Laparoscopic pyeloplasty for newborns with severe hydronephrosis.

Aim: We aimed to investigate the short-term efficacy and safety of laparoscopic pyeloplasty for treating newborns with severe hydronephrosis due to ureteropelvic junction obstruction (UPJO). Methods: A retrospective analysis was performed on 16 newborn patients with severe neonatal hydronephrosis who underwent laparoscopic pyeloplasty at our hospital from January 2021 to November 2022. All patients were regularly followed up. Laparoscopic pyeloplasty with double J stent placement was performed after the presence of severe hydronephrosis was confirmed. Results: Among the 16 pediatric patients (13 males, 3 females), the left side was affected in 13 cases and the right side in 3. The average age at surgery was 9.50 (8.50-12.00) days, with an average weight of 3.30 ± 0.95 kg. Laparoscopic pyeloplasty was performed in all cases without the need for open conversion. The mean surgery duration was 292.06 ± 73.60 min, with minimal blood loss (2.50, 2.00-5.00 ml). Postoperative hospital stays averaged 13.44 ± 4.70 days. No anastomotic leakage occurred, and follow-ups at 1, 3, 6, and 12 months showed no stent displacement, except for one case where the stent was removed at 1 month, and the others at 3 months. There were no cases of worsened hydronephrosis, except for one with renal atrophy at the 6-month follow-up. Changes in renal pelvis anteroposterior diameter exhibited a time effect (F = 49.281, P < 0.001), with significant differences at 1, 3, 6, and 12 months postoperatively compared to preoperative values (P < 0.05). Notably, differences were observed between 6 and 3 months, as well as between 12 and 3 months postoperatively (P < 0.05). Similarly, renal parenchymal thickness changes showed a time effect Pediatric urology, Guangdong Women and Children Hospital, Guangzhou, China (F = 49.281, P < 0.001), with significant differences at 1, 3, 6, and 12 months postoperatively compared to preoperative values (P < 0.05). Significant differences were also noted between 6 and 1 month, as well as between 12 and 1 month postoperatively (P < 0.05). There was one case of urinary tract infection after surgery, and no case of recurrence was observed. Conclusion: Severe neonatal hydronephrosis must be treated promptly. Laparoscopic pyeloplasty is a safe and feasible treatment with minimal complications for newborn patients with severe hydronephrosis due to UPJO.

Adeno-to-squamous transition drives resistance to KRAS inhibition in LKB1 mutant lung cancer.

KRASG12C inhibitors (adagrasib and sotorasib) have shown clinical promise in targeting KRASG12C-mutated lung cancers; however, most patients eventually develop resistance. In lung patients with adenocarcinoma with KRASG12C and STK11/LKB1 co-mutations, we find an enrichment of the squamous cell carcinoma gene signature in pre-treatment biopsies correlates with a poor response to adagrasib. Studies of Lkb1-deficient KRASG12C and KrasG12D lung cancer mouse models and organoids treated with KRAS inhibitors reveal tumors invoke a lineage plasticity program, adeno-to-squamous transition (AST), that enables resistance to KRAS inhibition. Transcriptomic and epigenomic analyses reveal ΔNp63 drives AST and modulates response to KRAS inhibition. We identify an intermediate high-plastic cell state marked by expression of an AST plasticity signature and Krt6a. Notably, expression of the AST plasticity signature and KRT6A at baseline correlates with poor adagrasib responses. These data indicate the role of AST in KRAS inhibitor resistance and provide predictive biomarkers for KRAS-targeted therapies in lung cancer.

Discovery of CDK signature and CDK5 as potential biomarkers for predicting prognosis and immunotherapeutic response in gastric cancer peritoneal metastases.

