CT-based radiomics research for discriminating the risk stratification of pheochromocytoma using different machine learning models: a multi-center study.

OBJECTIVES: The purpose of this study was to explore and verify the value of various machine learning models in preoperative risk stratification of pheochromocytoma. METHODS: A total of 155 patients diagnosed with pheochromocytoma through surgical pathology were included in this research (training cohort: n = 105; test cohort: n = 50); the risk stratification scoring system classified a PASS score of < 4 as low risk and a PASS score of ≥ 4 as high risk. From CT images captured during the non-enhanced, arterial, and portal venous phase, radiomic features were extracted. After reducing dimensions and selecting features, Logistic Regression (LR), Extra Trees, and K-Nearest Neighbor (KNN) were utilized to construct the radiomics models. By adopting ROC curve analysis, the optimal radiomics model was selected. Univariate and multivariate logistic regression analyses of clinical radiological features were used to determine the variables and establish a clinical model. The integration of radiomics and clinical features resulted in the creation of a combined model. ROC curve analysis was used to evaluate the performance of the model, while decision curve analysis (DCA) was employed to assess its clinical value. RESULTS: 3591 radiomics features were extracted from the region of interest in unenhanced and dual-phase (arterial and portal venous phase) CT images. 13 radiomics features were deemed to be valuable. The LR model demonstrated the highest prediction efficiency and robustness among the tested radiomics models, with an AUC of 0.877 in the training cohort and 0.857 in the test cohort. Ultimately, the composite of clinical features was utilized to formulate the clinical model. The combined model demonstrated the best discriminative ability (AUC, training cohort: 0.887; test cohort: 0.874). The DCA of the combined model showed the best clinical efficacy. CONCLUSION: The combined model integrating radiomics and clinical features had an outstanding performance in differentiating the risk of pheochromocytoma and could offer a non-intrusive and effective approach for making clinical decisions.

Understory ferns promote the restoration of soil microbial diversity and function in previously degraded lands.

Microorganisms facilitate the recovery of previously degraded soils, such as degraded lands experiencing vegetation restoration and understory expansion, through vital soil functions like nutrient cycling and decomposing organic matter. Despite the role of microorganisms in recovery, little is known about the effects of the process on microbial diversity and function. Here, we performed an understory fern, Dicranopteris dichotoma (Thunb.) Berhn removal treatments nested within three Masson pine (Pinus massoniana L.) plantations with different restoration years in subtropical China. Three ferns treatments including no ferns cover, with ferns cover, and the ferns removal treatments were established to assess the impact of the ferns on soil microbial diversity and function during revegetation and drivers of observed changes. We combined high-throughput sequencing, network structure modeling, and function prediction of soil bacterial and fungal communities to determine microbial diversity and functions. Our results showed that soil bacterial and fungal diversity increased with restoration time. Understory ferns significantly increased soil microbial diversity in the un-restored land but the effect became smaller in two restored sites. Understory ferns significantly increased the relative abundance of bacterial phyla Proteobacteria and Acidobacteria, but decreased that of Chloroflexi and Firmicutes. Furthermore, the presence of ferns increased the abundance of Basidiomycota, but increased the abundance of Ascomycota. Co-occurrence network analysis revealed that the presence of ferns leads to more complex of bacterial networks with more connections, nodes, average degrees, betweenness, and degrees. The functional predictions indicate that aerobic chemoheterotrophy, chemoheterotrophy, and nitrogen fixation functional groups play key roles in the nutrient cycling of soils with ferns cover. The bacterial and fungal community compositions were strongly affected by revegetation and understory ferns as litter biomass and soil nitrogen were identified as the key environmental factors. Our study highlights the role of understory in facilitating microbial diversity and function recovery during degraded lands restoration.

Comparison of the prophylactic antithrombotic effect of indobufen and warfarin in patients with nephrotic syndrome: a randomized controlled trial.

