Objective To elucidate the potential mechanisms by which mesothelin(MSLN)contributes to chemotherapy resistance in high-grade serous ovarian cancer(HGSOC).Methods A Meta-analysis utilizing public ovarian cancer databases was performed to evaluate the correlation between MSLN expression levels and overall survival(OS)in ovarian cancer patients.Pathway enrichment analysis was employed to identify key signaling pathways regulated by MSLN and their roles in chemotherapy resistance.Additionally,the TCGA-HGSOC database was analyzed to examine genomic features associated with MSLN-mediated chemotherapy resistance.To validate the biological function of MSLN in chemotherapy resistance,an intraperitoneal metastasis model was established using MSLN-knockdown ID8 ovarian cancer cells in mice.Results Elevated MSLN expression was significantly associated with poor patient prognosis(HR:1.42,95%CI:1.16-1.74).Differential gene expression and pathway enrichment analyses revealed that high MSLN expression upregulates resistance-associated genes and pathways involved in drug metabolism and DNA-binding signaling.Genomic association analysis showed a negative correlation between high MSLN expression and chromosomal instability features,specifically CX3,CX11,and CX13 scores.In vivo studies demonstrated that MSLN knockdown enhanced the tumor-suppressive effects of cisplatin.Conclusion High MSLN expression represents a potential biomarker for poor prognosis and chemotherapy resistance in HGSOC patients,suggesting MSLN as a promising target for therapeutic intervention.

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

As the operation volume in hospitals is increasing year by year, surgical instruments are widely used, which pose a great challenge to the daily management of surgical instruments. The authors investigated the existing problems which occurred in the management of surgical instruments, and came out with instruments coding navigation index and specialized placement scheme for the operating room as solutions. The specific measures included dividing sterile items into specialized categories, setting cabinets respectively for specialized and general subjects, building equipment coding and identification, establishing surgical instruments navigation index and carrying out training program, to serve as reference for efficient and fine management of surgical instruments.

Objective To understand Clonorchis sinensis infections in cats in Nanning City, so as to provide evidence for the control of the reservoir host of C. sinensis. Methods The cat livers were purchased from cat slaughterhouses in Nanning City. The cat gallbladder and liver were dissected, and liver flukes were collected and counted. Then, the worms were subjected to morphological observation, amplification of the ITS2 gene and sequencing. The species of the worms were identified using BLAST. Results A total of 105 cat livers were collected from two cat slaughterhouses, and 68 were detected with C. sinensis infections, with an infection rate of 64.76%. The highest burden was 980 worms in a single liver, and the mean burden was 72 worms in a liver. There were 3 types of liver flukes with various size and morphology, and all were identified as C. sinensis by means of morphological observation, ITS2 gene amplification, sequencing and sequence alignment. Conclusion There is a high infection rate of C. sinensi in marketed cats in Nanning City, and it is therefore suggested that targeted interventions should be intensified for the management of C. sinensis infections in cats.

