Association between CYP2E1 C-1054T and 96-bp I/D genetic variations and the risk of polycystic ovary syndrome in Chinese women.

PURPOSE: To investigate the association of cytochrome P450 2E1 (CYP2E1) C-1054T (rs2031920) and 96-bp I/D genetic variations with the risk of polycystic ovary syndrome (PCOS), and to estimate the effects of genotypes on the clinical, metabolic, hormonal, and oxidative stress indicators. METHODS: This case-control study included 762 control women and 1034 patients with PCOS. Genotypes were determined using polymerase chain reaction and/or restriction fragment length polymorphism analysis. Clinical and biochemical parameters were also analyzed. RESULTS: Frequencies of the TT + CT genotype (35.4 vs. 28.9%) and T allele (19.6 vs. 16.0%) of the CYP2E1 C-1054T polymorphism were significantly higher in the PCOS group than in the control group (OR = 1.350, 95% CI 1.103-1.652, P = 0.004 for the dominant model). Genotype TT + CT remained a significant predictor of PCOS in a logistic regression model including age, body mass index (BMI), and recruitment year of participants (OR = 1.345, 95% CI 1.071-1.688, P = 0.011). No statistical differences were found in the genotype and allele frequencies of CYP2E1 96-bp I/D polymorphism. However, the combined genotype DD/TT + CT was related to an increased risk of PCOS when the DD/CC wild-type combined genotype was used as a reference. Patients with the I allele of 96-bp I/D polymorphism had a lower BMI but higher plasma apolipoprotein B and oxidized low-density lipoprotein cholesterol levels than those with the DD genotype. CONCLUSION: CYP2E1 C-1054T, but not 96-bp I/D, genetic polymorphism is associated with an increased risk of PCOS in Chinese women.

Effluent trading planning and its application in water quality management: A factor-interaction perspective.

In this study, a Bayesian risk-induced interval stochastic modeling framework (BRISF) is proposed for planning effluent trading program among point and nonpoint sources as well as identifying interactions of important trading factors under system risk. BRISF incorporates nutrient fate modeling with soil and water assessment tool (SWAT), Bayesian inference with random walk Metropolis algorithm (RWM), and constraint-violation risk-based two-stage stochastic programming (CRTSP) within a general framework. Bayesian inference is employed for uncertainty analysis of SWAT model parameters and uncertain prediction of nutrient loadings; this process provides the random inputs for optimization process. CRTSP is capable of dealing with multiple uncertainties in modeling effluent trading program as well as system risk of environmental allowance violation. BRISF is applied to a real case of Xiangxihe watershed in China for water quality management. Solutions for optimal trading scheme corresponding to different risk levels are generated. Thousands of scenarios are examined to analyze the individual and interactive effects of trading ratios and treatment rates on trading system. Comparison between cross-industry and intra-industry effluent trading scheme is also conducted. It is proved that cross-industry trading would bring about higher benefit with reduced pollution loading; cross-industry effluent trading scheme would be recommended to achieve optimal water quality management and system benefit.

Antioxidant supplementation, effect on post-thaw spermatozoan function in three sturgeon species.

High levels of reactive oxygen species (ROS), which may be associated with reduced sperm quality, can be detected during cryopreservation of sperm of some species. Our objective was to investigate whether the addition of antioxidants to cryopreservation extenders influenced post-thaw sperm characteristics and fertility in Acipenser dabryanus, Acipenser sinensis and Acipenser baerii. Prior to freezing, sperm samples were diluted with a base extender as control or in extender supplemented with catalase (CAT), glutathione (GSH), cysteine (NAC), ascorbic acid (VC) or their paired combinations. Protective concentrations of CAT, GSH and VC in the three species were 25 U/ml, 0.25-0.5 mg/ml and 0.5 mg/ml, respectively. Cysteine showed no protective effect against ROS. The addition of CAT, GSH and VC positively affected either acrosome or membrane integrity of post-thawed sperm in the three species, as well as spermatozoan motility in A. sinensis. The combination of antioxidants did not show a positive synergistic effect. This study suggested that the use of antioxidants in the cryopreservation of sturgeon sperm has potential to decrease intracellular ROS, and consequently preserve acrosome and membrane integrity, as well as spermatozoan motility.

Disaccharide combinations and the expression of enolase3 and plasma membrane Ca2+ ATPase isoform in sturgeon sperm cryopreservation.

