Crohn's disease as the intestinal manifestation of pan-lymphatic dysfunction: An exploratory proposal based on basic and clinical data.

Crohn's disease (CD) is caused by immune, environmental, and genetic factors. It can involve the entire gastrointestinal tract, and although its prevalence is rapidly increasing its etiology remains unclear. Emerging biological and small-molecule drugs have advanced the treatment of CD; however, a considerable proportion of patients are non-responsive to all known drugs. To achieve a breakthrough in this field, innovations that could guide the further development of effective therapies are of utmost urgency. In this review, we first propose the innovative concept of pan-lymphatic dysfunction for the general distribution of lymphatic dysfunction in various diseases, and suggest that CD is the intestinal manifestation of pan-lymphatic dysfunction based on basic and clinical preliminary data. The supporting evidence is fully summarized, including the existence of lymphatic system dysfunction, recognition of the inside-out model, disorders of immune cells, changes in cell plasticity, partial overlap of the underlying mechanisms, and common gut-derived fatty and bile acid metabolism. Another benefit of this novel concept is that it proposes adopting the zebrafish model for studying intestinal diseases, especially CD, as this model is good at presenting and mimicking lymphatic dysfunction. More importantly, the ensuing focus on improving lymphatic function may lead to novel and promising therapeutic strategies for CD.

Ten-Day Vonoprazan-Amoxicillin Dual Therapy vs Standard 14-Day Bismuth-Based Quadruple Therapy for First-Line Helicobacter pylori Eradication: A Multicenter Randomized Clinical Trial.

INTRODUCTION: Whether 10-day short-course vonoprazan-amoxicillin dual therapy (VA-dual) is noninferior to the standard 14-day bismuth-based quadruple therapy (B-quadruple) against Helicobacter pylori eradication has not been determined. This trial aimed to compare the eradication rate, adverse events, and compliance of 10-day VA-dual regimen with standard 14-day B-quadruple regimen as first-line H. pylori treatment. METHODS: This prospective randomized clinical trial was performed at 3 institutions in eastern China. A total of 314 treatment-naive, H. pylori -infected patients were randomly assigned in a 1:1 ratio to either 10-day VA-dual group or 14-day B-quadruple group. Eradication success was determined by 13 C-urea breath test at least 4 weeks after treatment. Eradication rates, adverse events, and compliance were compared between groups. RESULTS: Eradication rates of VA-dual and B-quadruple groups were 86.0% and 89.2% ( P = 0.389), respectively, by intention-to-treat (ITT) analysis; 88.2% and 91.5% ( P = 0.338), respectively, by modified ITT analysis; and 90.8% and 91.3% ( P = 0.884), respectively, by per-protocol (PP) analysis. The efficacy of the VA-dual remained noninferior to B-quadruple therapy in all ITT, modified ITT, and PP analyses. The incidence of adverse events in the VA-dual group was significantly lower compared with that in the B-quadruple group ( P < 0.001). Poor compliance contributed to eradication failure in the VA-dual group ( P < 0.001), while not in the B-quadruple group ( P = 0.110). DISCUSSION: The 10-day VA-dual therapy provided satisfactory eradication rates of >90% (PP analysis) and lower rates of adverse events compared with standard 14-day B-quadruple therapy as first-line H. pylori therapy. TRAIL REGISTRATION NUMBER: ChiCTR2300070100.

The legacies of the "Father of Hybrid Rice" and the seven representative achievements of Chinese rice research: A pioneering perspective towards sustainable development.

The "Father of Hybrid Rice", Yuan Longping, created high-yield hybrid rice that can feed tens of millions of people annually. The research achievements of Yuan and his team on low cadmium-accumulating rice and sea rice, in addition to hybrid rice, as well as those of a large number of Chinese scientists engaged in rice research in other six areas, including the rice genome, purple endosperm rice, de novo domestication of tetraploid rice, perennial rice, rice blast disease, and key genes for high nitrogen use efficiency, play an important role in promoting the realization of the United Nations Sustainable Development Goals 2 and 12. The purpose of this review is not to elaborate on the details of each research, but to innovatively summarize the significance and inspiration of these achievements to ensure global food security and achieve sustainable agriculture. In the future, cultivating new rice varieties through modern biotechnology, such as genome editing, will not only reduce hunger, but potentially reduce human-land conflicts, improve the environment, and mitigate climate change.

