Risk stratification of hemodynamically significant patent ductus arteriosus by clinical and genetic factors.

BACKGROUND: Hemodynamically significant patent ductus arteriosus (hsPDA) is associated with increased comorbidities in neonates. Early evaluation of hsPDA risk is critical to implement individualized intervention. The aim of the study was to provide a powerful reference for the early identification of high-risk hsPDA population and early treatment decisions. METHODS: We enrolled infants who were diagnosed with PDA and performed exome sequencing. The collapsing analyses were used to find the risk gene set (RGS) of hsPDA for model construction. The credibility of RGS was proven by RNA sequencing. Multivariate logistic regression was performed to establish models combining clinical and genetic features. The models were evaluated by area under the receiver operating curve (AUC) and decision curve analysis (DCA). RESULTS: In this retrospective cohort study of 2199 PDA patients, 549 (25.0%) infants were diagnosed with hsPDA. The model [all clinical characteristics selected by least absolute shrinkage and selection operator regression (all CCs)] based on six clinical variables was acquired within three days of life, including gestational age (GA), respiratory distress syndrome (RDS), the lowest platelet count, invasive mechanical ventilation, and positive inotropic and vasoactive drugs. It has an AUC of 0.790 [95% confidence interval (CI) = 0.749-0.832], while the simplified model (basic clinical characteristic model) including GA and RDS has an AUC of 0.753 (95% CI = 0.706-0.799). There was a certain consistency between RGS and differentially expressed genes of the ductus arteriosus in mice. The AUC of the models was improved by RGS, and the improvement was significant (all CCs vs. all CCs + RGS: 0.790 vs. 0.817, P < 0.001). DCA demonstrated that all models were clinically useful. CONCLUSIONS: Models based on clinical factors were developed to accurately stratify the risk of hsPDA in the first three days of life. Genetic features might further improve the model performance. Video Abstract (MP4 86834 kb).

[Clinical practice of whole-genome sequencing in the rapid diagnosis of critically ill neonates]. / é‡‡ç”¨å ¨åŸºå› ç»„æµ‹åºæŠ€æœ¯å¿«é€Ÿè¯Šæ–­å±é‡ç—‡æ–°ç”Ÿå„¿çš„ä¸´åºŠå®žè·µ.

OBJECTIVES: To explore the application of whole-genome sequencing (WGS) in the rapid clinical diagnosis of critically ill neonates. METHODS: The critically ill neonates who admitted to the neonatal intensive care unit of Children's Hospital of Fudan University and underwent WGS from August to September, 2019 were enrolled in this prospective study. The genetic testing results and clinical outcome were analyzed with reference to the sequencing data and clinical features of the neonates. RESULTS: A total of 15 neonates were tested, among whom there were 9 boys and 6 girls. The main reason for hospitalization included abnormal breathing in 7 neonates, poor response in 2 neonates, feeding difficulty in 2 neonates, fever in 1 neonate, hypothermia in 1 neonate, preterm birth in 1 neonate, and convulsion in 1 neonate. The mean turn-around time was 4.5 days for WGS. Finally a genetic diagnosis was obtained for 3 neonates, with a positive diagnostic rate of 20% (3/15). Among the 3 neonates, 2 neonates were withdrawn from the treatment due to severe conditions and 1 neonate died on the day when the sample was sent for genetic testing, whose etiology could be explained by the results of genetic testing. CONCLUSIONS: WGS technique can provide a timely and effective diagnosis for critically ill neonates suspected of genetic diseases and provide genetic evidence for clinical treatment of critically ill cases.

Secondary genomic findings in the 2020 China Neonatal Genomes Project participants.

BACKGROUND: During next generation sequencing (NGS) data interpretation in critically ill newborns, there is a potential for recognizing and reporting secondary findings (SFs). Early awareness of SFs may provide clues for disease prevention. In this study, we assessed the frequency of SFs in the China Neonatal Genomes Project (CNGP) participants. METHODS: A total of 2020 clinical exome sequencing (CES) datasets were screened for variants from a list of 59 genes recommended by the American College of Medical Genetics and Genomics (ACMG) for secondary findings reporting v2.0 (ACMG SF v2.0). Identified variants were classified according to the evidence-based guidelines reached by a joint consensus of the ACMG and the Association for Molecular Pathology (AMP). RESULTS: Among the 2020 CES datasets, we identified 23 ACMG-reportable genes in 61 individuals, resulting in an overall frequency of SFs at 3.02%. A total of 53 unique variants were identified, including 35 pathogenic and 18 likely pathogenic variants. The common disease categories of SFs associated were cardiovascular and cancer disease. The SF results affected the medical management and follow-up strategy in 49 (80.3%) patients. CONCLUSIONS: We presented the frequency of SFs and their impact on clinical management strategies in CNGP participants. Our study demonstrated that SFs have important practical value in disease prevention and intervention at an early stage.