Acipenser sinensis and Acipenser dabryanus are critically endangered species, so germplasm conservation via cryopreservation of sperm is necessary. Disaccharides can act as membrane-impermeable cryoprotectants, and enolase3 (ENO3) and plasma membrane Ca2+ ATPase isoform (PMCA2) are proteins associated with sperm quality. We considered seven characteristics of sperm quality in cultured brood stock from A. sinensis and A. dabryanus. We tested use of sucrose or trehalose alone and in combination at different concentrations for cryopreservation of A. dabryanus sperm. A low concentration of sucrose plus trehalose (S15 T15 ) was optimal. Mixing of the extender with sucrose, lactose, or trehalose alone or with pairwise mixtures revealed that a mixture of lactose and trehalose (L15 T15 ) gave the best results for both A. sinensis and A. dabryanus. Enolase3 and PMCA2 expression levels were measured in cryopreserved A. sinensis sperm via Western blotting. Relative ENO3 and PMCA2 expression levels were examined, and the relationship between disaccharide composition, sperm quality and protein expression was explored in A. sinensis. The results showed that relative ENO3 and PMCA2 expression levels were the highest at L15 T15 in cryopreserved A. sinensis sperm. There were significant positive correlations between ENO3 expression and percentage membrane integrity, and between PMCA2 expression and sperm motility parameters (percentage of motile sperm, curvilinear velocity, straight-line velocity and average path velocity; p < .05) in cryopreserved A. sinensis sperm. Our results indicate the optimal disaccharide combination and concentrations for cryopreservation of A. sinensis and A. dabryanus sperm and suggest that ENO3 and PMCA2 expression levels could serve as a valuable indicator of sperm quality in A. sinensis.

Predictors of liver histological changes and a sustained virological response to peginterferon among chronic hepatitis B e antigen-positive patients with normal or minimally elevated alanine aminotransferase levels.

A proportion of chronic hepatitis B patients with normal or only minimally elevated alanine aminotransferase (ALT) levels display significant histologic changes and would benefit from antiviral therapy. We aim to evaluate the histologic abnormalities seen in these patients and then determine which of them would most likely respond to peginterferon therapy. One hundred and thirteen hepatitis B e antigen (HBeAg)-positive patients with a normal or minimally elevated ALT level and moderate-to-severe histologic changes in their liver tissue were selected to receive peginterferon monotherapy and participate in a follow-up analysis. A multiple logistic regression analysis indicated that increasing age (P=.049) and lower hepatitis B virus (HBV) DNA levels (P=.038) were associated with significant histological abnormalities in patients with a normal or minimally elevated ALT. Our predictive model which incorporated HBeAg testing at treatment week 12 combined with hepatitis B surface antigen (HBsAg) testing at treatment week 24 was able to identify which patients with a normal ALT level would achieve a sustained virological response (SVR) (positive predictive value [PPV]: 66.7%, negative predictive value [NPV]: 90.0%). Lower HBsAg and HBeAg levels at treatment week 24 were associated with a SVR in patients with a minimally elevated ALT level (PPV: 100.0%, NPV: 100.0%). A liver biopsy and antiviral therapy should be strongly considered when treating HBeAg-positive patients with a normal or minimally elevated ALT level, low HBV DNA level, and aged >35 years. On-treatment quantification of combined HBsAg and HBeAg test results may be useful for predicting a SVR to peginterferon monotherapy in these patients.

Increased levels of IL-21 responses are associated with the severity of liver injury in patients with chronic active hepatitis B.

Interleukin-21 (IL-21) participates in tissue damage in various immune-mediated diseases. Its role in the pathogenesis of chronic active hepatitis B (CAHB) has not been clarified. The frequency of circulating IL-21(+) T cells and the levels of serum and intrahepatic IL-21 have been characterized in 70 CAHB patients, 32 inactive carrier (IC), 18 chronic hepatitis C (CHC) and 20 healthy controls (HC). Their potential association with liver injury was analysed. The percentages of IL-21(+) CD3(+) CD8(-) and IL-21(+) CD3(+) CD8(+) T cells and the levels of serum IL-21 in CAHB patients were significantly higher than that in the IC, CHC patients and HC (P < 0.001) and were correlated positively with the levels of serum alanine aminotransferase (ALT, r = 0.424, P < 0.001; r = 0.392, P = 0.001) and aspartate aminotransferase (AST, r = 0.388, P = 0.001; r = 0.329, P = 0.005) in CAHB patients, respectively. The levels of IL-21 expression in the liver tissues were associated significantly with increased degrees of inflammation and fibrosis in CAHB patients (P < 0.01 or P < 0.05). Our findings suggest that aberrant IL-21 responses may be associated with the progression of CHB.