PURPOSE: The risk of thromboembolic events is elevated in patients with nephrotic syndrome, and warfarin use has been associated with an increased risk of bleeding. Indobufen, a selective cyclooxygenase-1 inhibitor, is currently being evaluated for the prevention of thromboembolic events in nephrotic syndrome. This study aimed to compare the efficacy and safety of indobufen with that of warfarin in patients with nephrotic syndrome. MATERIALS AND METHODS: This multicenter, randomized, three-arm, open-label, parallel controlled trial involved a total of 180 adult patients with nephrotic syndrome from four centers in China. Patients were randomly assigned to receive 100 mg indobufen (bid), 200 mg indobufen (bid), and 3 mg warfarin (qd) daily for 12 weeks. The primary endpoints included thromboembolic and bleeding events, while laboratory results and adverse events constituted secondary endpoints. RESULTS: No thromboembolic events occurred in the high-/low-dose indobufen and warfarin groups. Moreover, the use of a low dose of indobufen significantly reduced the risk of minor bleeding events compared with warfarin use (2% versus 18%, p < .05). Finally, adverse events were more frequent in warfarin-treated patients. CONCLUSIONS: This study found that indobufen therapy provided equivalent effects in preventing thromboembolic events compared with warfarin therapy, while low dose of indobufen was associated with a reduced risk of bleeding events, thus it should be recommended for the prevention of thromboembolic events in clinical practice in patients with nephrotic syndrome. TRIAL REGISTRATION NUMBER: ChiCTR-IPR-17013428.

Corrigendum: Docetaxel-loaded novel nano-platform for synergistic therapy of non-small cell lung cancer.

[This corrects the article DOI: 10.3389/fphar.2022.832725.].

Docetaxel-Loaded Novel Nano-Platform for Synergistic Therapy of Non-Small Cell Lung Cancer.

Nowadays, non-small cell lung cancer (NSCLC) is threatening the health of all mankind. Although many progresses on treatment of lung cancer have been achieved in the past few decades, the current treatment methods are still traditional surgery, radiotherapy, and chemotherapy, which had poor selectivity and side effects. Lower-toxicity and more efficient treatments are in sore need. In this paper, a smart nanodelivery platform based on photothermal therapy, chemotherapy, and immunotherapy was constructed. The nanoparticles are composed of novel photothermal agents, Mn-modified phthalocyanine derivative (MnIIIPC), docetaxel (DTX), and an effective targeting molecule, hyaluronic acid. The nanoplatform could release Mn2+ from MnIIIPC@DTX@PLGA@Mn2+@HA(MDPMH) and probably activate tumor immunity through cGAS-STING and chemotherapy, respectively. Furthermore, DTX could be released in the process for removal of tumor cells. The "one-for-all" nanomaterial may shed some light on treating NSCLC in multiple methods.

Development and Interpretation of a Genomic Instability Derived lncRNAs Based Risk Signature as a Predictor of Prognosis for Clear Cell Renal Cell Carcinoma Patients.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a kind of frequently diagnosed cancer, leading to high death rate in patients. Genomic instability (GI) is regarded as playing indispensable roles in tumorigenesis and impacting the prognosis of patients. The aberrant regulation of long non-coding RNAs (lncRNAs) is a main cause of GI. We combined the somatic mutation profiles and expression profiles to identify GI derived lncRNAs (GID-lncRNAs) in ccRCC and developed a GID-lncRNAs based risk signature for prognosis prediction and medication guidance. METHODS: We decided cases with top 25% cumulative number of somatic mutations as genomically unstable (GU) group and last 25% as genomically stable (GS) group, and identified differentially expressed lncRNAs (GID-lncRNAs) between two groups. Then we developed the risk signature with all overall survival related GID-lncRNAs with least absolute shrinkage and selection operator (LASSO) Cox regression. The functions of the GID-lncRNAs were partly interpreted by enrichment analysis. We finally validated the effectiveness of the risk signature in prognosis prediction and medication guidance. RESULTS: We developed a seven-lncRNAs (LINC00460, AL139351.1, AC156455.1, AL035446.1, LINC02471, AC022509.2, and LINC01606) risk signature and divided all samples into high-risk and low-risk groups. Patients in high-risk group were in more severe clinicopathologic status (higher tumor grade, pathological stage, T stage, and more metastasis) and were deemed to have less survival time and lower survival rate. The efficacy of prognosis prediction was validated by receiver operating characteristic analysis. Enrichment analysis revealed that the lncRNAs in the risk signature mainly participate in regulation of cell cycle, DNA replication, material metabolism, and other vital biological processes in the tumorigenesis of ccRCC. Moreover, the risk signature could help assess the possibility of response to precise treatments. CONCLUSION: Our study combined the somatic mutation profiles and the expression profiles of ccRCC for the first time and developed a GID-lncRNAs based risk signature for prognosis predicting and therapeutic scheme deciding. We validated the efficacy of the risk signature and partly interpreted the roles of the seven lncRNAs composing the risk signature in ccRCC. Our study provides novel insights into the roles of genomic instability derived lncRNAs in ccRCC.

