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To evaluate the risk factors of recurrent high-grade cervical intraepithelial neoplasia grade 2 or worse (CIN2+) after loop electrosurgical excision procedure (LEEP).This retrospective study included patients with histopathologically confirmed CIN2/3 who underwent LEEP in 2015-2020. Cox regression analysis was used to evaluate the risk factors of recurrence.Recurrent CIN2+ was found in 268 patients after LEEP (268/4369, recurrence rate, 6.1%). High-risk (hr-) HPV infection (hazard ratio [HR] 12.09, 95% confidence interval [CI] 7.78-18.79), margin status (HR 6.48, 95% CI 4.75-8.84), baseline diagnosis (HR 1.45, 95% CI 1.08-1.95), smoking (HR 3.17, 95% CI 2.27-4.43), and immunosuppression (HR 1.96, 95% CI 1.33-2.91) were significant independent risk factors of recurrence. HPV16 (HR 3.61, 95% CI 2.43-5.37), HPV33 (HR 2.62, 95% CI 1.12-6.12), and HPV52 (HR 1.61, 95% CI 1.02-2.55) infection showed a higher risk of recurrence. High-risk HPV had the highest accuracy (sensitivity 88.5%; negative predictive values 98.7%) in predicting recurrence compared with liquid-based cytology test and margins.Given that positive margins present a higher risk, wide excision may be required to avoid residual lesions. More attention should be paid to the correlation between recurrence and hr-HPV genotypes. After treatment for high-grade CIN, HPV-based testing is recommended at 6 months. Timely identification of high-risk factors enables risk stratification, and enables individual management or individual follow-up and recall strategies.

Since its implementation in China, ecological non-commercial forest certification (ENCFC) has achieved certain ecological, social, and economic effects. In this study, we review domestic and foreign literature to examine the development of ENCFC in China, which is led and enforced by the Chinese government. We found that the ENCFC program is facing several key challenges, including insufficient compensation, single compensation fund sources, and a lack of post-certification evaluation and supervision systems. The government should introduce market mechanisms to optimize ENCFC and consider whether it is necessary to continue to expand the ENCFC program. In addition, more research is needed on the performance evaluation of ENCFC implementation.

BackgroundFew patients with prostate cancer benefit from current immunotherapies. Therefore, we aimed to explore new strategies to change this paradigm.MethodsHuman tissues, cell lines and in vivo experiments were used to determine whether and how N-cadherin impacts the production of programmed death ligand-1 (PD-L1) and indole amine 2,3-dioxygenase (IDO-1) and whether N-cadherin can increase the production of effector (e)Treg cells. Then, we used PC3-bearing humanized non-obese diabetic/severe combined immunodeficiency IL2Rγnull (hNSG) mice with an intravenous injection of human CD34+ hematopoietic stem cells into the tail vein to evaluate whether the N-cadherin antagonist N-Ac-CHAVC-NH2 (designated ADH-1) could improve the therapeutic effect of tumor-infiltrating lymphocyte (TIL)-related treatment.ResultsN-cadherin dramatically upregulated the expression of PD-L1 and IDO-1 through IFN-γ (interferongamma) signaling and increasing the production of free fatty acids that could promote the generation of eTreg cells. In preclinical experiments, immune reconstitution mediated by TILs slowed tumor growth and extended the survival time; however, this effect disappeared after immune system suppression by PD-L1, IDO-1 and eTreg cells. Furthermore, ADH-1 effectively reduced immunosuppression and enhanced TIL-related therapy.ConclusionsThese data show that the N-cadherin antagonist ADH-1 promotes TIL antitumor responses. This important hurdle must be overcome for tumors to respond to immunotherapy.

Complex hydrogeological conditions in China’s coal mines have contributed to frequent mine water disasters. A simple and effective method to determine water inflow sources and paths is therefore essential. The Longmen Mine, located in Henan Province, in central China was used as a case study. A Piper diagram and cluster analysis were used to screen the characteristic values of 18 water samples from potential aquifers. A comprehensive fuzzy evaluation of the groundwater ions was carried out to determine the main source of the total mine inflow. Then, based on conservation of ionic masses, a matrix function was established to calculate the groundwater recharge composition. Finally, using measured water inflows for the Cambrian limestone aquifer, the calculated and observed results were compared. The results showed that the Carboniferous Taiyuan Formation limestone aquifer (the L7 limestone aquifer) accounts for 60.8% of the total mine inflow, while the Cambrian limestone and roof sandstone aquifers account for 34.8 and 4.4% of the inflow, respectively. The normal mine inflow totals about 19,200 m3/day, of which 6,840 m3/day is from the Cambrian limestone aquifer. This agrees well with the calculated value of 6,720 m3/day. Thus, the method is feasible and reliable.

