Integrin signaling in cancer: bidirectional mechanisms and therapeutic opportunities.

Integrins are transmembrane receptors that possess distinct ligand-binding specificities in the extracellular domain and signaling properties in the cytoplasmic domain. While most integrins have a short cytoplasmic tail, integrin ß4 has a long cytoplasmic tail that can indirectly interact with the actin cytoskeleton. Additionally, 'inside-out' signals can induce integrins to adopt a high-affinity extended conformation for their appropriate ligands. These properties enable integrins to transmit bidirectional cellular signals, making it a critical regulator of various biological processes.Integrin expression and function are tightly linked to various aspects of tumor progression, including initiation, angiogenesis, cell motility, invasion, and metastasis. Certain integrins have been shown to drive tumorigenesis or amplify oncogenic signals by interacting with corresponding receptors, while others have marginal or even suppressive effects. Additionally, different α/ß subtypes of integrins can exhibit opposite effects. Integrin-mediated signaling pathways including Ras- and Rho-GTPase, TGFß, Hippo, Wnt, Notch, and sonic hedgehog (Shh) are involved in various stages of tumorigenesis. Therefore, understanding the complex regulatory mechanisms and molecular specificities of integrins are crucial to delaying cancer progression and suppressing tumorigenesis. Furthermore, the development of integrin-based therapeutics for cancer are of great importance.This review provides an overview of integrin-dependent bidirectional signaling mechanisms in cancer that can either support or oppose tumorigenesis by interacting with various signaling pathways. Finally, we focus on the future opportunities for emergent therapeutics based on integrin agonists. Video Abstract.

[Outcome indicators in randomized controlled trials on traditional Chinese medicine intervention of sepsis-induced myocardial injury in recent five years].

This study aims to analyze the outcome indicators of randomized controlled trial(RCT) on traditional Chinese medicine(TCM) intervention of sepsis-induced myocardial injury(SIMI) in recent five years, which is expected to lay a basis for the construction of core outcome set(COS) for this disease treated by TCM. To be specific, RCT on the treatment of SIMI with TCM was retrieved from 4 Chinese databases, 3 English databases, and 2 clinical trial protocol registries. The quality of the included studies was evaluated with Cochrane risk-of-bias(ROB) tool, and the outcome indicators were analyzed. Finally, 42 RCTs were included, of which 2 were clinical trial registration schemes. The study found that 42 RCTs had a high risk of bias, and reported a total of 86 indicators in "clinical effective rate, disease severity, TCM syndrome score, inflammation, myocardium, cardiac structure and hemodynamics, electrocardiogram, immunology, metabolism and liver and kidney function, and safety". Outcome indicators on myocardium had the highest emergence frequency, followed by indicators on the cardiac structure and hemodynamics. A total of 8 RCTs reported TCM syndrome scores. Further analysis suggested the following problems in the selection of outcome indicators in the RCTs on TCM intervention of SIMI: no classification of primary and secondary indicators, disregard of endpoint indicators, irrational selection of alternative indicators, neglection of TCM characteristics, no assessment of patients' immune status, and no emphasis on economic indicators and safety indicators. Therefore, according to the recommendations of the core outcome measures in effectiveness trials(COMET) working group, a COS for TCM intervention of TCM for SIMI should be developed, so as to facilitate clinical researchers to select appropriate outcome indicators, the combination of conclusions of similar clinical studies, and the promotion of TCM interventions.

AQP3-mediated H2 O2 uptake inhibits LUAD autophagy by inactivating PTEN.