[Correlation of single nucleotide polymorphisms of the osteopontin gene with astheozoospermia].

OBJECTIVE: To investigate the correlation of the single nucleotide polymorphisms (SNP) rs1126772, rs117291487, rs11730582, rs142608941 and rs6813526 of the osteopontin (OPN) gene with the risk of asthenozoospermia (AZS). METHODS: We included 135 AZS patients in the AZS group and another 239 fertile men as normal controls. Using the SNaPshot technique, we genotyped the rs1126772, rs117291487, rs11730582, rs142608941 and rs6813526 polymorphisms of the OPN gene in all the subjects and analyzed the correlation of the five SNPs with AZS. RESULTS: The GA genotype and A allele of the OPN gene rs1126772 were found to be correlated with the risk of AZS (GA vs AA: OR = 0.55, 95% CI: 0.35－0.86, P = 0.009; A vs G: OR = 0.64, 95% CI: 0.46－0.89, P = 0.007), and so was the CT genotype and T allele at the RS11730582 locus (CT vs TT: OR = 0.526, 95% CI: 0.34－0.82, P = 0.009; T vs C: OR = 0.60, 95% CI: 0.44－0.83, P = 0.002). Haplotype analysis showed that the AATCT haplotype decreased the risk of AZS (AATCT: OR = 0.61, 95% CI: 0.42－0.88, P = 0.008) . CONCLUSIONS: The polymorphisms of the OPN gene RS1126772 and RS11730582 may reduce the risk of AZS.

Genetic etiologies associated with infantile hydrocephalus in a Chinese infantile cohort.

BACKGROUND: Infantile hydrocephalus (IHC) is commonly related to other central nervous system diseases, which may have adverse effects on prognosis. The causes of IHC are heterogeneous, and the genetic etiologies are not fully understood. This study aimed to analyze the genetic etiologies of an IHC cohort. METHODS: The data for 110 IHC patients who had received exome sequencing at the Clinical Genetic Center of the Children's Hospital of Fudan University between 2016 and 2019 were reviewed and analyzed retrospectively. An exome-wide association analysis (EWAS) was performed within this cohort using IHC as the study phenotype. RESULTS: Of the 110 IHC patients, a pathogenic or likely pathogenic variant was identified in 16 (15%) patients, spanning 13 genes. The genes were mainly associated with metabolic disorders, brain abnormalities, and genetic syndromes. IHC patients who had unclear clinical etiology were more likely to possess a genetic etiology. Based on previous studies and on our EWAS results, ZEB1, SBF2, and GNAI2 were over-represented among IHC patients and might affect the signaling pathways involved in IHC formation. CONCLUSIONS: Our study showed heterogeneous genetic etiologies in an IHC cohort. It is essential to perform genetic testing on IHC patients who have unclear clinical etiology, and genes associated with metabolic disorders, brain abnormalities, and genetic syndromes should be noted. In addition, when aiming to discover IHC susceptibility genes, genes that might influence the signaling pathways involved in IHC formation should be prioritized.

Association of LncRNA-GAS5 gene polymorphisms and PBMC LncRNA-GAS5 level with risk of systemic lupus erythematosus in Chinese population.

