Expression of CCL2 signaling pathway genes in patients with periodontitis and atherosclerosis.

OBJECTIVE: Periodontitis and atherosclerosis are chronic inflammatory diseases characterized by leukocyte infiltration. We investigated the expression of CCL4, CCR5, c-Jun, c-Fos, NF-κB, and CCL2 as well as the possible mechanism involved in the regulation of CCL2 in human periodontitis tissues and atherosclerotic aorta based on previous research on the CCL4/CCR5/c-Jun and c-Fos/CCL2 pathway leading to CCL2 expression in collagen-induced arthritis (CIA) rat. METHODS: Sixty-five volunteers were recruited and the condition of their gingiva and coronary arteries were assessed. The subjects were divided into four groups: healthy control, chronic periodontitis (CP), coronary artery diseases (CAD), and noncoronary artery diseases (non-CAD). Total RNA was isolated from gingiva in periodontitis patients and control populations and from the aorta in patients with and without CAD. PCR was used to examine CCL4, CCR5, c-Jun, c-Fos, NF-κB, and CCL2 levels. The production of CCL2 in the gingiva and aorta was analyzed by immunostaining. RESULTS: PCR revealed that CCL4, CCR5, and CCL2 mRNA levels were increased in CP patients' gingivae and aortas from coronary artery bypass grafting (CABG) patients. Marked c-Jun, c-Fos, and NF-κB gene productions were detected in CP patients' gingivae but did not show statistical differences between the CAD and non-CAD groups. Stronger immunoreactivity against CCL2 was observed in periodontitis gingiva and aorta from CABG patients. CONCLUSIONS: Our findings suggest that the CCL4/CCR5/c-Jun and c-Fos/CCL2 pathways may be involved in CCL2 expression in periodontitis. CCL4, CCR5, and CCL2 might act as possible nodes to link the presence of periodontitis and atherosclerosis.

Integrated analysis of single-cell and bulk RNA-sequencing reveals a novel signature based on NK cell marker genes to predict prognosis and immunotherapy response in gastric cancer.

Natural killer (NK) cells play essential roles in the tumor development, diagnosis, and prognosis of tumors. In this study, we aimed to establish a reliable signature based on marker genes in NK cells, thus providing a new perspective for assessing immunotherapy and the prognosis of patients with gastric cancer (GC). We analyzed a total of 1560 samples retrieved from the public database. We performed a comprehensive analysis of single-cell RNA-sequencing (scRNA-seq) data of gastric cancer and identified 377 marker genes for NK cells. By performing Cox regression analysis, we established a 12-gene NK cell-associated signature (NKCAS) for the Cancer Genome Atlas (TCGA) cohort, that assigned GC patients into a low-risk group (LRG) or a high-risk group (HRG). In the TCGA cohort, the areas under curve (AUC) value were 0.73, 0.81, and 0.80 at 1, 3, and 5 years. External validation of the predictive ability for the signature was then validated in the Gene Expression Omnibus (GEO) cohorts (GSE84437). The expression levels of signature genes were measured and validated in GC cell lines by real-time PCR. Moreover, NKCAS was identified as an independent prognostic factor by multivariate analysis. We combined this with a variety of clinicopathological characteristics (age, M stage, and tumor grade) to construct a nomogram to predict the survival outcomes of patients. Moreover, the LRG showed higher immune cell infiltration, especially CD8+ T cells and NK cells. The risk score was negatively associated with inflammatory activities. Importantly, analysis of the independent immunotherapy cohort showed that the LRG had a better prognosis and immunotherapy response when compared with the HRG. The identification of NK cell marker genes in this study suggests potential therapeutic targets. Additionally, the developed predictive signatures and nomograms may aid in the clinical management of GC.

Predictive value of TCM tongue characteristics for chemotherapy-induced myelosuppression in patients with lung cancer.