A non-invasive and more sensitive method for detection of HE4 is very important for the early screening and detection of ovarian carcinoma. In this study, we improved our previous localized surface plasmon resonance (LSPR) biosensor for detection of HE4 in urine to overcome disadvantages of conventional methods. Protein G directional fixed method was firstly used for LSPR biosensor to improved sensitivity, and standard HE4 and clinical samples were detected separately using this new biosensor. Compared to our previous LSPR biosensor, this new sensor was more sensitive, with other advantages as before. Under optimum conditions, this new biosensor could display a detection limit of 1 pM and wide dynamic range of 1 pM to 10,000 pM. This new biosensor was effective for detection of HE4 in urine of early ovarian cancer patients, without label and purification. To the best of our knowledge, this is first work to investigate LSPR biosensor for detection of tumor marker in urine, with great advantages and clinical application potentials.

The heterogeneity of deeply buried carbonates (burial depth >4500 m) is directly related to the morphology of the micropores and connectivity of the pore network. It is important to know the fractal characteristics of the microstructure to understand the heterogeneity and fluid flow properties. In this study, N2 gas adsorption measurements, mercury intrusion porosimetry, and nuclear magnetic resonance were conducted. Based on the pore size distribution (PSD), we compared the mono- and multifractal characteristics and established the relationship between the fractal parameters and petrophysical properties (porosity, permeability, median capillary pressure, and the cutoff value of transversal relaxation time (T2cutoff)). Finally, two multifractal parameters were introduced to characterize the pore structure. A cross-plot of D0 (capacity dimension) vs f0 (fractal spectrum) was established for the pore structure classification with predefined parameters such as the porosity and permeability. The results show that the PSD can be obtained by integrating the three above-mentioned measurement methods. The mono fractal dimensions are weakly correlated with the petrophysical parameters, whereas D0 obtained from multifractal analysis correlates with the porosity, permeability, median capillary pressure, and T2cutoff. The unique multifractal characteristics of D0 and f0 can be used as indicators of pore structure types in case studies. This study introduces an effective method that can be used for the pore structure characterization and classification of carbonates.

Granite is one rock type used to host high-level radioactive waste repositories, and the structure of microcracks in the rock can influence its hydraulic characteristics. Thus, a quantitative analysis of granite microcracks is relevant for understanding the hydrogeological characteristics of the rocks surrounding geological repositories. The analysis can also contribute scientific data to a seepage model for low permeability rocks and materials with microscopic pores. In this study, seven granite core samples were drilled from different depths up to 600 m in Alxa, Inner Mongolia, China. Using a grid survey method and image processing technology, micrographs were converted into binary images of microcracks. The geometric parameters of the microcracks, including their quantity, width, cranny ratio, crack intersections and dimensional parameters of the fracture network, were analyzed in order to fully describe their spatial distribution. In addition, the morphological characteristics and elemental compositions of the microcracks were analyzed by scanning electron microscopy energy dispersive X-ray analysis (SEM-EDS), and the natural moisture content was also determined through heated. Finally, two-dimensional microcrack network seepage models of the granite samples were simulated using the Lattice Boltzmann method (LBM), which revealed the influence of the microcrack structure on their connectivity. The results show that the growth and development of microcracks in the granite samples generally decreases as sampling depth increases in this study area. Connectivity is positively correlated with a number of the geometric parameters: the quantity of microcracks, the cranny ratio, the number of crack intersections and dimensional parameters of the fracture network, which is revealed in the two-dimensional microcrack network seepage models for these granite samples.