Growth arrest-specific 5 (GAS5) is a kind of long non-coding RNAs (lncRNAs). Previous studies showed that down-regulation of LncRNA-GAS5 was involved in the development of systemic lupus erythematosus (SLE). However, the regulatory mechanism of down-expressed LncRNA-GAS5 in SLE remains obscure. In this study, we aimed to investigate the association of LncRNA-GAS5 polymorphism with SLE risk. And further explore how LncRNA-GAS5 is involved in the occurrence of SLE. Here, we evaluated the relationship between the risk for the development of SLE and the 5-base pair (AGGCA/-) insertion/deletion (I/D) polymorphism (rs145204276) in the LncRNA-GAS5 promoter region. A custom 36-Plex SNPscan kit was used for genotyping the LncRNA-GAS5 polymorphisms. The LncRNA-GAS5 and miR-21 target prediction was performed using bioinformatics software. Enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR (qRT-PCR) were performed to assess GAS5 and miR-21 mRNA expression and PTEN protein expression. The results revealed that rs145204276 resulted in a decreased risk of SLE (DD genotypes vs II genotypes: adjusted OR = 0.538, 95% CI, 0.30-0.97, P = .039; ID genotypes vs II genotypes: adjusted OR = 0.641, 95% CI, 0.46-0.89, P = .007; ID/DD genotypes vs II genotypes: adjusted OR = 0.621, 95% CI, 0.46-0.84, P = .002; D alleles vs I alleles: adjusted OR = 0.680, 95% CI, 0.53-0.87, P = .002). A reduced incidence of renal disorders in SLE was found to be related to ID/DD genotypes and D alleles (ID/DD genotypes vs II genotypes: OR = 0.57, 95% CI, 0.36-0.92, P = .020; D alleles vs I alleles: OR = 0.63, 95% CI, 0.43-0.93, P = .019). However, no significant association of rs2235095, rs6790, rs2067079 and rs1951625 polymorphisms with SLE risk was observed (P > .05). Additionally, haplotype analysis showed that a decreased SLE risk resulted from the A-A-C-G-D haplotype (OR = 0.67, 95% CI, 0.49-0.91, P = .010). Also, patients in the SLE group showed a down-regulated expression of LncRNA-GAS5 and PTEN than the healthy volunteers; however, patients with rs145204276 ID/DD genotypes showed up-regulated expression of LncRNA-GAS5 and PTEN compared with patients carrying the II genotype. Furthermore, the miR-21 levels were considerably up-regulated in the SLE group than the healthy volunteers, and patients with rs145204276 ID/DD genotype had lower miR-21 levels than the ones with the II genotype. Thus, we found that the LncRNA-GAS5/miR-21/PTEN signalling pathway was involved in the development of SLE, where LncRNA-GAS5 acted as an miR-21 target, and miR-21 regulated the expression of PTEN. These findings indicated that the rs145204276 ID/DD genotypes in the LncRNA-GAS5 gene promoter region may be protected against SLE by up-regulating the expression of LncRNA-GAS5, which consecutively regulated miR-21 and PTEN levels.

The critical role of ASD-related gene CNTNAP3 in regulating synaptic development and social behavior in mice.

Accumulated genetic evidences indicate that the contactin associated protein-like (CNTNAP) family is implicated in autism spectrum disorders (ASD). In this study, we identified genetic mutations in the CNTNAP3 gene from Chinese Han ASD cohorts and Simons Simplex Collections. We found that CNTNAP3 interacted with synaptic adhesion proteins Neuroligin1 and Neuroligin2, as well as scaffolding proteins PSD95 and Gephyrin. Significantly, we found that CNTNAP3 played an opposite role in controlling the development of excitatory and inhibitory synapses in vitro and in vivo, in which ASD mutants exhibited loss-of-function effects. In this study, we showed that the male Cntnap3-null mice exhibited deficits in social interaction， spatial learning and prominent repetitive behaviors. These evidences elucidate the pivotal role of CNTNAP3 in synapse development and social behaviors, providing mechanistic insights into ASD.

A Genetic Variant of miR-34a Contributes to Susceptibility of Ischemic Stroke Among Chinese Population.

