Dissected subgroups predict the risk of recurrence of stage II colorectal cancer and select rational treatment.

Background: Stage II colorectal cancer(CRC) patients after surgery alone have a five-year survival rate of ~60-80%; the incremental benefit of adjuvant chemotherapy is <5%. Predicting risk of recurrence and selecting effective personalized adjuvant drugs for stage II CRC using formalin-fixed, paraffin-embedded(FFPE) samples is a major challenge. Methods: 1319 stage II CRC patients who enrolled in 2011-2019 at Sun Yat-sen University Cancer Center were screened. RNAseq data of FFPE tumor samples of 222 stage II microsatellite stable(MSS) CRC patients(recurrence (n=47), norecurrence (n=175), median follow-up=41 months) were used to develop a method TFunctionalProg for dissecting heterogeneous subgroups of recurrence and predicting risk of recurrence. Results: TFunctionalProg showed significant predictive values in 222 stage II MSS CRCs. The TFunctionalProg low-risk group had significantly better recurrence free survival (validation set: HR=4.78, p-value=1e-4, low-risk group three-year recurrence free survival=92.6%, high-risk group three-year recurrence free survival=59.7%). TFunctionalProg dissected two subgroups of transition states of stage II MSS CRCs at a high risk of recurrence; each state displays distinct levels of hybrid epithelial-mesenchymal traits, CD8+ T cell suppression mechanisms and FOLFOX resistance. Based on mechanisms in two subgroups, TFunctionalProg proposed personalized rational adjuvant drug combinations of immunotherapy, chemotherapy and repurposed CNS drugs. TFunctionalProg provides different utilities from ctDNA-based prognostic biomarkers. Conclusion: TFunctionalProg was validated using FFPE samples to predict the risk of recurrence and propose rational adjuvant drug combinations for stage II CRC.

SUN Shen-tian's clinical experience in treating Tourette's syndrome with acupuncture / 中国针灸

To introduce the clinical experience of professor SUN Shen-tian in treatment of Tourette's syndrome (TS) with acupuncture. TS is a psychosomatic disease and the core pathogenesis refers to blood deficiency producing internal wind. The disease is located in the heart and liver. Acupoints are selected according to the functional orientation of the cerebral cortex. The extrapyramidal system area is preferred for tic disorder, and the emotional area is for behavioral disorder. The treatment focuses on regulating the mind by multiple methods, including manual needling technique used the transcranial repeated acupuncture, and regulating the mind by taking multiple acupoints, Baihui (GV 20), Neiguan (PC 6), Shenmen (HT 7) and Dazhong (KI 4) are stimulated. For abdominal twitching and mental symptoms of TS children, the first and third abdominal areas are selected. The target symptoms (biao) are treated specially by local acupoints, the combination of the starting and ending acupoints of the affected meridian, or the acupoints of the meridians with same name. The modified chaihu longgu muli decoction and siwu decoction are prescribed to sooth liver, nourish blood and soothe wind. In association with the characteristics and target symptoms of TS, the sequential therapy is used with filiform needling, intradermal needling, Chinese herbal medication and psychotherapy.

Professor SUN Shen-tian's experience in acupuncture treatment of depression based on "psychosomatic medicine" / 中国针灸

This paper introduces professor SUN Shen-tian's clinical thoughts and his characteristics of acupuncture techniques for the treatment of depression based on "psychosomatic medicine". Professor SUN, the master of traditional Chinese medicine, believes that depression refers to comorbidity of "heart mind" and "body", resulting from the "body-mind" disharmony, specially dominated by the emotional disorder. This disease is located in the brain, with the injury of mind and closely related to the heart and liver dysfunction. In pathogenesis, the dysfunction of brain mind and the unhealthy conditions of body and mind are involved. The treatment should focus on "regulating the mind, improving the intelligence, co-modulating the abdominal and brain functions and treating the physical and mental disorders". Baihui (GV 20), Ningshen (Extra) and emotional area on the head are selected as the main points to benefit the intelligence and calming down the mind; the abdominal region 1 and region 8 of "Sun's abdominal acupuncture" are used as the main points of the abdomen to regulate the brain functions. The point prescription is modified according to the symptoms and etiologies. The repeated transcranial acupuncture stimulation and electroacupuncture at low frequency (2 Hz) are crucial to the therapeutic effect. Reliving anxious emotions is specially considered before acupuncture, and the mind is protected and deqi is consolidated during acupuncture.