Aim The aim of this study was to investigate whether a functional insertion/deletion polymorphism (rs3783553) located in the 3′-untranslated regions of interleukin-1 A is associated with susceptibility to endometrial cancer (EC) in Chinese Han women. Methods A total of 272 patients and 294 age-matched healthy controls were included in the study. The genotype of the rs3783553 polymorphism was determined by polymerase chain reaction polyacrylamide gel electrophoresis. Results Our results showed that a significantly reduced risk of EC was found to be associated with the II (insertion/insertion) genotype compared with DD (deletion/deletion) only (P = 0.037, odds ratio = 0.56, 95% confidence interval = 0.32–0.97) as well as compared with the DD + DI (deletion/insertion) genotype (P = 0.032, odds ratio = 0.57, 95% confidence interval = 0.34–0.96) in the recessive model. No significant association was detected between certain clinical features of EC patients and genotype of rs3783553. Conclusions This study demonstrates that the rs3783553 polymorphism may be involved in susceptibility to EC. The II genotype seems to be a protective factor for EC in Chinese Han women.

Hydrothermal dolomitization is an important diagenetic process that affects the quality of carbonate reservoirs. While geochemical modeling is a useful tool to improve our understanding of this process, comparatively little research has been focused on producing reservoir intervals. This study examines deeply buried (over 4500 m deep), Lower Ordovician dolomitized limestones (more than 50 m revealed by the borehole) in an exploration well in the Tazhong Uplift, Tarim Basin. The well penetrated a fault zone that was affected by extensive hydrothermal activity during the Permian. Batch geochemical modeling and reactive transport modeling (RTM) were used to evaluate the potential sources of hydrothermal fluid and the associated mechanisms that resulted in a relatively restricted distribution of dolomitization in the study area. Simulation results show that the RTM, which can include geological heterogeneity, provides more reliable constraints for the volume of hydrothermal fluids required for the observed scale of dolomitization, compared to batch geochemical modeling. According to the simulation results, the interstitial fluids released from underlying Cambrian formations due to high pressure and high temperature are not the only source of hydrothermal dolomitization. Other mechanism like long-lasting recharge of seawater-derived basement brines may be took place. Scenario simulations also indicate that the patterns of hydrothermal dolomitization and porosity distributions are strongly related to permeability heterogeneity in the formation. This study shows the ability and feasibility of geochemical modeling as a tool to quantitatively evaluate and further understand hydrothermal dolomitization processes, which are also helpful for other similar geological process research. However, reliable and detailed geological information, geological constrains, especially geological heterogeneity distributions, are crucial to achieve beneficial conclusions.

Groundwater flow dynamics plays a crucial role in social development and ecosystem protection. This study investigated the impacts of long-term climate change on the regional groundwater flow in Alashan, China to reveal the spatial variability of groundwater flow response to climate change and the dynamic patterns of both deep and shallow groundwater flow velocity. To this end, the hydrogeologic conditions and climate evolution history were analyzed. Based on these, four future scenarios of long-term climate change were designed, including linearly varying and cyclic changes, and numerical groundwater flow modeling was then conducted to investigate the effects of long-term climate changes on groundwater flow dynamics (including groundwater level and flow velocity). It was found that groundwater level dynamics were notably influenced by climate changes; the time scale and initial change pattern of cyclic climate influenced the amplitude and mean level of groundwater level fluctuations. In addition, our results also revealed that, for a regional groundwater system, climate change impacts on groundwater level had obvious spatial variability. Groundwater level in recharge and discharge areas were sensitive to drying and wetting climates, respectively. Thus, the spatial variability of groundwater level dynamics reflected climate change information. Moreover, groundwater flow velocity dynamics were also affected by climate changes. However, linearly varying and cyclic climates had different influences. Linearly wetting climate generally increased the groundwater flow velocity in recharge and discharge areas, but decreased that in runoff area, whereas cyclic climate induced periodical fluctuation of groundwater flow velocity. The fluctuation period of shallow groundwater flow velocity matched the full climate cycle period, whereas of the deep groundwater flow velocity was only half. This unique behavior of deep groundwater flow velocity is caused by fluctuation of the vertical velocity alternating between positive (upward flow) and negative (downward flow) values. This finding of groundwater flow velocity dynamics contributes to deeper understanding of long-term climate change effects on groundwater flow dynamics.