Molecular docking and molecular simulation studies for N-degron selectivity of chloroplastic ClpS from Chlamydomonas reinhardtii.

Regarding the importance of N-degron pathway in protein degradation network, the adaptor protein ClpS recognizes the substrates bearing classical N-degrons, and delivers them to caseinolytic protease complex ClpAP for degradation. Interestingly, the majority of N-degrons located near the N-terminus of protein substrate are belonged to the hydrophobic type amino acids. Chloroplast, an important organelle for plant photosynthesis, contain a diversified Clp degradation system. Despite several studies have confirmed that chloroplastic ClpS is able to interact with classical N-degrons derived from prokaryotes, whereas, the molecular mechanism underlying how the chloroplastic ClpS protein could recognize the substrate tagged by N-degrons is still unclear until now. Chlamydomonas reinhardtii is a kind of unicellular model organism for photosynthesis researches, which possesses a large cup-shaped chloroplast, and the corresponding genome data indicates that it owns bacterial homologous adaptor protein, named CrClpS1. However, the relevant biochemical knowledges, and protein structure researches for CrClpS1 adaptor aren't reported up to date. The molecular interactions between CrClpS1 and possible N-degrons are undefined as well. Here, we build a reliable homology model of CrClpS1 and find a hydrophobic pocket for N-degron binding. We combine molecular docking, molecular dynamic simulations, and MM/PBSA, MM/GBSA binding free energy estimations to elucidate the molecular properties of CrClpS1-N-degron interactions. Besides, we investigate the conformational changes for CrClpS1-apo in water-solvent environment and analyze its possible biological significances through a long time molecular dynamic simulation. Specifically, the adaptor CrClpS1 displays the stronger interactions with Phe, Trp, Tyr, His and Ile with respect to other amino acids. Using the residue decomposition analysis, the interactions between CrClpS1 and N-degrons are heavily depended on several conservative residues, which are located around the hydrophobic pocket, implying that chloroplast isolated from Chlamydomonas reinhadtii adopts a relatively conservative N-degron recognition mode. Besides, the opening-closure of hydrophobic pocket of CrClpS1 might be beneficial for the N-degron selectivity.

High-fat diet aggravates colitis via mesenteric adipose tissue derived exosome metastasis-associated lung adenocarcinoma transcript 1.

BACKGROUND: Obesity is associated with an increased risk of developing Crohn's disease (CD), higher disease activity, and comparatively worse clinical outcomes. AIM: To investigate the role of mesenteric adipose tissue-derived exosomes in the pathogenesis of CD aggravation in obese individuals. METHODS: First, we induced colitis in mice initiated on high-fat and normal diets and compared the severity of colitis. We then extracted and identified exosomes from mesenteric adipose tissue and determined the levels of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in mesenteric adipose tissue-derived exosomes and the colon. Next, we demonstrated an interaction between MALAT1 and the miR-15a-5p/activating transcription factor 6 (ATF6) axis. Finally, we explored the effects of mesenteric adipose tissue-derived exosomes extracted from mice fed a high-fat or normal diet on the severity of 2,4,6-trinitrobe-nzenesulfonic acid (TNBS)-induced colitis and ATF6-related endoplasmic reticulum stress pathways. RESULTS: High-fat diet was found to aggravate TNBS-induced colitis in mice. The expression of MALAT1 in mesenteric adipose tissue-derived exosomes of high-fat diet-fed mice increased. The increased expression of MALAT1 in colon tissue exacerbated TNBS-induced colitis and activated the ATF6 endoplasmic reticulum stress pathway. This effect was partially reversed by the reduced expression of MALAT1 and overexpression of miR-15a-5p. CONCLUSION: Mesenteric adipose tissue-derived exosome-encapsulated long noncoding RNAs MALAT1 targets the colon and aggravates TNBS-induced colitis in obese mice, which may potentially act on the miR-15a-5p/ATF6 axis and activate endoplasmic reticulum stress.

Analysis of medial tibial plateau fracture injury patterns using quantitative 3D measurements.