It is widely accepted that redox reprogramming participates in malignant transformation of lung adenocarcinoma (LUAD). However, the source of excessive reactive oxygen species (ROS) and the downstream signaling regulatory mechanism are complicated and unintelligible. In the current study, we newly identified the aquaporin 3 (AQP3) as a LUAD oncogenic factor with capacity to transport exogenous hydrogen peroxide (H2 O2 ) and increase intracellular ROS levels. Subsequently, we demonstrated that AQP3 was necessary for the facilitated diffusion of exogenous H2 O2 in LUAD cells and that the AQP3-dependent transport of H2 O2 accelerated cell growth and inhibited rapamycin-induced autophagy. Mechanistically, AQP3-mediated H2 O2 uptake increased intracellular ROS levels to inactivate PTEN and activate the AKT/mTOR pathway to subsequently inhibit autophagy and promote proliferation in LUAD cells. Finally, we suggested that AQP3 depletion retarded subcutaneous tumorigenesis in vivo and simultaneously decreased ROS levels and promoted autophagy. These findings underscore the importance of AQP3-induced oxidative stress in malignant transformation and suggest a therapeutic target for LUAD.

Theoretical and experimental investigation of heating of biased Si avalanche photodiodes in an external circuit due to irradiation by a millisecond-pulse laser.

The interaction mechanism between external laser and Si avalanche photodiodes (Si-APDs) in practical circuits and the law of temperature increase are vital for the laser protection of Si-APDs. This study establishes the heating model of Si-APDs in an external circuit irradiated by a millisecond-pulse laser. The law of surface temperature increase in Si-APDs is determined via simulation and experiment. Results show that both laser energy density and external capacitance significantly affect the temperature increase. The theoretical simulation and experimental results are consistent, thereby validating the theoretical model.

[Expert consensus statement on Diemailing~® Kudiezi Injection in clinical practice].

Diemailing~® Kudiezi Injection( DKI) is widely used in the treatment of cerebral infarction,coronary heart disease and angina pectoris. Long-term clinical application and related research evidence showed that DKI has a good effect in improving the clinical symptoms of cardiovascular and cerebrovascular diseases. However,this injection has not been included in any clinical practice guideline. It has been found that the use of DKI is in wrong way in clinical practice in recent years. Therefore,clinical experts from the field of cardiovascular and cerebrovascular diseases nationwide are invited to compile this expert consensus in order to guide clinicians.GRADE system is used to grade the quality of evidence according to different outcomes according to degrading factors. Then it forms the recommendation or consensus suggestion through the nominal group method. The formation of expert consensus mainly considers six factors: quality of evidence,economy,efficacy,adverse reactions,patient acceptability and others. Based on these six aspects,if the evidence is sufficient,a " recommendation" supported by evidence is formed,and GRADE grid voting rule is adopted. If the evidence is insufficient,a " consensus suggestions" will be formed,using the majority voting rule. In this consensus,the clinical indications,efficacy,safety evidences and related preliminary data of DKI were systematically and comprehensively summarized in a concise and clear format,which could provide valuable reference for the clinical use of DKI. This consensus has been approved by China association of Chinese medicine which is numbered GS/CACM 202-2019.

Feasibility and clinical outcomes of rotational atherectomy for heavily-calcified side branches of complex coronary bifurcation lesions in the real-world practice of the drug-eluting stent era.

OBJECTIVES: To evaluate the outcomes of rotational atherectomy for heavily-calcified side branches of coronary bifurcation lesions. BACKGROUND: Side-branch (SB) preservation is clinically important but technically challenging in heavily-calcified non-left main true bifurcation lesions. SB rotational atherectomy (SB RA) is sometimes mandatory but the clinical outcomes are not well studied. METHODS: We retrospectively studied the outcomes of patients who underwent RA at our institute for heavily calcified, balloon-uncrossable or-undilatable SB lesions over an approximately 5-year period (January 2011 to September 2016). RESULTS: Two hundred and forty-four patients underwent main vessel only RA (SB-MV + RA group) and another 48 patients underwent SB RA (SB + MV ± RA group) for 49 side branches. The demographic variables were comparable between the two groups. However, patients underwent SB RA experienced more SB perforations and greater acute contrast-induced nephropathy (CIN). Among the SB RA patients, 30 (62.5%) underwent RA for both SB and MV (SB + MV + RA subgroup), whereas the other 18 underwent SB only RA (SB + MV-RA subgroup). Patients in these two subgroups could be completed with similar procedural, fluoroscopic durations, and contrast doses. The long-term MACE rate of SB RA was 27.1% over a mean follow-up period of 25.1 months with no differences between the two subgroups. CONCLUSIONS: RA for SB preservation in complex and heavily-calcified bifurcation lesions was feasible with high success rate and quite favorable long-term outcomes in the drug-eluting stent (DES) era. Given the higher rates in SB perforation and acute CIN, we recommend that SB RA should be conducted by experienced operators.

