Objective:To investigate the role of mechanosensor Yes-associated protein 1 (YAP1) in urothelial cells in inducing bladder dysfunction in a partial bladder outlet obstruction (pBOO) model.Methods:Ten female C57BL/6 mice were included in this study and randomly divided into pBOO and sham groups based on body weight using a stratified pairing method, with 5 mice in each group. The pBOO group underwent proximal urethral ligation surgery, while the sham group underwent a sham operation. Two weeks after surgery, the urinary pattern was analyzed using the urine spot test. The significant increase in urine spot numbers indicated the successful establishment of the pBOO model. The mice were then sacrificed, and bladder tissues were weighed and stained with hematoxylin and eosin (HE) to observe morphological changes. The bladder urothelial layer was further isolated, and total cell proteins were extracted to detect the expression levels of YAP1 protein using Western blotting. Mouse immortalized bladder urothelial cells were divided into three experimental groups: the negative control (NC) group, which was treated with YAP1-NC lentivirus; the overexpression (OE) group, which was treated with YAP1-OE lentivirus to induce YAP1 protein overexpression; and the verteporfin treatment (VP) group, which was treated with verteporfin on the basis of the OE group. Real-time quantitative PCR and Western blotting were used to verify the transcription and expression levels of YAP1 protein, the co-transcriptional activator TEAD4 protein, and the phosphorylated protein DRP1-616 (at serine 616) of dynamin-related protein 1 (DRP1). An ATP detection kit was used to measure the ATP release concentration in the NC, OE, and VP groups. The interaction between YAP1 and TEAD4 was investigated using co-immunoprecipitation, and the expression of the mitochondrial marker translocase of the outer mitochondrial membrane 20 (Tom20) was observed using immunofluorescence staining.Results:The results of the urine spot test showed that the number of urine spots on the filter paper in the pBOO group was higher than that in the sham group within 6 hours [(283.0±9.1) spots vs. (3.7±0.3) spots, P<0.01], and the urine spots were scattered. The bladder wet weight in the pBOO group was significantly higher than that in the sham group [(105.70±6.84) mg vs. (22.33±1.20) mg, P<0.01]. Histological observations revealed reduced bladder mucosal folds and increased detrusor muscle thickness in the pBOO group. The expression of YAP1 protein in the bladder urothelial cells of the pBOO group was significantly upregulated compared to the sham group [(1.26±0.08) vs. (0.50±0.04), P<0.01]. In vitro experiments showed that compared to the NC group, the OE group had significantly increased expression of DRP1-616 [(0.94±0.05) vs. (0.33±0.01), P<0.01] and higher ATP release concentration [(24.45±0.16) μmol/mg vs. (19.67±0.42) μmol/mg, P<0.01]. In contrast, the VP group had significantly decreased expression of DRP1-616 [(0.29±0.04) vs. (0.94±0.05), P<0.01] and lower ATP release concentration [(10.55±0.01) μmol/mg vs. (24.45±0.16) μmol/mg, P<0.01] compared to the OE group. Co-immunoprecipitation experiments using YAP1 and TEAD4 antibodies showed that YAP1 and TEAD4 proteins could interact and form a transcriptional complex to regulate ATP release. Immunofluorescence staining revealed increased expression of Tom20 in the OE group compared to the NC group [(104.20±3.28) vs. (74.51±3.87), P<0.01]. Conclusions:In the pBOO-induced bladder dysfunction model, YAP1 is highly expressed in urothelial cells. YAP1 forms a transcriptional complex with TEAD4 to regulate ATP release by promoting mitochondrial fission via DRP1-616 expression, which is a key mechanism underlying pBOO-induced bladder dysfunction.

