Anlotinib in Chinese patients aged ≥70 years with advanced non-squamous non-small cell lung cancer without prior chemotherapy: a multicenter, single-arm pilot trial.

Background: Based on pharmacoeconomics, drug availability and actual treatment, optimal treatment regimens for Chinese non-small-cell lung carcinoma (NSCLC) patients over 70 years old are needed. Methods: This multicenter, single-arm pilot trial enrolled patients with advanced non-squamous NSCLC who refused systemic chemotherapy. Eligible patients received anlotinib (12 mg/day, d1-14, Q3W) until disease progression, intolerant toxicities, or withdrawal from the study. The primary endpoint was progression-free survival (PFS). Results: Forty-nine patients were screened between January 2019 and September 2021, of whom 40 patients were eligible. The median age was 76 years. With a median follow-up period of 16.20 (95% CI: 8.77, 25.10) months, the median PFS was 5.45 months (95% CI: 3.52-9.23) and the median overall survival was 10.32 months (95% CI: 6.44-12.78). Three patients achieved a partial response and 34 had stable disease, with an objective response rate of 7.5% and a disease control rate of 92.5%. Thirty-three (82.5%; 33/40) patients reported treatment-related adverse events (TRAEs) of any grade, and the incidence rate of grade ≥3 TRAEs was 35% (14/40). The most common grade ≥3 TRAEs were hypertension (4/40; 10.0%), hand-foot syndrome (3/40; 7.5%), and proteinuria (2/40; 5.0%). Conclusion: Anlotinib treatment was feasible and safe in Chinese elderly patients with advanced non-squamous NSCLC who did not receive any systemic chemotherapy.

Atomic Oxygen-Induced Surface Erosion Behavior and Mechanical Degradation of Polyether Ether Ketone via Reactive Molecular Dynamics Simulations.

Atomic oxygen (AO) collision is one of the most serious threats to polymeric materials exposed to the space environment, yet understanding the structural changes and degradation of materials caused by AO impact remains a tremendous issue. Herein, we systematically evaluate the erosion collision and mechanical degradation of polyether ether ketone (PEEK) resin under hypervelocity AO impact using reactive molecular dynamics simulations. The interaction process and local evolution mechanism between high-speed AO and PEEK are investigated for the first time, suggesting that AO will either be scattered or adsorbed by PEEK, which is strongly correlated with the main degraded species evolution including O2, OH, CO, and CO2. Different AO fluxes and AO incidence angle simulations indicate that high-energy AO collision on the surface transfers kinetic energy to PEEK's thermal energy, thus inducing mass loss and surface penetration mechanisms. Vertically impacted AO causes less erosion on the PEEK matrix, rather than obliquely. Furthermore, PEEK chains modified with functional side groups are comprehensively investigated by 200 AO impact and high strain rate (1010 s-1) tensile simulations, demonstrating that the spatial configuration and stable benzene functionality of phenyl side groups can significantly improve the AO resistance and mechanical properties of PEEK at 300 and 800 K. This work revealed useful insights into the interaction mechanisms between AO and PEEK at the atomic scale and may provide a protocol for screening and designing new polymers of high AO tolerance.

Cancer-associated fibroblasts, and clinicopathological characteristics and prognosis of gastric cancer: A systematic review and meta-analysis.