Prevalence and characterization of Salmonella enterica in dried milk-related infant foods in Shaanxi, China.

The aim of this study was to investigate the existence and characteristics of Salmonella enterica in dried milk-related infant foods. Twenty-four (3.4%) of 705 samples, including 5 (2.0%) of 246 powdered infant formula, 18 (4.0%) of 445 infant rice cereal, and 1 (7.1%) of 14 other infant foods, were positive for Salmonella. Fifteen serotypes were identified in 40 Salmonella isolates; Salmonella Duesseldorf (15.0%) and Salmonella Indiana (15.0%) were more frequently detected than other serotypes. Resistance to chloramphenicol (82.5%) was most common, followed by tetracycline (57.5%), ceftiofur (52.5%), kanamycin (52.5%), streptomycin (50.0%), gentamycin (45.0%), nalidixic acid (35.0%), ceftriaxone (32.5%), ciprofloxacin (25.0%), amikacin (20.0%), and cefoxitin (15.0%). Twenty-eight (70.0%) isolates were resistant to ≥ 8 antimicrobials, with 5 (12.5%) being resistant to 14 antimicrobials. Amino acid substitutions in gyrase A (GyrA) were most frequently detected as Ser83Arg/Asp87Glu and in p53-associated Parkin-like cytoplasmic protein (ParC), they were all Ser80Arg; the quinolone resistance gene qnrS (47.5%) was commonly detected as well as aminoglycoside acetyltransferase [aac(6')-Ib; 25.0%], qnrA (17.5%), and qnrB (15.0%) genes. Thirty distinct pulsed-field gel electrophoresis patterns were identified among 40 isolates; no identical pulsed-field gel electrophoresis pattern was detected among Salmonella isolates with the same serovar that was recovered in 2010 and 2012. Our results suggest that dried milk-related infant foods could be contaminated with Salmonella and highlight that the dangers to infant health should not be neglected.

Workplace safety and health programs, practices, and conditions in auto collision repair businesses.

This article describes the results of a pre-intervention safety assessment conducted in 49 auto collision repair businesses and owners' commitments to specific improvements. A 92-item standardized audit tool employed interviews, record reviews, and observations to assess safety and health programs, training, and workplace conditions. Owners were asked to improve at least one-third of incorrect, deficient, or missing (not in compliance with regulations or not meeting best practice) items, of which a majority were critical or highly important for ensuring workplace safety. Two-thirds of all items were present, with the highest fraction related to electrical safety, machine safety, and lockout/tagout. One-half of shops did not have written safety programs and had not conducted recent training. Many had deficiencies in respiratory protection programs and practices. Thirteen businesses with a current or past relationship with a safety consultant had a significantly higher fraction of correct items, in particular related to safety programs, up-to-date training, paint booth and mixing room conditions, electrical safety, and respiratory protection. Owners selected an average of 58% of recommended improvements; they were most likely to select items related to employee Right-to-Know training, emergency exits, fire extinguishers, and respiratory protection. They were least likely to say they would improve written safety programs, stop routine spraying outside the booth, or provide adequate fire protection for spray areas outside the booth. These baseline results suggest that it may be possible to bring about workplace improvements using targeted assistance from occupational health and safety professionals.

[Risk factors of early myocardial injury and the impact of early myocardial injury on prognosis of patients with extensive burns].