This study aimed to investigate the clinical predictors, including traditional Chinese medicine tongue characteristics and other clinical parameters for chemotherapy-induced myelosuppression (CIM), and then to develop a clinical prediction model and construct a nomogram. A total of 103 patients with lung cancer were prospectively enrolled in this study. All of them were scheduled to receive first-line chemotherapy regimens. Participants were randomly assigned to either the training group (n = 52) or the test group (n = 51). Tongue characteristics and clinical parameters were collected before the start of chemotherapy, and then the incidence of myelosuppression was assessed after treatment. We used univariate logistic regression analysis to identify the risk predictors for assessing the incidence of CIM. Moreover, we developed a predictive model and a nomogram using multivariate logistic regression analysis. Finally, we evaluated the predictive performance of the model by examining the area under the curve value of the receiver operating characteristic, calibration curve, and decision curve analysis. As a result, a total of 3 independent predictors were found to be associated with the CIM in multivariate regression analysis: the fat tongue (OR = 3.67), Karnofsky performance status score (OR = 0.11), and the number of high-toxic drugs in chemotherapy regimens (OR = 4.78). Then a model was constructed using these 3 predictors and it exhibited a robust predictive performance with an area under the curve of 0.82 and the consistent calibration curves. Besides, the decision curve analysis results suggested that applying this predictive model can result in more net clinical benefit for patients. We established a traditional Chinese medicine prediction model based on the tongue characteristics and clinical parameters, which could serve as a useful tool for assessing the risk of CIM.

Transcriptome sequencing reveals novel biomarkers and immune cell infiltration in esophageal tumorigenesis.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide, and its development comprises a multistep process from intraepithelial neoplasia (IN) to carcinoma (CA). However, the critical regulators and underlying molecular mechanisms remain largely unknown. AIM: To explore the genes and infiltrating immune cells in the microenvironment that are associated with the multistage progression of ESCC to facilitate diagnosis and early intervention. METHODS: A mouse model mimicking the multistage development of ESCC was established by providing warter containing 4-nitroquinoline 1-oxide (4NQO) to C57BL/6 mice. Moreover, we established a control group without 4NQO treatment of mice. Then, transcriptome sequencing was performed for esophageal tissues from patients with different pathological statuses, including low-grade IN (LGIN), high-grade IN (HGIN), and CA, and controlled normal tissue (NOR) samples. Differentially expressed genes (DEGs) were identified in the LGIN, HGIN, and CA groups, and the biological functions of the DEGs were analyzed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The CIBERSORT algorithm was used to detect the pattern of immune cell infiltration. Immunohistochemistry (IHC) was also conducted to validate our results. Finally, the Luminex multiplex cytokine analysis was utilized to measure the serum cytokine levels in the mice. RESULTS: Compared with those in the NOR group, a total of 681541, and 840 DEGs were obtained in the LGIN, HGIN, and CA groups, respectively. Using the intersection of the three sets of DEGs, we identified 86 genes as key genes involved in the development of ESCC. Enrichment analysis revealed that these genes were enriched mainly in the keratinization, epidermal cell differentiation, and interleukin (IL)-17 signaling pathways. CIBERSORT analysis revealed that, compared with those in the NOR group, M0 and M1 macrophages in the 4NQO group showed stronger infiltration, which was validated by IHC. Serum cytokine analysis revealed that, compared with those in the NOR group, IL-1ß and IL-6 were upregulated, while IL-10 was downregulated in the LGIN, HGIN, and CA groups. Moreover, the expression of the representative key genes, such as S100a8 and Krt6b, was verified in external human samples, and the results of immunohistochemical staining were consistent with the findings in mice. CONCLUSION: We identified a set of key genes represented by S100a8 and Krt6b and investigated their potential biological functions. In addition, we found that macrophage infiltration and abnormal alterations in the levels of inflammation-associated cytokines, such as IL-1ß, IL-6, and IL-10, in the peripheral blood may be closely associated with the development of ESCC.

Splenic monocytes mediate inflammatory response and exacerbate myocardial ischemia/reperfusion injury in a mitochondrial cell-free DNA-TLR9-NLRP3-dependent fashion.