Irisin: A New Code Uncover the Relationship of Skeletal Muscle and Cardiovascular Health During Exercise.

Exercise not only produces beneficial effects on muscle itself via various molecular pathways, but also mediates the interaction between muscles and other organs in an autocrine/paracrine manner through myokines, which plays a positive role in maintaining overall health. Irisin, an exercise-derived myokine, has been found involved in the regulation of some cardiovascular diseases. However, the relationship between irisin and cardiovascular health is not fully elucidated and there are some divergences on the regulation of irisin by exercise. In this review, we present the current knowledge on the origin and physiology of irisin, describe the regulation of irisin by acute and chronic exercises, and discuss the divergences of the related research results. Importantly, we discuss the role of irisin as a biomarker in the diagnosis of cardiovascular diseases and describe its treatment and molecular mechanism in some cardiovascular diseases. It is expected that irisin will be used as a therapeutic agent to combat cardiovascular diseases or other disorders caused by inactivity in the near future.

Decline in the contribution of microbial residues to soil organic carbon along a subtropical elevation gradient.

There has been an increasing interest in studying microbial necromasses and their contribution to soil organic carbon (SOC) accumulation. However, it remains unclear how the interaction among climate, plants, and soil influence the microbial anabolism and how microbial necromass contribute to SOC formation. Here, we assessed the relative contribution of microbial residues to SOC pool across a subtropical elevation gradient (ranged from 630 to 2130 m a.s.l.) representing a subtropical ecosystem on Wuyi Mountain in China, by using amino sugars as tracers. Analysis of topsoil (0-10 cm) amino sugars and the composition of microbial community across this gradient revealed that the soil total amino sugars accounting for 12.2-25.7% of the SOC pool, decreased with increasing elevation. Moreover, the linear reduction in the bacterial-derived carbon (C) and an increase in the ratio of fungal- to bacterial-derived C with increasing elevation suggested the reduction in the contribution of bacterial-derived C to SOC pool across this elevation gradient. The divergent changes in the contribution of the microbial residues to SOC infer a potential change in SOC composition and stability. The microbial-derived SOC formation and its climatic responses are influenced by the interaction of vegetation types and soil properties, with soil amorphous Fe being the determiner of soil amino sugar accrual. Our work highlights the importance of understanding ecosystem type and mineral composition in regulating microbial-mediated SOC formation and accumulation in responses to climate change in subtropical ecosystems.

Needlescopic Video-Assisted Thoracic Bilateral T4 Sympathicotomy for the Treatment of Primary Palmar Hyperhidrosis: An Analysis of 200 Cases.