Objective: To analyze the risk factors of early myocardial injury and the impact of early myocardial injury on prognosis of patients with extensive burns. Methods: A retrospective case series study was conducted. From January 2018 to August 2022, 361 patients with extensive burns who met the inclusion criteria were admitted to Tongren Hospital of Wuhan University & Wuhan Third Hospital, including 231 males and 130 females, aged 50 (36, 58) years, with total burn area of 45% (35%, 60%) total body surface area. According to the highest level of creatine kinase isoenzyme-MB (CK-MB) within 72 h post injury, the patients were divided into early myocardial injury group (CK-MB≥75 U/L, 182 patients) and non-early myocardial injury group (CK-MB<75 U/L, 179 patients). The following data of patients in the 2 groups were collected and analyzed, including gender, age, total burn area, admission time post injury, combination with shock on admission, combination with inhalation injury on admission; the main blood test indexes such as myocardial enzyme spectrum, blood routine, liver and kidney function, and electrolytes within 72 h post injury; and treatment outcomes and fatality rate. Data were statistically analyzed with chi-square test, independent sample t test, or Mann-Whitney U test. The multivariate logistic regression analysis was conducted to screen the independent risk factors for early myocardial injury and for death in patients with extensive burns. Results: There were statistically significant differences in gender, combination with shock on admission, total burn area, and admission time post injury of patients between the two groups (with χ2 values of 6.40 and 6.10, Z values of 5.41 and 3.03, respectively, P<0.05). There were no statistically significant differences in age, combination with inhalation injury on admission of patients between the two groups (P>0.05). The CK-MB, creatine kinase, lactate dehydrogenase, α-hydroxybutyrate dehydrogenase, white blood cell count, neutrophil-to-lymphocyte ratio (NLR), alanine aminotransferase (ALT), aspartate aminotransferase, potassium, and hemoglobin within 72 h post injury were significantly higher than those in non-early myocardial injury group (with Z values of 15.40, 6.26, 7.59, 7.02, 2.64, 4.53, 4.07, 6.32, and 4.12, t=2.34, respectively, P<0.05), while the level of calcium was significantly lower than that in non-early myocardial injury group (Z=2.72, P<0.05). There were no statistically significant differences in other blood test indexes of patients between the two groups (P>0.05). The total burn area, admission time post injury, NLR and ALT within 72 h post injury were the independent risk factors for early myocardial injury in patients with extensive burns (with odds ratios of 1.03, 1.07, 1.04, and 1.02, 95% confidence intervals of 1.02-1.05, 1.00-1.11, 1.02-1.07, and 1.00-1.03, respectively, P<0.05). The fatality rate of patients in early myocardial injury group was 8.8% (16/182), which was significantly higher than 2.8% (5/179) in non-early myocardial injury group (χ2 =5.93, P<0.05). Early myocardial injury, age, combination with shock on admission, and combination with inhalation injury on admission were the independent risk factors for death in patients with extensive burns (with odds ratios of 3.60, 1.04, 6.53, and 3.14, 95% confidence intervals of 1.17-11.05, 1.01-1.07, 1.39-30.68, and 1.15-8.56, respectively, P<0.05). Conclusions: The total burn area, admission time post injury, NLR and ALT within 72 h post injury were the independent risk factors for early myocardial injury in patients with extensive burns. Patients with extensive burns with early myocardial injury have a higher fatality rate, and early myocardial injury is an independent risk factor for the patients' death.

Detection of p53 gene mutation by using a novel biosensor based on localized surface plasmon resonance.

Few studies to date have reported on the development and application of a nanobiosensor based on localized surface plasmon resonance (LSPR) for detecting gene mutations. This study aimed to develop a novel LSPR biosensor used for detecting p53 mutation. Nanosphere lithography was used to fabricate the silver nanoparticles. The DNA probe was designed to recognize the target sequence and immobilized on the chip surface by a covalent-coupling method using amine-group ligands. Synthetic oligonucleotides or PCR products were amplified from genomic DNA taken from blood samples and hybridized with the immobilized probe. Wild-type and mutant p53 was detected by measuring shifts in peak of LSPR extinction spectra. The low detection limit of the sensor for target sequence was 10 nM, and detection occurred over a wide dynamic range (10 nM - 10 µM). Importantly, the differences in measuring signal between wild-type and mismatched p53 DNA was significant, allowing for this sensor to effectively discriminate against single base mutations. In conclusion, we developed a biosensor with potential as a rapid, label-free, sensitive, and low-cost method for detecting p53 mutation. Our results suggest that such an LSPR-based biosensor provides an attractive alternative for clinical detection of genetic mutation.

[Analysis of the development trend of burn discipline from the literature published in Chinese Journal of Burns in 22 years].