Gastric cancer peritoneal metastases (GCPM) are a leading cause of death in gastric cancer patients. In this study, we focused on the expression of cyclin-dependent protein kinases (CDK), essential regulators of transcription, metabolism, and cell differentiation, in GCPM. Utilizing the GSE62254 cohort, we established a CDK signature (CDKS) model comprising ten CDK gene family members. Analysis of both the GSE62254 and TCGA cohorts revealed that patients with low CDKS had a worse prognosis compared to those with high CDKS. Furthermore, patients with high CDKS demonstrated positive responses from immunotherapy, as observed in the KIM cohort. We investigated the association between CDKS and the tumor microenvironment, including immune escape mechanisms. Immunohistochemistry analysis revealed a positive correlation between CDK5 and PD-L1 expression in gastric cancer. Furthermore, we found that CDK5 knockdown led to the inhibition of PD-L1 expression in gastric cancer cells. Our findings highlight the potential of CDKS as a prognostic biomarker and an indicator of immunotherapy response in gastric cancer patients. Moreover, our study suggests that targeting CDK5 could provide a new pathway for exploring immunotherapeutic research.

Gastric cancer peritoneal metastasis related signature predicts prognosis and sensitivity to immunotherapy in gastric cancer.

Gastric cancer peritoneal metastases (GCPM) is a leading cause of GC-related death. Early detection of GCPM is critical for improving the prognosis of advanced GC. Differentially expressed genes (DEGs) were identified in the GSE62254 database to distinguish between GCPM and non-GCPM. The gastric cancer peritoneal metastases signature (GCPMs) was developed using DEGs. We analysed the effectiveness of GCPMs as indicators for prognosis, chemotherapy, and immune therapy response in GC patients. Subsequently, we analysed the correlation between GCPMs and immune microenvironment as well as immune escape in GC patients. Random forest model and immunohistochemistry was utilized to identify the crucial genes that can aid in the diagnosis of GCPM. We identified five DEGs and utilized their expression to construct GCPMs. Patients with high GCPMs had a higher likelihood of a poor prognosis, while those with low GCPMs appeared to potentially benefit more from chemotherapy. GCPMs were a dependable marker for predicting the response to immunotherapy. Additionally, GCPMs was found to be significantly linked to stromal score and cancer-associated fibroblasts. SYNPO2 has been identified as the gene with the highest significance in the diagnosis of GCPM. Immunohistochemistry suggests that SYNPO2-positive expression in tumour cells, fibroblasts, inflammatory cell may be associated with promoting peritoneal metastasis in GC. GCPMs have shown to be a promising biomarker for predicting the prognosis and response of GC patients to chemotherapy and immunotherapy. The use of GCPMs for individual tumour evaluation may pave the way for personalized treatment for GC patients in the future.

Oxidative stress-triggered Wnt signaling perturbation characterizes the tipping point of lung adeno-to-squamous transdifferentiation.

Lkb1 deficiency confers the Kras-mutant lung cancer with strong plasticity and the potential for adeno-to-squamous transdifferentiation (AST). However, it remains largely unknown how Lkb1 deficiency dynamically regulates AST. Using the classical AST mouse model (Kras LSL-G12D/+;Lkb1flox/flox, KL), we here comprehensively analyze the temporal transcriptomic dynamics of lung tumors at different stages by dynamic network biomarker (DNB) and identify the tipping point at which the Wnt signaling is abruptly suppressed by the excessive accumulation of reactive oxygen species (ROS) through its downstream effector FOXO3A. Bidirectional genetic perturbation of the Wnt pathway using two different Ctnnb1 conditional knockout mouse strains confirms its essential role in the negative regulation of AST. Importantly, pharmacological activation of the Wnt pathway before but not after the tipping point inhibits squamous transdifferentiation, highlighting the irreversibility of AST after crossing the tipping point. Through comparative transcriptomic analyses of mouse and human tumors, we find that the lineage-specific transcription factors (TFs) of adenocarcinoma and squamous cell carcinoma form a "Yin-Yang" counteracting network. Interestingly, inactivation of the Wnt pathway preferentially suppresses the adenomatous lineage TF network and thus disrupts the "Yin-Yang" homeostasis to lean towards the squamous lineage, whereas ectopic expression of NKX2-1, an adenomatous lineage TF, significantly dampens such phenotypic transition accelerated by the Wnt pathway inactivation. The negative correlation between the Wnt pathway and AST is further observed in a large cohort of human lung adenosquamous carcinoma. Collectively, our study identifies the tipping point of AST and highlights an essential role of the ROS-Wnt axis in dynamically orchestrating the homeostasis between adeno- and squamous-specific TF networks at the AST tipping point.

Outcome analysis of immediate and delayed laparoscopic pyeloplasty in infants with severe ureteropelvic junction obstruction.