KEAP1 promotes anti-tumor immunity by inhibiting PD-L1 expression in NSCLC.

Immunotherapy has become a prominent first-line cancer treatment strategy. In non-small cell lung cancer (NSCLC), the expression of PD-L1 induces an immuno-suppressive effect to protect cancer cells from immune elimination, which designates PD-L1 as an important target for immunotherapy. However, little is known about the regulation mechanism and the function of PD-L1 in lung cancer. In this study, we have discovered that KEAP1 serves as an E3 ligase to promote PD-L1 ubiquitination and degradation. We found that overexpression of KEAP1 suppressed tumor growth and promoted cytotoxic T-cell activation in vivo. These results indicate the important role of KEAP1 in anti-cancer immunity. Moreover, the combination of elevated KEAP1 expression with anti-PD-L1 immunotherapy resulted in a synergistic effect on both tumor growth and cytotoxic T-cell activation. Additionally, we found that the expressions of KEAP1 and PD-L1 were associated with NSCLC prognosis. In summary, our findings shed light on the mechanism of PD-L1 degradation and how NSCLC immune escape through KEAP1-PD-L1 signaling. Our results also suggest that KEAP1 agonist might be a potential clinical drug to boost anti-tumor immunity and improve immunotherapies in NSCLC.

Features of complementary and alternative medicine use by patients with coronary artery disease in Beijing: a cross-sectional study.

BACKGROUND: Complementary and alternative medicine (CAM) is commonly used in China for the management of coronary artery disease (CAD). However, few studies have been conducted to investigate the prevalence, perceived effectiveness, types, and reasons of CAM use in patients diagnosed with CAD. METHODS: A cross-sectional study design was adopted. Questionnaires were distributed at the outpatient cardiac clinics of four tertiary-level teaching general hospitals in Beijing. Quantitative data were analyzed using Student's t-test. Categorical data were analyzed using chi-square test. Logistic regression was employed to explore factors associated with the use of CAM as well as CAM use features in Chinese medicine (CM) hospitals when significant differences were found upon comparisons. RESULTS: From May to July, 2009, a total of 600 questionnaires were distributed, and 546 patients with a diagnosis of CAD responded with valid values and were included in the present study. CAM was used by 69.1% of the patients with CAD; the majority (75.9%) of these CAM users believes that CAM is effective. "Few side effects" (49.6%) was the main reason of CAM use; whereas "doubt of effect" (61.5%) was the main reason for non-use. Patent herbal medicine (90.7%) was the most commonly used CAM type. Compared with non-CAM users, CAM users tended to be older (p < 0.01), have a longer disease duration (p = 0.02) and better current health status. In addition, CAM users had significant lower odds for emergency admission and hospitalization within the past one year. Patients with CAD from CM and WM hospitals differ in CAM use frequency, types, perceived effectiveness, as well as reasons for CAM use or non-CAM use. CONCLUSION: The present study suggested a group of significant factors which could influence the use of CAM in patients with CAD. CAM use patterns differ in patients from CM and WM hospitals.

Biological function, regulatory mechanism, and clinical application of mannose in cancer.

Studies examining the regulatory roles and clinical applications of monosaccharides other than glucose in cancer have been neglected. Mannose, a common type of monosaccharide found in human body fluids and tissues, primarily functions in protein glycosylation rather than carbohydrate metabolism. Recent research has demonstrated direct anticancer effects of mannose in vitro and in vivo. Simply supplementing cell culture medium or drinking water with mannose achieved these effects. Moreover, mannose enhances the effectiveness of current cancer treatments including chemotherapy, radiotherapy, targeted therapy, and immune therapy. Besides the advancements in basic research on the anticancer effects of mannose, recent studies have reported its application as a biomarker for cancer or in the delivery of anticancer drugs using mannose-modified drug delivery systems. This review discusses the progress made in understanding the regulatory roles of mannose in cancer progression, the mechanisms underlying its anticancer effects, and its current application in cancer diagnosis and treatment.