Objective: To systematically evaluate the relationship between cancer-associated fibroblasts (CAFs) and clinicopathological characteristics and prognosis of gastric cancer, so as to provide new directions and clinical evidence for the diagnosis and treatment of this disease. Methods: We searched PubMed, Embase, Web of Science, and The Cochrane Library to identify studies on the correlation between tumor-associated fibroblasts and the diagnosis and prognosis of gastric cancer. Two researchers screened the literature independently to extract data, evaluated the quality of the included studies, and used the Review Manager 5.4 software to perform a meta-analysis. Results: A total of 14 studies involving a total of 2,703 patients were included. The meta-analysis results showed that high expression of CAFs was associated with stage III-IV gastric cancer (relative risk ratio [RR]=1.59; 95% confidence interval [CI]: [1.24-2.04]; P=0.0003), lymph node metastasis (RR=1.51; 95% CI: [1.23-1.87]; P=0.0001), serosal infiltration (RR=1.56, 95% CI: [1.24-1.95]; P=0.0001), diffuse and mixed types in Lauren classification (RR=1.43; 95% CI: [1.18-1.74]; P=0.0003), vascular invasion (RR=1.99; 95% CI: [1.26-3.14]; P=0.003), and overall survival (hazard ratio [HR]=1.38; 95% CI: [1.22-1.56]; P<0.00001). However, the high expression of CAFs was not significantly correlated with poorly differentiated gastric cancer (RR=1.03; 95% CI: [0.96-1.10]; P=0.45) and gastric cancer with tumor diameter >5 cm (RR=1.34; 95% CI: [0.98-1.83]; P=0.07). Conclusion: The findings of this meta-analysis demonstrated that high expression of CAFs is closely associated with the traditional pathological indicators related to poor prognosis in gastric cancer, and is a valuable prognostic factor in this setting. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022358165.

Optimising the measurement of intra-bladder pressure in patients with predicted severe acute pancreatitis.

BACKGROUND: Measuring intra-abdominal pressure (IAP) is important for management of patients with severe acute pancreatitis (SAP). Intra-bladder pressure (IBP) is an indirect index that reflects IAP, but measuring techniques vary. We sought to optimise IBP measuring techniques in predicted SAP patients. METHODS: Predicted SAP patients consecutively admitted between June 2018 and January 2020 were scrutinised. Eligible patients had their IBP monitored for the first 72 h at 6-h intervals, and were then sequentially allocated into three research scenarios: (1) in the supine position along with head of bed elevation(HoBE)of 0, 15 and 30° at various points including the iliac crest the midaxillary line, pubic symphysis, and right atrium level, instilled with 25 mL normal saline (NS) at room temperature (RT); (2) NS instillation volume from 0, 10, 25, 40-50 mL at the iliac crest with HoBE15 at RT; and (3) NS instillation (25 mL) at either RT or 37 °C with HoBE15. RESULTS: The dynamic IBP values measured at the pubic symphysis and iliac crest were fairly similar between HoBE0 and HoBE15 (all P > 0.05), but greatly increased at HoBE30 (all P < 0.01). IBP was significantly increased with escalating instillation volumes of NS (all P < 0.01 versus 0 mL NS), while there was no significant difference between 25 mL and 10 mL (P = 0.055). IBP was similar between NS at RT and under 37 °C (P = 0.643). CONCLUSION: In predicted SAP patients, measuring IBP at the iliac crest with HoBE15 after instilling 10 mL of NS seems to be appropriate for monitoring IAP.

Characterization of the ABC Transporter G Subfamily in Pomegranate and Function Analysis of PgrABCG14.

ATP-binding cassette subfamily G (ABCG) proteins play important roles in plant growth and development by transporting metabolites across cell membranes. To date, the genetic characteristics and potential functions of pomegranate ABCG proteins (PgrABCGs) have remained largely unknown. In this study, we found that 47 PgrABCGs were divided into five groups according to a phylogenetic analysis; groups I, II, III, and IV members are half-size proteins, and group V members are full-size proteins. PgrABCG14, PgrABCG21, and PgrABCG47 were highly expressed in the inner seed coat but had very low expression levels in the outer seed coat, and the expression levels of these three PgrABCG genes in the inner seed coats of hard-seeded pomegranate 'Dabenzi' were higher than those of soft-seeded pomegranate 'Tunisia'. In addition, the expression of these three PgrABCG genes was highly correlated with the expression of genes involved in lignin biosynthesis and hormone signaling pathways. The evolution of PgrABCG14 presents a highly similar trend to the origin and evolution of lignin biosynthesis during land plant evolution. Ectopic expression of PgrABCG14 in Arabidopsis promoted plant growth and lignin accumulation compared to wild type plants; meanwhile, the expression levels of lignin biosynthesis-related genes (CAD5, C4H, and Prx71) and cytokinin response marker genes (ARR5 and ARR15) were significantly upregulated in transgenic plants, which suggests the potential role of PgrABCG14 in promoting plant growth and lignin accumulation. Taken together, these findings not only provide insight into the characteristics and evolution of PgrABCGs, but also shed a light on the potential functions of PgrABCGs in seed hardness development.

