Among gynecologic malignancies, ovarian cancer is the most lethal, primarily due to its insidious early symptoms, lack of effective screening methods, and high risk of recurrence. It poses substantial challenges to clinical diagnosis and treatment. In recent years, the clinical application of poly ADP-ribose polymerase inhibitors has promoted a comprehensive management model that integrates targeted therapy with conventional treatments. This review, aiming to provide new perspectives and approaches for future research, summarizes the high-risk factors and first-line treatment strategies for ovarian cancer. Further studies should focus on optimizing personalized treatment strategies and exploring novel targeted therapies to improve patient survival outcomes.

Objective:To investigate the differences in clinical characteristics and antibiotic resistance of neonatal sepsis（NS）caused by different Gram-staining pathogens.Methods:A retrospective study was conducted on confirmed NS cases admitted to the Neonatal Ward of the Pediatric Department at The First Affiliated Hospital of Dali University，from June 1，2014，to May 31，2024.Patients were divided into Gram-positive and Gram-negative groups based on blood or cerebrospinal fluid（CSF）culture results.Clinical characteristics，pathogen distribution，and antibiotic resistance were compared between the two groups.Results:A total of 98 cases were included，with 81 in the Gram-positive group and 17 in the Gram-negative group.Multivariate logistic regression analysis revealed that NS cases with a high neutrophil percentage（ OR=0.933，95% CI：0.899-0.969）or hemorrhagic symptoms/signs（ OR=0.059，95% CI：0.008-0.458）were less likely to have Gram-positive pathogens detected in blood or CSF cultures（ P<0.05）.Common Gram-positive pathogens included Staphylococcus epidermidis with 35 strains（33.65%）and Staphylococcus hominis with 22 strains（21.15%）.The predominant Gram-negative pathogen was Escherichia coli with 14 strains（13.46%）.Gram-positive pathogens exhibited high resistance to oxacillin（91.30%），erythromycin（90.91%），and penicillin G（90.00%），but low resistance to tigecycline（0），linezolid（0），and vancomycin（0）.Gram-negative pathogens showed high resistance to ampicillin（92.31%），cefazolin（90.00%），and ampicillin/sulbactam（75.00%），but low resistance to amikacin（6.25%），latamoxef（0），and ertapenem（0）.The incidence of concurrent purulent meningitis was lower in the Gram-positive group than in the Gram-negative group（9.88% vs.47.06%， χ2=11.628， P<0.05），and there was significant difference. Conclusion:NS cases with high neutrophil percentages or hemorrhagic symptoms/signs are less likely to be caused by Gram-positive pathogens.Staphylococcus epidermidis and Staphylococcus hominis are common Gram-positive pathogens，while Escherichia coli is the predominant Gram-negative pathogen in NS.Both Gram-positive and Gram-negative pathogens exhibit resistance to specific antibiotics.NS caused by Gram-positive pathogens is less likely to be complicated by purulent meningitis compared to those caused by Gram-negative pathogens.