Objective: The treatment timing of ureteropelvic junction obstruction (UPJO) in infants remains controversial. This study aimed to compare the recovery effect of renal morphology of immediate and delayed laparoscopic pyeloplasty in infants with severe UPJO. Methods: The infants with severe UPJO-induced hydronephrosis who underwent laparoscopic pyeloplasty according to their age at the time of surgery [the immediate treatment (IT) group: ≤1 month of birth, the delayed treatment (LT) group: 3-6 months of birth] in our center between 2010 and 2019 were enrolled in this study. Ultrasonography was used to assess renal morphology, including anteroposterior diameter (APD) of a pelvic, parenchymal thickness (PT), polar length (PL), and Society of Fetal Urology (SFU) grade. Preoperative and postoperative renal morphological outcomes at 6, 12, and 24 months were measured and compared. Results: During this period, a total of 135 patients were assigned to receive either IT (n = 73) or LT (n = 62) and were included for analysis. There were no significant differences in renal morphology indices at baseline between groups of IT and LT. The APD, PT, and PL in both groups all recovered to certain degrees compared with those at baseline, however, the IT group recovered more significantly than the LT group. Despite there being no significant difference in SFU grade between the two groups before and after surgery, the reduction of SFU grade in the IT group was more significant than that in the LT group during the 6-, 12- and 24-month follow-up periods. The PL, SFU, and APD were greater in the IT group than in the LT group at 6, 12, and 24 months of follow-up. At 6 months PL was not significantly higher between the two groups, while the outcome was significantly different at 12 months and 24 months. Conclusion: Immediate laparoscopic pyeloplasty for the infant with severe ureteropelvic junction obstruction is effective, and it can accelerate the recovery of renal morphological indices in infants with severe UPJO-induced hydronephrosis.

Effect of SRB and Applied Potential on Stress Corrosion Behavior of X80 Steel in High-pH Soil Simulated Solution.

The effect of SRB and applied potential on the stress corrosion sensitivity of X80 pipeline steel was analyzed in high-pH soil simulated solution under different conditions using a slow strain rate tensile test, electrochemical test, and electronic microanalysis. The experimental results showed that X80 pipeline steel has a certain degree of SCC sensitivity in high-pH simulated solution, and the crack growth mode was trans-granular stress corrosion cracking. In a sterile environment, the SCC mechanism of X80 steel was a mixture mechanism of anode dissolution and hydrogen embrittlement at -850 mV potential, while X80 steel had the lowest SCC sensitivity due to the weak effect of AD and HE; after Sulfate Reducing Bacteria (SRB) were inoculated, the SCC mechanism of X80 steel was an AD-membrane rupture mechanism at -850 mV potential. The synergistic effect of Cl- and SRB formed an oxygen concentration cell and an acidification microenvironment in the pitting corrosion pit, and this promoted the formation of pitting corrosion which induced crack nucleation, thus significantly improving the SCC sensitivity of X80 steel. The strong cathodic polarization promoted the local corrosion caused by SRB metabolism in the presence of bacteria, whereby the SCC sensitivity in the presence of bacteria was higher than that in sterile conditions under strong cathodic potential.

Stem Cell Factor SOX2 Confers Ferroptosis Resistance in Lung Cancer via Upregulation of SLC7A11.

Ferroptosis is a lipid peroxidation-dependent cell death caused by metabolic dysfunction. Ferroptosis-associated enzymes are promising therapeutic targets for cancer treatment. However, such therapeutic strategies show limited efficacy due to drug resistance and other largely unknown underlying mechanisms. Here we report that cystine transporter SLC7A11 is upregulated in lung cancer stem-like cells (CSLC) and can be activated by stem cell transcriptional factor SOX2. Mutation of SOX2 binding site in SLC7A11 promoter reduced SLC7A11 expression and increased sensitivity to ferroptosis in cancer cells. Oxidation at Cys265 of SOX2 inhibited its activity and decreased the self-renewal capacity of CSLCs. Moreover, tumors with high SOX2 expression were more resistant to ferroptosis, and SLC7A11 expression was positively correlated with SOX2 in both mouse and human lung cancer tissue. Together, our study provides a mechanism by which cancer cells evade ferroptosis and suggests that oxidation of SOX2 can be a potential therapeutic target for cancer treatment. SIGNIFICANCE: This study uncovers a SOX2-SLC7A11 regulatory axis that confers resistance to ferroptosis in lung cancer stem-like cells.