Objective: To analyze the literature published in Chinese Journal of Burns (now Chinese Journal of Burns and Wounds) in the last 22 years, and to explore the development trend of burn discipline. Methods: The relevant clinical and research literature published in Chinese Journal of Burns from January 1, 2000 to December 31, 2021 were retrieved through China National Knowledge Infrastructure database. Bibliometrics was used to classify and analyze the literature by research types, involved research fields, and reported causes of injury, and compare them every 3 years according to the year of publication (with literature published in 2021 being included in the last time period). Keywords of all the literature were retrieved, which were corrected and conversed later. CiteSpace 6.1.R2 software was used to visually cluster the included keywords, count high-frequency and high-centrality keywords, and divide the high-frequency keywords by time as before for segment comparison. Results: A total of 4 485 relevant papers were included, with an average of about 204 papers each year. The research types analysis of literature showed that clinical diagnosis and treatment literature had the highest proportion, reaching 65.3% (2 929/4 485), followed by cell experiment and animal experiment literature, accounting for 18.1% (812/4 485) and 13.2% (591/4 485), respectively. The proportion of various research types of the literature in each time period was basically stable. The analysis of the research fields involved in the literature showed that the literature in the field of systemic treatment of burns accounted for the highest proportion, reaching 60.2% (2 699/4 485), followed by the literature in the fields of acute wounds and plastic surgery, accounting for 20.2% (908/4 485) and 7.3% (326/4 485), respectively. The proportion of the literature in the field of systemic treatment of burns decreased from 84.0% (430/512) in 2000-2002 to 40.3% (373/926) in 2018-2021, with a decreasing proportion of 43.7%. While compared with that in 2000-2002, the proportions of literature in the fields of acute wounds, plastic surgery, chronic wounds, and burn rehabilitation were on the rise, with the proportions in 2018-2021 increased by 11.7%, 9.1%, 10.7%, and 5.5%, respectively. In the first 6 time periods, the number of literature in the field of discipline management was few and remained in single digits, but it increased to 49 in 2018-2021. Among the 1 099 literature in the field of systemic treatment of burns with a clear cause of injury, the literature on thermal burns was the most, accounting for 58.5% (643/1 099), followed by the literature on electrical burns and chemical burns, accounting for 19.8% (218/1 099) and 12.6% (138/1 099), respectively. The comparison by time period showed that the proportion of literature reporting thermal burns showed a significant downward trend, while the proportion of literature reporting other causes of injury did not change significantly. A total of 6 822 keywords from 2 236 literature were included for analysis. Visual cluster analysis showed that relevant studies focused on burns, surgical flaps, scars, and wound healing. The top 3 keywords in frequency were burns, wound healing, and surgical flaps, and the top 3 keywords in centrality were burns, scars, and skin transplantation. The comparison by time period showed that the only keyword with a stable frequency in the top 10 ranks was burns; with the passage of time, some keywords such as endotoxin/endotoxins and fibroblasts gradually dropped out of the top 10 ranks, while keywords such as wounds and injuries, surgical flaps, and negative-pressure wound therapy gradually entered the top 10 ranks. Conclusions: Among the literature published in Chinese Journal of Burns during the last 22 years, the literature on systemic treatment of burns and thermal burns has gradually decreased, while the literature on chronic wounds and burn rehabilitation has increased. Surgical flaps, wound healing, and scar prevention and treatment are the current research hot spots in burn discipline.

[Identification of traditional Chinese drugs containing active ingredients for treating myocardial infarction and analysis of their therapeutic mechanisms by network pharmacology and molecular docking].

OBJECTIVE: To identify traditional Chinese drugs that contain active ingredients for treatment of myocardial infarction (MI) and explore their therapeutic mechanisms using network pharmacology and molecular docking technology. METHODS: The TCMSP database was used for screening the traditional Chinese drugs containing active ingredients for treating MI, and the related targets of MI and the candidate drugs were obtained from Genecards, OMIM, PharmGkb and PharmMapper databases. The common target network of the drug targets and disease targets was established using Venny2.1.0 software. GO and KEGG signal pathway enrichment analysis of the common targets was performed, and the protein-protein interaction (PPI) network was constructed for the targets. The targets in the PPI network were analyzed to identify the key targets, for which GO and KEGG pathway enrichment analyses were performed. Molecular docking was performed for the candidate ingredients and the key targets, and a total score ≥6 was used as the criteria for screening the therapeutic ingredients and their docking binding with key targets was verified. A human umbilical vein endothelial cell (HUVEC) model of oxygen-glucose deprivation (OGD) was used to validate the candidate ingredients and the key therapeutic targets for MI by Western blotting. RESULTS: Our analysis identified Salvia miltiorrhiza and Dalbergiae odoriferae as the candidate drugs rich in active ingredients for treatment of MI. These ingredients involved 16 key therapeutic targets for MI, which participated in such biological processes as inflammatory response, angiogenesis, energy metabolism and oxidative stress and the pathways including HIF-1, VEGF, and TNF pathways. Sclareol and PTGS2 in Salvia miltiorrhiza and formononetin and KDR in Dalbergiae odoriferae all had high docking total scores. Western blotting showed that at medium and high doses, sclareol significantly inhibited PTGS2 expression and formononetin promoted KDR expressions in the cell models in a dose-dependent manner (P < 0.05). CONCLUSION: Both Salvia miltiorrhiza and Dalbergiae odoriferae have good therapeutic effects on MI. Sclareol in Salvia miltiorrhiza and formononetin in Dalbergiae odoriferae regulate the expressions of KDR and PTGS2, respectively, to modulate the inflammatory response, angiogenesis, oxidative stress and energy metabolism and thus produce myocardial protective effects.