BACKGROUND: The Wahlquist system classifies tibial medial plateau fractures into three types based on the sagittal fracture line location, with type C at highest risk of complications. However, the injury mechanism of tibial medial plateau fractures, especially tibial rotation movement, remains unclear. The purpose of the present study was to determine the injury patterns of medial tibial plateau fractures using 3D model simulation and quantitative 3D measurements. METHODS: Seventy-eight consecutive AO/OTA type 41-B tibial plateau fractures were retrospectively analyzed using CT-based 3D models and quantitative 3D measurements. The knee posture at the moment of fracture occurrence was simulated, and various knee angles in the sagittal, coronal, and axial planes were measured to evaluate the mechanism of medial tibial plateau fracture. The mean valgus-varus, hyperextension-flexion, and internal-external rotation angles were determined, and the chi-square test was used for comparisons of categorical varus and valgus force data to determine the main force direction in Wahlquist type C fractures. RESULTS: Angle measurements in the coronal planes showed that 28 (35.9%) medial tibial plateau fractures resulted from a varus injury pattern, while 50 fractures (64.1%) resulted from a valgus pattern. Valgus force produced significantly more Wahlquist type C fractures (37 of 50 fractures) than varus force (2 of 28 fractures) (p < 0.05). There was no significant difference in the cases of patients with type C fractures between the tibial internal and external rotation injury patterns(P > 0.05). CONCLUSIONS: Valgus force was the cause of 64.1% of the medial tibia plateau fractures in the present cohort. Furthermore, valgus force produced more Wahlquist type C fractures than varus force. The present findings will help orthopedists understand the injury mechanism of the Wahlquist classification system, and will facilitate the identification of the common features of medial tibial plateau fractures induced by specific injury patterns.

Palmitoylation in Crohn's disease: Current status and future directions.

S-palmitoylation is one of the most common post-translational modifications in nature; however, its importance has been overlooked for decades. Crohn's disease (CD), a subtype of inflammatory bowel disease (IBD), is an autoimmune disease characterized by chronic inflammation involving the entire gastrointestinal tract. Bowel damage and subsequent disabilities caused by CD are a growing global health issue. Well-acknowledged risk factors for CD include genetic susceptibility, environmental factors, such as a westernized lifestyle, and altered gut microbiota. However, the pathophysiological mechanisms of this disorder are not yet comprehensively understood. With the rapidly increasing global prevalence of CD and the evident role of S-palmitoylation in CD, as recently reported, there is a need to investigate the relationship between CD and S-palmitoylation. In this review, we summarize the concept, detection, and function of S-palmitoylation as well as its potential effects on CD, and provide novel insights into the pathogenesis and treatment of CD.

Tracking the evolutionary innovations of plant terrestrialization.

The gradual transition of the algal ancestor from the freshwater to land has always attracted evolutionary biologists. The recent report of high-quality reference genomes of five Charophyta algae (Spirogloea muscicola, Mesotaenium endlicherianum, Mesostigma viride, Chlorokybus atmophyticus and Penium margaritaceum) and one hornwort (Anthoceros angustus) species sheds light on this fascinating transition. These early diverging plants and algae could have gained new genes from soil bacteria and fungi through horizontal gene transfer (HGT), which was so common during plant terrestrialization and may outrun our expectations. Through reviewing and critical thinking about the advancements on these plant genomes, here, I propose three prospective research directions that need to address in the future: (i) due to the ubiquitous nature of viruses that is similar to soil bacteria and fungi, there is less attention to viruses that probably also play an important role in the genome evolution of plants via HGT; (ii) multicellularity has occurred many times independently, but we still know a little about the biological and ecological mechanisms leading to multi-cellularity in Streptophyta; (iii) and most importantly, the quantitative relationships between genetic innovations and environmental variables such as temperature, precipitation and solar radiation, need pioneering research collaborated by biological evolutionists, computer scientists, and ecologists, which are crucial for understanding the macroevolution of plants and could also be used to simulate the evolution of plants under future climate change.

[Application of artificial intelligence combined with multi-parametric MRI in the early diagnosis of prostate cancer].