OBJECTIVE: To analyze the expression of CCR7 and Tim-3 in childhood patients with acute lymphoblastic leukemia (ALL) and their predictive value for prognosis. METHODS: Eighty-six newly diagnosed ALL childhood patients from January 2007 to January 2017 treated in our hospital were selected. The expression level of CCR7 and Tim-3 in bone marrow isolated cells of ALL patients were detected by flow cytometry, all the patients were divided into the recurrence group and non-recurrence group according to the follow-up results, the differences in the expressions of CCR7, Tim-3 between the two groups were compared. The correlation between the expression of CCR7 , Tim-3 and the clinicopathologic features of ALL patients were analyzed, the predictive value of CCR7 and Tim-3 for the prognosis of newly ALL patients were evaluated by ROC curve, and the relationship between serum CCR7, Tim-3 and prognosis were analyzed. RESULTS: The expression levels of CCR7 and Tim-3 in recurrence group were significantly higher than those in non-recurrence group(P<0.05). The critical value of CCR7 for diagnosis of recurrence was 45.97%, the sensitivity was 66.7%, the specificity was the 84.5% and the area under ROC curve (AUC) was 0.798 (95CI 0.777-0.939). The critical value of Tim-3 for diagnosis of recurrence was 53.54%, the sensitivity was 73.3%, the specificity was the 80.3% and the AUC was 0.806 (95CI 0.792-0.947). The AUC of the combined detection of CCR7 and Tim-3 was 0.895 (95CI 0.914-0.996), sensitivity 86.6%, specificity 78.9% (P<0.05); There was no significant correlation between CCR7, Tim-3 expression and age, sex, hemoglobin concentration, number of white blood cells, bone marrow blasts, platelets, central nervous system invasion, fusion gene (P>0.05). The exogenous infiltration rate of patients with high expression of CCR7 and Tim-3 was significantly higher than those in low expression group (P<005). The high expression rate 76.9% of Tim-3 in patients with T-ALL was significantly higher than that of B-ALL patients with Tim-3 high expression rate 45.2% (P<0.05). The median OS of patients with CCR7 level ≥45.97% and <45.97% were 9.3 months and 13.6 months respectively(P=0.004), and the Tim-3≥53.54% and Tim-3<53.54% were 9.1 months and 13.6 months respectively(P=0.001). The results of Cox's multi-factor regression analysis showed that CCR7 level(HR=1.024, 95 CI 1.001-1.049) and Tim-3 level (HR=1.879, 95 CI 1.183- 2.985) were the independent risk factors that affect the OS in ALL patients(P<0.05). CONCLUSION The expression of CCR7 and Tim-3 in bone marrow isolated cells of ALL patients shows good predictive value for prognosis, and the combination of CCR7 and Tim-3 can improve the sensitivity of the detection, the higher expression of CCR7 and Tim-3 can be used as potential indexes in prognosis evaluate.
Bone Marrow ; Child ; Hepatitis A Virus Cellular Receptor 2 ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Receptors, CCR7

BACKGROUNDSmD1-amino-acid 83-119 peptide (SmD183-119) is the major epitope of Smith (Sm) antigen, which is specific for adult systemic lupus erythematosus (SLE). The anti-SmD183-119 antibody has exhibited higher sensitivity and specificity than anti-Sm antibody in diagnosing adult SLE. However, the utility of anti-SmD183-119antibodies remains unclear in children with SLE (cSLE). This study aimed to assess the characteristics of anti-SmD183-119antibody in the diagnosis of cSLE.

METHODSSamples from 242 children with different rheumatological and immunological disorders, including autoimmune diseases (SLE [n = 46] and ankylosing spondylitis [AS, n = 11]), nonautoimmune diseases (Henoch-Schonlein purpura [HSP, n = 60], idiopathic thrombocytopenia purpura [n = 27], hematuria [n = 59], and arthralgia [n = 39]) were collected from Shanghai Children's Medical Center from March 6, 2012 to February 27, 2014. Seventy age- and sex-matched patients were enrolled in this study as the negative controls. All the patients' sera were analyzed for the anti-SmD183-119, anti-Sm, anti-U1-nRNP, anti-double-stranded DNA (dsDNA), anti-nucleosome, anti-SSA/Ro60, anti-SSA/Ro52, anti-SSB, anti-Scl-70, and anti-histone antibodies using the immunoblotting assay. The differences in sensitivity and specificity between anti-SmD183-119 and anti-Sm antibodies were compared by Chi-square test. The correlations between anti-SmD183-119and other auto-antibodies were analyzed using the Spearman's correlation analysis. A value of P< 0.05 was considered statistically significant.