Objective To explore the effect of Yinchenhao Decoction plus Zexie Decoction on ferroptosis mediated by IRE1 signaling pathway of endoplasmic reticulum stress in NASH mice.Methods Fifty C57BL/6J mice were randomly divided into blank control group,model group,Yinchenhao decoction group,Zexia decoction group and Hefang group,with 10 mice in each group.Except the blank control group,the other groups were fed with high-fat diet.After 20 weeks,Yinchenhao Tang group,Zexia Tang group and Hefang group were respectively given the corresponding drug by intragastric administration,once a day for 8 weeks.HE staining,oil red O staining and Masson staining were used to observe the pathological changes of liver tissue,automatic biochemical analyzer was used to detect blood lipid and liver function indexes,and RT-qPCR was used to detect the mRNA levels of TFR1,FPN,XBP1,Xbp1s and XBP1-dependent UPR target genes.The expressions of GRP78,P-IRE1α,GPX4,TFR1 and FPN proteins in liver were detected by Western Blot,the contents of Fe2+and MDA were detected by colorimetry,SOD activity was detected by WST-8,ROS content was detected by ELISA,and TG content in mouse liver tissue was detected by GPO-PAP.Results Compared with the model group,the NAS scores of Yinchenhao Tang group,Zexia Tang group and Hefang group were significantly reduced,and the effect of Hefang group was more significant.Compared with the blank control group,the liver lipid deposition of model mice was obvious,and the liver lipid deposition of Yinchenhao Tang group,Zexia group and Hefang group were improved to varying degrees,and the effect of Hefang group was more significant.Masson staining results showed that compared with blank control group,liver fibrosis was obvious in model group,Yinchenhao Decoction group,Zexia group and Hefang group,the degree of liver fibrosis was improved,and the effect of Hefang group was more significant.Compared with the blank control group,the levels of serum TC,HDL-C,LDL-C,AST and ALT in the model group were significantly increased,the contents of TG,Fe2+,MDA and ROS in the liver were significantly increased,and the activity of SOD was significantly decreased.The mRNA expression levels of Xbp1,Xbp1s,Dnajb9,Edem1,Sec61a1,Bip,Chop and TFR1were significantly up-regulated,the mrna expression levels of FPN were significantly down-regulated,and the protein expression levels of GRP78,P-IREα,GPX4 and TFR1 in liver were significantly increased.The expression level of FPN protein decreased significantly.Compared with model group,the serum levels of TG,TC,LDL-C,AST and ALT in the combined formula group were significantly decreased,the contents of TG,Fe2+,MDA and ROS in the liver of the combined formula group were significantly decreased,and the activity of SOD was significantly increased.The mRNA expression levels of Xbp1,Xbp1s,Dnajb9,Edem1,Sec61a1,Bip,Cho and TFR1 in liver were significantly decreased,the mrna expression level of FPN was significantly increased,and the protein expression levels of GRP78,P-IRE1α,GPX4 and TFR1 in liver were significantly down-regulated.The expression level of FPN protein was significantly up-regulated.Conclusion Yinchenhao Decoction plus Zexie Decoction may ameliorate NASH by inhibiting ferroptosis of hepatocytes through IRE1α pathway of endoplasmic reticulum stress.

Objective To explore the effect of Yinchenhao Decoction plus Zexie Decoction on ferroptosis mediated by IRE1 signaling pathway of endoplasmic reticulum stress in NASH mice.Methods Fifty C57BL/6J mice were randomly divided into blank control group,model group,Yinchenhao decoction group,Zexia decoction group and Hefang group,with 10 mice in each group.Except the blank control group,the other groups were fed with high-fat diet.After 20 weeks,Yinchenhao Tang group,Zexia Tang group and Hefang group were respectively given the corresponding drug by intragastric administration,once a day for 8 weeks.HE staining,oil red O staining and Masson staining were used to observe the pathological changes of liver tissue,automatic biochemical analyzer was used to detect blood lipid and liver function indexes,and RT-qPCR was used to detect the mRNA levels of TFR1,FPN,XBP1,Xbp1s and XBP1-dependent UPR target genes.The expressions of GRP78,P-IRE1α,GPX4,TFR1 and FPN proteins in liver were detected by Western Blot,the contents of Fe2+and MDA were detected by colorimetry,SOD activity was detected by WST-8,ROS content was detected by ELISA,and TG content in mouse liver tissue was detected by GPO-PAP.Results Compared with the model group,the NAS scores of Yinchenhao Tang group,Zexia Tang group and Hefang group were significantly reduced,and the effect of Hefang group was more significant.Compared with the blank control group,the liver lipid deposition of model mice was obvious,and the liver lipid deposition of Yinchenhao Tang group,Zexia group and Hefang group were improved to varying degrees,and the effect of Hefang group was more significant.Masson staining results showed that compared with blank control group,liver fibrosis was obvious in model group,Yinchenhao Decoction group,Zexia group and Hefang group,the degree of liver fibrosis was improved,and the effect of Hefang group was more significant.Compared with the blank control group,the levels of serum TC,HDL-C,LDL-C,AST and ALT in the model group were significantly increased,the contents of TG,Fe2+,MDA and ROS in the liver were significantly increased,and the activity of SOD was significantly decreased.The mRNA expression levels of Xbp1,Xbp1s,Dnajb9,Edem1,Sec61a1,Bip,Chop and TFR1were significantly up-regulated,the mrna expression levels of FPN were significantly down-regulated,and the protein expression levels of GRP78,P-IREα,GPX4 and TFR1 in liver were significantly increased.The expression level of FPN protein decreased significantly.Compared with model group,the serum levels of TG,TC,LDL-C,AST and ALT in the combined formula group were significantly decreased,the contents of TG,Fe2+,MDA and ROS in the liver of the combined formula group were significantly decreased,and the activity of SOD was significantly increased.The mRNA expression levels of Xbp1,Xbp1s,Dnajb9,Edem1,Sec61a1,Bip,Cho and TFR1 in liver were significantly decreased,the mrna expression level of FPN was significantly increased,and the protein expression levels of GRP78,P-IRE1α,GPX4 and TFR1 in liver were significantly down-regulated.The expression level of FPN protein was significantly up-regulated.Conclusion Yinchenhao Decoction plus Zexie Decoction may ameliorate NASH by inhibiting ferroptosis of hepatocytes through IRE1α pathway of endoplasmic reticulum stress.