[A cohort study on the new infections and natural clearance of anal human papillomavirus types 16 and 18 in men who have sex with men].

Objective: To understand the infection status and elimination of anal human papillomavirus (HPV) among men who have sex with men (MSM) in Urumqi, Xinjiang. Methods: The sample size formula in cohort study, a dynamic cohort study method, was used, with the sample size estimated to be 712 according to the new infection rate of HPV16. With the help from non-government organzitions in Urumqi, we recruited 810 MSMs by the snowballing method, and a follow-up program was carried every six months. Anal exfoliated cells were collected to analyze HPV type 16 and 18 infection rates. For statistical analyses, Poisson regression was used to estimate the density of new infections and persistent infections. Cox proportional hazard model was used to explore the influencing factors on both new and persistent infections and the diseases' natural clearing. Results: A total of 810 MSM were recruited, and 482 MSMs with the number of follow-ups more than 2 times were included in the analysis, with the total follow-up numbers as 994.7 person-years. The median number of follow-up and follow-up times was 4 (P25,P75:3,5) times , and 2.2 (P25,P75:1.8, 2.6) years. The baseline infection rates of HPV16 and HPV18 were 8.5% (41/482) and 3.3% (16/482), respectively. And the baseline mixed infection rate of the two types was 0.6% (3/482). The first new infection densities of HPV16 and HPV18 were 10.06 (95%CI:8.12-12.45)/100 person-years and 5.24 (95%CI:3.95-6.96)/100 person-years. The rate of natural infection clearance of HPV16 and HPV18 were 71.2% (89/125) and 71.8% (46/64), respectively. The natural clearance rate of HPV18 after 1.5 years follow-up was higher than HPV16 (97.7% vs. 94.1%). The persistent infection rate of HPV16 and HPV18 were 4.5% (20/441) and 1.7% (8/466), respectively. The risk of persistent HPV16 infection among unmarried subjects was lower than that of married subjects (aHR=0.29,95%CI:0.12-0.71). The natural clearance rate of HPV18 without condom use in anal intercourse in the last six months was 2.63 times higher than that of condom use (95%CI:1.08-6.42). Conclusions: HPV16 and 18 new infections are more common among MSM in Urumqi, and the natural clearance rate is higher. Compared with HPV18, HPV16 has a higher density of new and persistent infections, a low natural clearance rate, and a greater risk of the diseases.

Combined vascular endothelial growth factor receptor and epidermal growth factor receptor (EGFR) blockade inhibits tumor growth in xenograft models of EGFR inhibitor resistance.

PURPOSE: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) gefitinib and erlotinib benefit some non-small cell lung cancer (NSCLC) patients, but most do not respond (primary resistance) and those who initially respond eventually progress (acquired resistance). EGFR TKI resistance is not completely understood and has been associated with certain EGFR and K-RAS mutations and MET amplification. EXPERIMENTAL DESIGN: We hypothesized that dual inhibition of the vascular endothelial growth factor (VEGF) and EGFR pathways may overcome primary and acquired resistance. We investigated the VEGF receptor/EGFR TKI vandetanib, and the combination of bevacizumab and erlotinib in vivo using xenograft models of EGFR TKI sensitivity, primary resistance, and three models of acquired resistance, including models with mutated K-RAS and secondary EGFR T790M mutation. RESULTS: Vandetanib, gefitinib, and erlotinib had similar profiles of in vitro activity and caused sustained tumor regressions in vivo in the sensitive HCC827 model. In all four resistant models, vandetanib and bevacizumab/erlotinib were significantly more effective than erlotinib or gefitinib alone. Erlotinib resistance was associated with a rise in both host and tumor-derived VEGF but not EGFR secondary mutations in the KRAS mutant-bearing A549 xenografts. Dual inhibition reduced tumor endothelial proliferation compared with VEGF or EGFR blockade alone, suggesting that the enhanced activity of dual inhibition is due at least in part to antiendothelial effects. CONCLUSION: These studies suggest that erlotinib resistance may be associated with a rise in both tumor cell and host stromal VEGF and that combined blockade of the VEGFR and EGFR pathways can abrogate primary or acquired resistance to EGFR TKIs. This approach merits further evaluation in NSCLC patients.