Comprehensive analysis of PLKs expression and prognosis in breast cancer.

OBJECTIVE: A thorough examination of PLKs in breast cancer, including their expression and prognosis. METHODS: With the help of the Oncomine database, the transcript levels of PLKs in breast cancer were examined. The changes in PLKs expression with tumor stage and indeed the relationship between PLKs expression and stage of cancer in women with breast cancer were scrutinized by using the GEPIA database. Based on Kaplan-Meier plots, breast cancer patients were assessed for their prognosis. Breast cancer gene expression and mutations were analyzed within the cBioPortal database. RESULTS: According to Oncomine data, PLK1 and PLK4 mRNA expression levels were dramatically elevated in breast cancer patients while PLK2 and PLK5P levels were significantly downregulated. PLK1 and PLK4 expression were discovered to be greater in breast cancer tissues than in healthy tissues following analysis of the GEPIA database (P < 0.05). High levels of PLK1 and PLK4 transcripts have been linked to poor relapse-free survival rates across all patients with breast cancer according to the Kaplan-Meier Plotter database. The high levels of PLK2, PLK3, and PLK5 were associated with a higher recurrence-free survival rate. In the cBioPortal database, PLK was altered in 9.6% of breast cancer samples. Genetic alterations occurred in 15.07% of clinically counted invasive breast cancers, with mutations in 4.11%, gene amplifications in 9.59%, and gene deletion mutations in 1.37%. Additionally, the KEGG database demonstrates that PLKs are crucial for the cell cycle. The findings imply that elevated PLK1 and PLK4 expression in tissues of breast cancer might contribute significantly to the carcinogenesis of breast cancer. Moreover, PLK1 and PLK4 are highly expressed in breast cancer, and their use as molecular markers to identify high-risk subsets from patients with breast cancer is potentially possible. CONCLUSIONS: For the precise therapy of breast cancers, PLK1 and PLK4 are potential targets, while PLK2, PLK3, and PLK5 are brand-new biomarkers for predicting the prognosis of breast cancer.

A detailed analysis of possible efficacy signals of NTHi-Mcat vaccine against severe COPD exacerbations in a previously reported randomised phase 2b trial.

BACKGROUND: An investigational vaccine containing non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) surface proteins did not show vaccine efficacy (VE) against combined moderate and severe (moderate/severe) exacerbations in a randomised, observer-blinded, placebo-controlled phase 2b trial of patients with chronic obstructive pulmonary disease (COPD). Nevertheless, observations on rates of severe exacerbations and hospitalisations encouraged further evaluation. METHODS: Patients with stable COPD (moderate to very severe airflow limitation, Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 2-4), 40-80 years and at least one moderate/severe exacerbation in the last year received two doses of NTHi-Mcat vaccine or placebo plus standard care. Secondary analyses were conducted on VE against exacerbations according to severity. Potential predictive factors at baseline for VE against severe exacerbations were explored in post-hoc analyses. RESULTS: Of 606 patients enrolled, 571 were included in the efficacy analysis (279 in NTHi-Mcat vaccine group, 292 in placebo group). VE against severe acute exacerbations of COPD (AECOPD) in various subgroups was 52.11 % (p = 0.015; frequent exacerbators), 65.43 % (p = 0.015; baseline GOLD grade 4), 38.24 % (p = 0.034; previous pneumococcal and/or influenza vaccination). VE was 52.49 % (p = 0.044) for the 6-12 months period after 1 month post-dose 2. Multivariable analysis identified two factors (frequent exacerbator status plus inhaled corticosteroid use at baseline) associated with significant VE against severe AECOPD; in this subpopulation, VE was 74.99 % (p < 0.001). CONCLUSION: Results suggest potential efficacy with the NTHi-Mcat vaccine against severe exacerbations in certain patients with COPD, in particular those who have frequent exacerbations and use inhaled corticosteroids. This potential signal requires confirmation in an appropriately designed prospective clinical trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03281876.

Essence of SUN Shen-tian's clinical features on acupuncture and moxibustion / 中国针灸

To summarize SUN Shen-tian's treatment ideas and clinical features. SUN applies meridian syndrome differentiation to the diagnosis and treatment of diseases; advocates that prevention and treatment of diseases should be regulated mind firstly; applies transcranial repetitive acupuncture combined modern cerebral cortex function positioning; emphasizes the application of multiple acupuncture methods and manipulation, and includes the meridian penetrating needling method, the flat needling and penetrating needling method, and the stagnant needle lifting method, pays attention to the importance of achieving qi and manipulation for the effect.