Landscape of RB1 alterations in 22,432 Chinese solid tumor patients.

Background: The human retinoblastoma susceptibility gene (RB1) is a tumor-suppressor gene mutated at different frequencies in many different cancers. The aim of the present study was to investigate the distribution of overall RB1 mutation and different mutation types in a range of Chinese patients with solid tumors. Methods: We investigated RB1 mutations in formalin-fixed, paraffin-embedded (FFPE) tissues of cancer patients who underwent next-generation sequencing (NGS) at 3DMed Clinical Laboratory Inc from January 1, 2017 to April 15, 2020. Results: Genomic alterations in RB1 were identified in 1,712 (7.6%) of 22,432 patients with more than 20 different cancer entities (58% males and 42% females, median age: 60 years). RB1 mutations occurred most frequently in small-cell lung cancer (SCLC; 138/165, 83.6%), followed by neuroendocrine neoplasms (40/170, 23.5%), bladder cancer (40/209, 19.1%), hepatocellular carcinoma (233/1,649, 14.1%), sarcomas (71/554, 12.8%), and esophageal cancer (32/293, 10.9%). Of these 1,712 patients, 185 (10.8%) had germline RB1 mutations. When stratified by mutational type, 1,258 (5.6%) had single-nucleotide variants (SNVs), 59 (0.3%) had fusions, and 210 (0.9%) had RB1 loss. Conclusions: Our findings indicate that RB1 alterations are widely distributed in solid cancers of many different histotypes in China, with specific mutations differing largely among different tumor types. The present study provides a comprehensive landscape of RB1 mutations in Chinese solid tumor patient and suggests a novel therapeutic target for cancer treatment.

The association between overweight/obesity and poor cognitive function is mediated by inflammation in patients with major depressive disorder.

BACKGROUND: Cognitive dysfunction is a common and core feature of major depressive disorder (MDD). Evidences exerted a potentially harmful role of obesity and higher peripheral levels of inflammation in cognitive function, but few studies have explored whether markers of peripheral inflammation might mediate the association between overweight/obesity and deficits in cognitive function. Our study aimed to examine the cognitive function in MDD patients and clarify the effects of overweight/obesity and inflammatory cytokines on cognitive dysfunction in this population. METHOD: We used a cross-sectional design in this study. A total of 265 patients with MDD were enrolled and divided into underweight, normal weight and overweight/obese groups. The MATRICS Consensus Cognitive Battery (MCCB) was administered to measure the cognition. Plasma levels of nineteen cytokines were measured using high sensitivity multiplex bead-based assays. RESULTS: We found overweight/obese MDD patients associated with higher plasma levels of tumor necrosis factor (TNF)-α, interleukin (IL)-8, and macrophage inflammatory protein (MIP)-1ß and worse performance in speed of processing and working memory. The mediation analysis found higher levels of IL-8 (direct: ß = -0.591 (95 % Confidence Interval (CI): -1.0 to -0.2), P = 0.002; indirect: ß = 0.060 (95 % CI.: 0.0-0.2), P = 0.032) and TNF-α (direct: ß = -0.589 (95 % CI.: -1.0 to -0.2), P = 0.002; indirect: ß = 0.059 (95 % CI.: 0.1-0.2), P = 0.037) were associated with more deficits in speed of processing, and partially mediated the relationship between body mass index and speed of processing. CONCLUSION: Our results suggest that elevated inflammation might be one biological mechanism underlying the link between higher body mass and deficits in processing speed in patients with MDD.

Phosphorus-Doped Iron Nitride Nanoparticles Encapsulated by Nitrogen-Doped Carbon Nanosheets on Iron Foam In Situ Derived from Saccharomycetes Cerevisiae for Electrocatalytic Overall Water Splitting.