Danhong Injection Up-regulates miR-125b in Endothelial Exosomes and Attenuates Apoptosis in Post-Infarction Myocardium.

OBJECTIVE: To investigate the involvement of endothelial cells (ECs)-derived exosomes in the anti-apoptotic effect of Danhong Injection (DHI) and the mechanism of DHI-induced exosomal protection against postinfarction myocardial apoptosis. METHODS: A mouse permanent myocardial infarction (MI) model was established, followed by a 14-day daily treatment with DHI, DHI plus GW4869 (an exosomal inhibitor), or saline. Phosphate-buffered saline (PBS)-induced ECs-derived exosomes were isolated, analyzed by miRNA microarray and validated by droplet digital polymerase chain reaction (ddPCR). The exosomes induced by DHI (DHI-exo), PBS (PBS-exo), or DHI+GW4869 (GW-exo) were isolated and injected into the peri-infarct zone following MI. The protective effects of DHI and DHI-exo on MI hearts were measured by echocardiography, Masson's trichrome staining, and TUNEL apoptosis assay. The Western blotting and quantitative reverse transcription PCR (qRT-PCR) were used to evaluate the expression levels of miR-125b/p53-mediated pathway components, including miR-125b, p53, Bak, Bax, and caspase-3 activities. RESULTS: DHI significantly improved cardiac function and reduced infarct size in MI mice (P<0.01), which was abolished by the GW4869 intervention. DHI promoted the exosomal secretion in ECs (P<0.01). According to the results of exosomal miRNA microarray assay, 30 differentially expressed miRNAs in the DHI-exo were identified (28 up-regulated miRNAs and 2 down-regulated miRNAs). Among them, DHI significantly elevated miR-125b level in DHI-exo and DHI-treated ECs, a recognized apoptotic inhibitor impeding p53 signaling (P<0.05). Remarkably, treatment with DHI and DHI-exo attenuated apoptosis, elevated miR-125b expression level, inhibited capsase-3 activity, and down-regulated the expression levels of proapoptotic effectors (p53, Bak, and Bax) in post-MI hearts, whereas these effects were blocked by GW4869 (P<0.05 or P<0.01). CONCLUSION: DHI and DHI-induced exosomes inhibited apoptosis, promoted the miR-125b expression level, and regulated the p53 apoptotic pathway in post-infarction myocardium.

Multidirectional characterization of cellular composition and spatial architecture in human multiple primary lung cancers.

Multiple primary lung cancers (MPLCs) pose diagnostic and therapeutic challenges in clinic. Here, we orchestrated the cellular and spatial architecture of MPLCs by combining single-cell RNA-sequencing and spatial transcriptomics. Notably, we identified a previously undescribed sub-population of epithelial cells termed as CLDN2+ alveolar type II (AT2) which was specifically enriched in MPLCs. This subtype was observed to possess a relatively stationary state, play a critical role in cellular communication, aggregate spatially in tumor tissues, and dominate the malignant histopathological patterns. The CLDN2 protein expression can help distinguish MPLCs from intrapulmonary metastasis and solitary lung cancer. Moreover, a cell surface receptor-TNFRSF18/GITR was highly expressed in T cells of MPLCs, suggesting TNFRSF18 as one potential immunotherapeutic target in MPLCs. Meanwhile, high inter-lesion heterogeneity was observed in MPLCs. These findings will provide insights into diagnostic biomarkers and therapeutic targets and advance our understanding of the cellular and spatial architecture of MPLCs.

A Study of Prognosis, Outcome, and Changing Tendency of Hospitalized AMI Patients in Beijing Third-Grade A-Level Traditional Chinese Medicine Hospitals from 1999 to 2008.