Global Pattern of CD8+ T-Cell Infiltration and Exhaustion in Colorectal Cancer Predicts Cancer Immunotherapy Response.

Background: The MSI/MSS status does not fully explain cancer immunotherapy response in colorectal cancer. Thus, we developed a colorectal cancer-specific method that predicts cancer immunotherapy response. Methods: We used gene expression data of 454 samples (MSI = 131, MSI-L = 23, MSS = 284, and Unknown = 16) and developed a TMEPRE method that models signatures of CD8+ T-cell infiltration and CD8+ T-cell exhaustion states in the tumor microenvironment of colorectal cancer. TMEPRE model was validated on three RNAseq datasets of melanoma patients who received pembrolizumab or nivolumab and one RNAseq dataset of purified CD8+ T cells in different exhaustion states. Results: TMEPRE showed predictive power in three datasets of anti-PD1-treated patients (p = 0.056, 0.115, 0.003). CD8+ T-cell exhaustion component of TMEPRE model correlates with anti-PD1 responding progenitor exhausted CD8+ T cells in both tumor and viral infection (p = 0.048, 0.001). The global pattern of TMEPRE on 454 colorectal cancer samples indicated that 10.6% of MSS patients and 67.2% of MSI patients show biological characteristics that can potentially benefit from anti-PD1 treatment. Within MSI nonresponders, approximately 50% showed insufficient tumor-infiltrating CD8+ T cells and 50% showed terminal exhaustion of CD8+ T cells. These terminally exhausted CD8+ T cells coexisted with signatures of myeloid-derived suppressor cells in colorectal cancer. Conclusion: TMEPRE is a colorectal cancer-specific method. It captures characteristics of CD8+ T-cell infiltration and CD8+ T-cell exhaustion state and predicts cancer immunotherapy response. A subset of MSS patients could potentially benefit from anti-PD1 treatment. Anti-PD1 resistance MSI patients with insufficient infiltration of CD8+ T cells or terminal exhaustion of CD8+ T cells need different treatment strategies.

The influence of tolfenpyrad on fitness, development, and reproduction in parents and offspring of Coccinella septempunctata.

Coccinella septempunctata (ladybird) is one of the foremost natural predators that feed on aphids. Thus, C. septempunctata serves as an effective biological control agent in integrated pest management (IPM) programs. To supplement the activity of biological control agents, IPM programs often incorporate chemical pesticides to bolster crop protection. To evaluate the effects of a potent insecticide, tolfenpyrad, on C. septempunctata, we tested the sublethal effects of tolfenpyrad on all developmental stages of the life cycle of C. septempunctata and its effects on the next generation. For sublethal testing of the parent generation, the LR50 of tolfenpyrad for C. septempunctata was determined to range from 1.04 to 8.43 g a.i. /hm2 within a set exposure period, while the hazard quotient (HQ) values were above our threshold value of 2 during the entire observation period. These data indicated a potential toxicity risk from tolfenpyrad exposure. The no observed effect application rates (NOERs) of tolfenpyrad on parents (F0) were determined for survival (0.485 g a.i. /hm2), developmental time of pupation (0.242 g a.i. /hm2), and fecundity (0.485 g a.i. /hm2). Application of sublethal doses to unexposed progeny (F1) of exposed parents, prolonged the L1 (1st instar of larvae) and L2 (2nd instar of larvae) stage, while the total longevity, intrinsic rate of increase (r), finite rate of increase (γ), net reproductive rate (R0), and mean generation time (T) were significantly reduced. These results demonstrated the negative influence of sublethal concentrations of tolfenpyrad on C. septempunctata and its persistent effects on subsequent generations.

Enhanced thermoelectric performance of graphene based nanocomposite coated self-powered wearable e-textiles for energy harvesting from human body heat.