It is vitally essential to propose a novel, economical, and safe preparation method to design highly efficient electrocatalysts. Herein, phosphorus-doped iron nitride nanoparticles encapsulated by nitrogen-doped carbon nanosheets are grown directly on the iron foam substrate (P-Fe3 N@NC NSs/IF) by in situ deriving from Saccharomycetes cerevisiae (S. cerevisiae), where anion elements of C, N, and P all from S. cerevisiae replace the hazardous CH4 , NH3 , and H3 P. The diffusion pattern of N, P in S. cerevisiae and contact form between metal and S. cerevisiae observably affect the composition and phase of the product during high-temperature calcination. The obtained P-Fe3 N@NC NSs/IF demonstrates superior electrocatalytic performance for the hydrogen evolution reaction and oxygen evolution reaction, also satisfying durability. Theoretical calculation confirms that Fe sites of P-Fe3 N serve as the active center, and N sites and P doping regulate the hydrogen binding strength to enhance catalytic ability. Additionally, the two-electrode electrolyzer assembled by P-Fe3 N@NC NSs/IF as both anode and cathode electrodes needs only 1.61 V to reach 10 mA cm-2 for overall water splitting with a superb stability. The S. cerevisiae-based process presents a feasible approach for synthesis of nitrides, carbides, phosphides, and electrocatalytic applications.

Multiple point mutations in PsORP1 gene conferring different resistance levels to oxathiapiprolin confirmed using CRISPR-Cas9 in Phytophthora sojae.

BACKGROUND: Oxathiapiprolin is among the first commercial oxysterol-binding protein inhibitors (OSBPIs) developed by DuPont Corporation and shows excellent activity against plant-pathogenic oomycetes. Although more than 21 target site mutations have been identified in insensitive oomycetes, only G770V, G839W, and ΔN837 have been verified to confer oxathiapiprolin resistance in Phytophthora capsici or P. sojae. The effect of other mutations on OSBPIs sensitivity requires urgent investigation. RESULTS: P. sojae transformants containing 16 mutations of PsORP1 were recovered using the CRISPR-Cas9 system. Transformants containing L733W, S768F, S768Y, N837Y, N837F, P861H, L863W, or I877Y showed high oxathiapiprolin resistance, with resistant factors (RFs) > 3000. Point mutations S768K, S768I, G770L, G770P, G770A, ΔG818/F819, N837I, and I877F exhibited low resistance, with RFs < 80. Phenotype assays revealed that the most highly resistant transformants showed enhanced or similar pathogenicity, oospore production, and cyst gemination. However, most transformants displayed decreased sporangia and zoospore production compared with parental wild-type P6497. CONCLUSION: This study demonstrated that L733W, S768F, S768Y, N837Y, N837F, P861H, L863W, and I877Y in PsORP1 confer high oxathiapiprolin resistance in P. sojae.

Embedded Nickel-Mesh Transparent Electrodes for Highly Efficient and Mechanically Stable Flexible Perovskite Photovoltaics: Toward a Portable Mobile Energy Source.

The rapid development of Internet of Things mobile terminals has accelerated the market's demand for portable mobile power supplies and flexible wearable devices. Here, an embedded metal-mesh transparent conductive electrode (TCE) is prepared on poly(ethylene terephthalate) (PET) using a novel selective electrodeposition process combined with inverted film-processing methods. This embedded nickel (Ni)-mesh flexible TCE shows excellent photoelectric performance (sheet resistance of ≈0.2-0.5 Ω sq-1 at high transmittance of ≈85-87%) and mechanical durability. The PET/Ni-mesh/polymer poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS PH1000) hybrid electrode is used as a transparent electrode for perovskite solar cells (PSCs), which exhibit excellent electric properties and remarkable environmental and mechanical stability. A power conversion efficiency of 17.3% is obtained, which is the highest efficiency for a PSC based on flexible transparent metal electrodes to date. For perovskite crystals that require harsh growth conditions, their mechanical stability and environmental stability on flexible transparent embedded metal substrates are studied and improved. The resulting flexible device retains 76% of the original efficiency after 2000 bending cycles. The results of this work provide a step improvement in flexible PSCs.

High-dispersion zero-valent iron particles stabilized by artificial humic acid for lead ion removal.