Objective:To explore the clinical characteristics and prognosis of malignant melanoma (MM) in the Xinjiang Uygur Autonomous Region.Methods:We collected the clinical and follow-up data of 503 MM patients admitted to the Affiliated Tumor Hospital of Xinjiang Medical University between 2010 and 2022. The Kaplan-Meier method was employed for survival analysis, with Log rank test used for comparing the survival rates between groups. Cox regression analysis was conducted to identify the influencing factors of patient prognosis.Results:From 2010 to 2022, the number of MM patients admitted to the Affiliated Tumor Hospital of Xinjiang Medical University demonstrated an upward trend. Among the 503 MM patients, the primary tumor sites were located in the extremities in 264 cases, the skin in 155 cases, the mucosal in 49 cases, and the ocular uvea in 22 cases, and in 13 cases the primary lesion was unknown. The median follow-up duration was 44 months, with a median overall survival time of 44.0 months. The overall survival rates at 1, 3, and 5 years were 85.2%, 54.3%, and 42.1%, respectively. Univariate analysis revealed that age, Breslow thickness, Clark grading, presence of ulcers, lactate dehydrogenase (LDH) levels, clinical stage at initial treatment, tumor recurrence, distant metastasis (lung, liver, bone, or brain), and postoperative adjuvant therapy were all associated with overall survival in MM patients (all P<0.05). Multivariate Cox regression analysis revealed that age ( HR=1.022, 95% CI: 1.013-1.032), LDH level ( HR=1.696, 95% CI: 1.223-2.353), clinical stage at initial treatment (TxN0M0 vs stage Ⅱ: HR=0.255, 95% CI: 0.096-0.679; TxN0M0 vs stage Ⅲ: HR=0.293, 95% CI: 0.190-0.452; TxN0M0 vs stage Ⅳ: HR=0.414, 95% CI: 0.284-0.603), bone metastasis ( HR=2.032, 95% CI: 1.252-3.298), and postoperative adjuvant therapy ( HR=0.551, 95% CI: 0.426-0.713) are independent factors influencing the overall survival of MM patients. Stratified analysis by different subtype indicated that age, clinical stage at initial treatment, gene mutations, and postoperative adjuvant therapy usage are independent factors affecting the overall survival of patients with limb MM, while age and clinical stage at initial treatment are independent factors influencing the overall survival of patients with skin and mucosal MM. Conclusions:The number of MM patients in Xinjiang Uygur Autonomous Region may be on the rise. Age, LDH level, clinical stage at initial treatment, presence of bone metastasis, and postoperative adjuvant therapy are independent risk factors for the prognosis of MM patients. Among these, age and clinical stage at initial treatment are common independent risk factors that affect the prognosis of different subtypes of MM patients.

OBJECTIVE To analyze the clinical characteristics of Brucellar spondylitis(BS)and provide references for clinical diagnosis and treatment.METHODS A retrospective analysis was conducted on the data of 123 patients with BS admitted to the Second Affiliated Hospital of Inner Mongolia Medical University from Jan.1,2015 to Jun.30,2024.The data included demographic characteristics,epidemiological history,clinical manifestations,la-boratory indicators,imaging features and treatment regimens.The clinical characteristics of BS were summarized.RESULTS Among the 123 patients with BS,there were 96 males and 27 females,with an average age of(59.19±11.71)years.The patients were predominantly farmers(74.80％),and 65.04％reported a history of livestock contact.All patients presented with local vertebral pain,mainly involving the lumbar region(56.10％),accompanied by systemic symptoms such as fever(34.96％)and fatigue(95.12％).Laboratory tests showed an abnormal plateletocrit rate of 93.50％,an abnormal C-reactive protein rate of 87.80％and an abnormal erythro-cyte sedimentation rate of 82.11％.Etiological examinations revealed a positive bacterial culture rate of 73.17％,with positive rates of 92.06％and 95.24％for the Rose Bengal plate agglutination test and tube agglutination test,respectively,and a total positive rate of 95.45％for enzyme-linked immunosorbent assay.Imaging examina-tions found a total of 308 involved vertebrae,with an average of(2.50±1.06)vertebrae involved per patient.Lumbar vertebra involvement was the highest(82.11％)and 42.28％of patients had paravertebral abscesses.In terms of treatment,45.53％of patients received comprehensive treatment with medication and surgery,and 91.06％achieved good outcomes.CONCLUSIONS Patients in high-incidence areas of brucellosis may not have a clear history of livestock contact,and atypical cases should be kept vigilant.Blood routine tests,CRP and ESR of-ten show abnormal manifestations in patients with BS.Lymphocyte count,platelet-to-lymphocyte ratio and mono-cyte-to-lymphocyte ratio have certain reference values in assessing the extent of spinal involvement in patients.