BACKGROUND: Primary palmar hyperhidrosis (PPH) is featured by aberrantly perspiration of the hands, which may bring a lot of inconvenience to patient's daily life and work. The purpose of this study is to summarize the clinical effect of needlescopic video-assisted thoracic bilateral T4 sympathicotomy for the treatment of PPH. PATIENTS AND METHODS: Between January 2009 and March 2014, 200 patients received needlescopic video-assisted thoracic bilateral T4 sympathicotomy. We, respectively, took two 5-mm incisions in the third intercostal space on the anterior axillary line and in the fifth intercostal space on the middle axillary line. After collapsing left lung, needlescopic exploration was the first step to determine the targeted sympathetic chain through the third intercostal space. Electric coagulation hook was inserted from another port to cut T4 sympathetic chain and the bypassing nerve fibers for 2 to 3 cm along the surface of the fourth rib. Right thoracic cavity was also administered the same procedure. The palmar temperature was recorded before and after sympathicotomy. The symptom improvement, operative complications, patients' recovery, and satisfaction were evaluated. FINDING: One hundred and ninety-seven patients uneventfully received two 5-mm port bilateral sympathicotomy, and another 3 patients with extensive pleural adhesions completed the surgery through enlarging the third intercostal incision to 2 cm without conversion to open surgery. All operative procedures were completed in 15 to 35 minutes. The hospital stay was 2 to 4 days. The palmar temperature increased by 2.0 ± 0.5°C, and hyperhidrosis immediately disappeared in both hands after surgery. The efficacy rate was 100%. The postoperative complications such as hemorrhage, hemopneumothorax, bradycardia, or Horner's syndrome had no occurrence. During 6 to 60 months follow-up, mild compensatory sweating of buttock, back, and thigh occurred in 30 patients (15%) at 2 to 5 days after surgery and gradually disappeared at postoperative 15 to 30 days or longer time. All patients were greatly satisfied with the effect with better confidence and quality of life. Until now, no recurrent palmar hyperhidrosis happened. CONCLUSION: Needlescopic video-assisted thoracic bilateral T4 sympathicotomy could reach an excellent and immediate result of treating PPH. It is a safe, convenient, and minimally invasive method appropriate for wide clinical use.

Emodin ameliorates renal fibrosis in rats via TGF-ß1/Smad signaling pathway and function study of Smurf 2.

BACKGROUND: Emodin is a natural active component extracted from Chinese herbs. In this study, we investigated the therapeutic effect of emodin on surgery-induced renal fibrosis in rat. Moreover, the function of Smad ubiquitination regulatory factor 2 (Smurf 2) was further studied in vitro. METHODS: The renal fibrosis rat model was established via 5/6 renal mass reduction. The histopathological abnormalities of renal tissues in rats were tested via staining method and microscopic examination. Renal function indicators, the serum creatinine, blood urea nitrogen and total urinary protein were measured via spectrophotometric method. The renal tissues were tested via Western blotting and real-time quantitative PCR. Moreover, Smurf 2 protein expression under different conditions and its regulatory function in vitro was measured via Western blotting. RESULTS: Our results showed that the histopathological abnormalities, the decrease in rat body weight and the abnormal renal function caused by renal fibrosis were improved by emodin. Further, mRNA expression of TGF-ß1 was decreased by emodin. Furthermore, extracellular matrix (ECM) components as well as TGF-ß1/Smad signaling-related Smurf 2 were decreased by emodin both in vivo and in vitro. The protein level of mothers against decapentaplegic homolog 7 (Smad7) was up-regulated. In addition, ECM components were increased by Smurf 2 over-expression and these effects were weakened by emodin co-treatment in vitro. CONCLUSION: Emodin showed an anti-fibrosis effect in surgery-induced renal fibrotic rats. And this effect was potentially achieved via down-regulating expressions of TGF-ß1 and Smurf 2 and up-regulating Smad7 expression.

Therapeutical effect of intrapleural perfusion with hyperthermic chemotherapy on malignant pleural effusion under video-assisted thoracoscopic surgery.