Nano zero-valent iron (nZVI), as a high-efficiency adsorbent for heavy metals, often suffers being oxidized and assembling together due to small size and super reactivity, further decreasing its adsorption performance and limiting application ranges. Herein, we have designed a novel adsorbent with high-dispersion nZVI stabilized by as-prepared artificial humic acid (AHA-nZVI) derived from hydrothermal humification (HTH) technology. Introduction of artificial humic acid (A-HA) can effectively reduce the oxidation and agglomeration of nZVI, leading to superior kinetic removal efficiency of Pb2+ (> 99.2%) and huge Langmuir removal capacity of 649.0 mg/g. The combination of nZVI and A-HA (contained abundant functional groups, i.e. -OH and -COOH) via C-O-Fe bonding makes nZVI have good dispersion and oxidation resistance. Multiple interaction mechanisms including reduction reaction, complexation and co-precipitation between heavy metals and AHA-nZVI samples are realized. Overall, AHA-nZVI is a promising material for high-performance heavy metal contaminated water treatment.

Electrochemical Flocculation Integrated Hydrogen Evolution Reaction of Fe@N-Doped Carbon Nanotubes on Iron Foam for Ultralow Voltage Electrolysis in Neutral Media.

Hydrogen (H2) production is a key step in solving the energy crisis in the future. Electrocatalytic water splitting suffers from sluggish anodic oxygen evolution reaction (OER) kinetics leading to low energy conversion efficiency. Herein, a strategy is presented that integrates anodic electrochemical flocculation with cathodic hydrogen production from water splitting in 0.5 m Na2SO4. Iron encapsulated in a nitrogen-doped carbon nanotubes array on iron foam (Fe@N-CNT/IF) is employed as an electrode for the hydrogen evolution reaction (HER), and the Fe@N-CNT/IF possesses superior HER activity requiring an overpotential of 525 mV to achieve 10 mA cm-2, which is close to that of 20 wt% Pt/C. Benefiting from the lower oxidation potential of iron (E°Fe/Fe2+, 0.44 V) than that of OER (E 0 OH-/O2, 1.23 V), the cell voltage for integrated electrochemical flocculation and H2 production is significantly reduced by 1.31 V relative to overall water splitting to achieve 20 mA cm-2. More important, the production of electrochemical flocculation can be applied to water purification, because of the excellent adsorption capacity. Finally, metal-carbon electrocatalysts are prepared again by pyrolysis of flocculation adsorbents containing toxic heavy metals and organics. This result provides a new direction for designing a heterogeneous electrolysis system for energy conversion and environmental treatment applications.

Bottom-up synthesis of WS2 nanosheets with synchronous surface modification for imaging guided tumor regression.

Two-dimensional transition metal dichalcogenides (TMDs) have been receiving great attention as NIR photothermal transducing agent in tumor photothermal therapy. Keeping in mind the low efficiency of the conventional top-down exfoliated 2D TMDs and the complexity of their surface modifications, we herein proposed a bottom-up strategy for the one-pot hydrothermal and controlled synthesis of surface polyvinyl pyrrolidone (PVP) modified WS2 nanosheets. The material design was based on the chelating-coordinating effect between the lone pair electrons of oxygen of PVP carbonyl group and the unoccupied orbital (5d orbitals) of tungsten. The WS2 nanosheets with synchronous surface PVP grafting showed an excellent photothermal conversion performance, while the surface anchored PVP guaranteed its colloidal stability. Moreover, the strong X-ray attenuation ability and near-infrared (NIR) absorbance of WS2-PVP360kDa enabled the sensitive in vitro and in vivo computed tomography and photoacoustic imaging. The WS2-PVP360kDa nanosheets were biocompatible and exhibited promising in vitro and in vivo anti-cancer efficacy. Findings in this report may greatly promote the design of colloidal stable and biocompatible 2D TMDs and their future clinical translations. STATEMENT OF SIGNIFICANCE: A bottom-up strategy for the one-pot and controlled synthesis of surface polyvinyl pyrrolidone (PVP) modified WS2 nanosheets was proposed for the first time. By hydrothermally treating the mixture solution of tetrathiotungstate and PVP, Owing to the chelating-coordinating effect between the lone pair electrons of oxygen of PVP carbonyl group and the unoccupied orbital (5d orbitals) of tungsten, PVP was synchronously graphed on WS2-PVP nanosheets surface. The formed WS2-PVP nanosheets were colloidal stable, biocompatible, and exhibited promising computed tomography, photoacoustic imaging and tumor photothermal therapy efficacy both in vitro and in vivo.