OBJECTIVE To analyze the clinical characteristics of Brucellar spondylitis(BS)and provide references for clinical diagnosis and treatment.METHODS A retrospective analysis was conducted on the data of 123 patients with BS admitted to the Second Affiliated Hospital of Inner Mongolia Medical University from Jan.1,2015 to Jun.30,2024.The data included demographic characteristics,epidemiological history,clinical manifestations,la-boratory indicators,imaging features and treatment regimens.The clinical characteristics of BS were summarized.RESULTS Among the 123 patients with BS,there were 96 males and 27 females,with an average age of(59.19±11.71)years.The patients were predominantly farmers(74.80％),and 65.04％reported a history of livestock contact.All patients presented with local vertebral pain,mainly involving the lumbar region(56.10％),accompanied by systemic symptoms such as fever(34.96％)and fatigue(95.12％).Laboratory tests showed an abnormal plateletocrit rate of 93.50％,an abnormal C-reactive protein rate of 87.80％and an abnormal erythro-cyte sedimentation rate of 82.11％.Etiological examinations revealed a positive bacterial culture rate of 73.17％,with positive rates of 92.06％and 95.24％for the Rose Bengal plate agglutination test and tube agglutination test,respectively,and a total positive rate of 95.45％for enzyme-linked immunosorbent assay.Imaging examina-tions found a total of 308 involved vertebrae,with an average of(2.50±1.06)vertebrae involved per patient.Lumbar vertebra involvement was the highest(82.11％)and 42.28％of patients had paravertebral abscesses.In terms of treatment,45.53％of patients received comprehensive treatment with medication and surgery,and 91.06％achieved good outcomes.CONCLUSIONS Patients in high-incidence areas of brucellosis may not have a clear history of livestock contact,and atypical cases should be kept vigilant.Blood routine tests,CRP and ESR of-ten show abnormal manifestations in patients with BS.Lymphocyte count,platelet-to-lymphocyte ratio and mono-cyte-to-lymphocyte ratio have certain reference values in assessing the extent of spinal involvement in patients.

Objective:To investigate the role of mechanosensor Yes-associated protein 1 (YAP1) in urothelial cells in inducing bladder dysfunction in a partial bladder outlet obstruction (pBOO) model.Methods:Ten female C57BL/6 mice were included in this study and randomly divided into pBOO and sham groups based on body weight using a stratified pairing method, with 5 mice in each group. The pBOO group underwent proximal urethral ligation surgery, while the sham group underwent a sham operation. Two weeks after surgery, the urinary pattern was analyzed using the urine spot test. The significant increase in urine spot numbers indicated the successful establishment of the pBOO model. The mice were then sacrificed, and bladder tissues were weighed and stained with hematoxylin and eosin (HE) to observe morphological changes. The bladder urothelial layer was further isolated, and total cell proteins were extracted to detect the expression levels of YAP1 protein using Western blotting. Mouse immortalized bladder urothelial cells were divided into three experimental groups: the negative control (NC) group, which was treated with YAP1-NC lentivirus; the overexpression (OE) group, which was treated with YAP1-OE lentivirus to induce YAP1 protein overexpression; and the verteporfin treatment (VP) group, which was treated with verteporfin on the basis of the OE group. Real-time quantitative PCR and Western blotting were used to verify the transcription and expression levels of YAP1 protein, the co-transcriptional activator TEAD4 protein, and the phosphorylated protein DRP1-616 (at serine 616) of dynamin-related protein 1 (DRP1). An ATP detection kit was used to measure the ATP release concentration in the NC, OE, and VP groups. The interaction between YAP1 and TEAD4 was investigated using co-immunoprecipitation, and the expression of the mitochondrial marker translocase of the outer mitochondrial membrane 20 (Tom20) was observed using immunofluorescence staining.Results:The results of the urine spot test showed that the number of urine spots on the filter paper in the pBOO group was higher than that in the sham group within 6 hours [(283.0±9.1) spots vs. (3.7±0.3) spots, P<0.01], and the urine spots