BACKGROUND: Patients with malignant pleural effusions (MPEs) have limited life expectancy. This study aims to investigate the feasibility of intrapleural perfusion with hyperthermic chemotherapy (IPHC) under video-assisted thoracoscopic surgery on MPE patients. METHODS: MPE patients were enrolled in the study and treated with IPHC. The treatment response was classified as complete response (CR, no re-accumulation of pleural fluid for 4 weeks), partial response (PR, re-accumulation above the post-IPHC level but below the pre-IPHC level for four weeks), no response (NR; re-accumulation or above the pre-IPHC level). The change of Karnofsky performance score (KPS) and tumour markers were also recorded. Follow-up was done every two weeks during first month and monthly thereafter until death. RESULTS: Eighty patients included 46 males and 34 females were included in the study. The total response rate was 100%, with 71.3% of CR and 28.7% of PR. The KPS scores were significantly elevated and the level of tumour markers in pleural effusion were dramatically decreased after IPHC. The median survival was 16.8 months ranged from 2.1 to 67.4 months. One-year and two-year survival rates were 82.5% and 23.8%, respectively. There were no serious clinical compilations during IPHC treatment. CONCLUSIONS: IPHC is a safety, effective and promising approach for MPE patients. It provides well survival benefit and minor toxicities.

Exercise coupled with dietary restriction reduces oxidative stress in male adolescents with obesity.

The increased oxidative stress is usually observed in obese population, but the control of body weight by calorie restriction and/or exercise training can ameliorate oxidative stress. In order to evaluate oxidative stress in response to exercise and dietary restriction in obese adolescents, a total of 20 obese volunteers were enrolled in a 4-week intervention program including exercise training and dietary restriction. Body compositions and blood samples were analysed before and after 4-week intervention, and biomarkers associated with oxidative stress were examined. After 4-week exercise training coupled with dietary restriction, physical composition parameters including body mass, body mass index (BMI), lean body mass, body fat mass and fat mass ratio had obvious reduction by 12.43%, 13.51%, 5.83%, 25.05% and 14.52%, respectively. In addition, the activities of antioxidant enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase (GPx) revealed a remarkable enhancement. On the other hand, protein carbonyls (PC) exhibited an obvious reduction. Moreover, total thiols and nitrites with respect to baseline revealed a reducing trend although no significant difference was observed. Therefore, the 4-week exercise intervention coupled with dietary restriction is benefit for the loss of body weight and the mitigation of oxidative stress in obese population so that it can be a recommendable intervention prescription for the loss of body weight.

A carboxymethyl chitosan and peptide-decorated polyetheretherketone ternary biocomposite with enhanced antibacterial activity and osseointegration as orthopedic/dental implants.

Carbon fiber-reinforced polyetheretherketone (CFRPEEK) possesses biomechanical properties such as elastic modulus similar to human bones and is becoming a dominant alternative to replace the traditional metallic implants. The defective osseointegration and bacterial infection risk of CFRPEEK, however, impede its clinical adoption. In the current study, a newly-developed carbon fiber-reinforced polyetheretherketone/nanohydroxyapatite (CFRPEEK/n-HA) ternary biocomposite was functionalized by covalently grafting carboxymethyl chitosan (CMC) followed by the decoration of a bone-forming peptide (BFP) assisted via the polydopamine tag strategy. Antibacterial test with Staphylococcus aureus (S. aureus) indicated that the CMC and peptide-conjugated substrates (pep-CMC-CFRPEEK/n-HA) significantly suppressed bacterial adhesion. In vitro cell attachment/growth, spreading assay, alkaline phosphatase activity, real-time PCR analysis, osteogenesis-related protein expression and calcium mineral deposition all disclosed greatly accelerated adhesion, proliferation and osteo-differentiation of human mesenchymal stem cells (hMSCs) on the pep-CMC-CFRPEEK/n-HA biocomposite due to the additive effect of the CMC polysaccharide and the small osteoinductive peptide. More importantly, in vivo evaluation of the beagle tibia model by means of micro-CT, histological analysis, SEM observation and fluorescent labeling confirmed the remarkably boosted bioactivity and osteointegration. The CFRPEEK/n-HA ternary composite with the dual functions of bacterial adhesion reduction and osteointegration promotion holds great potential as a bioactive implant material in orthopedic/dental applications based on this scheme.