Bottom-up synthesis of ultra-small molybdenum disulfide-polyvinylpyrrolidone nanosheets for imaging-guided tumor regression.

The two-dimensional molybdenum disulfide (MoS2) nanosheet has been extensively studied as a novel photothermal transducing agent. However, top-down exfoliation to produce MoS2 nanosheets is inefficient, and MoS2 nanosheet surface modification procedures are complex. Here, we report the synchronous synthesis and surface modification of 2D MoS2 nanosheets with a polyvinylpyrrolidone (PVP)-assisted one-pot hydrothermal method. Due to the chelating-coordinating effect between the lone-pair electrons of the PVP carbonyl oxygen and the unoccupied 4d orbitals of molybdenum, the PVP chains could graft onto the surface of MoS2 and guide the growth of the nanosheets. The resultant MoS2-PVP nanosheets were ultra-small (21.4 ± 4.4 nm) and exhibited excellent colloidal stability. Moreover, the strong near-infrared absorption of the MoS2-PVP nanosheets enabled sensitive photothermal conversion performance (with a mass extinction coefficient of 23.33 L g-1 cm-1) and in vitro/in vivo photoacoustic imaging. The MoS2-PVP nanosheets had excellent in vitro and in vivo compatibility and were used for highly efficient tumor photothermal therapy in xenograft tumor-bearing mice. The findings in this report will facilitate the rational design of stable colloidal 2D transition-metal dichalcogenides for effective photothermal cancer therapy.

Downregulation of L1CAM inhibits proliferation, invasion and arrests cell cycle progression in pancreatic cancer cells in vitro.

The aim of the present study was to establish the effect of silencing L1 cell adhesion molecule (L1CAM) on the proliferation, invasion, cell cycle progression and apoptosis of pancreatic cancer cells, and to determine the potential molecular mechanisms that are involved. The human Capan-2 pancreatic cancer cell line was infected with lentivirus-mediated short hairpin RNA (shRNA) to target L1CAM. Cell proliferation and invasion were analyzed using cell counting kit-8 and Transwell assays, respectively, and cell cycle progression and apoptosis were analyzed using flow cytometry. L1CAM protein expression in Capan-2 cells decreased following shRNA-L1CAM infection. Furthermore, knockdown of L1CAM significantly inhibited cell proliferation and reduced the number of invasive cells, while increasing the percentage of cells in the G0/G1 phase (P<0.05). However, the effect on apoptosis was not identified to be statistically significant. In addition, L1CAM silencing may induce activation of p38/extracellular signal regulated kinase 1/2. Downregulation of L1CAM may inhibit proliferation, invasion and arrests cell cycle progression in pancreatic cancer via p38/ERK1/2 signal pathway, and therefore, L1CAM may serve as a potential target for gene therapy in pancreatic cancer.

Low expression of IGFBP7 is associated with poor outcome of pancreatic ductal adenocarcinoma.

BACKGROUND: Insulin-like growth factor binding protein 7(IGFBP7) has been implicated as a potential tumor suppressor in various human cancers, although the role of IGFBP7 in pancreatic ductal adenocarcinoma (PDAC) is still unknown. We investigated the expression pattern and clinical significance of IGFBP7 in human PDAC. METHODS: IGFBP7 expression was evaluated by immunohistochemistry in 190 patients with PDAC who underwent surgical tumor resection. Expression of IGFBP7 was correlated with that of p53 and Ki-67, clinicopathologic features. We also evaluated overall survival (OS) according to expression of IGFBP7 by Kaplan-Meier and Cox regression analyses. RESULTS: IGFBP7 expression was significantly downregulated in pancreatic cancer tissues compared with adjacent normal pancreas (P < 0.001) and was inversely associated with Ki-67 expression (r = -0.284, P < 0.001). No significant relationships were found for clinicopathologic features, such as diameter of tumor, node status, grade, and stage. Importantly, low expression of IGFBP7 was associated with poor OS, and this was also significant in multivariate Cox regression analysis (hazard ratio [HR], 1.38; 95 % confidence interval [95 % CI], 1.00-1.91; P = 0.05). CONCLUSIONS: We demonstrate for the first time that IGFBP7 is downregulated in pancreatic cancer, and low expression of IGFBP7 is correlated with increased proliferation and poor postoperative survival. IGFBP7 may be a tumor suppressor in PDAC.