Nanog maintains stemness of Lkb1-deficient lung adenocarcinoma and prevents gastric differentiation.

Growing evidence supports that LKB1-deficient KRAS-driven lung tumors represent a unique therapeutic challenge, displaying strong cancer plasticity that promotes lineage conversion and drug resistance. Here we find that murine lung tumors from the KrasLSL-G12D/+ ; Lkb1flox/flox (KL) model show strong plasticity, which associates with up-regulation of stem cell pluripotency genes such as Nanog. Deletion of Nanog in KL model initiates a gastric differentiation program and promotes mucinous lung tumor growth. We find that NANOG is not expressed at a meaningful level in human lung adenocarcinoma (ADC), as well as in human lung invasive mucinous adenocarcinoma (IMA). Gastric differentiation involves activation of Notch signaling, and perturbation of Notch pathway by the γ-secretase inhibitor LY-411575 remarkably impairs mucinous tumor formation. In contrast to non-mucinous tumors, mucinous tumors are resistant to phenformin treatment. Such therapeutic resistance could be overcome through combined treatments with LY-411575 and phenformin. Overall, we uncover a previously unappreciated plasticity of LKB1-deficient tumors and identify the Nanog-Notch axis in regulating gastric differentiation, which holds important therapeutic implication for the treatment of mucinous lung cancer.

[Quantitative assessment of surface hydrological connectivity in Momoge National Nature Reserve, Northeast China]. / èŽ«èŽ«æ ¼å›½å®¶çº§è‡ªç„¶ä¿æŠ¤åŒºåœ°è¡¨æ°´æ–‡è¿žé€šæ€§å®šé‡è¯„ä¼°.

Quantitative assessment of hydrological connectivity is a hot but difficult issue in current research. Using the 30-m resolution global monthly surface water remote sensing dataset released by the EU Joint Research Center and three indicators of geostatistical connectivity, maximum distance of connection (MDC), and surface water extent of connectome (i.e., seasonally connected water bodies), we quantified the hydrological connectivity of surface water in Momoge National Nature Reserve in different months of a normal year (May to October 2016), and in September of different hydrological years (a wet year, namely 1998; a normal year, namely 2016; a drought year, namely 2002), and different directions (west-east and north-south). Our results showed that: 1) the geostatistical connectivity function (GCF) along the west-east direction was better than that along the north-south direction. The GCF in August and July was better than that in other months. The GCF along the west-east direction of each hydrological year was better than that in the drought year, whereas the GCF in the drought year was better than the corresponding value in the normal year. The GCF along the north-south direction in each hydrological year was better than that in the normal year, whereas the GCF in the normal year was better than that in the drought year. The MDC along the west-east direction in June, July, September, and October of the normal year was all concentrated at 25.26 km. MDC was more concentrated along the north-south direction, with 10 km for all months. The MDC in the normal and drought years was relatively close, but both were much smaller than that in the wet year. 2) frequent seasonal connections between the Yuelianghu Reservoir and the Nenjiang River, and between Etoupao and its neighboring lakes occurred in the study area during the normal year, while most of the other lakes remained isolated. The patterns of hydrological connection in the study area differed across different hydrological years: two giant connectomes were formed in the wet year, some lakes are periodically connected in the normal year, and all lakes remain isolated in the drought year. 3) As a drainage area for farmland receding water, the surface water extent of the Etoupao connectome increased visibly during the three water supplement seasons (spring, summer, and autumn). By quantifying the surface hydrological connectivity in Momoge National Nature Reserve with multiple water sources from different perspectives, our results provide a scientific basis for wetland protection and restoration and integrated management of watershed water resources.

Spectrum of gene mutations identified by targeted next-generation sequencing in Chinese leukemia patients.