Variation of human papillomavirus 16 in cervical and lung cancers in Sichuan, China.

Although the crucial role of human papillomaviruses (HPVs), especially HPV-16 in various cancers has been confirmed, the variation of HPV-16 among different cancers have not been investigated in a specific geographic location. In order to elucidate whether similar HPV-16 variants are involved in different kinds of cancers in the same geographic location, the analysis of sequence variants of E6 and E7 oncogenes and L1 gene of HPV-16 in cervical and lung cancers in Sichuan, China, was carried out. Tissue samples from 122 cervical cancers, 104 lung cancers, and 138 controls were subjected to RT-PCR or PCR, sequencing, and sequence analysis. The infection rates of HPV-16 in cervical, lung cancers, and non-malignant controls were 68.9%, 17.3%, and 37.0%, respectively. Asian prototype variants prevailed in cervical and lung cancers, while European prototype variants in non-malignant controls. In comparison to the lung cancer, cervical cancer showed a much higher diversity of HPV-16 oncogenes. These results indicate that in Sichuan, China, Asian prototype variants of HPV-16 are more pathogenic than their European counterparts.

[Advances in the research of psychological rehabilitation of pediatric burn patients].

Pediatric burn patients are often accompanied by psychological disorders. The authors reviewed the types, prevalence, and treatment methods of common psychological disorders among pediatric burn patients in three stages according to the burn treatment process, in order to provide reference for study and treatment of pediatric burn patients' psychological rehabilitation. The review showed that during the admission and intensive care stage, pediatric medical traumatic stress and acute stress disorder were common, and it was recommended to focus on prevention and monitoring, including providing medical-related information for pediatric burn patients and their parents, encouraging parents to accompany pediatric burn patients, and screening these acute stress disorders in time. In the stage of wound healing, symptoms of pediatric medical traumatic stress and acute stress disorder continued to progress, and the trauma-focused cognitive behavioral therapy was recommended. In the rehabilitation and reintegration stage, post-traumatic stress disorder and anxiety were common, and camp activities and sports were recommended. In addition, the parents of burned children were often accompanied by psychological disorders too, therefore, the mental health of the burned children's parents should be concerned about. At the same time, the parents play a key role in the psychological intervention of the burned children. The psychological intervention of burned children should be done with the participation and help of their parents.

[Effect of fluid resuscitation guided by pulse contour cardiac output monitoring technology on organ function in extremely severe burn patients].