The demand for highly flexible and self-powered wearable textile devices has increased in recent years. Graphene coated textile-based wearable devices have been used for energy harvesting and storage due to their outstanding mechanical, electrical and electronic properties. However, the use of metal based nanocomposites is limited in textiles, due to their poor bending, fixation, and binding on textiles. We present here reduced graphene oxide (rGO) as an n-type and conductive polymer poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) as a p-type material for a wearable thermoelectric nanogenerator (TEG) using a (pad-dry-cure) technique. We developed a reduced graphene oxide (rGO) coated textile-based wearable TEG for energy harvesting from low-grade human body heat. The conductive polymer (PEDOT:PSS) and (rGO) nanocomposite were coated using a layer by layer approach. The resultant fabric showed higher weight pickup of 60-80%. The developed textile based TEG device showed an enhanced Seebeck coefficient of (25-150 µV K-1), and a power factor of (2.5-60 µW m-1 K-1). The developed TE device showed a higher potential to convert the low-grade body heat into electrical energy, between the human body temperature of (36.5 °C) and an external environment of (20.0 ± 5 °C) with a temperature difference of (2.5-16.5 °C). The wearable textile-based TEG is capable of producing an open circuit output voltage of 12.5-119.5 mV at an ambient fixed temperature of (20 °C). The rGO coated textile fabric also showed reduced electrical sheet resistance by increasing the number of dyeing cycles (10) and increased with the number of (20) washing cycles. The developed reduced graphene oxide (rGO) coated electrodes showed a sheet resistance of 185-45 kΩ and (15 kΩ) for PEDOT:PSS-rGO nanocomposites respectively. Furthermore, the mechanical performance of the as coated textile fabric was enhanced from (20-80 mPa) with increasing number of padding cycles. The thermoelectric performance was significantly improved, without influencing the breath-ability and comfort properties of the resultant fabric. This study presents a promising approach for the fabrication of PEDOT:PSS/rGO nano-hybrids for textile-based wearable thermoelectric generators (TEGs) for energy harvesting from low-grade body heat.

Identification of Two Subgroups of FOLFOX Resistance Patterns and Prediction of FOLFOX Response in Colorectal Cancer Patients.

To dissect gene expression subgroups of FOLFOX resistance colorectal cancer(CRC) and predict FOLFOX response, gene expression data of 83 stage IV CRC tumor samples (FOLFOX responder n = 42, non-responder n = 41) are used to develop a novel iterative supervised learning method IML. IML identified two mutually exclusive subgroups of CRC patients that rely on different DNA damage repair proteins and resist FOLFOX. IML was validated in two validation sets (HR = 2.6, p Value = 0.02; HR = 2.36, p value = 0.02). A subgroup of mesenchymal subtype patients benefit from FOLFOX. Different subgroups of FOLFOX nonresponders may need to be treated differently.

Effects of Sirt1 on proliferation, migration, and apoptosis of endothelial progenitor cells in peripheral blood of SD rats with chronic obstructive pulmonary disease

Objective: To explore the effect of Sirt1 on the function of endothelial progenitor cells (EPCs) in rats with chronic obstructive pulmonary disease (COPD). Methods: A rat COPD model was established via smoking and endotoxin administration for three months. The peripheral circulating EPCs were isolated by gradient centrifugation, and their functions, cell cycle distribution, apoptosis, and Sirt1 expression were examined. The function changes of EPCs in the presence or absence of Sirt1 agonist and inhibitor were estimated; meanwhile, the expressions of Sirt1, FOXO3a, NF-κB, and p53 were also evaluated. Results: The proliferation, adhesion, and migration of EPCs decreased while the apoptosis rate was increased in the COPD rats. The expression of Sirt1 protein in EPCs of the COPD group was significantly lower than that in the control group (P<0.01). The overexpression of the Sirt1 gene using a gene transfection technique or Sirt1 agonists (SRT1720) improved the proliferation, migration, and adhesion, and decreased the apoptosis of EPC. However, Sirt1 inhibitor (EX527) decreased EPC functions in the COPD group. The effect of Sirt1 expression on EPC function may be related to reduction of FOXO3a and increase of NF-κB and p53 activity. Conclusions: Increased expression of Sirt1 can improve the proliferation and migration of EPCs and reduce their apoptosis in COPD rats. This change may be related to FOXO3a, NF-κB, and p53 signaling pathways.