The spleen contributes importantly to myocardial ischemia/reperfusion (MI/R) injury. Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) recruits inflammasomes, initiating inflammatory responses and mediating tissue injury. We hypothesize that myocardial cell-free DNA (cfDNA) activates the splenic NLRP3 inflammasome during early reperfusion, increases systemic inflammatory response, and exacerbates myocardial infarct. Mice were subjected to 40 min of ischemia followed by 0, 1, 5, or 15 min, or 24 h of reperfusion. Splenic leukocyte adoptive transfer was performed by injecting isolated splenocytes to mice with splenectomy performed prior to left coronary artery occlusion. CY-09 (4 mg/kg) was administered 5 min before reperfusion. During post-ischemic reperfusion, splenic protein levels of NLRP3, cleaved caspase-1, and interleukin-1ß (IL-1ß) were significantly elevated and peaked (2.1 ± 0.2-, 3.4 ± 0.4-, and 3.2 ± 0.2-fold increase respectively, p < 0.05) within 5 min of reperfusion. In myocardial tissue, NLRP3 was not upregulated until 24 h after reperfusion. Suppression by CY09, a specific NLRP3 inflammasome inhibitor, or deficiency of NLRP3 significantly reduced myocardial infarct size (17.3% ± 4.2% and 33.2% ± 1.8% decrease respectively, p < 0.01). Adoptive transfer of NLRP3-/- splenocytes to WT mice significantly decreased infarct size compared to transfer of WT splenocytes (19.1% ± 2.8% decrease, p < 0.0001). NLRP3 was mainly activated at 5 min after reperfusion in CD11b+ and LY6G- splenocytes, which significantly increased during reperfusion (24.8% ± 0.7% vs.14.3% ± 0.6%, p < 0.0001). The circulating cfDNA level significantly increased in patients undergoing cardiopulmonary bypass (CPB) (43.3 ± 5.3 ng/mL, compared to pre-CPB 23.8 ± 3.5 ng/mL, p < 0.01). Mitochondrial cfDNA (mt-cfDNA) contributed to NLRP3 activation in macrophages (2.1 ± 0.2-fold increase, p < 0.01), which was inhibited by a Toll-like receptor 9(TLR9) inhibitor. The NLRP3 inflammasome in splenic monocytes is activated and mediates the inflammatory response shortly after reperfusion onset, exacerbating MI/R injury in mt-cfDNA/TLR9-dependent fashion. The schema reveals splenic NLRP3 mediates the inflammatory response in macrophages and exacerbates MI/R in a mitochondrial cfDNA/ TLR9-dependent fashion.

Reversible Solid-Solid Conversion of Sulfurized Polyacrylonitrile Cathodes in Lithium-Sulfur Batteries by Weakly Solvating Ether Electrolytes.

Despite carbonate electrolytes exhibiting good stability to sulfurized polyacrylonitrile (SPAN), their chemical incompatibility with lithium (Li) metal anode leads to poor electrochemical performance of Li||SPAN full cells. While the SPAN employs conventional ether electrolytes that suffer from the shuttle effect, leading to rapid capacity fading. Here, we tailor a dilute electrolyte based on a low solvating power ether solvent that is both compatible with SPAN and Li metal. Unlike conventional ether electrolytes, the weakly solvating ether electrolyte enables SPAN to undergo reversibly "solid-solid" conversion. It features an anion-rich solvation structure that allows for the formation of a robust cathode electrolyte interphase on the SPAN, effectively blocking the dissolution of polysulfides into the bulk electrolyte and avoiding the shuttle effect. What's more, the unique electrolyte chemistry endowed Li ions with fast electroplating kinetics and induced high reversibility Li deposition/stripping process from 25 °C to -40 °C. Based on tailored electrolyte, Li||SPAN full cells matched with high loading SPAN cathodes (≈3.6 mAh cm-2 ) and 50 µm Li foil can operate stably over a wide range of temperatures. Additionally, Li||SPAN pouch cell under lean electrolyte and 5 % excess Li conditions can continuously operate stably for over a month.

Electroacupuncture for the treatment of cancer pain: a systematic review and meta-analysis of randomized clinical trials.

Objective: This paper aims to review the current evidence on electroacupuncture as an effective and safe therapy for cancer pain management. Methods: Five databases were searched from their inception through November 11, 2022. Only the randomized controlled trials that meet the eligibility criteria were finally included in the study. Literature screening and data extraction were performed independently by two reviewers, and RevMan 5.3 used for meta-analysis. Results: A total of 17 RCTs met our inclusion criteria. We used 8 indicators to estimate the meta-analysis results, most of which proved statistically significant, including VAS scores, NRS scores, and KPS scores. To be specific, VAS scores (MD = -1.41, 95% CI: -2.42 to -0.41, P = 0.006) and NRS scores (MD = -1.19, 95% CI: -1.72 to -0.66, P < 0.0001) were significantly lower in the treatment group compared to the control group. The treatment group's KPS scores (MD = 5.48, 95% CI: 3.27 to 7.69, P < 0.00001) were higher than those of the control group. Also, in the treatment group, the number of burst pain (MD = -2.66, 95% CI: -3.32 to -1.99, P < 0.00001) and side effect rates (RR = 0.51, 95% CI: 0.39 to 0.67, P < 0.00001) greatly reduced, while the response rate (RR = 1.17, 95% CI: 1.09 to 1.26, P < 0.0001) significantly increased compared to the control group. Conclusion: This study demonstrates the advantages of electroacupuncture in the treatment of cancer pain. Meanwhile, rigorous RCTs should be designed and conducted in the future to further demonstrate the exact efficacy of electroacupuncture. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022376148.