Objective: To investigate the effect of fluid resuscitation guided by pulse contour cardiac output (PiCCO) monitoring technology on the organ function in extremely severe burn patients. Methods: From May 2015 to March 2019, 52 patients with extremely severe burn hospitalized in Tongren Hospital of Wuhan University & Wuhan Third Hospital, meeting the inclusion criteria, were recruited to conduct a prospectively randomized control study. The patients were divided into PiCCO monitoring rehydration group (25 cases, 17 males and 8 females) and traditional rehydration group (27 cases, 20 males and 7 females) according to the random number table, with the ages of (47±9) and (49±8) years respectively. After admission, all the patients were rehydrated according to the rehydration formula of the Third Military Medical University during shock stage. In traditional rehydration group, fluid resuscitation of the patients was performed by monitoring the traditional shock indicators such as urine volume and central venous pressure, while PiCCO monitoring was performed in patients in PiCCO monitoring rehydration group, and the global end-diastolic volume index combined with the other relevant indicators of PiCCO monitoring were used to guide rehydration on the basis of the monitoring indicators of traditional rehydration group. The rehydration coefficients and urine volumes per kilogram of body weight per hour during the first and second 24 h post injury were compared between the two groups, which were compared with the corresponding rehydration scheme value of the Third Military Medical University (hereinafter referred to as the scheme value) at the same time. The total rehydration volumes within post injury hour (PIH) 8 and during the first and second 24 h post injury, the urine volumes per hour during the first and second 24 h post injury, and the levels of creatinine, urea nitrogen, lactate clearance rate, procalcitonin, creatine kinase isoenzyme (CK-MB) in blood and mean arterial pressure (MAP) on post injury day (PID) 1, 2, and 3 were measured. The incidence of complications, the application case number of mechanical ventilation, and the mechanical ventilation time within PID 28 were analyzed. Data were statistically analyzed with analysis of variance for repeated measurement, t test, Bonferroni correction, Mann-Whitney U test, chi-square test, and Fisher's exact probability method test. Results: During the second 24 h post injury, the rehydration coefficient of patients in traditional rehydration group was significantly higher than the scheme value (t=5.120, P<0.01). During the first and second 24 h post injury, the rehydration coefficients of patients in PiCCO monitoring rehydration group were significantly higher than the scheme values (t=3.655, 10.894, P<0.01) and those in traditional rehydration group (t=3.172, 2.363, P<0.05 or P<0.01). Within PIH 8, the total rehydration volumes of patients between the two groups were similar. During the first and second 24 h post injury, the total rehydration volumes of patients in PiCCO monitoring rehydration group were significantly higher than those in traditional rehydration group (t=4.428, 3.665, P<0.01). During the first and second 24 h post injury, the urine volumes per kilogram of body weight per hour of patients in traditional rehydration group were significantly higher than the schema values (t=4.293, 6.362, P<0.01), and the urine volumes per kilogram body weight per hour of patients in PiCCO monitoring rehydration group were significantly higher than the schema values (t=6.461, 8.234, P<0.01). The urine volumes per kilogram of body weight per hour and urine volumes per hour of patients in PiCCO monitoring rehydration group during the second 24 h post injury were significantly higher than those in traditional rehydration group (t=2.849, 3.644, P<0.05 or P<0.01). The creatinine levels of patients between the two groups on PID 1, 2, and 3 were similar. The urea nitrogen levels of patients in PiCCO monitoring rehydration group on PID 1, 2, and 3 were (6.8±1.5), (5.6±1.4), (4.4±1.4) mmol/L respectively, which were significantly lower than (8.6±1.8), (6.6±1.5), (5.5±1.4) mmol/L in traditional rehydration group (t=3.817, 2.511, 2.903, P<0.05 or P<0.01). The lactate clearance rates of patients in PiCCO monitoring rehydration group on PID 1, 2, and 3 were significantly higher than those in traditional rehydration group (t=2.516, 4.540, 3.130, P<0.05 or P<0.01). The procalcitonin levels of patients in PiCCO monitoring rehydration group on PID 2 and 3 were significantly lower than those in traditional rehydration group (Z=-2.491, -2.903, P<0.05). The CK-MB level of patients in PiCCO monitoring rehydration group on PID 3 was (35±10) U/L, which was significantly lower than (51±16) U/L in traditional rehydration group (t=4.556, P<0.01). The MAP levels of patients between the two groups on PID 1, 2, and 3 were similar. Within PID 28, the incidence of complications of patients in traditional rehydration group was significantly higher than that in PiCCO monitoring rehydration group (χ(2)=4.995, P<0.05), and the application case number of mechanical ventilation and the mechanical ventilation time of patients between the two groups were similar. Conclusions: The use of PiCCO monitoring technology to guide the early fluid resuscitation of extremely severe burn patients is beneficial for accurate determination of the fluid volume required by the patients and reduction of organ injury caused by improper rehydration.

XTP8 stimulates migration and invasion of gastric carcinoma through interacting with TGIF1.

OBJECTIVE: To determine expression characteristics of XTP8 and TGIF1 in gastric carcinoma (GC), and the potential roles of XTP8/TGIF1 axis in influencing the progression of GC. MATERIALS AND METHODS: The expression levels of XTP8 and TGIF1 in GC tissues and cells were detected. Their functions in prognosis in GC patients were evaluated by the Kaplan-Meier method. The correlation between the XTP8 level and the pathological indexes of the GC patients were analyzed. The changes in the proliferation, migration, and invasion capacities of MKN-45 and SGC-7901 cells affected by XTP8 and TGIF1 were assessed. The interaction between XTP8 and TGIF1 was determined through Dual-Luciferase reporter gene assay and rescue experiments. RESULTS: XTP8 was upregulated in GC tissues and cells. XTP8 level was positively correlated with lymphatic and distant metastasis, as well as poor prognosis of GC patients. The silence of XTP8 attenuated proliferation, migration, and invasion capacities of MKN-45 and SGC-7901 cells. TGIF1 was the downstream gene binding to XTP8, which was downregulated in GC, and XTP8 negatively regulated the TGIF1 level in GC tissues. Importantly, the knockdown of TGIF1 could abolish the regulatory effect of XTP8 on GC cell behaviors. CONCLUSIONS: XTP8 is upregulated in GC and is closely linked to lymphatic metastasis, distant metastasis, and poor prognosis of GC patients. Besides, it accelerates the malignant progression via negatively regulating TGIF1.