Effects of Sirt1 on proliferation, migration, and apoptosis of endothelial progenitor cells in peripheral blood of SD rats with chronic obstructive pulmonary disease

Objective: To explore the effect of Sirt1 on the function of endothelial progenitor cells (EPCs) in rats with chronic obstructive pulmonary disease (COPD). Methods: A rat COPD model was established via smoking and endotoxin administration for three months. The peripheral circulating EPCs were isolated by gradient centrifugation, and their functions, cell cycle distribution, apoptosis, and Sirt1 expression were examined. The function changes of EPCs in the presence or absence of Sirt1 agonist and inhibitor were estimated; meanwhile, the expressions of Sirt1, FOXO3a, NF-κB, and p53 were also evaluated. Results: The proliferation, adhesion, and migration of EPCs decreased while the apoptosis rate was increased in the COPD rats. The expression of Sirt1 protein in EPCs of the COPD group was significantly lower than that in the control group (P<0.01). The overexpression of the Sirt1 gene using a gene transfection technique or Sirt1 agonists (SRT1720) improved the proliferation, migration, and adhesion, and decreased the apoptosis of EPC. However, Sirt1 inhibitor (EX527) decreased EPC functions in the COPD group. The effect of Sirt1 expression on EPC function may be related to reduction of FOXO3a and increase of NF-κB and p53 activity. Conclusions: Increased expression of Sirt1 can improve the proliferation and migration of EPCs and reduce their apoptosis in COPD rats. This change may be related to FOXO3a, NF-κB, and p53 signaling pathways.

Research progress in the children dietary index / 中国学校卫生

Abstract@#Given the improved understanding of the complexity of individual diets, the method of evaluating dietary characteristics by analyzing the overall dietary pattern has been widely explored. The Dietary Index is commonly used to assess dietary patterns. Some countries have established dietary indices that are suitable for the diet and growth characteristics of children in their domestic population. The study aimed to review widely used and representative dietary indices for children, and to analyze the characteristics of the established index system and the scoring methods that were used for each dietary index, so as to provide a basis for developing a more accurate assessment of overall diet quality in children.

Influence of different types of rapid maxillary expansion on root resorption: a systematic review / 华西口腔医学杂志

OBJECTIVES@#This study aimed to assess the influence of different types of rapid maxillary expansion on root resorption (RR).@*METHODS@#Literature searches were carried out electronically in five English and two Chinese databases. Randomized controlled trials (RCTs), controlled clinical trials (CCTs), cohort studies, and case-control studies were included. The data were extracted by three authors. The risk of bias in the RCTs and nonrandomized studies were assessed in accordance with corresponding scales.@*RESULTS@#Among the 400 articles identified, seven were included for the final analysis. Three studies were graded as high value of evidence, while two and another two studies were graded as moderate value and low value, respectively. According to the available evidence, the tooth-borne maxillary expansion caused more obvious RR of anchorage teeth than the bone-borne one. In addition, the Haas-type palatal acrylic pads could not effectively reduce the degree of RR. The difference in the design of the retainer between the tooth-borne maxillary expansion (the use of a band or wire framework to connect the anchorage tooth) did not cause the difference in the incidence and degree of RR.@*CONCLUSIONS@#Clinical evidence suggested that bone-borne maxillary expansion may decrease the amount of RR, while the amounts of resorption did not significantly differ between Haas and Hyrax and between different retainer types of Hyrax.