RESULTSThirty-six out of 46 patients with cSLE were found to be positive for anti-SmD183-119, while 12 patients from the cSLE cohort were found to be positive for anti-Sm. Compared to cSLE, it has been shown that anti-SmD183-119 was only detected in 27.3% of patients with AS and 16.7% of patients with HSP. In comparison with anti-Sm, it has been demonstrated that anti-SmD183-119 had a higher sensitivity (78.3% vs. 26.1%, χ2 = 25.1, P< 0.05) and a lower specificity (90.8% vs. 100%, χ2 = 13.6, P< 0.05) in the diagnosis of cSLE. Further analysis revealed that anti-SmD183-119antibodies were positively correlated with anti-dsDNA, anti-nucleosome, and anti-histone antibodies in cSLE. Moreover, it has been clearly shown that anti-SmD183-119 was more sensitive than anti-Sm in discriminating autoimmune diseases from nonautoimmune disorders in patients with arthralgia or hematuria.

CONCLUSIONSMeasurement of anti-SmD183-119in patients with cSLE has a higher sensitivity and a marginally lower specificity than anti-Sm. It has been suggested that inclusion of anti-SmD183-119testing in the integrated laboratory diagnosis of cSLE may significantly improve the overall sensitivity in child populations.

Autoantibodies ; immunology ; Autoantigens ; immunology ; Child ; Female ; Humans ; Immune System Diseases ; immunology ; Immunoblotting ; Lupus Erythematosus, Systemic ; immunology ; Male ; Peptides ; chemistry ; immunology ; snRNP Core Proteins ; immunology

Objective To explore the clinical effect of Shenqifuzheng injection combined with CAF regmien on expression of soluble interleukin 2 receptor(sIL2R), interleukin 6(IL-6), tumor necrosis factor alpha ( TNF-α) in breast cancer patients.Methods One hundred and sixty patients with mammary cancer were randomly divided into the observed group(n=80) and patients in the control group(n=80).They all ac-cepted the treatment of CAF regmien, and patients in the observed group accepted the treatment of Shenqifuzheng injection as well.The concentra-tion of sIL2R, IL -6 and TNF -αwere detected by enzyme -linked immunosorbent assay before and after treatment.Results After treat-ment, the effective rate in the observed group(55.00%) was significant-ly higher than that in the control group(38.75%)(P<0.05);the con-centration of sIL2R, IL-6 and TNF-αafter treatment were significantly lower than those before treatment in the both of the two groups (P<0.01);the concentration of sIL2R, IL-6 and TNF-αin the ob-served group was significantly lower than those in the control group ( P<0.01);the incidence of adverse reactions like blood cells reduce in the observed group ( 35.00%) was significantly lower than that in the control group(52.50%)(P<0.05).Conclusion shenqifuzheng injec-tion could reduce the concentration of sIL2R, IL -6 and TNF -αin breast cancer patients, improve the clinical efficacy, and reduce the adverse reactions.

Objective To explore the effect of the combination of Weifu-chun and retinoic acid on the expression of Rb Gene and C -erbB -2 Gene in the patients with gastric precancerous lesions.Methods One hundred and fifteen patients with gastric precancerous lesions were ran-domly divided into the observed group ( n =60 ) and the control group ( n=60 ).the group were all given omeprazole enteric -coated capsules and hydrotalcite tablets , and at the same time the observed group was ad-ministrated with Weifuchun ( 1.436 g every time , tid ) and retinoic acid (10 mg every time,tid).The expressions of Rb gene and C -erbB-2 gene were detected by immunohistochemistry and compared after 12 months treatment.Results The positive rate of Rb gene after treatment in the observed group(87.93%) was significantly higher than that before treatment in the observed group (68.97%) and after treatment in the con-trol group(71.93%)(P<0.05).The positive rate of C-erbB-2 gene after treatment in the observed group ( 12.07%) was significantly lower than that before treatment in the observed group ( 34.48%) and after treatment in the control group(29.82%)(P<0.05).Conclusion We-ifuchun and retinoic acid could medicate the expressions of gene Rb and C-erbB-2.