Objectives. To survey and analyse the prognosis, outcome, and changing tendency of the Acute Myocardial Infarction (AMI) patients in Beijing third-grade A-level Traditional Chinese Medicine (TCM) hospitals. Methods. We collected the clinical datum of hospitalized AMI patients in Beijing 6 TCM hospitals from January 1999 to December 2008 and then analysed the clinical datum. Results. (1) The mean age of patients had showed a slowly rising tendency during this ten years. The patients who had previous history of cerebrovascular diseasea and multiple comorbidities had increased year by year. (2) The rate of reperfusion therapy, revascularization and standardized using of drug, and usage of TCM of AMI patients presented a significant increasing tendency in these hospitals. (3) The proportion of AMI patients combined with cardiac arrhythmia and heart failure had decreased significantly. (4) The AMI mortality presented a decreasing tendency in 10 years. Conclusions. The AMI patients in Beijing TCM hospitals had their own unique clinical features, and it can improve their prognosis by combined therapy of Western Medicine and Traditional Chinese Medicine.

Traditional Chinese medicine injections with activating blood circulation, equivalent effect of anticoagulation or antiplatelet, for acute myocardial infarction: A protocol for the systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: In spite of a growing number in the use of percutaneous coronary intervention (PCI) in China, the mortality of acute myocardial infarction (AMI) has not decreased. Traditional Chinese medicine injections for Activating Blood Circulation (TCMi-ABC), equivalent effect of anticoagulation or antiplatelet, are widely used in China; however, the improvement of fatality towards AMI is unclear. Therefore, we intend to conduct a systematic review and meta-analysis to evaluate the efficacy and safety of TCMi-ABC in treatment with AMI. METHODS: Based on the "National Medical Products Administration of China," TCMi-ABC with AMI treatment indication will be selected, including Danhong injection, Sodium Tanshinone IIA Sulfonate injection, Danshen Chuanxiongqin injection, and Puerarin injection. Randomized controlled studies will be searched from as follows: PubMed, Embase, the CENTRAL in Cochrane Library, Chinese Biomedical Literature Database (SinoMed), China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang Data Knowledge Service Platform. Two researchers will work independently on literature selection, data extraction, and quality assessment. The outcomes focus on the effects of TCMi-ABC on fatality of patients with AMI in hospitalization and in the long term, the incidence of malignant arrhythmia, left ventricular ejection fraction, and adverse events. RevMan 5.4.1 software was used for mate analysis. RESULTS: This study will conduct a comprehensive literature search and provide a systematic synthesis of current published data to explore the efficacy and safety of TCMi-ABC for AMI. CONCLUSION: This study will provide high-quality evidence for treatment of AMI with TCMi-ABC in terms of efficacy and safety, which may help clinicians make a better complementary treatment schedule of patients with AMI.

Clinical Characteristics and Risk Factors of Periprocedural Myocardial Injury in Patients with Elective PCI in a TCM Hospital.