Clinical Efficacy on Erchentang Combined with Sanzi Yangqintang in Treatment of Cough Variant Asthma in Children with Phlegm Evil Accumulation Lung Syndrome / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of Erchentang combined with Sanzi Yangqintang in the treatment of cough variant asthma （CVA） in children with phlegm-evil accumulation lung syndrome and its influence on airway inflammation and airway hyperresponsiveness （AHR）. Method:A total of one hundred and sixteen children were randomly divided into observation group and control group 58 cases in each group. Patients in both groups took montelukast sodium chewable tablets orally， 5 mg/time， once daily， at night before bedtime. In observation group， patients took Erchentang and Sanzi Yangqintang modified granules orally. While patients in control group took Erchentang and Sanzi Yangqintang placebo granules orally. Treatment course continued six weeks for two groups. Before and after treatment， the cough symptom scores and phlegm evil accumulating lung syndrome scores were recorded every week. The cough remission time and cough disappearance time were recorded， followed up for 24 weeks to record cough recurrence. Leicester Cough quality of life questionnaire （LCQ） was scored before and after treatment. The ratio of induced sputum eosinophils （EOS） and the levels of interleukin-4 （IL-4）， IL-5， IL-12， IL-13 were measured before and after treatment. The cumulative doses of exhaled nitric oxide （FeNO） and methacholine （PD20） were measued before and after therapy. Safety evaluation was conducted. Result:The scores of cough symptom and phlegm-evil accumulation lung syndrome at different time points were decreased gradually in two groups of children after treatment （<italic>F</italic>_{control group}=5.277， <italic>F</italic>_{observation group}=7.636，<italic>P</italic><0.01）. The scores of cough symptom and phlegm-evil accumulation in the lung syndrome of observation group were lower than those in control group （<italic>P</italic><0.01） at the same period. The durations of cough relief and cough disappearance in observation group were shorter than those in control group （<italic>P</italic><0.01）. Within 24 weeks of follow-up， the recurrence rate of children in observation group was 68.97% （40/58）， lower than 84.48% （49/58） in control group （<italic>χ</italic>²=3.917，<italic>P</italic><0.05）. Children in observation group had fewer relapses than those in control group （<italic>P</italic><0.01）. The total LCQ scores and scores of all dimensions in observation group were higher than those in control group （<italic>P</italic><0.01）. The EOS， IL-4， IL-5 and IL-13 levels in observation group were lower than the data in control group， and IL-12 level was higher than that in control group （<italic>P</italic><0.01）. FeNO of children in observation group was lower than that in control group （<italic>P</italic><0.01）， while PD20 was more than that of control group （<italic>P</italic><0.01）. The total effective rate of clinical curative effect of children in observation group was 96.55% （56/58）， which was higher than 82.76% （48/58） in control group （<italic>χ</italic>²=5.948，<italic>P</italic><0.05）. Conclusion:Erchentang combined with Sanzi Yangqintang for children with CVA phlegm evil accumulation lung syndrome can further control the symptoms of cough， shorten the course of cough， improve the quality of life， and reduce airway inflammation and AHR， reduce the recurrence rate. The clinical efficacy is better than using montelukast only， and it is safe and has good clinical value.

Helpless Priming Sends CD8+ T Cells on the Road to Exhaustion.

Persistent antigen exposure in chronic infection and cancer has been proposed to lead to cytotoxic T lymphocyte (CTL) "exhaustion", i.e., loss of effector function and disease control. Recent work identifies a population of poorly differentiated TCF-1+PD-1+ CD8+ T cells as precursors of the terminally exhausted CTL pool. These "predysfunctional" CTLs are suggested to respond to PD-1 targeted therapy by giving rise to a pool of functional CTLs. Supported by gene expression analyses, we present a model in which lack of CD4+ T cell help during CD8+ T cell priming results in the formation of predysfunctional CTLs. Our model implies that predysfunctional CTLs are formed during priming and that the remedy for CTL dysfunction is to provide "help" signals for generation of optimal CTL effectors. We substantiate that this may be achieved by engaging CD4+ T cells in new CD8+ T cell priming, or by combined PD-1 blocking and CD27 agonism with available immunotherapeutic antibodies.

Investigating the concordance in molecular subtypes of primary colorectal tumors and their matched synchronous liver metastasis.

To date, no systematic analyses are available assessing concordance of molecular classifications between primary tumors (PT) and matched liver metastases (LM) of metastatic colorectal cancer (mCRC). We investigated concordance between PT and LM for four clinically relevant CRC gene signatures. Twenty-seven fresh and 55 formalin-fixed paraffin-embedded pairs of PT and synchronous LM of untreated mCRC patients were retrospectively collected and classified according to the MSI-like, BRAF-like, TGFB activated-like and the Consensus Molecular Subtypes (CMS) classification. We investigated classification concordance between PT and LM and association of TGFBa-like and CMS classification with overall survival. Fifty-one successfully profiled matched pairs were used for analyses. PT and matched LM were highly concordant in terms of BRAF-like and MSI-like signatures, (90.2% and 98% concordance, respectively). In contrast, 40% to 70% of PT that were classified as mesenchymal-like, based on the CMS and the TGFBa-like signature, respectively, lost this phenotype in their matched LM (60.8% and 76.5% concordance, respectively). This molecular switch was independent of the microenvironment composition. In addition, the significant change in subtypes was observed also by using methods developed to detect cancer cell-intrinsic subtypes. More importantly, the molecular switch did not influence the survival. PT classified as mesenchymal had worse survival as compared to nonmesenchymal PT (CMS4 vs CMS2, hazard ratio [HR] = 5.2, 95% CI = 1.5-18.5, P = .0048; TGFBa-like vs TGFBi-like, HR = 2.5, 95% CI = 1.1-5.6, P = .028). The same was not true for LM. Our study highlights that the origin of the tissue may have major consequences for precision medicine in mCRC.