BACKGROUND: Despite targeted sequencing have identified several mutations for leukemia, there is still a limit of mutation screening for Chinese leukemia. Here, we used targeted next-generation sequencing for testing the mutation patterns of Chinese leukemia patients. METHODS: We performed targeted sequencing of 504 tumor-related genes in 109 leukemia samples to identify single-nucleotide variants (SNVs) and insertions and deletions (INDELs). Pathogenic variants were assessed based on the American College of Medical Genetics and Genomics (ACMG) guidelines. The functional impact of pathogenic genes was explored through gene ontology (GO), pathway analysis, and protein-protein interaction network in silico. RESULTS: We identified a total of 4,655 SNVs and 614 INDELs in 419 genes, in which PDE4DIP, NOTCH2, FANCA, BCR, and ROS1 emerged as the highly mutated genes. Of note, we were the first to demonstrate an association of PDE4DIP mutation and leukemia. Based on ACMG guidelines, 39 pathogenic and likely pathogenic mutations in 27 genes were found. GO annotation showed that the biological process including gland development, leukocyte differentiation, respiratory system development, myeloid leukocyte differentiation, mesenchymal to epithelial transition, and so on were involved. CONCLUSION: Our study provided a map of gene mutations in Chinese patients with leukemia and gave insights into the molecular pathogenesis of leukemia.

Investigating the potential use of Sentinel-1 data for monitoring wetland water level changes in China's Momoge National Nature Reserve.

BACKGROUND: Interferometric Synthetic Aperture Radar (InSAR) has become a promising technique for monitoring wetland water levels. However, its capability in monitoring wetland water level changes with Sentine-1 data has not yet been thoroughly investigated. METHODS: In this study, we produced a multitemporal Sentinel-1 C-band VV-polarized SAR backscatter images and generated a total of 28 interferometric coherence maps for marsh wetlands of China's Momoge National Nature Reserve to investigate the interferometric coherence level of Sentinel-1 C-VV data as a function of perpendicular and temporal baseline, water depth, and SAR backscattering intensity. We also selected six interferogram pairs acquired within 24 days for quantitative analysis of the accuracy of water level changes monitored by Sentinel-1 InSAR. The accuracy of water level changes determined through the Sentinel-1 InSAR technique was calibrated by the values of six field water level loggers. RESULTS: Our study showed that (1) the coherence was mainly dependent on the temporal baseline and was little affected by the perpendicular baseline for Sentinel-1 C-VV data in marsh wetlands; (2) in the early stage of a growing season, a clear negative correlation was found between Sentinel-1 coherence and water depth; (3) there was an almost linear negative correlation between Sentinel-1 C-VV coherence and backscatter for the marsh wetlands; (4) once the coherence exceeds a threshold of 0.3, the stage during the growing season, rather than the coherence, appeared to be the primary factor determining the quality of the interferogram for the marsh wetlands, even though the quality of the interferogram largely depends on the coherence; (5) the results of water level changes from InSAR processing show no agreement with in-situ measurements during most growth stages. Based on the findings, we can conclude that although the interferometric coherence of the Sentinel-1 C-VV data is high enough, the data is generally unsuitable for monitoring water level changes in marsh wetlands of China's Momoge National Nature Reserve.

[Review on wetland water level monitoring using interferometric synthetic aperture radar]. / å¹²æ¶‰åˆæˆå­”å¾„é›·è¾¾ç›‘æµ‹æ¹¿åœ°æ°´ä½ç ”ç©¶ç»¼è¿°.

Water level is an important indicator of wetland hydrological regime. Detection of wetland water levels through interferometric synthetic aperture radar (InSAR) has outstanding advantage, including high spatial resolution, high accuracy, low cost, and high efficiency. We introduced prerequisites for the monitoring of wetland water levels with InSAR, discussed the types of InSAR techniques, the influencing factors for monitoring wetland water levels and their advantages and disadvantages. There are three prerequisites for effectively detecting wetland water levels with InSAR techniques: 1) the presence of emergent aquatic plants; 2) the main backscattering mechanism is double bounce scattering; and 3) the interferometric coherence exceeds a certain threshold. Current water level monitoring techniques have been developed from traditional InSAR techniques to advanced InSAR techniques, such as STBAS, MM, and DSI. These techniques evolve from detecting relative water level changes to estimate absolute water level and water depth time series. The influencing factors of InSAR techniques for monitoring wetland water levels include operating para-meters of the synthetic aperture radar (SAR) and characteristics of the wetlands themselves. Finally, we proposed the key directions for future research in this field: i) investigating the potential use of specific water level monitoring techniques in other regions with different backscattering and interferometric coherence characteristics; ii) developing new algorithms to integrate multi-sensor, multi-track, multi-band, multi-polarization, and multi-temporal InSAR repeat-pass observation; iii) considering alternative sources of SAR data; and (iv) strengthening research on "by-products" of wetland water level monitoring with InSAR, such as wetland hydrological connectivity, flow direction, and flow regime.

