.02, respectively. It was significantly higher than genotypic TT pregnant women (all P<0.05), and islet β cell function index (HOMA-β) was significantly lower than genotypic TT pregnant women (188.84±43.34) ( P<0.05). Pre-pregnancy body mass index (BMI) and average weekly weight gain during pregnancy in the observation group were (23.81±1.92)kg/m 2 and (445.50±35.65)g, respectively, which were significantly higher than those in the control group (all P<0.05). The proportion of family history of diabetes in the observation group was 8.60%, which was significantly higher than that in the control group ( P<0.05). Logistic regression analysis showed that preconception BMI and average weekly weight gain during pregnancy were the influential factors for the occurrence of gestational diabetes (all P<0.05). Conclusions:The occurrence of gestational diabetes mellitus has no significant correlation with miR-137 gene polymorphism, but is related to pre-pregnancy BMI and average weekly weight gain during pregnancy. Compared with other miR-137 genotypes, GT+ GG patients were more likely to develop abnormal blood glucose.

Inflammatory bowel disease (IBD) is a formidable disease due to its complex pathogenesis. Macrophages, as a major immune cell population in IBD, are crucial for gut homeostasis. However, it is still unveiled how macrophages modulate IBD. Here, we found that LIM domain only 7 (LMO7) was downregulated in pro-inflammatory macrophages, and that LMO7 directly degraded 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) through K48-mediated ubiquitination in macrophages. As an enzyme that regulates glycolysis, PFKFB3 degradation led to the glycolytic process inhibition in macrophages, which in turn inhibited macrophage activation and ultimately attenuated murine colitis. Moreover, we demonstrated that PFKFB3 was required for histone demethylase Jumonji domain-containing protein 3 (JMJD3) expression, thereby inhibiting the protein level of trimethylation of histone H3 on lysine 27 (H3K27me3). Overall, our results indicated the LMO7/PFKFB3/JMJD3 axis is essential for modulating macrophage function and IBD pathogenesis. Targeting LMO7 or macrophage metabolism could potentially be an effective strategy for treating inflammatory diseases.

【Objective】 To explore the safety and efficacy of flexible ureteroscope in the treatment of upper and middle ureteral calculi complicated with lower ureteral stricture after the failure of rigid ureteroscopy. 【Methods】 Clinical data of 36 patients with middle and upper ureteral calculi and lower ureteral stricture treated with rigid ureteroscopy but failed during Oct.2019 and Oct.2021 were retrospectively analyzed. The patients’ average age was (46.2±13.2) years, and the maximum diameter of calculi was (1.3±0.3) cm. The intraoperative, postoperative and follow-up data were recorded. 【Results】 All 36 patients successfully completed first-stage operation. Intraoperatively, the stenosis degree was F6-8 and could be dilated to F9-11. The mean length of stenosis was (1.1±0.34) cm. No serious postoperative complications such as infection or bleeding occurred. Two patients were lost and 34 patients were followed up. There was no obvious hydronephrosis on ultrasound examination. The stone removal rates were 76.5%, 88.2% and 97.1%, respectively, in months 1, 2 and 3 after operation. One patient with residual stones underwent secondary ureteroscopy in month 3 and large stones were removed with stone removal basket. 【Conclusion】 In patients with middle and upper ureteral calculi and lower ureteral stricture, after the failure of rigid ureteroscopy, flexible ureteroscope is safe and effective, and can significantly increase the success rate of first-stage surgery.