Objective: To investigate the clinical characteristics of patients with unstable angina (UA) who received elective percutaneous coronary intervention (PCI) in a traditional Chinese medicine (TCM) hospital and to analyze the related risk factors of periprocedural myocardial injury (PMI). Methods: On the basis of cross-sectional investigation, the case-control method was adopted. We retrospectively collected clinical data of patients with UA who successfully received elective PCI in Beijing Hospital of TCM from February 2017 to February 2019. Based on the occurrence of PMI, the case-control was formed. The influence of related factors on PMI occurrence was analyzed using the logistic multiple regression equation based on the parameters between the comparison groups. Results: 1. Incidence of PMI and related clinical features: Of the 265 UA patients, the incidence of PMI was 26.4%, nearly one quarter (23.4%) had old myocardial infarction, nearly half (45.3%) had previously received coronary intervention. The prevalence of patients with previous hypertension (75.8%), type 2 diabetes (57%), and high-low-density lipoprotein cholesterolemia (69.3%) exceeded 50%, more than 50% of the patients have triple-vessel disease (50.2%). 2. Features of TCM syndrome elements: The main TCM syndromes of the investigated patients are blood stasis syndrome (81.1%) and Qi deficiency syndrome (77.3%), the others include Phlegm turbidity syndrome (53.2%), Yang deficiency syndrome (50.9%), Yin deficiency syndrome (50.1%), Qi stagnation syndrome (30.1%), and coagulated cold syndrome (17.1%). 3. Factors of PMI occurrence: According to the occurrence of PMI, 265 patients were divided into PMI group (n = 70) and non-PMI group (n = 195). The comparison between groups shows that the preoperative SYNTAX score, the number of stents, and the total length of stents of the patients in the PMI group were higher than those in the non-PMI group (P < 0.05); the patients in the PMI group treated by Shen-Yuan-Dan (SYD), a Chinese medicine prescription with Qi-supplementing and blood stasis-purging, were significantly lower than those in the non-PMI group (P < 0.05). Brought these four factors (preoperative SYNTAX score, number of stents implanted, total length of implanted stents, and treated by SYD) into the binary logistic regression equation, those who were only treated by SYD have statistical significance in the equation as a protective factor (OR 0.327, 95% CI 0.117-0.916, P=0.033). Conclusion: Patients with UA who received elective PCI in TCM institutions may have clinical characteristics including multiple accompanying diseases and high stenosis coronary artery, in which the incidence of poor blood glucose control and high rate of three-vessel coronary disease are particularly significant. The TCM syndromes are mainly Qi deficiency and blood stasis syndromes. The decrease of PMI may be attributed to the application of SYD in the real world. This trial is registered at ChiCTR2100043465.

A randomized, placebo-controlled, double-blind trial to evaluate efficacy and safety of Shen-Yuan-Dan capsules, a traditional Chinese medicine, for treatment of peri-procedure myocardial injury following percutaneous coronary intervention.

BACKGROUND: Peri-procedural myocardial injury (PMI) is a common complication of percutaneous coronary intervention (PCI), which cannot be entirely avoided using available treatments. The findings of earlier research have shown that Shen-Yuan-Dan (SYD) capsules, a traditional Chinese medicine, can potentially alleviating PMI. This study aimed to confirm further this hypothesis in a rigorous, well-designed randomized controlled study. METHODS: Our clinical trial was randomized, double-blinded, and placebo-controlled. A total of 181 patients with unstable angina (UA) undergoing elective PCI were randomized to pretreatment with SYD or a placebo under the basis of conventional treatment; 87 patients were pretreated with SYD (4 capsules, 3 times a day, with a further 4 capsules 2 h before PCI) 3 days before the procedure, and 94 patients were given a placebo. No patients received reloading statins before PCI, and SYD or placebo was maintained for 1 month after PCI. The primary endpoint was the incidence of PMI. The secondary endpoint was calculating the incidence rate of all 30-day major adverse cardiovascular events (all-cause mortality, non-fatal myocardial infarction, unplanned revascularization). The safety outcomes, including abnormalities in electrocardiogram and serum biochemical examinations caused by drug use, were also tested. RESULTS: The levels of creatine kinase-myocardial band (CK-MB) in both the SYD and placebo groups were increased at 4 h and 24 h after PCI compared with before the procedure (P < 0.05). The incidence rate of PMI in the SYD group (10.3 %) was lower than that in the placebo group (34 %) (absolute difference, 23.7 % [95 % CI, 11.7-34.8 %], P < 0.01). After taking SYD, the relative risk reduction (RRR) and absolute risk reduction (ARR) were 69.7 % and 24.3 %, respectively; further, number needed to treat (NNT) was 4.2. The 30-day major adverse cardiovascular event (MACE) rate was not statistically different between the SYD and placebo groups (6.9 % vs. 9.6 %, P = 0.352). There were no abnormal situations during the trial. CONCLUSION: These findings showed that pretreatment with SYD could safely reduce the incidence rate of PMI in patients with UA undergoing elective PCI. Further study on the effects of SYD and how it can improve adverse cardiovascular events outcomes is needed.

Efficacy and safety of esophagectomy via left thoracic approach versus via right thoracic approach for middle and lower thoracic esophageal cancer: a multicenter randomized clinical trial (NST1501).