m6A methylation: a process reshaping the tumour immune microenvironment and regulating immune evasion.

N6-methyladenosine (m6A) methylation is the most universal internal modification in eukaryotic mRNA. With elaborate functions executed by m6A writers, erasers, and readers, m6A modulation is involved in myriad physiological and pathological processes. Extensive studies have demonstrated m6A modulation in diverse tumours, with effects on tumorigenesis, metastasis, and resistance. Recent evidence has revealed an emerging role of m6A modulation in tumour immunoregulation, and divergent m6A methylation patterns have been revealed in the tumour microenvironment. To depict the regulatory role of m6A methylation in the tumour immune microenvironment (TIME) and its effect on immune evasion, this review focuses on the TIME, which is characterized by hypoxia, metabolic reprogramming, acidity, and immunosuppression, and outlines the m6A-regulated TIME and immune evasion under divergent stimuli. Furthermore, m6A modulation patterns in anti-tumour immune cells are summarized.

Diagnostic efficacy of high-frequency ultrasound and X-ray contrast enema in colonic strictures after necrotizing enterocolitis: a retrospective study.

OBJECTIVE: To compare the efficacy of high-frequency ultrasound and X-ray contrast enema in the diagnosis of colonic strictures after necrotizing enterocolitis. METHODS: This study included pediatric patients who developed progressive abdominal distension or constipation after conservative treatment for necrotizing enterocolitis at our hospital between June 2012 and April 2020. All patients had high-frequency ultrasounds and X-ray contrast enema, and we used surgery, pathology, and telephone return visits as the reference standard. Patients with colonic strictures were confirmed by surgery and pathology. A patient was considered without colonic stricture if no stricture was reported or did not have related symptoms during telephone return visits. The areas under the Receiver operating characteristic (ROC) curves were used as evaluation indexes to compare the differential efficacy of high-frequency ultrasound and X-ray contrast enema. RESULTS: A total of 81 patients have been included in this study. Among them, 49 patients were diagnosed with colonic strictures after necrotizing enterocolitis. The AUCs for high-frequency ultrasound and X-ray contrast enema were 0.990 vs 0.938, respectively (p > 0.05). CONCLUSION: The diagnostic efficacy of high-frequency ultrasound was similar to that of X-ray contrast enema, furthermore this study also demonstrates the benefits of using high-frequency ultrasound to identify colonic strictures after necrotizing enterocolitis.

The interactions between traditional Chinese medicine and gut microbiota: Global research status and trends.

Background: There is a crosstalk between traditional Chinese medicine (TCM) and gut microbiota (GM), many articles have studied and discussed the relationship between the two. The purpose of this study is to use bibliometric analysis to explore the research status and development trends of the TCM/GM research, identify and analyze the highly cited papers relating to the TCM/GM. Methods: A literature search regarding TCM/GM publications from 2004 to 2021 was undertaken on August 13, 2022. The main information (full record and cited references) of publications was extracted from the Science Citation Index Expanded (SCI-E) of Web of Science Core Collection (WoSCC). The Bibliometrix of R package, CiteSpace and VOSviewer were used for bibliometric analysis. Results: A total of 830 papers were included. The publication years of papers were from 2004 to 2021. The number of papers had increased rapidly since 2018. China had the most publications and made most contributions to this field. Nanjing University of Chinese Medicine and Beijing University of Chinese Medicine were in the leading productive position in TCM/GM research, Chinese Academy of Chinese Medical Sciences had the highest total citations (TC). Duan Jin-ao from Nanjing University of Chinese Medicine had the largest number of publications, and Tong Xiao-lin from China Academy of Chinese Medical Sciences had the most TC. The Journal of Ethnopharmacology had the most published papers and the most TC. The main themes in TCM/GM included the role of GM in TCM treatment of glucolipid metabolism diseases and lower gastrointestinal diseases; the mechanism of interactions between GM and TCM to treat diseases; the links between TCM/GM and metabolism; and the relationship between GM and oral bioavailability of TCM. Conclusion: This study gained insight into the research status, hotspots and trends of global TCM/GM research, identified the most cited articles in TCM/GM and analyzed their characteristics, which may inform clinical researchers and practitioners' future directions.