Preparation, characterization, cellular response and in vivo osseointegration of polyetheretherketone/nano-hydroxyapatite/carbon fiber ternary biocomposite.

As FDA-approved implantable material, polyetheretherketone (PEEK) is becoming a prime candidate to replace traditional surgical metallic implants made of titanium (Ti) and its alloys, since it has a lower elastic modulus than Ti. The bioinertness and defective osteointegration of PEEK, however, limit its clinical adoption as load-bearing dental/orthopedic material. The present work aimed at developing a PEEK bioactive ternary composite, polyetheretherketone/nano-hydroxyapatite/carbon fiber (PEEK/n-HA/CF), and evaluating it as a potential bone-repairing material by assessment of growth and differentiation of osteoblast-like MG63 cells and by estimation of osteointegration in vivo. Our results indicated that the adhesion, proliferation and osteogenic differentiation of cells, as well as the mechanical properties were greatly promoted for the PEEK/n-HA/CF biocomposite compared with pure PEEK matrix. More importantly, the ternary composite implant boosted in vivo bioactivity and osseointegration in canine tooth defect model. Thus, the PEEK/n-HA/CF ternary biocomposite with enhanced mechanics and biological performances hold great potential as bioactive implant material in dental and orthopedic applications.

Tantalum Nitride-Decorated Titanium with Enhanced Resistance to Microbiologically Induced Corrosion and Mechanical Property for Dental Application.

Microbiologically induced corrosion (MIC) of metallic devices/implants in the oral region is one major cause of implant failure and metal allergy in patients. Therefore, it is crucial to develop practical approaches which can effectively prevent MIC for broad clinical applications of these materials. In the present work, tantalum nitride (TaN)-decorated titanium with promoted bio-corrosion and mechanical property was firstly developed via depositing TaN layer onto pure Ti using magnetron sputtering. The microstructure and chemical constituent of TaN coatings were characterized, and were found to consist of a hard fcc-TaN outer layer. Besides, the addition of TaN coatings greatly increased the hardness and modulus of pristine Ti from 2.54 ± 0.20 to 29.88 ± 2.59 GPa, and from 107.19 ± 6.98 to 295.46 ± 19.36 GPa, respectively. Potentiodynamic polarization and electrochemical impedance spectroscopy studies indicated that TaN coating exhibited higher MIC resistance in comparison to bare Ti and TiN-coated coating in two bacteria-containing artificial saliva solutions. Moreover, the biofilm experiment showed that the TaN-decorated Ti sample possessed good antibacterial performance. The SEM and XPS results after biofilm removal demonstrated that TaN film remained its integrity and stability, while TiN layer detached from Ti surface in the bio-corrosion tests, demonstrating the anti-MIC behavior and the strong binding property of TaN coating to Ti substrate. Considering all these results, TaN-decorated Ti material exhibits the optimal comprehensive performance and holds great potential as implant material for dental applications.

The radiation damage of crystalline silicon PN diode in tritium beta-voltaic battery.

A tritium beta-voltaic battery using a crystalline silicon convertor composed of (100)Si/SiO2/Si3N4 film degrades remarkably with radiation from a high intensity titanium tritide film. Simulation and experiments were carried out to investigate the main factor causing the degradation. The radiation damages mainly comes from the x-ray emitted from the titanium tritide film and beta particle can relieve the damages. The x-ray radiation induced positive charges in the SiO2 film destroying the output property of the PN diode with the induction of an electric field.

Antibiotic-decorated titanium with enhanced antibacterial activity through adhesive polydopamine for dental/bone implant.