Objective:To investigate the application effect of the compound flap transfer in tubularized incised plate (TIP) urethroplasty.Methods:Children with hypospadias who received TIP in the Department of Pediatric Urology, the Affiliated Xuzhou Children’s Hospital of Xuzhou Medical University from January 2018 to March 2022 were prospectively divided into compound flap transfer group (group A) and traditional TIP group (group B) by random number method. Group A was treated with TIP modified by compound flap transfer, and group B was treated with traditional TIP covered with fascia.The improvement of the compound flap transfer for TIP operation is mainly reflected in the multi-layer cover of the new urethra and the free skin embedded in the incision of the penile head. According to the intention-to-treat (ITT) principle, the final full analysis set (FAS) includes both group A and group B. Some patients were excluded from the analysis of the primary endpoint events due to reasons such as loss to follow-up or treatment group switch. Additionally, the final per-protocol set (PPS) consisting of group A and group B, which adheres to the study protocol, is subjected to statistical analysis.Independent sample t-test or Wilcoxon rank sum test was used for average age, the width of the penile head, degree of chordee, length of neourethra, and operative time. The classification of hypospadias, proportion of dorsal tunica albuginea plication, and incidence of postoperative complications were compared using the Chi-square test or Fisher’s exact test, P < 0.05 was considered statistically significant. Results:According to ITT principles, 50 children were included in FAS group A, ranging in age from 8 months to 15 years and 2 months, with an average age of 4 years. Group B included 50 children, ranging in age from 10 months to 14 years and 9 months, with an average age of 4 years and 1 month. Thirty-seven children in PPS group A were included, ranging in age from 1 year 2 months to 12 years 1 month, with an average age of 4 years. Group B consisted of 41 children, ranging in age from 1 year 2 months to 11 years 9 months, with an average age of 4 years 2 months. Statistical analysis showed that no matter FAS set or PPS, there were no statistically significant differences in the mean age, hypospadias type, average penile head width, average penile subcurvature number, number of dorsal tunica albuginea plication, and the average length of plastic neourethra between group A and group B ( P > 0.05). The average operative time of group A was higher than that of group B. The difference was statistically significant ( P < 0.05). The postoperative follow-up was 3 to 48 months, with an average follow-up of 2 years and 3 months. The complication rate of group A was lower than that of group B [10.81% (4/37) vs 29.27% (12/41)], and the difference was statistically significant ( P< 0.05). Urethral fistula occurred in 3 cases (8.11%), respectively and 6 cases (14.63%) in the two groups, the difference was not statistically significant ( P>0.05); urethral stricture occurred in 1 case (2.70%) and 5 cases (12.20%) respectively, the difference was not statistically significant ( P>0.05), There were 0 case and 1 case (2.44%) of urethral orifice descending or urethral dehiscence respectively, and the difference was not statistically significant ( P> 0.05). Conclusion:TIP with an improved compound flap transfer can reduce the overall postoperative complication rate and is worthy of promotion.