Global research trends on the links between gut microbiota and cancer immunotherapy: A bibliometric analysis (2012-2021).

Background: There is a crosstalk between gut microbiota (GM) and cancer immunotherapy (CI). The purpose of this study is to use bibliometric analysis to identify the highly cited papers relating to GM/CI and explore the research status and development trends of the GM/CI research. Methods: A literature search regarding GM/CI publications from 2012 to 2021 was undertaken on July 4, 2022. The article titles, journals, authors, institutions, countries, total citations, keywords, and other information were extracted from the Science Citation Index Expanded (SCIE) of Web of Science Core Collection (WoSCC). The Bibliometrix of R package and VOSviewer were used for bibliometric analysis. Results: A total of 665 papers were extracted. The number of papers has increased rapidly over the past decade, especially after 2018. The United States and China had the most publications and made great contributions to this field. Th5e Univ Texas MD Anderson Canc Ctr and Univ Paris Saclay were absolutely in the leading position in GM/CI. The most influential authors were Zitvogel L and Routy B. Frontiers in Immunology had the most publications and Science had the most total citations. Historical direct citation analysis explained the historical evolution in GM/CI. Highly cited papers and high-frequency keywords illustrated the current status and trends of GM/CI. Four clusters were identified and the important topics included the role of GM and antibiotics in CI, the methods of targeting GM to improve CI outcomes, the mechanism by which GM affects CI and the application of ICIs in melanoma. "Tumor microbiome", "proton pump inhibitors" and "prognosis" may be the new focus of attention in the next few years. Conclusion: This study filtered global publications on GM/CI correlation and analyzed their bibliometric characteristics, identified the most cited papers in GM/CI, and gained insight into the status, hotspots and trends of global GM/CI research, which may inform researchers and practitioners of future directions.

Systemic Therapy for Hepatocellular Carcinoma: Chinese Consensus-Based Interdisciplinary Expert Statements.

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and causes many cancer-related deaths worldwide; in China, it is the second most prevalent cause of cancer deaths. Most patients are diagnosed clinically with advanced stage disease. Summary: For more than a decade, sorafenib, a small-molecular-weight tyrosine kinase inhibitor (SMW-TKI) was the only molecular targeted drug available with a survival benefit for the treatment of advanced HCC. With the development of novel TKIs and immune checkpoint inhibitors for advanced HCC, the management of patients has been greatly improved. However, though angiogenic-based targeted therapy remains the backbone for the systemic treatment of HCC, to date, no Chinese guidelines for novel molecular targeted therapies to treat advanced HCC have been established. Our interdisciplinary panel on the treatment of advanced HCC comprising hepatologists, hepatobiliary surgeons, oncologists, radiologists, pathologists, orthopedic surgeons, traditional Chinese medicine physicians, and interventional radiologists has reviewed the literature in order to develop updated treatment regimens. Key Messages: Panel consensus statements for the appropriate use of new molecular -targeted drugs including doses, combination therapies, adverse reaction management as well as efficacy evaluation, and predictions for treatment of advanced HCC with evidence levels based on published data are presented, thereby providing an overview of molecular targeted therapies for healthcare professionals.

Rewiring of the Endocrine Network in Triple-Negative Breast Cancer.