were scattered. The bladder wet weight in the pBOO group was significantly higher than that in the sham group [(105.70±6.84) mg vs. (22.33±1.20) mg, P<0.01]. Histological observations revealed reduced bladder mucosal folds and increased detrusor muscle thickness in the pBOO group. The expression of YAP1 protein in the bladder urothelial cells of the pBOO group was significantly upregulated compared to the sham group [(1.26±0.08) vs. (0.50±0.04), P<0.01]. In vitro experiments showed that compared to the NC group, the OE group had significantly increased expression of DRP1-616 [(0.94±0.05) vs. (0.33±0.01), P<0.01] and higher ATP release concentration [(24.45±0.16) μmol/mg vs. (19.67±0.42) μmol/mg, P<0.01]. In contrast, the VP group had significantly decreased expression of DRP1-616 [(0.29±0.04) vs. (0.94±0.05), P<0.01] and lower ATP release concentration [(10.55±0.01) μmol/mg vs. (24.45±0.16) μmol/mg, P<0.01] compared to the OE group. Co-immunoprecipitation experiments using YAP1 and TEAD4 antibodies showed that YAP1 and TEAD4 proteins could interact and form a transcriptional complex to regulate ATP release. Immunofluorescence staining revealed increased expression of Tom20 in the OE group compared to the NC group [(104.20±3.28) vs. (74.51±3.87), P<0.01]. Conclusions:In the pBOO-induced bladder dysfunction model, YAP1 is highly expressed in urothelial cells. YAP1 forms a transcriptional complex with TEAD4 to regulate ATP release by promoting mitochondrial fission via DRP1-616 expression, which is a key mechanism underlying pBOO-induced bladder dysfunction.

Objective:To explore the clinical characteristics and prognosis of malignant melanoma (MM) in the Xinjiang Uygur Autonomous Region.Methods:We collected the clinical and follow-up data of 503 MM patients admitted to the Affiliated Tumor Hospital of Xinjiang Medical University between 2010 and 2022. The Kaplan-Meier method was employed for survival analysis, with Log rank test used for comparing the survival rates between groups. Cox regression analysis was conducted to identify the influencing factors of patient prognosis.Results:From 2010 to 2022, the number of MM patients admitted to the Affiliated Tumor Hospital of Xinjiang Medical University demonstrated an upward trend. Among the 503 MM patients, the primary tumor sites were located in the extremities in 264 cases, the skin in 155 cases, the mucosal in 49 cases, and the ocular uvea in 22 cases, and in 13 cases the primary lesion was unknown. The median follow-up duration was 44 months, with a median overall survival time of 44.0 months. The overall survival rates at 1, 3, and 5 years were 85.2%, 54.3%, and 42.1%, respectively. Univariate analysis revealed that age, Breslow thickness, Clark grading, presence of ulcers, lactate dehydrogenase (LDH) levels, clinical stage at initial treatment, tumor recurrence, distant metastasis (lung, liver, bone, or brain), and postoperative adjuvant therapy were all associated with overall survival in MM patients (all P<0.05). Multivariate Cox regression analysis revealed that age ( HR=1.022, 95% CI: 1.013-1.032), LDH level ( HR=1.696, 95% CI: 1.223-2.353), clinical stage at initial treatment (TxN0M0 vs stage Ⅱ: HR=0.255, 95% CI: 0.096-0.679; TxN0M0 vs stage Ⅲ: HR=0.293, 95% CI: 0.190-0.452; TxN0M0 vs stage Ⅳ: HR=0.414, 95% CI: 0.284-0.603), bone metastasis ( HR=2.032, 95% CI: 1.252-3.298), and postoperative adjuvant therapy ( HR=0.551, 95% CI: 0.426-0.713) are independent factors influencing the overall survival of MM patients. Stratified analysis by different subtype indicated that age, clinical stage at initial treatment, gene mutations, and postoperative adjuvant therapy usage are independent factors affecting the overall survival of patients with limb MM, while age and clinical stage at initial treatment are independent factors influencing the overall survival of patients with skin and mucosal MM. Conclusions:The number of MM patients in Xinjiang Uygur Autonomous Region may be on the rise. Age, LDH level, clinical stage at initial treatment, presence of bone metastasis, and postoperative adjuvant therapy are independent risk factors for the prognosis of MM patients. Among these, age and clinical stage at initial treatment are common independent risk factors that affect the prognosis of different subtypes of MM patients.