Background: Left thoracic approach (LTA) has been a favorable selection in surgical treatment for esophageal cancer (EC) patients in China before minimally invasive esophagectomy (MIE) is popular. This study aimed to demonstrate whether right thoracic approach (RTA) is superior to LTA in the surgical treatment of middle and lower thoracic esophageal squamous cell carcinoma (TESCC). Methods: Superiority clinical trial design was used for this multicenter randomized controlled two-parallel group study. Between April 2015 and December 2018, cT1b-3N0-1M0 TESCC patients from 14 centers were recruited and randomized by a central stratified block randomization program into LTA or RTA groups. All enrolled patients were followed up every three months after surgery. The software SPSS 20.0 and R 3.6.2. were used for statistical analysis. Efficacy and safety outcomes, 3-year overall survival (OS) and disease-free survival (DFS) were calculated and compared using the Kaplan-Meier method and the log-rank test. Results: A total of 861 patients without suspected upper mediastinal lymph nodes (umLN) were finally enrolled in the study after 95 ineligible patients were excluded. 833 cases (98.7%) were successfully followed up until June 1, 2020. Esophagectomies were performed via LTA in 453 cases, and via RTA in 408 cases. Compared with the LTA group, the RTA group required longer operating time (274.48±78.92 vs. 205.34±51.47 min, P<0.001); had more complications (33.8% vs. 26.3% P=0.016); harvested more lymph nodes (LNs) (23.61±10.09 vs. 21.92±10.26, P=0.015); achieved a significantly improved OS in stage IIIa patients (67.8% vs. 51.8%, P=0.022). The 3-year OS and DFS were 68.7% and 64.3% in LTA arm versus 71.3% and 63.7% in RTA arm (P=0.20; P=0.96). Conclusions: Esophagectomies via both LTA and RTA can achieve similar outcomes in middle or lower TESCC patients without suspected umLN. RTA is superior to LTA and recommended for the surgical treatment of more advanced stage TESCC due to more complete lymphadenectomy. Trial Registration: ClinicalTrials.gov NCT02448979.

Toripalimab plus chemotherapy in treatment-naïve, advanced esophageal squamous cell carcinoma (JUPITER-06): A multi-center phase 3 trial.

Platinum-based chemotherapy is the standard first-line treatment for advanced esophageal squamous cell carcinoma (ESCC). In this phase 3 study (ClinicalTrial.gov: NCT03829969), 514 patients with treatment-naïve advanced ESCC were randomized (1:1) to receive toripalimab or placebo in combination with paclitaxel plus cisplatin (TP) every 3 weeks for up to 6 cycles, followed by toripalimab or placebo maintenance. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS is observed for the toripalimab arm over the placebo arm (hazard ratio [HR] = 0.58; 95% CI, 0.46-0.74; p < 0.0001). The prespecified interim analysis of overall survival (OS) also reveals a significant OS improvement for patients treated with toripalimab plus TP over placebo plus TP (HR = 0.58; 95% CI, 0.43-0.78; p = 0.0004). The incidences of grade ≥3 treatment-emergent adverse events are similar between the two arms. Toripalimab plus TP significantly improves PFS and OS in patients with treatment-naïve, advanced ESCC, with a manageable safety profile.

[Surgical treatment of primary tracheal tumors in 63 cases].

OBJECTIVE: To summarize the experience in diagnosis and treatment of primary tracheal tumors, and to improve the life quality of patients. METHODS: Sixty-three patients with primary tracheal tumors treated in the First Affiliated Hospital of China Medical University during the past 40 years were included in this study, among them, there were 42 cases of malignant tumors and 21 cases of benign tumors. The 61 patients underwent surgery including tracheal sleeve resection (22), carinal resection and reconstruction (6), semi-carinal resection and reconstruction (6), tracheal resection for tracheal tumors (17); tracheostomy (4), tracheal resection, partial resection of the thyroid (goiter) and esophagomyotomy (1), tracheal tumor resection and vertical hemilaryngectomy with reconstruction of laryngeal ventricle and trachea by sternocleidomastoid flap (2), cervical trachea and laryngeal resection (1), and carinal scrape (2). RESULTS: Fifty-five patients had an uneventful recovery. Eight patients suffered from postoperative complications, among them 3 patients died postoperatively. CONCLUSIONS: Primary tracheal tumors often present atypical symptoms, are easily misdiagnosed and with poor prognosis. The main aim of treatment remains to remove the airway obstruction.