OBJECTIVE: To explore the value of artificial intelligence combined with multi-parametric MRI (AI-mpMRI) in the early diagnosis of prostate cancer. METHODS: This retrospective study included 64 cases of prostate cancer confirmed by biopsy and treated by radical prostatectomy from May 2017 to February 2018. The mpMRI images of T2 weighted imaging (T2WI), diffusion weighted imaging (DWI) and dynamic-contrast enhanced (DCE) MRI and the pathological sections corresponding to the three sequential MRI images were collected. The benign and malignant regions were labeled on the pathological slice level, the three sequential MRI axial images at the same level were virtually covered with the pathological slice using computer-aided transparent mapping technology, and selected the fixed-sized benign and malignant regions of interest (ROI). The MATLAB software was used to display the features of the images and screen out the characteristic parameters with P < 0.05, so as to derive high-accuracy analytical methods for the diagnosis of prostate cancer. RESULTS: A total of 31 image characteristics were extracted with the MATLAB software, and 3 high-accuracy analytical methods screened out for the diagnosis of prostate cancer, including the linear discrimination, logistic regression analysis, and support vector machine classification, with the accuracy rates of 75.9%, 75.4% and 74.9% and the areas under the curve (AUC) of 0.83, 0.82 and 0.82, respectively. CONCLUSIONS: AI-mpMRI can achieve a high detection rate in the early diagnosis of prostate cancer and therefore has a high clinical application value.

Plant extinction excels plant speciation in the Anthropocene.

BACKGROUND: In the past several millenniums, we have domesticated several crop species that are crucial for human civilization, which is a symbol of significant human influence on plant evolution. A pressing question to address is if plant diversity will increase or decrease in this warming world since contradictory pieces of evidence exit of accelerating plant speciation and plant extinction in the Anthropocene. RESULTS: Comparison may be made of the Anthropocene with the past geological times characterised by a warming climate, e.g., the Palaeocene-Eocene Thermal Maximum (PETM) 55.8 million years ago (Mya)-a period of "crocodiles in the Arctic", during which plants saw accelerated speciation through autopolyploid speciation. Three accelerators of plant speciation were reasonably identified in the Anthropocene, including cities, polar regions and botanical gardens where new plant species might be accelerating formed through autopolyploid speciation and hybridization. CONCLUSIONS: However, this kind of positive effect of climate warming on new plant species formation would be thoroughly offset by direct and indirect intensive human exploitation and human disturbances that cause habitat loss, deforestation, land use change, climate change, and pollution, thus leading to higher extinction risk than speciation in the Anthropocene. At last, four research directions are proposed to deepen our understanding of how plant traits affect speciation and extinction, why we need to make good use of polar regions to study the mechanisms of dispersion and invasion, how to maximize the conservation of plant genetics, species, and diverse landscapes and ecosystems and a holistic perspective on plant speciation and extinction is needed to integrate spatiotemporally.

Current status of Helicobacter pylori eradication and risk factors for eradication failure.

BACKGROUND: The Helicobacter pylori (H. pylori) eradication rate is decreasing in the general population of China. AIM: To evaluate the H. pylori eradication status in real-world clinical practice and to explore factors related to eradication failure. METHODS: Patients with H. pylori infection who were treated with standard 14-d quadruple therapy and received a test of cure at a provincial medical institution between June 2018 and May 2019 were enrolled. Demographic and clinical data were recorded. Eradication rates were calculated and compared between regimens and subgroups. Multivariate analysis was performed to identify predictors of eradication failure. RESULTS: Of 2610 patients enrolled, eradication was successful in 1999 (76.6%) patients. Amoxicillin-containing quadruple regimens showed a higher eradication rate than other quadruple therapy regimens (83.0% vs 69.0%, P < 0.001). The quadruple therapy containing amoxicillin plus clarithromycin achieved the highest eradication rate (83.5%). Primary therapy had a higher eradication rate than rescue therapy (78.3% vs 66.5%, P < 0.001). In rescue therapy, the amoxicillin- and furazolidone-containing regimens achieved the highest eradication rate (80.8%). Esomeprazole-containing regimens showed a higher eradication rate than those containing other proton pump inhibitors (81.8% vs 74.9%, P = 0.001). Multivariate regression analysis found that older age, prior therapy, and use of omeprazole or pantoprazole were associated with an increased risk of eradication failure. CONCLUSION: The total eradication rate is 76.6%. Amoxicillin-containing regimens are superior to other regimens. Age, prior therapy, and use of omeprazole or pantoprazole are independent risk factors for eradication failure.

Adipose-derived mesenchymal stem cells alleviate TNBS-induced colitis in rats by influencing intestinal epithelial cell regeneration, Wnt signaling, and T cell immunity.