One of the main environmental issues associated with hydraulic fracturing (HF) is the upward migration of the HF fluids from a shale reservoir to reach the shallow drinking water aquifers through preferential flow paths, such as fractures or faults. Oversimplified model structures or arbitrary boundary conditions were used in the previous studies, resulting in inaccurate results. To better describe the flow and transport in fractures/faults and matrix pores, a dual-medium model including fracture (fault) and matrix was established in this study to understand the evolution that occurs in reservoir pressure during HF and the long-term migration of HF fluids in deep geological formations, considering Sichuan Basin, China, as a case study. Both HF fractures and pre-existing natural faults were characterized as highly permeable preferential flow channels. Simulation results show that the spatial distribution of pressure in shallow aquifers is mainly controlled by the topography while it is controlled by overpressure in the deep strata. HF fluids were not found to contaminate the shallow groundwater throughout the simulation period, even in the worst scenario. A sensitivity analysis is carried out to quantify and understand the influence of a broad range of possibilities of parameters, such as HF fracture, reservoir properties and HF operation. The results suggest that the reservoir properties and the duration over which the injection of HF fluid take place are the most important factors influencing the spatiotemporal distribution of HF. Moreover, HF fluids are removed from the formation by the production of gas, meaning that these fluids are unlikely to contaminate the shallow aquifers of the Sichuan Basin.

Maternal bacterial sepsis during pregnancy and the postpartum period is a common cause of maternal mortality and fetal morbidity and mortality. This study was performed to analyze perinatal prognosis and related factors of maternal bacterial sepsis in west China. We conducted a cross-sectional study of pregnant women with bacterial sepsis who were admitted into a tertiary care center in western China between 2011and 2015. Data from these cases were collected and analyzed. Eighty six women were identified with bacterial sepsis in our hospital, and the incidence of maternal bacterial sepsis was 1.7 per 1000 maternities, the incidence of septic shock was 1.8 per 10,000 maternities, and 1 maternal death occurred. Among the 86 pregnant women with bacterial sepsis, genital tract infection was the most common source of infection (41/86, 47.7%). The most common bacteria in the Gram-positive bacteria group was Listeria monocytogenes and in the Gram-negative bacteria group was Escherichia coli. The premature delivery rate (65.7%) was substantially higher in the Gram-negative bacteria group (P = .011), and the miscarriage rate (31.3%) was higher in the Gram-positive bacteria group (P = .042). The fetal/neonatal mortality rate was 20% (21/105) and higher in the Gram-positive bacteria group (P = .008), and the infant mortality rate in 1 year was 7.1% (6/84). Bacterial sepsis remains an alarming cause of both maternal and fetal morbidity and mortality, and infant mortality. Key treatment involves a multi-disciplinary group of clinicians with experience in all aspects of the care of pregnant women with sepsis and early initiation of appropriate antibiotics according to the type of bacterial infection. The effect of maternal sepsis on long-term fetal outcome should be investigated.

Bare nanoscale zero-valent iron (NZVI) particles in aqueous suspensions aggregate into micron to submicron sizes. The transport process of enlarged aggregates or multi-sized aggregates is different from that of nanoparticles. In this work, we performed aggregate size distribution analysis of NZVI suspension using a laser grain size analyzer and conducted a series of continuous injection column experiments with different injected NZVI concentrations. The results show that aggregates in NZVI suspensions range from submicron to submillimeter size and are mainly distributed around 5–9 μm and 50–100 μm. Quantitative calculation of iron transport and retention showed that the retained iron linearly correlates with injected concentration. The cross-section images revealed that clogging weakened from inlet to outlet. Furthermore, larger aggregates (>40 μm) appeared more often in the rising-declining stages of breakthrough curves, whereas small aggregates (

Background Eisenmenger’s syndrome (ES) consists of pulmonary hypertension with a reversed or bidirectional shunt at the atrioventricular, or aortopulmonary level. The cardiovascular changes that occur during the pregnancy contribute to the high maternal morbidity and mortality in patients with ES. This study is to assess maternal and fetal outcomes in patients with ES. Methods This study is a retrospective analysis of 11 pregnancies in women with ES who delivered at a tertiary care center in west China between 2010 and 2014. Cases were divided into group I (maternal survival) and group II (maternal death). Clinical data were noted and analyzed. Results All ES patients presented with severe pulmonary arterial hypertension (PAH). Four maternal deaths were recorded (maternal mortality of 36%). Only one pregnancy continued to term. Ventricular septal defect diameter in group II was larger than that in group I (2.93 ± 0.76 cm vs. 1.90 ± 0.54 cm, p