Intervening Effect of Promoting Lung and Resolving Phlegm Method on Mouse Model Combining Disease and Syndrome of Human Coronavirus Pneumonia with Cold-dampness Pestilence Attacking Lung / 中国实验方剂学杂志

Objective:To observe the therapeutic effect of Kesuting syrups and Keqing capsules, which have the function of promoting lung and resolving phlegm, on a mouse model combining disease and syndrome of human coronavirus pneumonia with cold-dampness pestilence attacking lung. Method:The therapeutic effects of Kesuting syrups (the doses of 22, 11 mL·kg-1) and Keqing capsules (the doses of 1.155, 0.577 5 g·kg-1) on this model were evaluated by the inflammatory changes of lung tissue, the expression of viral nucleic acid, the contents of inflammatory factors [interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α and interferon-γ (IFN-γ)], and the percentages of immune cells in peripheral blood (CD4+ T cells, CD8+ T cells and B cells). Result:Compared with the model group, high- and low-dose groups of Keqing capsules and Kesuting syrups could significantly reduce the inflammatory damage in the lung tissues of mice, Keqing capsules could significantly increase the percentages of CD4+ T cells, CD8+ T cells and B cells in peripheral blood, Keqing capsules and Kesuting syrups could reduce the expression levels of IL-6, IL-10, TNF-α and IFN-γ, inhibit the viral load in lung tissue, as well as improve the pathogenic manifestations of lung tissue. Conclusion:As the first-line drugs for novel coronavirus pneumonia, Keqing capsules and Kesuting syrups have significant therapeutic effect on the mouse model combining disease and syndrome of human coronavirus pneumonia with cold-dampness pestilence attacking lung, and the mechanism may be related to regulating immune function and reducing cytokine storm.

Research progress of pulmonary tuberculosis and COPD / 中国医师杂志

Chronic obstructive pulmonary disease (COPD) complicated with pulmonary tuberculosis (PTB) is becoming more and more common. The coexistence of two diseases brings difficulty to the control of the disease. Smoking, biofuel exposure, vitamin D deficiency and diabetes may be common risk factors for both diseases. Complementary prevention and control strategies can be designed for the above risk factors. This article contains review with tuberculosis as a risk factor for COPD, COPD combined with tuberculosis, and the prevention strategies for both diseases.

Effects of Combined Infusion of Mesenchymal Stem Cells and Endothelial Progenitor Cells on Lung Injury after Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of combined infusion of mesenchymal stem cells (MSC) and endothelial progenitor cells (EPC) on lung injury after hematopoietic stem cell transplantation (HSCT).@*METHODS@#The experiment was divided into normal control group, irradiation group, bone marrow cell transplantation group (BMT group), BMT+EPC group, BMT+MSC group and BMT+EPC+MSC group. The model of HSCT was established, on the 30th day after transplantation, the mice were sacrificed. Then lung tissue was taken for testing. The mRNA expression levels of VEGF, IL-18, IL-12b were detected by RT-PCR, and protein expression level of NLRP3 was detected by Western blot. The expression of MPO and CD146 was observed by immunohistochemistry assay.@*RESULTS@#The expression level of VEGF gene in BMT+EPC+MSC group was significantly higher than that in other groups (P＜0.01). The expression level of IL-18 and IL-12b gene was the highest in BMT group and the lowest in BMT+EPC+MSC group, and the difference was statistically significant (P＜0.05). HSCT could increase the expression of NLRP3 protein, and the BMT+EPC+MSC could significantly reduce the level of NLRP3 protein in lung cells, tending to normal. Compared with normal tissues, the BMT+EPC+MSC could improve the lung tissue structure more effectively, the expression of MPO positive cells was lower, and the expression of VEGF positive cells was higher.@*CONCLUSIONS@#The combined infusion of MSC and EPC can promote capillary regeneration, alleviate inflammation and promote lung repair after HSCT, which is superior to single EPC or MSC infusion.