Pathological transition as the arising mechanism for drug resistance in lung cancer.

Despite the tremendous efforts for improving therapeutics of lung cancer patients, its prognosis remains disappointing. This can be largely attributed to the lack of comprehensive understanding of drug resistance leading to insufficient development of effective therapeutics in clinic. Based on the current progresses of lung cancer research, we classify drug resistance mechanisms into three different levels: molecular, cellular and pathological level. All these three levels have significantly contributed to the acquisition and evolution of drug resistance in clinic. Our understanding on drug resistance mechanisms has begun to change the way of clinical practice and improve patient prognosis. In this review, we focus on discussing the pathological changes linking to drug resistance as this has been largely overlooked in the past decades.

Bacterial cellulose synthesis mechanism of facultative anaerobe Enterobacter sp. FY-07.

Enterobacter sp. FY-07 can produce bacterial cellulose (BC) under aerobic and anaerobic conditions. Three potential BC synthesis gene clusters (bcsI, bcsII and bcsIII) of Enterobacter sp. FY-07 have been predicted using genome sequencing and comparative genome analysis, in which bcsIII was confirmed as the main contributor to BC synthesis by gene knockout and functional reconstitution methods. Protein homology, gene arrangement and gene constitution analysis indicated that bcsIII had high identity to the bcsI operon of Enterobacter sp. 638; however, its arrangement and composition were same as those of BC synthesizing operon of G. xylinum ATCC53582 except for the flanking sequences. According to the BC biosynthesizing process, oxygen is not directly involved in the reactions of BC synthesis, however, energy is required to activate intermediate metabolites and synthesize the activator, c-di-GMP. Comparative transcriptome and metabolite quantitative analysis demonstrated that under anaerobic conditions genes involved in the TCA cycle were downregulated, however, genes in the nitrate reduction and gluconeogenesis pathways were upregulated, especially, genes in three pyruvate metabolism pathways. These results suggested that Enterobacter sp. FY-07 could produce energy efficiently under anaerobic conditions to meet the requirement of BC biosynthesis.

Gene variation in IL10 and susceptibility to chronic hepatitis B.

OBJECTIVES: To evaluate the correlation between IL-10 gene polymorphisms and hepatitis B infection. METHODS: Tag single nucleotide polymorphisms (SNPs) were used to investigate the relationship between IL-10 gene polymorphisms and susceptibility to chronic hepatitis B virus (HBV) infection by comparing 996 chronic HBV infection cases to 301 acute infection controls. RESULTS: This study found that rs3024490 G/T allele, located in the intron 1 region and highly prevalent in Chinese populations, was significantly different between the chronic HBV infection cases and the acute infection controls in single allele analysis, genetic models analysis, and haplotypes analysis. CONCLUSIONS: This suggested that the rs3024490 within IL-10 was associated with susceptibility to chronic hepatitis B in a Chinese Han population.

The role of crocetin in protection following cerebral contusion and in the enhancement of angiogenesis in rats.

The protective role of crocetin following cerebral contusion and its effects on the enhancement of angiogenesis in rats was investigated. A total of 60 Sprague-Dawley rats were divided into three groups (n = 20 each): crocetin therapy group (cerebral contusion treated with crocetin), cerebral trauma control group (without treatment), sham operation control group. The effect of crocetin was examined by modified Neurological Severity Scores (mNSS), electron microscopy, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) procedure, western blotting analysis of Bcl-2 protein expression, microvessel count (MVC), endothelial cell culture and immunocyto-chemistry. The mNSS results indicated that neurological function of therapy group was significantly recovered seven days and fifteen days after the trauma. The TUNEL staining and electron microscopy revealed that crocetin treatment led to an inhibition of neuronal apoptosis 72 h following treatment; this finding was confirmed by western blot analysis of B cell lymphoma/leukemia-2 (Bcl-2) protein expression. Expression levels of vascular endothelial growth factor receptor-2 (VEGFR-2) and serum response factor (SRF) were higher in the crocetin therapy group in comparison to the two other experimental groups. Our results demonstrate that the protective effects of crocetin upon brain injury may be related to its ability to inhibit apoptosis at early stages of the injury and its ability to promote angiogenesis at the sub-acute stage.