miRNAs are small non-coding RNAs modulating gene expression, and variants in miRNA genes are involved in the pathogenesis of ischemic stroke (IS). However, the effect of miR-34a polymorphisms on IS susceptibility has rarely been reported. In the present study, we investigated the association between rs12128240, rs2666433, and rs6577555 of the miR-34a gene and IS susceptibility. Snapshot assay was used to detect miR-34a polymorphisms in 548 IS patients and 560 controls. Relative expression of miR-34a was measured by quantitative real-time PCR. We found that rs2666433 was associated with a significantly increased risk of IS (AA vs. GG: OR = 1.61, 95% CI = 1.05-2.52, P = 0.031; AA vs. GG+GA: OR = 1.58, 95% CI = 1.05-2.45, P = 0.026). For the IS subtypes, rs2666433 was associated with large artery atherosclerosis (AA vs. GG: OR = 2.09, 95% CI = 1.16-3.51, P = 0.007; AA vs. GG+GA: OR = 2.02, 95% CI = 1.15-3.33, P = 0.007; A vs. G: OR = 1.36, 95% CI = 1.07-1.81, P = 0.021). Additionally, the level of miR-34a was significantly up-regulated in IS patients compared to the controls (P < 0.001), and patients with rs2666433 AA genotype had a higher level of miR-34a than those with GG+GA genotypes (P < 0.001). Furthermore, increased level of homocysteine was observed in IS patients compared to the controls (P < 0.001), especially in patients carrying the rs2666433AA genotype compared to those carrying the rs2666433 GG+GA genotypes (P < 0.001). However, no significant association between rs12128240 or rs6577555 and IS was found. Collectively, our study found the association between miR-34a polymorphisms and the risk of IS among the Chinese population. The results may provide an explanation for etiology of IS and a potential biomarker or therapeutic target for IS. HIGHLIGHTS-MiR-34a rs2666433 polymorphism was associated with an increased risk of ischemic stroke.-The level of miR-34a was significantly up-regulated in ischemic stroke patients compared with controls, and patients with rs2666433 AA genotype had a higher level miR-34a than those with GG+GA genotypes.-Furthermore, increased level of homocysteine was showed in IS patients compared to controls, and in patients carrying the rs2666433AA compared to those carrying the rs2666433 GG+GA.

Association between polymorphisms in the promoter region of miR-17-92 cluster and systemic lupus erythematosus in a Chinese population.

The aim of this study was to investigate the association of genetic polymorphisms in the promoter region of miR-17-92 with systemic lupus erythematosus (SLE). The gene polymorphism was analysed using SNaPshot in 312 SLE patients and 396 controls. Relative expression of miR-17-92 was measured by quantitative real-time PCR. Association was found between rs9515692 and a decreased risk of SLE (CT vs CC: OR = 0.65, 95%CI, 0.46-0.92, P = .014; CT+TT vs CC: OR = 0.64, 95%CI, 0.46-0.90, P = .009; T vs C: OR = 0.69, 95%CI, 0.52-0.92, P = .010, respectively). Haplotype analysis showed that C-G-G, C-A-A haplotypes were associated with an increased SLE risk (OR=4.46, 95%CI, 2.17-9.17, P < 0.001; OR=2.33, 95%CI, 1.44-3.76, P < 0.001, respectively). T allele and CT+TT genotypes in rs9515692 were associated with decreased risk of anti-dsDNA in SLE (CT+TT vs CC: OR = 0.42, 95%CI = 0.24-0.72, P = .002; T vs A: OR = 0.49, 95%CI = 0.31-0.79, P = .003). Moreover, rs9515692 CT+TT genotypes had a higher level of miR-17 as compared to CC genotype (P = .017). These findings suggest that the rs9515692 CT+TT genotypes were a protective factor for the susceptibility of SLE, probably by increasing the expression of miR-17.

Association of S100B polymorphisms and serum S100B with risk of ischemic stroke in a Chinese population.

The levels of serum S100B were elevated in patients with ischemic stroke (IS), which may be a novel biomarker for diagnosing IS. The aim of this study was to investigate the association of S100B polymorphisms and serum S100B with IS risk. We genotyped the S100B polymorphisms rs9722, rs9984765, rs2839356, rs1051169 and rs2186358 in 396 IS patients and 398 controls using polymerase chain reaction-single base extension (SBE-PCR). Serum S100B levels were measured by enzyme-linked immunosorbent assay (ELISA). Rs9722 was associated with an increased risk of IS (AA vs. GG: adjusted OR = 2.172, 95% CI, 1.175-4.014, P = 0.013; dominant: adjusted OR = 1.507, 95% CI, 1.071-2.123, P = 0.019; recessive: adjusted OR = 1.846, 95% CI, 1.025-3.323, P = 0.041; additive: adjusted OR=1.371, 95% CI, 1.109-1.694, P = 0.003). The A-C-C-C-A haplotype was associated with an increased risk of IS (OR = 1.325, 95% CI, 1.035-1.696, P = 0.025). In addition, individuals carrying the rs9722 GA/AA genotypes had a higher serum S100B compared with the rs9722 GG genotype in IS patients (P = 0.018). Our results suggest that the S100B gene rs9722 polymorphism may contribute to the susceptibility of IS, probably by promoting the expression of serum S100B.