Objective To investigate the effects of Huanglian Jiedu Decoction Aqueous Extract(HJDAE)on the gut microbiota structure and colon metabolites of rats using 16S rRNA technology and non targeted metabolomics technology.Methods SD rats were continuously gavaged with HJDAE for 7 days and then Euthanized under anesthesia to extract the colon contents of the rats,,the contents of the rats'colon were taken,and 16S rRNA high-throughput sequencing was performed on the gut microbiota of the rats'colon segments using the Illumina Miseq platform.The differential microbiota,differential metabolites,and related pathways were analyzed in combination with the fecal non targeted metabonomics method.Results The results showed that HJDAE could affect the structure of gut microbiota in rats while maintaining a relatively stable proportion of various phyla of gut microbiota,and had significant promoting and inhibitory effects on multiple bacterial genera.Among them,it had the strongest inhibitory effect on Lactobacillus and Limosilactobacillus,and the most obvious promoting effect on Clostridium.Analyzing the data from two sets of experimental results,76 differential metabolites and 70 potential biomarkers were found.Among them,the top ten differential metabolites and their differences were xylose,acetic acid,propionic acid,and dimethylglycine with reduced production,while the production of palmitoleic acid,proline,and T-α-MCA,T-β-MCA,3-DHCA,HCA increased.The eight strongest metabolic pathways involved are Propanoate Metabolism,Butanoate Metabolism,TCA cycle,Alanine-Aspartate-Glutamate Metabolism,D-Glutamine and D-Glutamate Metabolism,Primary Bile Acid Biosynthesis,Nitrogen Metabolism,Valine-Leucine-Isoleucine Biosythesis,all of which are closely related to bile acid production.Conclusion The HJDAE promotes the production of primary bile acids by promoting the metabolism of sugars,amino acids,and fatty acids in rats.At the same time,the HJDAE causes a large number of Clostridium species to proliferate,and multiple Clostridium species metabolize primary bile acids into secondary bile acids,jointly leading to positive regulation of bile acid metabolism.

Objective:To explore the key copy number variation (CNV) regions, abortion candidate genes and signaling pathways associated with recurrent spontaneous abortion (RSA).Methods:A retrospective cohort study was conducted based on the data of 1 870 miscarriage cases of RSA patients who received CNV analysis by high-throughput sequencing technology in the Laboratory Medicine Department of the Third Affiliated Hospital of Zhengzhou University from January 2016 to September 2022. These cases were divided into different groups based on the age of miscarriage and gestational age of the pregnant women. Chi-square test or Fisher's exact test was used to analyze the distribution of chromosome abnormalities and CNV. Gene functions and signaling pathways in RSA-related CNV were identified by gene enrichment analysis.Results:Among the 1 870 tissues, 1 001 (53.53%) cases were detected with chromosomal abnormalities. A total of 140 CNVs were detected in 93 tissues (9.29%), including 34 submicroscopic CNVs (segment<10 Mb) and 106 large CNVs with segment≥10 Mb. Submicroscopic pathogenicity CNVs with statistical differences were involved 1p36.33p36.23, 2q37.3, 4p16.3, 22q11.21 (χ 2=6.99, P=0.008) in early RSA embryos (≤12 weeks). 16p11.2 and Xp11.23p11.22 microdeletion were firstly reported in abortion cases. Significantly recurrent large CNVs were mainly involved 18q22q23 (del/dup), 4p16p15, 9p24p22, 8p23p22, and Xp22.3 regions, and the candidate genes mainly concentrated on PI3K-Akt and JAK-STAT signaling pathway. Conclusion:Rare submicroscopic CNVs and recurrent large CNVs were associated with RSA in early pregnancy. GO and KEGG database analysis revealed potential abortion candidate genes and signaling pathways, providing new information for the genetic etiology of RSA.