The immunohistochemical definition of estrogen/progesterone receptors dictates endocrine feasibility in the treatment course of breast cancer. Characterized by the deficiency of estrogen receptor α, ERα-negative breast cancers are dissociated from any endocrine regimens in the routine clinical setting, triple-negative breast cancer in particular. However, the stereotype was challenged by triple-negative breast cancers' retained sensitivity and vulnerability to endocrine agents. The interplay of hormone action and the carcinogenic signaling program previously underscored was gradually recognized along with the increasing investigation. In parallel, the overlooked endocrine-responsiveness in ERα-negative breast cancers attracted attention and supplied fresh insight into the therapeutic strategy in an ERα-independent manner. This review elaborates on the genomic and non-genomic steroid hormone actions and endocrine-related signals in triple-negative breast cancers attached to the hormone insensitivity label. We also shed light on the non-canonical mechanism detected in common hormone agents to showcase their pleiotropic effects.

Surface Plasmon-Enhanced Photoelectrochemical Sensor Based on Au Modified TiO2 Nanotubes.

Based on the enhanced charge separation efficiency of the one-dimensional structure and strong surface plasmon resonance (SPR) of gold, a gold modified TiO2 nanotube (Au/TiO2NTs) glucose photoelectrochemical (PEC) sensor was prepared. It could be activated by visible red light (625 nm). Under optimal conditions, the Au/TiO2NTs sensor exhibited a good sensitivity of 170.37 µA·mM-1·cm-2 in the range of 1-90 µM (R2 = 0.9993), and a detection limit of 1.3 µM (S/N = 3). Due to its high selectivity, good anti-interference ability, and long-term stability, the fabricated Au/TiO2NTs sensor provides practical detection of glucose. It is expected to be used in the construction of non-invasive PEC biosensors.

Efficacy of Wen-Luo-Tong on Peripheral Neuropathy Induced by Chemotherapy or Target Therapy: A Randomized, Double-Blinded, Placebo-Controlled Trial.

OBJECTIVE: To evaluate the efficacy of Wen-Luo-Tong Granules (WLT) local administration in the treatment of patients with peripheral neuropathy (PN) induced by chemotherapy or target therapy. METHODS: This study is a randomized, double-blinded, and placebo-controlled trial. Seventy-eight patients with PN induced by chemotherapy or target therapy were enrolled from China-Japan Friendship Hospital between July 2019 and January 2020. They were randomly assigned to WLT (39 cases) and control groups (39 cases) using a block randomization method. The WLT group received WLT (hand and foot bath) plus oral Mecobalamin for 1 week, while the control group received placebo plus oral Mecobalamin. The primary endpoint was PN grade evaluated by the National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE). The secondary endpoints included quantitative touch-detection threshold, neuropathy symptoms, Quality of Life Questionnaire-Chemotherapy Induced Peripheral Neuropathy (QLQ-CIPN20), and Quality of Life Questionnaire-Core30 (QLQ-C30). RESULTS: After treatment, the PN grade in the WLT group was significantly lower than that in the control group (1.00 ± 0.29 vs. 1.75 ± 0.68, P<0.01). The total effective rate in the WLT group was significantly higher than that in the control group (82.05% vs. 51.28%, P<0.01). Compared with the control group, the touch-detection thresholds at fingertips, neuropathy symptom score, QLQ-CIPN 20 (sensory scale, motor scale, autonomic scale, and sum score), and QLQ-C30 (physical functioning, role functioning, emotional functioning, and global health) in the WLT group significantly improved after treatment (P<0.01 or P<0.05). CONCLUSION: WLT local administration was significantly effective in the treatment of patients with PN induced by chemotherapy or target therapy. (Trial registration No. ChiCTR1900023862).

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.

A Single-Arm Phase II Study to Evaluate Efficacy and Safety of First-Line Treatment With DCVAC/LuCa, Standard of Care Chemotherapy and Shenqi Fuzheng Injection in Advanced (Stage IIIB/IV) Non-Small Cell Lung Cancer Patients.