Damage of the interstitial cells of Cajal and myenteric neurons causing ileus in acute necrotizing pancreatitis rats.

BACKGROUND: Small intestinal motility is impaired in acute necrotizing pancreatitis (ANP). The present study was designed to detect the impairment in small intestinal motility and to assess the role of interstitial cells of Cajal (ICC), myenteric neurons and the associated mechanism in the pathogenesis of ileus during experimentally induced acute pancreatitis. METHODS: ANP was induced by intraperitoneal injections of 30% L-ornithine at a dose of 3 g/kg at hourly intervals. The alterations of small intestine electrical activity--migrating myoelectric complexes (MMCs), and slow waves--were measured 24 hr after ANP induction. The spontaneous mechanical activity and the contractile response to ACh, KCl, tetrodotoxin (TTX) and the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine (L-NNA) were evaluated by organ bath technique, and the morphologic alterations of the network of ICC, myenteric neurons and neuronal nitric oxide synthase (nNOS) immunoreactive cells were evaluated using the markers of c-Kit, PGP9.5, and nNOS, respectively. To demonstrate the deficiencies in enteric neuronal origin, we also measured nNOS expression in the muscular layer of ileum. RESULTS: L-ornithine-induced necrotizing pancreatitis manifests with multiple symptoms, including decreased amplitude of spontaneous contractions in small intestinal smooth muscle, declined contractile response to ACh, TTX, and L-NNA in vitro, disrupted MMC cycle length, decreased dominant frequency and dominant power of slow waves in vivo. Furthermore, the morphologic studies demonstrated the damage of ICC (ANP group versus control; P = .000), myenteric neurons (ANP group versus control; P = .001) and nNOS immunoreactive neurons (ANP group versus control; P = .000). We also observed a substantial loss in the expression of nNOS protein in muscular layer of the small intestine (ANP group versus control; P = .032). CONCLUSION: Our results suggest that the pathogenesis of the small intestinal paralysis in ANP may be related to the deficiencies in ICC and nNOS neurons.

[Epidemiological study of high risk human papillomavirus infection in 25 to 54 years old married women in Beijing.].

OBJECTIVE: To investigate high risk human papillomavirus (HR-HPV) prevalence among married women in Beijing and to study the high risk factors. METHODS: During March 2007 to September 2008, a total of 6185 married women sampled from 137 communities in 12 districts were screened by HR-HPV DNA test and cytological test. The interview was carried out with unified questionnaires. The database was set up and twice entered in EpiData 3.0. After checked up, the data were analyzed in SPSS 15.0. RESULTS: (1) The HR-HPV infection rate was 9.89%. The HR-HPV infection rate of the city zone, the suburb and the exurb were 9.34%, 10.51% and 9.51% (P > 0.05). The HR-HPV infection rate of the native and the outlander were 9.53%, 11.30% (P < 0.05). (2) The age distribution of HR-HPV infection was that the rate was around 10% among 25 to 44 age groups, which was the highest (11.21%) in 30 to 34 age group; then the rate was descended as the age raising, the rate of 50 to 54 age group was the lowest (7.78%). (3) Multiple logistic regression showed that the related risk factors of HR-HPV infection mainly included 1000 RMB and above of family income per person per month, possessing more than 1 sexual partner of her husband, outlander and high levels of education. (4) The prevalence of cervical intraepithelial neoplasia (CIN) in HR-HPV positive group was significantly higher than that in HR-HPV negative group (29.76% vs 3.32%, P < 0.01). CONCLUSIONS: (1) The HR-HPV infection rate among aged 25 to 54 years was 9.9% and there was no significant difference in area distribution. (2) The high risk population which should strengthen screening was the married bearing-age women with high level of family income, outlander, high levels of education and her husband possessing more than 1 sexual partner. (3) HR-HPV infection is the main risk factor for CIN and cervical cancer, while does not provide a causal relationship with them. The high risk population should be checked regularly to understand the development of HR-HPV infection and CIN incidence.