This study was purposed to explore the effects induced by puerariae radix flavones (PRF) on human acute myeloid leukemia SHI-1 cells, apoptosis induced by PRF in vitro and its molecular mechanism. SHI-1 cells were treated with PRF in various concentration, then the inhibitory effect of cell proliferation were detected by MTT method, the cell cycle was analyzed by flow cytometry, the mRNA expression levels of Caspase-3, Caspase-8, Caspase-9, Bcl-2 and MLL-AF6 were detected by real-time polymerase chain reaction (R-T PCR), the protein expression levels of MAPK, p-MAPK and NF-κB were assayed by Western blot, and the activity of MMP was analyzed by Gelatin zymography. The results indicated that the PRF could inhibit the proliferation of SHI-1 cells in a time-and dose-dependent manner, and the cell cycle was arrested in S phase. When SHI-1 cells were treated with 25, 50 and 75 µg/ml PRF respectively, mRNA levels of Caspase-3, Caspase-8 and Caspase-9 increased in a dose-dependent manner (P < 0.05), Bcl-2 mRNA decreased in a concentration-dependent manner (P > 0.05), and the mRNA level of fusion gene MLL-AF6 did not changed as compared with the control group. Different concentration of PRF was used to treat SHI-1 cells, the expression levels of intracellular JNK, p-JNK, P38 MAPK and p-P38 MAPK increased in the concentration-dependent manner (P < 0.01); the expression of p-ERK1/2 and NF-κB decreased in the concentration-dependent manner, and the activity of MMP-2 and MMP-9 in the cell supernatant did not change in each groups. It is concluded that a certain concentration of PRF can induce the apoptosis of SHI-1 cells in vitro, its molecular mechanism may be related to the activation of Caspase hydrolase, activation of MAPK, downregulation of NF-κB, Bcl-2 and other signal molecules. However, it seemed that all these effects are not relate with the MLL-AF6 fusion gene.
Apoptosis ; drug effects ; Cell Line, Tumor ; Flavones ; pharmacology ; Humans ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Myeloid-Lymphoid Leukemia Protein ; metabolism ; NF-kappa B ; metabolism ; Oncogene Proteins, Fusion ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Pueraria ; chemistry ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVETo compare the apical microleakage of Vitapex (calcium hydroxide based paste) with that of AH-plus and zinc oxide eugenol sealer when used with laterally condensed gutta percha obturation technique.

METHODSOne hundred single rooted human anterior teeth were instrumented and randomly divided into three experimental groups (A, B, C) of 30 teeth each and two control groups (D, E) of 5 teeth each. Group A was filled with laterally condensed gutta-percha using Vitapex as sealer. Group B was filled with laterally condensed gutta-percha using AH-plus as sealer. Group C was filled with laterally condensed gutta-percha using zinc oxide eugenol as sealer. Group D was the positive control. Group E was the negative control, which were coated with nail polish to entire root surface. Teeth were then suspended in 2% methylene blue. After this, teeth were demineralized dehydrated and cleared. Linear dye penetration was determined under stereomicroscope with calibrated eye piece.

RESULTSThe mean dye penetration for group A, B, C were respectively (0.57 +/- 0.56) mm, (0.79 +/- 0.96) mm and (1.07 +/- 1.12) mm. Group D demonstrated maximum dye penetration. Group E showed no dye penetration. There was no statistically significant difference between group B and group C (P > 0.05). However, there was statistically significant difference between group A and group B, C (P < 0.01).

CONCLUSIONThis study showed that Vitapex used as endodontic sealer material are better than AH-plus sealer and zinc oxide eugenol sealer.

Calcium Hydroxide ; Dental Leakage ; Dental Pulp Cavity ; Gutta-Percha ; Humans ; Molar ; Root Canal Filling Materials ; Root Canal Obturation ; Silicones ; Zinc Oxide-Eugenol Cement