Interleukin-32 (IL-32), a pro-inflammatory chemokine, has been reported to be involved in inflammatory, infectious diseases and even cancers. This study aimed to investigate whether two genetic variants (rs28372698 and rs12934561) of IL-32 were associated with susceptibility to endometrial cancer (EC) in Chinese Han women by a hospital-based study with 272 EC patients and 337 healthy controls. Our results showed that the frequencies of TT genotype (P = 0.012, OR = 2.37, 95 % CI = 1.32–4.28) and T allele (P = 0.026, OR = 1.320, 95 % CI = 1.036–1.681) of rs28372698 in EC patients were significantly higher than controls. Clinical analyses indicated the TT genotype frequency was relevant to high clinical stage and cervical invasion. Furthermore, the frequencies of CC genotype (P = 0.0077, OR = 1.62, 95 % CI = 1.05–2.50) and C allele (P = 0.043, OR = 1.269, 95 % CI = 1.011–1.592) of rs12934561 were also significantly higher in EC patients than controls. Stratification analyses revealed that CC genotype was more frequent in endometrioid adenocarcinoma or EC without parametrial invasion. This study demonstrates that IL-32 gene polymorphisms are significantly associated with increased EC susceptibility in Chinese Han women.

Qianying Zhao,1 Ruiqi Duan,1 Jialing Yuan,1 Yi Quan,1 Huan Yang,2 Mingrong Xi1 1Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, 2State Key Laboratory of Optical Technologies for Micro-fabrication, Institute of Optics and Electronics, Chinese Academy of Science, Chengdu, Sichuan, People's Republic of China Abstract: Squamous cell carcinoma antigen (SCCa), as a tumor biomarker, plays an important role in adjuvant diagnosis, treatment evaluation, and prognosis prediction for cervical cancer patients. Localized surface plasmon resonance (LSPR) technique based on noble metal nanoparticles bypasses the disadvantages of traditional testing strategies, in terms of free-labeling, short assay time, good sensitivity, and selectivity. Herein, we develop a novel and reusable LSPR biosensor for the detection of SCCa. First, a triangle-shaped silver nanoparticle array was fabricated using the nanosphere lithography method. Next, we investigated and verified the feasibility of amino coupling method using 11-mercaptoundecanoic acid (MUA) to form a functionalized chip surface with monoclonal anti-SCCa antibodies on the silver nanoparticles for distinct detection of SCCa. Different concentrations of SCCa were successfully tested in both buffer and human serum by the ultrasensitive and specific LSPR system, with a linear quantitative detection range of 0.1–1,000 pM under optimal conditions. With appropriate regeneration solution, for example 50 mM glycine-HCl (pH 2.0), the LSPR biosensor featured effective fabrication reproducibility, which reduced both production cost and testing time. Our study represents the first application of the LSPR biosensor in cervical cancer, and demonstrates that the rapid, simple, and reusable nanochip can serve as a potential alternative for clinical serological diagnosis of SCCa in cervical cancer patients. Keywords: localized surface plasmon resonance, nanotechnology, biosensor, cervical cancer biomarker, squamous cell carcinoma antigen

Background Detection of the human epididymis secretory protein 4 (HE4) biomarker plays an important role in the early diagnosis of ovarian cancer. This study aimed to develop a novel localized surface plasmon resonance (LSPR) biosensor for detecting HE4 in blood samples from patients with ovarian cancer. Methods Silver nanoparticles were fabricated using a nanosphere lithography method. The anti-HE4 antibody as a probe, which can distinctly recognize HE4, was assembled onto the nanochip surface using an amine coupling method. Detection was based on the shift in the extinction maximum of the LSPR spectrum before and after the HE4-anti-HE4 antibody reaction. These nanobiosensors were applied to detect HE4 in human serum samples and compare them using an enzyme-linked immunosorbent assay. Results Tests relating to the detection of HE4 demonstrated that the LSPR-based biosensor featured a fast detection speed, good specificity, effective reproducibility, and long-term stability. The linear range for LSPR was between 10 pM and 10,000 pM, with a detection limit of 4 pM. An excellent correlation between LSPR and enzyme-linked immunosorbent assay results was observed in human serum. Conclusion This study is the first clinical diagnostic application of the LSPR biosensor in ovarian cancer. The LSPR biosensor, a rapid, low-cost, label-free and portable screening tool, can serve as a very effective alternative for the clinical serological diagnosis of ovarian cancer.