Implant-associated infections, which are normally induced by microbial adhesion and subsequent biofilm formation, are a major cause of morbidity and mortality. Therefore, practical approaches to prevent implant-associated infections are in great demand. Inspired by adhesive proteins in mussels, here we have developed a novel antibiotic-decorated titanium (Ti) material with enhanced antibacterial activity. In this study, Ti substrate was coated by one-step pH-induced polymerization of dopamine followed by immobilization of the antibiotic cefotaxime sodium (CS) onto the polydopamine-coated Ti through catechol chemistry. Contact angle measurement and X-ray photoelectron spectroscopy confirmed the presence of CS grafted on the Ti surface. Our results demonstrated that the antibiotic-grafted Ti substrate showed good biocompatibility and well-behaved haemocompatibility. In addition, the antibiotic-grafted Ti could effectively prevent adhesion and proliferation of Escherichia coli (Gram-negative) and Streptococcus mutans (Gram-positive). Moreover, the inhibition of biofilm formation on the antibiotic-decorated Ti indicated that the grafted CS could maintain its long-term antibacterial activity. This modified Ti substrate with enhanced antibacterial activity holds great potential as implant material for applications in dental and bone graft substitutes.

Intervention effect and dose-dependent response of tanreqing injection on airway inflammation in lipopolysaccharide-induced rats.

OBJECTIVE: To assess the effect of Tanreqing injection on airway inflammation in rats. METHODS: A rat model of airway inflammation was generated with lipopolysaccharide (LPS). Tanreqing injection was given by intratracheal instillation, and bronchoalveolar lavage fluid (BALF) from the right lung was collected. BALF total cell and neutrophil counts were then determined. In addition, BALF levels of inflammatory cytokines interleukin-13, cytokine-induced neutrophil chemoat-tractant-1, and tumor necrosis factor-alpha were measured using enzyme linked immunosorbent assay. The middle lobe of the right lung was stained with hematoxylin-eosin and histological changes examined. RESULTS: LPS increased airway inflammation, decreased BALF inflammatory cell count, inflammatory cytokine levels, and suppressed leukocyte influx of the lung. The LPS-induced airway inflammation peaked at 24 h, decreased beginning at 48 h, and had decreased markedly by 96 h. CONCLUSION: Tanreqing injection contains anti-inflammatory properties, and inhibits airway inflammation in a dose-dependent manner.

Radiology-pathology conference: primary peritoneal mesothelioma.

Primary peritoneal mesothelioma is a rare neoplasm which carries a dismal prognosis. These highly aggressive tumors arise from mesothelial cells lining the peritoneum and are rapidly fatal. The neoplasm is typically associated with crocidolite asbestos exposure. We present the case of a 75-year-old man with primary peritoneal mesothelioma, with invasion into the right hepatic lobe.

Secondary mutation in a coding mononucleotide tract in MSH6 causes loss of immunoexpression of MSH6 in colorectal carcinomas with MLH1/PMS2 deficiency.

Immunohistochemical staining for DNA mismatch repair proteins may be affected by various biological and technical factors. Staining variations that could potentially lead to erroneous interpretations have been recognized. A recently recognized staining variation is the significant reduction of staining for MSH6 in some colorectal carcinomas. The frequency and specific characteristics of this aberrant MSH6 staining pattern, however, have not been well analyzed. In this study of 420 colorectal carcinoma samples obtained from patients fulfilling the Revised Bethesda Guidelines, we detected 9 tumors (2%) showing extremely limited staining for MSH6 with positive staining present in <5% of the tumor cells. Our analyses showed that these tumors belonged to two distinct categories: (1) MLH1 and/or PMS2 protein-deficient carcinomas (n=5, including 1 with a pathogenic mutation in PMS2); and (2) MLH1, PMS2 and MSH2 normal but with chemotherapy or chemoradiation therapy before surgery (n=4). To test our hypothesis that somatic mutation in the coding region microsatellite of the MSH6 gene might be a potential underlying mechanism for such limited MSH6 staining, we evaluated frameshift mutation in a (C)(8) tract in exon 5 of the MSH6 gene in seven tumors that had sufficient DNA for analysis, and detected mutation in four; all four tumors belonged to the MLH1/PMS2-deficient group. In conclusion, our data outline the main scenarios where significant reduction of MSH6 staining is more likely to occur in colorectal carcinoma, and suggest that somatic mutations of the coding region microsatellites of the MSH6 gene is an underlying mechanism for this staining phenomenon in MLH1/PMS2-deficient carcinomas.