Characteristics and advantages of traditional Chinese medicine in the treatment of acute myocardial infarction.

OBJECTIVE: To obtain epidemiological data on Traditional Chinese Medicine (TCM) therapeutic status of acute myocardial infarction (AMI) and to determine TCM characteristics and advantages to improve the level of TCM prevention and treatment of AMI. METHODS: Clinical epidemiology methods were used to register and survey the TCM therapeutic status of hospitalized AMI patients. In 2001, the Chinese Association of Integrative Medicine surveyed the therapeutic status of 3308 AMI patients hospitalized in 30 hospitals in Beijing and Shanghai from 2000-2001. The Beijing Collaborative Study Group on Therapeutic Status of Acute Myocardial Infarction (the Study Group) then conducted a 10-year-long register survey on hospitalized AMI patients in Third-grade A-Level TCM hospitals in Beijing. After 2002, the Study Group further surveyed the treatment conditions of AMI-hospitalized patients in 10 Second-grade A-Level TCM hospitals. The therapeutic status in 8 Third-grade A-Level Western medicine hospitals was surveyed in 2001 and 2005 as a control. In 2008, in cooperation with the China Association of Chinese Medicine, the Study Group further performed a survey at 26 Third-grade A-Level TCM hospitals nation-wide. Approximately 5000 cases were investigated to obtain authoritative data on the therapeutic status of AMI patients in TCM hospitals in China. RESULTS: We found that Chinese herbal intravenous preparations may be beneficial in reducing the mortality of AMI. Major complications of AMI, such as heart failure and arrhythmia, were significantly less during the 10-year survey period. The mortality of hospitalized AMI patients showed a decline. TCM treatment was helpful for AMI patients in improving their quality of life. Ten-year dynamic monitoring showed that the ability to perform reperfusion and to use drugs appropriately, as well as an effort to carry out the Clinical Guidelines has made great progress in TCM hospitals. However, TCM hospitals still have some problems in treating AMI, including a lack of standardized TCM syndrome diagnosis, the need for syndrome differentiation and treatment standardization, and clinical skills in reperfusion and standardized drug treatment still need to be further improved. Compared with AMI patients in Western medicine hospitals during the same period, those in TCM hospitals had the following characteristics: they were admitted to hospital later; they were older when they had a heart attack; there were more females, they had more problems in their medical history, and they had more concomitant illnesses and complications. Therefore, the demographic baseline data were significantly different between AMI patients in TCM hospitals and those in Western medicine hospitals. This indicated that patients in TCM hospitals were more critical than those in Western medicine hospitals. CONCLUSIONS: TCM has special advantages in treating AMI. TCM hospitals are making continuous progress in standardized treatment of AMI, but further improvement is still required. AMI patients in TCM hospitals have some special characteristics, and their condition may be more critical. Further clinical research on TCM treatment of AMI is required.

The double-edged roles of ROS in cancer prevention and therapy.

Reactive oxygen species (ROS) serve as cell signaling molecules generated in oxidative metabolism and are associated with a number of human diseases. The reprogramming of redox metabolism induces abnormal accumulation of ROS in cancer cells. It has been widely accepted that ROS play opposite roles in tumor growth, metastasis and apoptosis according to their different distributions, concentrations and durations in specific subcellular structures. These double-edged roles in cancer progression include the ROS-dependent malignant transformation and the oxidative stress-induced cell death. In this review, we summarize the notable literatures on ROS generation and scavenging, and discuss the related signal transduction networks and corresponding anticancer therapies. There is no doubt that an improved understanding of the sophisticated mechanism of redox biology is imperative to conquer cancer.