Association of interleukin 13 gene polymorphisms and plasma IL 13 level with risk of systemic lupus erythematosus.

Interleukin (IL) 13 plays a critical role in inflammatory diseases, including systemic lupus erythematosus (SLE). This study aims to explore the potential association of IL-13 polymorphisms with the risk of SLE. We genotyped IL-13 rs20541, rs848 and rs1295686 using Snapshot SNP genotyping assays. Plasma IL-13 level was determined by enzyme-linked immunosorbent assay (ELISA). We found that rs20541 was associated with increased risk of SLE (CT vs. CC: adjusted OR=1.43, 95%CI, 1.04-1.99, P=.030; TT vs. CC: adjusted OR=1.73, 95%CI, 1.10-2.73, P=.018; CT/TT vs. CC: adjusted OR=1.50, 95%CI, 1.10-2.04, P=.010; T vs. C adjusted OR=1.34, 95%CI, 1.08-1.93, P=.031). CT and TT genotypes in rs20541 were associated with increased risk of renal disorder in SLE (CT vs. CC: adjusted OR=1.97, 95%CI, 1.18-3.28, P=.009; TT vs. CC: adjusted OR=2.42, 95%CI, 1.22-4.77, P=.011). Moreover, The concentration of IL-13 was significantly elevated in rs20541 CT/TT genotypes compared with CC genotype (P<.001). These results suggest that rs20541 CT/TT genotypes may be a risk factor for SLE, probably by increasing the level of IL-13.

The association of IL-17A polymorphisms with IL-17A serum levels and risk of ischemic stroke.

The aim of our study was to investigate the association of interleukin-17A (IL-17A) polymorphisms with IL-17A serum levels and risk of ischemic stroke (IS) in a Chinese population. 392 IS patients and 443 controls were included in this study. The polymorphisms of IL-17A gene were determined by Snapshot SNP genotyping assay and DNA sequencing. Serum IL-17A levels were measured by enzyme-linked immunosorbent assay (ELISA). We found that the G allele, GA and GG genotypes, and GA/GG vs. AA model of rs2275913 polymorphism were associated with increased risk of IS even after adjusted by clinical characters such as age, gender and diabetes (G vs. A: OR=1.27, 95% CI, 1.05∼1.54, P=0.014; GA vs. AA: OR=1.72, 95% CI, 1.05∼2.81, P=0.032; GG vs. AA: OR=1.99, 95% CI, 1.08∼3.67, P=0.028; GA/GG vs. AA: OR=1.78, 95% CI, 1.11∼2.86, P=0.017). Serum IL-17A levels were increased in IS patients compared with controls (P<0.01). Individuals carrying rs2275913 GA or GG genotype present higher serum IL-17A levels compared with the rs2275913AA genotype in the IS group (P<0.01). In conclusion, this is the first study reporting the rs2275913 polymorphism as a risk factor for IS, which may be partly explained by influencing the levels of IL-17A cytokine.

A Specially Designed Multi-Gene Panel Facilitates Genetic Diagnosis in Children with Intrahepatic Cholestasis: Simultaneous Test of Known Large Insertions/Deletions.

BACKGROUND AND AIMS: Large indels are commonly identified in patients but are not detectable by routine Sanger sequencing and panel sequencing. We specially designed a multi-gene panel that could simultaneously test known large indels in addition to ordinary variants, and reported the diagnostic yield in patients with intrahepatic cholestasis. METHODS: The panel contains 61 genes associated with cholestasis and 25 known recurrent large indels. The amplicon library was sequenced on Ion PGM system. Sequencing data were analyzed using a routine data analysis protocol and an internal program encoded for large indels test simultaneously. The validation phase was performed using 54 patients with known genetic diagnosis, including 5 with large insertions. At implement phase, 141 patients with intrahepatic cholestasis were evaluated. RESULTS: At validation phase, 99.6% of the variations identified by Sanger sequencing could be detected by panel sequencing. Following the routine protocol, 99.8% of false positives could be filtered and 98.8% of retained variations were true positives. Large insertions in the 5 patients with known genetic diagnosis could be correctly detected using the internal program. At implementation phase, 96.9% of the retained variations, following the routine protocol, were confirmed to be true. Twenty-nine patients received a potential genetic diagnosis when panel sequencing data were analyzed using the routine protocol. Two additional patients, who were found to harbor large insertions in SLC25A13, obtained a potential genetic diagnosis when sequencing data were further analyzed using the internal program. A total of 31 (22.0%) patients obtained a potential genetic diagnosis. Nine different genetic disorders were diagnosed, and citrin deficiency was the commonest. CONCLUSION: Specially designed multi-gene panel can correctly detect large indels simultaneously. By using it, we assigned a potential genetic diagnosis to 22.0% of patients with intrahepatic cholestasis.