BACKGROUND: Conventional Crohn's disease (CD) treatments are supportive rather than curative and have serious side effects. Adipose-derived mesenchymal stem cells (ADSCs) have been gradually applied to treat various diseases. The therapeutic effect and underlying mechanism of ADSCs on CD are still not clear. AIM: To investigate the effect of ADSC administration on CD and explore the potential mechanisms. METHODS: Wistar rats were administered with 2,4,6-trinitrobenzene sulfonic acid (TNBS) to establish a rat model of CD, followed by tail injections of green fluorescent protein (GFP)-modified ADSCs. Flow cytometry, qRT-PCR, and Western blot were used to detect changes in the Wnt signaling pathway, T cell subtypes, and their related cytokines. RESULTS: The isolated cells showed the characteristics of ADSCs, including spindle-shaped morphology, high expression of CD29, CD44, and CD90, low expression of CD34 and CD45, and osteogenic/adipogenic ability. ADSC therapy markedly reduced disease activity index and ameliorated colitis severity in the TNBS-induced rat model of CD. Furthermore, serum anti-sacchromyces cerevisiae antibody and p-anti-neutrophil cytoplasmic antibody levels were significantly reduced in ADSC-treated rats. Mechanistically, the GFP-ADSCs were colocalized with intestinal epithelial cells (IECs) in the CD rat model. GFP-ADSC delivery significantly antagonized TNBS-induced increased canonical Wnt pathway expression, decreased noncanonical Wnt signaling pathway expression, and increased apoptosis rates and protein level of cleaved caspase-3 in rats. In addition, ADSCs attenuated TNBS-induced abnormal inflammatory cytokine production, disturbed T cell subtypes, and their related markers in rats. CONCLUSION: Successfully isolated ADSCs show therapeutic effects in CD by regulating IEC proliferation, the Wnt signaling pathway, and T cell immunity.

Efficacy, safety and prognosis of treating neurological deficits caused by spinal tuberculosis within 4 weeks' standard anti-tuberculosis treatment: A single medical center's experience.

The present study aimed to retrospectively analyze the safety and efficacy of the early surgical management of thoracic tuberculosis (TB) in patients with neurological deficits. The medical data of patients with thoracic TB exhibiting neurological deficit in the Chest Hospital of Hebei Province were retrospectively reviewed. A total of 234 cases, including 123 males and 115 females, were recruited in the present study. Their pre- and postoperative neurological deficit and pain levels were assessed using the 2002 American spinal injury association (ASIA) impairment scale and visual analog scale, respectively. Patients were divided into two groups according to whether their preoperative standardized anti-TB treatment time was ≥4 weeks or <4 weeks. There was no difference in blood loss and operation time between the two groups. The erythrocyte sedimentation rate was higher in patients receiving standard anti-TB <4 weeks prior to and 1 month following surgery compared with the ≥4 weeks group, but the difference was not significant 6 months following surgery. ASIA scale scores all increased significantly 1 month following surgery in the <4 weeks group compared with the ≥4 weeks group (P=0.001) though there was no difference between the scores prior to surgery. ASIA scale scores improved to 4.4±0.5 and 4.5±0.4 in patients with anti-TB treatment times of ≥4 weeks and <4 weeks, respectively, 24 months following surgery (P=0.0895). The present study demonstrated that for patients with thoracic TB exhibiting neurological deficit, early surgical management following <4 weeks' standard anti-TB treatment is recommended. It may relieve spinal cord compression and also benefit the early recovery of neurological function in these patients.

Allyl isothiocyanate ameliorates lipid accumulation and inflammation in nonalcoholic fatty liver disease via the Sirt1/AMPK and NF-κB signaling pathways.