Objective:To explore the key copy number variation (CNV) regions, abortion candidate genes and signaling pathways associated with recurrent spontaneous abortion (RSA).Methods:A retrospective cohort study was conducted based on the data of 1 870 miscarriage cases of RSA patients who received CNV analysis by high-throughput sequencing technology in the Laboratory Medicine Department of the Third Affiliated Hospital of Zhengzhou University from January 2016 to September 2022. These cases were divided into different groups based on the age of miscarriage and gestational age of the pregnant women. Chi-square test or Fisher's exact test was used to analyze the distribution of chromosome abnormalities and CNV. Gene functions and signaling pathways in RSA-related CNV were identified by gene enrichment analysis.Results:Among the 1 870 tissues, 1 001 (53.53%) cases were detected with chromosomal abnormalities. A total of 140 CNVs were detected in 93 tissues (9.29%), including 34 submicroscopic CNVs (segment<10 Mb) and 106 large CNVs with segment≥10 Mb. Submicroscopic pathogenicity CNVs with statistical differences were involved 1p36.33p36.23, 2q37.3, 4p16.3, 22q11.21 (χ 2=6.99, P=0.008) in early RSA embryos (≤12 weeks). 16p11.2 and Xp11.23p11.22 microdeletion were firstly reported in abortion cases. Significantly recurrent large CNVs were mainly involved 18q22q23 (del/dup), 4p16p15, 9p24p22, 8p23p22, and Xp22.3 regions, and the candidate genes mainly concentrated on PI3K-Akt and JAK-STAT signaling pathway. Conclusion:Rare submicroscopic CNVs and recurrent large CNVs were associated with RSA in early pregnancy. GO and KEGG database analysis revealed potential abortion candidate genes and signaling pathways, providing new information for the genetic etiology of RSA.

Objective To investigate the effects of Huanglian Jiedu Decoction Aqueous Extract(HJDAE)on the gut microbiota structure and colon metabolites of rats using 16S rRNA technology and non targeted metabolomics technology.Methods SD rats were continuously gavaged with HJDAE for 7 days and then Euthanized under anesthesia to extract the colon contents of the rats,,the contents of the rats'colon were taken,and 16S rRNA high-throughput sequencing was performed on the gut microbiota of the rats'colon segments using the Illumina Miseq platform.The differential microbiota,differential metabolites,and related pathways were analyzed in combination with the fecal non targeted metabonomics method.Results The results showed that HJDAE could affect the structure of gut microbiota in rats while maintaining a relatively stable proportion of various phyla of gut microbiota,and had significant promoting and inhibitory effects on multiple bacterial genera.Among them,it had the strongest inhibitory effect on Lactobacillus and Limosilactobacillus,and the most obvious promoting effect on Clostridium.Analyzing the data from two sets of experimental results,76 differential metabolites and 70 potential biomarkers were found.Among them,the top ten differential metabolites and their differences were xylose,acetic acid,propionic acid,and dimethylglycine with reduced production,while the production of palmitoleic acid,proline,and T-α-MCA,T-β-MCA,3-DHCA,HCA increased.The eight strongest metabolic pathways involved are Propanoate Metabolism,Butanoate Metabolism,TCA cycle,Alanine-Aspartate-Glutamate Metabolism,D-Glutamine and D-Glutamate Metabolism,Primary Bile Acid Biosynthesis,Nitrogen Metabolism,Valine-Leucine-Isoleucine Biosythesis,all of which are closely related to bile acid production.Conclusion The HJDAE promotes the production of primary bile acids by promoting the metabolism of sugars,amino acids,and fatty acids in rats.At the same time,the HJDAE causes a large number of Clostridium species to proliferate,and multiple Clostridium species metabolize primary bile acids into secondary bile acids,jointly leading to positive regulation of bile acid metabolism.