Characterization of a joint recirculation of concentrated leachate and leachate to landfills with a microaerobic bioreactor for leachate treatment.

With comparison of a traditional landfill, a joint recirculation of concentrated leachate and leachate to landfills with or without a microaerobic reactor for leachate treatment was investigated in this study. The results showed that the joint recirculation of concentrated leachate and leachate with a microaerobic reactor for leachate treatment could not only utilize the microaerobic reactor to buffer the fluctuation of quality and quantity of leachate during landfill stabilization, but also reduce the inhibitory effect of acidic pH and high concentrations of ammonium in recycled liquid on microorganisms and accelerate the degradation of landfilled waste. After 390 days of operation, the discharge of COD and total nitrogen (TN) from the landfill with leachate pretreatment by a microaerobic reactor was 7.4 and 0.9 g, respectively, which accounted for 0.7% and 2.6% of COD, 1.9% and 7.5% of the TN discharge from the landfills without recirculation and directly recirculated with leachate and concentrated leachate, respectively. The degradation of the organic matter and biodegradable matter (BDM) in the landfill reactors could fit well with the first-order kinetics. The highest degradation of the organic matter and BDM was observed in the joint recirculation system with a microaerobic reactor for leachate treatment with the degradation constant of the first-order kinetics of 0.001 and 0.002.

Cold hardiness and biochemical response to low temperature of the unfed bush tick Haemaphysalis longicornis (Acari: Ixodidae).

BACKGROUND: The survival of overwintering ticks, is critical for their subsequent population dynamics in the spring, and consequent transmission of tick-borne diseases. Survival is largely influenced by the severity of the winter temperatures and their degree of cold hardiness at the overwintering stage. The bush tick Haemaphysalis longicornis, is widely distributed in China, and can transmit various pathogens that pose serious medical/veterinary problems. In the present study we investigated the effect of low temperature stress to tick survival, super-cooling point and body content of water, glycerol and total protein. METHODS: After various temperature acclimations, the super-cooling point was measured by Ni/CrNi-thermocouples with a precision temperature recorder. Water content was determined from weight loss of the sample exposed to 60°C for 48 h. Glycerol content was determined using Free Glycerol Reagent as directed by the manufacturer, and total protein was determined using the Bradford assay. RESULTS: The 50% mortality temperatures for the adults and nymphs were -13.7°C and -15.2°C, respectively; and the discriminating temperatures for the adults and nymphs were -16.0°C and -17.0°C, respectively. The super-cooling points of the adults and nymphs were -19.0°C and -22.7°C, respectively. The water content of adult H. longicornis decreased substantially after acclimation at 0°C for 10 d, whereas the nymphs decreased after acclimation at 0°C for 20 d, and the glycerol and proteins of both nymphs and adults were significantly increased (p < 0.01) when stressed at 0°C for 10 d. CONCLUSIONS: In H. longicornis, low temperature stress can enhance its cold hardiness and trigger appropriate responses, including reducing water content, and increasing glycerol and total protein content.

[Expressions of bFGF and PTEN in cervical carcinoma and their clinical significance].