[Long-term immunogenicity and effectiveness of live attenuated hepatitis A vaccine (H2-strain)-a study on the result of 15 years' follow up].

OBJECTIVE: To evaluate the long-term immunogenicity and effectiveness of live attenuated hepatitis A (HA) vaccine (H2 strain) after one dose injection, through a 15 years' follow up observation. METHODS: A total of 220 children with negative anti-HAV antibody (aged 1-3 y) were involved and followed up in Jiaojiang district, Taizhou city, Zhejiang province. Indicators would include seroconversion and geometric mean titer (GMT) levels after inoculation the vaccine with single dose at 2 m, 12 m, 6 years, 10 years and 15 years. Epidemiological observation was carried out within the 15 years to evaluate the relationship between vaccine coverage, the incidence of HA and the overall effectiveness. In the studied population, serum was tested by ELISA (calibrated by WHO international reference) and ABBOTT Axsym HAVAB mEIA. RESULTS: Seroconversion rates were found to be 98.6% and 81.3% after 2 months and 15 years of inoculation and slowly decreased. GMT level was 128 mIU/ml after 15 years, significantly higher than the required protective level of 20 mIU/ml, recommended by WHO experts. Effectiveness through the 15-year follow up program showed a significant correlation between vaccine coverage and incidence of HA in 1-15 years aged group (Kendall-Rank test, τ =-0.931, P<0.01). There was no HA case seen among the observed accumulated 236 413 person-year vaccines, compared to 4 HA cases discovered in the 27 206 person-year of the non-vaccinees. The overall protective rate reached 100%. Through a mass vaccination program on children, the whole population established an immune-defence to enable the incidence of HA decreased by 96.7%. CONCLUSION: The long-term immunogenicity and effectiveness of live attenuated hepatitis A vaccine (H2 strain) after one dose injection could last as long as 15 years.

[Relationship between the expression of P-glycoprotein, glutathione S-transferase-pi and thymidylate synthase proteins and adenosine triphosphate tumor chemosensitivity assay in cervical cancer].

OBJECTIVE: To explore the feasibility of the adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA) in human cervical cancer chemosensitivity testing and to analyze the relationship between the three drug resistance-associated proteins: P-glycoprotein (P-gp); glutathione S-transferase-pi (GST-pi); thymidylate synthase (TS) and ATP-TCA. METHODS: ATP-TCA was used to detect the sensitivity of 35 specimens of fresh cervical cancer to six cytotoxic drugs as follows: paclitaxel (TAX), cisplatin (DDP), bleomycin (BLM), gemcitabine (GEM), 5-fluorouracil (5-FU), irinotecan (CPT-11). Consecutive sections from 35 cases of cervical cancer were assessed immunohistochemically for expression of P-gp, GST-pi and TS proteins. RESULTS: (1) Thirty-two of 35 assays were completed successfully, with an evaluability rate of ATP-TCA at 91% (32/35). There was a marked heterogeneity of chemosensitivity in cervical cancer. The ex vivo sensitive rate of TAX was 88% (28/32), of 5-FU 72% (23/32), of GEM 62% (20/32), of DDP 19% (6/32), of BLM 16% (5/32), and of CPT-11 12% (4/32). (2) The expression of GST-pi and TS protein in cervical cancer was 66% (21/32) and 44% (14/32), which was associated with the resistance to DDP and 5-FU ex vivo (P=0.011, P=0.022), respectively; but the expression of P-gp protein was not associated with any resistance to TAX, 5-FU, GEM, DDP, BLM or CPT-11 ex vivo (P>0.05). CONCLUSIONS: ATP-TCA could be used to individualize chemotherapy by selecting agents for particular patients of cervical cancer. The expression of GST-pi and TS protein might be useful biomarkers to predict the resistance to DDP and 5-FU in patients with cervical cancer.