OBJECTIVE To evaluate the effectiveness， safety， economy， innovation， suitability and accessibility of recombinant Mycobacterium tuberculosis fusion protein （EC）， and to provide evidence for selecting skin detection methods for tuberculosis infection diagnosis and auxiliary diagnosis of tuberculosis. METHODS The effectiveness and safety of EC compared with purified protein derivative of tuberculin （TB-PPD） were analyzed by the method of systematic review. Cost minimization analysis， cost-effectiveness analysis and cost-utility analysis were used to evaluate the short-term economy of EC compared with TB-PPD， and cost-utility analysis was used to evaluate the long-term economy. The evaluation dimensions of innovation， suitability and accessibility were determined by systematic review and improved Delphi expert consultation， and the comprehensive score of EC and TB-PPD in each dimension were calculated by the weight of each indicator. RESULTS The scores of effectiveness， safety， economy， innovation and suitability of EC were all higher than those of TB-PPD. The affordability scores of the two drugs were consistent， while the availability score of EC was lower than those of TB-PPD. After considering dimensions and index weight， the scores of effectiveness， safety， economy， innovation， suitability， accessibility and the comprehensive score of EC were all higher than those of TB-PPD. CONCLUSIONS Compared with TB-PPD， EC performs better in all dimensions of effectiveness， safety， economy， innovation， suitability and accessibility. However， it is worth noting that EC should further improve its availability in the dimension of accessibility.

Objective:To investigate the application effect of the compound flap transfer in tubularized incised plate (TIP) urethroplasty.Methods:Children with hypospadias who received TIP in the Department of Pediatric Urology, the Affiliated Xuzhou Children’s Hospital of Xuzhou Medical University from January 2018 to March 2022 were prospectively divided into compound flap transfer group (group A) and traditional TIP group (group B) by random number method. Group A was treated with TIP modified by compound flap transfer, and group B was treated with traditional TIP covered with fascia.The improvement of the compound flap transfer for TIP operation is mainly reflected in the multi-layer cover of the new urethra and the free skin embedded in the incision of the penile head. According to the intention-to-treat (ITT) principle, the final full analysis set (FAS) includes both group A and group B. Some patients were excluded from the analysis of the primary endpoint events due to reasons such as loss to follow-up or treatment group switch. Additionally, the final per-protocol set (PPS) consisting of group A and group B, which adheres to the study protocol, is subjected to statistical analysis.Independent sample t-test or Wilcoxon rank sum test was used for average age, the width of the penile head, degree of chordee, length of neourethra, and operative time. The classification of hypospadias, proportion of dorsal tunica albuginea plication, and incidence of postoperative complications were compared using the Chi-square test or Fisher’s exact test, P < 0.05 was considered statistically significant. Results:According to ITT principles, 50 children were included in FAS group A, ranging in age from 8 months to 15 years and 2 months, with an average age of 4 years. Group B included 50 children, ranging in age from 10 months to 14 years and 9 months, with an average age of 4 years and 1 month. Thirty-seven children in PPS group A were included, ranging in age from 1 year 2 months to 12 years 1 month, with an average age of 4 years. Group B consisted of 41 children, ranging in age from 1 year 2 months to 11 years 9 months, with an average age of 4 years 2 months. Statistical analysis showed that no matter FAS set or PPS, there were no statistically significant differences in the mean age, hypospadias type, average penile head width, average penile subcurvature number, number of dorsal tunica albuginea plication, and the average length of plastic neourethra between group A and group B ( P > 0.05). The average operative time of group A was higher than that of group B. The difference was statistically significant ( P < 0.05). The postoperative follow-up was 3 to 48 months, with an average follow-up of 2 years and 3 months. The complication rate of group A was lower than that of group B [10.81% (4/37) vs 29.27% (12/41)], and the difference was statistically significant ( P< 0.05). Urethral fistula occurred in 3 cases (8.11%), respectively and 6 cases (14.63%) in the two groups, the difference was not statistically significant ( P>0.05); urethral stricture occurred in 1 case (2.70%) and 5 cases (12.20%) respectively, the difference was not statistically significant ( P>0.05), There were 0 case and 1 case (2.44%) of urethral orifice descending or urethral dehiscence respectively, and the difference was not statistically significant ( P> 0.05). Conclusion:TIP with an improved compound flap transfer can reduce the overall postoperative complication rate and is worthy of promotion.