OBJECTIVE: To investigate the expressions of bFGF and PTEN in cervical carcinoma and their clinical significance. METHODS: Tissue microarray technique and immunohistochemistry SP method were used to detect the expressions of bFGF and PTEN in 143 cases of invasive carcinoma of cervix (ICC) and 20 cases of normal cervical epithelium remote from tumor (NCE). The relationship between the expressions of bFGF and PTEN in ICC and some factors relating to clinical pathology of cervical carcinoma such as histopathological grading, lymph node metastasis, stroma involvement and FIGO staging were analyzed. RESULTS: The rate of the positive expression of bFGF in ICC was significantly higher than that in NCE 88.8% (127/143) vs. 25.0% (5/20, P = 0.000). The rate of positive expression of PTEN in ICC was significantly lower than that in NCE 67.1% (96/143) vs. 100.0% (20/20, P = 0.000). The expression of bFGF was positively correlated with lymph node metastasis and histopathological grading (r = 0.239, P = 0.004 and r = 0.369, P = 0.000, respectively). The expression of PTEN was negatively correlated with FIGO staging, histopathological grading and lymph node metastasis (r = -0.189, P = 0.024; r = -0.211, P = 0.011; r = -0.321, P = 0.000, respectively). The expression of bFGF was negatively correlated with the expression of PTEN in ICC (r = -0.261, P = 0.002). CONCLUSION: The overexpression of bFGF and underexpression of PTEN are closely related to the invasion and growth of cervical carcinoma. Detection of the expression of both bFGF and PTEN may be of value in further understanding the biological behavior and predicting the prognosis of cervical carcinoma.

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival in selected patients with peritoneal carcinomatosis from abdominal and pelvic malignancies: results of 21 cases.

We evaluated the perioperative safety profile and efficacy of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in 21 patients with peritoneal carcinomatosis (PC) from gastrointestinal and gynecological cancers. Twenty-one patients with PC (12 gastric cancer, 5 colorectal cancer, 2 ovarian cancer, 1 pseudomyxoma peritonei, 1 malignant mesothelioma) were treated with CRS + HIPEC with hydroxycamptothecin 20 mg and mitomycin C 30 mg in 12,000 mL of normal saline at 43 +/- .5 degrees C for 60 to 90 minutes. Vital signs were recorded for 5 days after surgery. We analyzed the following: local and systemic infections; gastrointestinal function recovery; hematological, hepatic, and renal parameters; wound healing time; adverse events; survival; and quality of life. The PC index was 2 to 33 (median, 11), the duration of operation 4 to 10 h (median, 8 h), and the highest temperature during 5 postoperative days 38.1 degrees C. Two patients developed generalized edema and were successfully treated. Five patients developed hypoproteinemia on day 1 after surgery. All routine blood tests checked at 1 week after surgery were normal. Time of gastric tube removal was 2 to 7 days. Liquid food intake time was 3 to 8 days. Time of removal of stitches was 8 to 18 days. No local or systemic infections, wound disruption, or other clinically important adverse events occurred. The follow-up was 8 to 43 months (median, 22.5 months). Eleven patients died, three survived with tumor, and seven survived free of tumor. CRS + HIPEC was well tolerated in our selected patients with PC, some of whom had improved survival.

[Expression of COX-2 and MMP-9 in cervical carcinoma and their clinical significance].

OBJECTIVE: To investigate the expressions of COX-2 and MMP-9 in cervical carcinoma and their clinical significance. METHODS: Immunohistochemical SP method was used to detect the expressions of COX-2 and MMP-9 in 72 cases of invasive carcinoma of cervix (ICC) and 16 cases of normal cervical epithelium remote from tumor (NCE), and the relationship between the expressions of COX-2 and MMP-9 in ICC and some factors relating to clinical pathology of cervical carcinoma such as histopathological grading, lymph node metastasis, stroma involvement and FIGO staging were analyzed statistically. RESULTS: The rates of positive expression of COX-2 and MMP-9 in ICC were significantly higher than those in NCE. COX-2: 88.9% in group ICC and 12.5% in group NCE, P = 0.000. MMP-9: 94.4% in group ICC and 43.8% in group NCE, P = 0.000. The expression of COX-2 was positively correlated with lymph node metastasis and stroma involvement (r = 0.296, P = 0.012 in group ICC and r = 0.257, P = 0.029 in group NCE, respectively). The expression of MMP-9 was positively correlated with FIGO staging (r = 0.329, P = 0.005) and histopathological grading (r = 0.351, P = 0.003). The expression of COX-2 was positively correlated with the expression of MMP-9 in ICC (r = 0.297, P = 0.011). CONCLUSION: The overexpressions of COX-2 and MMP-9 are closely related to the invasion and growth of cervical carcinoma. The tissue with overexpression of COX-2 has strong invasion ability. COX-2 and MMP-9 have synergistic effect on proliferation, invasion and metastasis of cancer cells. Detecting the expression of both COX-2 and MMP-9 may be of value in further understanding the biological behavior and predicting the prognosis of cervical carcinoma.