BACKGROUND: Allyl isothiocyanate (AITC), a classic anti-inflammatory and antitumorigenic agent, was recently identified as a potential treatment for obesity and insulin resistance. However, little is known about its direct impact on the liver. AIM: To investigate the effect and underlying mechanism of AITC in nonalcoholic fatty liver disease (commonly referred to as NAFLD). METHODS: To establish a mouse and cellular model of NAFLD, C57BL/6 mice were fed a high fat diet (HFD) for 8 wk, and AML-12 cells were treated with 200 µM palmitate acid for 24 h. For AITC treatment, mice were administered AITC (100 mg/kg/d) orally and AML-12 cells were treated with AITC (20 µmol/L). RESULTS: AITC significantly ameliorated HFD-induced weight gain, hepatic lipid accumulation and inflammation in vivo. Furthermore, serum alanine aminotransferase and aspartate aminotransferase levels were markedly reduced in AITC-treated mice. Mechanistically, AITC significantly downregulated the protein levels of sterol regulatory element-binding protein 1 (SREBP1) and its lipogenesis target genes and upregulated the levels of proteins involved in fatty acid ß-oxidation, as well as the upstream mediators Sirtuin 1 (Sirt1) and AMP-activated protein kinase α (AMPKα), in the livers of HFD-fed mice. AITC also attenuated the nuclear factor kappa B (NF-κB) signaling pathway. Consistently, AITC relieved palmitate acid-induced lipid accumulation and inflammation in AML-12 cells in vitro through the Sirt1/AMPK and NF-κB signaling pathways. Importantly, further studies showed that the curative effect of AITC on lipid accumulation was abolished by siRNA-mediated knockdown of either Sirt1 or AMPKα in AML-12 cells. CONCLUSION: AITC significantly ameliorates hepatic steatosis and inflammation by activating the Sirt1/AMPK pathway and inhibiting the NF-κB pathway. Therefore, AITC is a potential therapeutic agent for NAFLD.

Dietary fiber, whole grains, carbohydrate, glycemic index, and glycemic load in relation to risk of prostate cancer.

BACKGROUND: The relationships between dietary fiber, whole grains, carbohydrate, glycemic index (GI), glycemic load (GL), and prostate cancer risk are unclear. We conducted a systematic review and meta-analysis to investigate these associations. METHODS: Relevant studies were identified by a search of PubMed database and EMBASE database up to April 2015. A random effects model was used to calculate the summary relative risks (RRs) and their corresponding 95% confidence intervals (CIs). RESULTS: Twenty-seven epidemiological studies (18 case-control studies and nine cohort studies) were included in the final analysis. The pooled RRs of prostate cancer were 0.94 (95% CI 0.85-1.05, P=0.285), 1.13 (95% CI 0.98-1.30, P=0.095), 0.96 (95% CI 0.81-1.14, P=0.672), 1.06 (95% CI 0.96-1.18, P=0.254), and 1.04 (95% CI 0.91-1.18, P=0.590) for dietary fiber, whole grains, carbohydrate, GI, and GL, respectively. There was no evidence of significant publication bias based on the Begg's test and Egger's test. CONCLUSION: The findings of this meta-analysis indicate that, based on available information, dietary fiber, whole grains, carbohydrate, GI, and GL are not associated with the risk of prostate cancer.

A Systematic Review and Meta-Analysis of Three Gene Variants Association with Risk of Prostate Cancer: An Update.

PURPOSE: Prostate cancer (PCa) is one of the most commonly diagnosed male malignancies. Nu­merous studies have investigated the role of genetic variants in PCa risk. However, the results re­main unclear. The purpose of this study was to evaluate the relationship between single-nucleo­tide polymorphism (SNP) rs2228001 in xeroderma pigmentosum group C (XPC), SNP rs4073 in interleukin 8 (IL8), and SNP rs2279744 in mouse double minute 2 (MDM2) homolog gene with PCa susceptibility. MATERIALS AND METHODS: Electronic database of PubMed, Medline, and Embase were searched for eligible articles published between January 2000 and April 2014. The odd ra­tio (OR) with its 95% confidence interval (CI) were calculated to estimate the strength of association. RESULTS: A total 18 case-control studies, including 5725 PCa cases and 5900 healthy controls, were screened out. Six studies were eligible for each SNP. For XPC 939A/C polymorphism, no significant association was found with PCa risk in the whole population (P > .05). No relationship in subgroup analysis was found by ethnicity. For IL8 -251T/A variant, the A allele was not related with PCa risk in any genetic models when compared with those individuals without A allele. For MDM2 -309T/G mutation, the G allele was not as­sociated with the increased risk of PCa in total population and subgroup analysis by ethnicity as well. CONCLUSION: Our study demonstrated that all these three genetic polymorphisms were not associated with an in­creased risk of developing PCa, which might also provide an insight into the future research. Further large-scale studies with concerning the gene-gene and gene-environment interactions are needed to elucidate final conclusion.