OBJECTIVE: To investigate the effect of calmodulin (CaM) and its mutants on binding to voltage-gated Na channel isoleucine-glutamine domain (Na1.2 IQ). METHODS: The cDNA of Na1.2 IQ was constructed by PCR technique, CaM mutants CaM, CaM and CaM were constructed with Quickchange site-directed mutagenesis kit (QIAGEN). The binding of Na1.2 IQ to CaM and CaM mutants under calcium and calcium free conditions were detected by pull-down assay. RESULTS: Na1.2 IQ and CaM were bound to each other at different calcium concentrations, while GST alone did not bind to CaM. The binding affinity of CaM and Na1.2 IQ at [Ca]-free was greater than that at 100 nmol/L [Ca] ( < 0.05). In the absence of calcium, the binding amount of CaM wild-type to Na1.2 IQ was greater than that of its mutant, and the binding affinity of CaM to Na1.2 IQ was the weakest among the three mutants ( < 0.05). CONCLUSIONS The binding ability of CaM and CaM mutants to Na1.2 IQ is Ca-dependent. This study has revealed a new mechanism of Na1.2 regulated by CaM, which would be useful for the study of ion channel related diseases.
Calcium ; metabolism ; Calmodulin ; genetics ; metabolism ; Mutation ; NAV1.2 Voltage-Gated Sodium Channel ; metabolism ; Protein Binding ; genetics

Objective To investigate the features of risk factors of minor stroke with CISS classification in Guangdong Province. Methods We retrospectively investigated the patients admitted within 3 days of the occurrence of a minor stroke, and were classified by CISS criteria as large artery atherosclerosis (LAA), cardiogenic stroke (CS), penetrating artery disease (PAD), other etiology (OE), undetermined etiology (UE). Results In this study, 303 pa-tients met the inclusion criteria of minor stroke. The highest percentage of the risk factors included hypertension (72.3%), hyperlipidemia (58.3%), and diabetes mellitus (39.9%). Among different subtypes, 41.9% were diagnosed with LAA, and 50.8% with PAD. Plasma triglyceride (TG)(1.765 ±1.18)mg/L vs.(2.19 ±1.84)mg/L,P=0.03], apolipoproteinsB (ApoB) [(0.95±0.29)mg/L vs.(1.11±0.46)mg/L,P=0.009]C-reactive protein (CRP) [(6.63±11.30) mg/L vs.(3.42 ±5.02)mg/L,P=0.042] and ApoB/ApoA1 ratio [(0.754 ±0.25)mg/L vs.(0.875 ±0.49)mg/L,P=0.019], differed significantly between group LAA and PAD. Conclusion Hypertension, hyperlipidemia and diabetes mellitus are the major risk factors of minor stroke. The most common subtypes of the minor stroke patients in Guangdong Province are LAA and PAD, and detecting their TG, apoB, CRP level and apoB/apoA1 ratio might help subclassify minor stroke according to CISS.

Animals ; COS Cells ; Cercopithecus aethiops ; Endoplasmic Reticulum ; GTP Phosphohydrolases ; antagonists & inhibitors ; chemistry ; genetics ; metabolism ; GTP-Binding Proteins ; antagonists & inhibitors ; chemistry ; genetics ; metabolism ; Gene Expression ; Genetic Complementation Test ; HeLa Cells ; Humans ; Kinetics ; Membrane Fusion ; genetics ; Membrane Proteins ; antagonists & inhibitors ; chemistry ; genetics ; metabolism ; Protein Multimerization ; RNA, Small Interfering ; genetics ; metabolism ; Recombinant Proteins ; chemistry ; genetics ; metabolism ; Saccharomyces cerevisiae ; genetics ; metabolism ; Saccharomyces cerevisiae Proteins ; genetics ; metabolism ; Vesicular Transport Proteins ; genetics ; metabolism