[Correlative study between length of first metatarsal and transfer metatarsalgia after osteotomy of first metatarsal].

OBJECTIVE: To evaluate the correlation between the length of first metatarsal, hallux valgus angle (HVA), intermetatarsal 1-2 angle (IMA1-2), plantar appearance, sesamoid position and postoperative 2-5 transfer metatarsalgia. METHODS: Retrospective analysis was performed for the clinical data of 375 cases (626 feet) undergoing osteotomy of first metatarsal with mini-incision. All cases were examined radiographically via weight-bearing and lateral views. HVA, IMA1-2 and the length of first metatarsal were measured preoperatively and postoperatively. Forefoot plantar pressure was measured during walking by Foot scan system preoperatively and postoperatively. RESULTS: After a mean follow-up period of 12-30 (18.5 ± 6.8) months, all patients had satisfactory bone healing without late healing or disunion. There were superficial wound infection (n = 1, 1 foot) and suture reaction (n = 1, 1 foot). HVA was 7.18° ± 4.55° postoperatively and corrected by 30.54°; IMA1-2 5.07° ± 1.70° and corrected by 12.33°. The number of shorting of first metatarsal during 0-2 mm was 424 feet, there was 1 case of transfer metatarsalgia at rays 4; the number during 2-4 mm was 186 feet, there were 5 cases of transfer metatarsalgia at rays 2. The center of pressure shifted laterally; the number during 2-4 mm was 16 feet, there were 4 cases of transfer metatarsalgia at rays 2 and 3. The center of pressure shifted evidently medially; the shorting of first metatarsal was 4.8 ± 0.46 mm. A negative correlation was found between length of metatarsal and transfer metatarsalgia at rays 2 and 3. No correlation existed between transfer metatarsalgia at rays 2 and 5, HVA and IMA1-2. A positive correlation existed between HVA decrease and patient satisfaction with their postoperative foot alignment. There was no correlation between lengthening of metatarsal and IMA1-2 decrease. CONCLUSION: Length preservation of first metatarsal seems to prevent the postoperative transfer metatarsalgia on second and third rays. The shorting of first metatarsal should be no more than 2 mm.

Transgenic nude mouse with green fluorescent protein expression-based human glioblastoma multiforme animal model with EGFR expression and invasiveness.

Previously, we developed an orthotopic xenograft model of human glioblastoma multiforme (GBM) with high EGFR expression and invasiveness in Balb/c nu/nu nude mice. Now we also developed the same orthotopic xenograft model in transgenic nude mice with green fluorescent protein (GFP) expression. The present orthotopic xenografts labeled by phycoerythrin fluorescing red showed high EGFR expression profile, and invasive behavior under a bright green-red dual-color fluorescence background. A striking advantage in the present human GBM model is that the change of tumor growth can be observed visually instead of sacrificing animals in our further antitumor therapy studies.

[Clinical investigation on intravesical instillation of high-dose pirarubicin during perioperative period to prevent bladder carcinoma recurrence].

OBJECTIVE: To evaluate the efficacy and safety of intravesical instillation of high-dose pirarubicin during perioperative period to prevent bladder carcinoma recurrence. METHODS: A prospective randomized controlled clinical trial was carried out. A total of 120 patients with bladder transitional cell carcinoma (TNM I-II) underwent partial cystectomy or transurethral resection of bladder tumour were randomly divided into 2 groups, which were chosen from the patients were hospitalized during June 2003 to May 2009. There were 62 patients were in group A and 58 patients were in group B. In group A, intravesical instillation of high-dose pirarubicin during perioperative period was conducted. In group B, intravesical perfusion of pirarubicin was performed regularly after operation. All the patients were followed up in order to record the relapse rates and adverse reaction. RESULTS: No significant difference was found between group A and group B from gender, age, pathological stage and operation methods (P > 0.05). The recurrence rates were 8.1% in group A, and 20.7% in group B. The adverse effect rates of urethrostenosis in group A and group B were 3.2% and 18.9%. The adverse effect rates of cystic stimulation including irritation signs of bladder and hematuria in group A and group B were 4.8% and 27.6%. There were significant differences in recurrence rates and adverse effect rates between the two groups (P > 0.05). CONCLUSION: Intravesical instillation of high-dose pirarubicin during perioperative period is an effective procedure for the prevention of bladder cancer recurrence.