OBJECTIVES: To evaluate the efficacy and safety of first-line treatment with a dendritic cell vaccination for lung cancer (DCVAC/LuCa), standard of care chemotherapy and Shenqi Fuzheng injection in patients with advanced (stage IIIB/IV) non-small cell lung cancer. PATIENTS AND METHODS: Patients with histologically or cytologically confirmed recurrent metastatic or advanced NSCLC (stage IIIB/IV) with wild-type epidermal growth factor receptor (EGFR) or EGFR mutation which does not confer increased tumor susceptibility to EGFR-interacting drugs were recruited. For the treatment period, the first cycle of standard of care therapy (SoC) started 2 to 14 days after the leukapheresis procedure. SoC continued 4 to 6 cycles. DCVAC/LuCa was administered from the second cycle of SoC. DCVAC/LuCa was administered in a 3-week cycle schedule (5 doses) and then in a 6-week cycle schedule. Shenqi Fuzheng injection was administered 3 days before each DCVAC/LuCa administration for a total of 14 daily doses. Patients would undergo disease evaluation by computed tomography (CT) scan every 3 months. The primary and secondary endpoint was efficacy with regard to objective response rate (ORR) and progression free survival (PFS). The safety profile was measured by: incidence, type, and severity of all adverse events (AEs), laboratory abnormalities (blood routine test, urine test, and chemical test), physical status, and vital signs. Qi insufficiency was evaluated by tongue diagnosis and questionnaire survey with "Classification and Determination of constitution in TCM." RESULTS: Twenty-three patients from 3 hospitals who received combination therapy were included. ORR was 34.8% (95% CI:16.4%-57.3%). Median duration of response was 5.51 m (95% CI:2.70-8.32). Median PFS was 10.72 m (95% CI:4.52-16.93), 1-year survival was 77.8%. mOS was 21.97 m (95% CI:13.68-30.25). There was 1 severe AE related to a history of heart disease and there were no adverse events related to DCVAC/LuCa treatment. Qi insufficiency was improved significantly (P < .0001) from 41.19 ± 14.58 before treatment to 10.52 ± 16.58 after treatment. CONCLUSION: DCVAC/LuCa, combined with standard of care chemotherapy and Shenqi Fuzheng injection exhibited good benefit in Chinese patients with recurrent metastatic or advanced (stage IIIB/IV) NSCLC, and also significantly improved Qi insufficiency constitution. There were no related adverse events with DCVAC/LuCa treatment.

Nrf2 participates in the protective effect of exogenous mitochondria against mitochondrial dysfunction in myocardial ischaemic and hypoxic injury.

OBJECTIVE: Coronary artery disease is one of the leading causes of death worldwide. Treatments including coronary artery intervention can cause complications, such as myocardial ischaemia-reperfusion injury (MIRI). Mitochondrial injury or dysfunction is a key pathology of MIRI. Mitochondrial transplantation is considered a promising therapeutic strategy for cardiac-related diseases, but its mechanism is still unclear. Nrf2 is a prominent player in supporting the structural and functional integrity of mitochondria. In our research, we focused on the effect of Nrf2 in the treatment of MIRI by mitochondrial transplantation. H9C2 cells were subjected to hypoxia/reoxygenation (H/R) and MIRI was induced in wild-type and Nrf2-/- mice by surgical ligation of the left coronary artery to elucidate the mechanism in vitro and in vivo, respectively. Exogenous mitochondria were extracted from healthy H9C2 cells and the pectoralis major and administered to H9C2 cells and mice with MIRI, respectively. Mitochondrial internalization, H9C2 cell injury or apoptosis, cardiac injury/function, mitochondrial function, morphology, mitochondrial dynamics, and the expression of components of the Nrf2 pathway were assessed. We found that exogenous mitochondria were internalized into H9C2 cardiomyocytes. Exogenous mitochondrial transplantation attenuated cardiomyocyte injury, cardiomyocyte apoptosis, and mitochondrial dysfunction. Exogenous mitochondrial transplantation increased the expression of Nrf2 and its downstream targets, attenuated cardiomyocyte injury, cardiac dysfunction, apoptosis, mitochondrial dysfunction, and mitochondrial fusion and fission imbalance, and improved mitophagy after MIRI in wild-type mice but not in Nrf2-/- mice. These results suggested that exogenous mitochondria can be internalized into cardiomyocytes and activate the Nrf2 pathway and that exogenous mitochondria improve cardiac function and ameliorate mitochondrial dysfunction via the Nrf2 pathway.

Constructing tongue coating recognition model using deep transfer learning to assist syndrome diagnosis and its potential in noninvasive ethnopharmacological evaluation.

ETHNOPHARMACOLOGICAL RELEVANCE: Tongue coating has been used as an effective signature of health in traditional Chinese medicine (TCM). The level of greasy coating closely relates to the strength of dampness or pathogenic qi in TCM theory. Previous empirical studies and our systematic review have shown the relation between greasy coating and various diseases, including gastroenteropathy, coronary heart disease, and coronavirus disease 2019 (COVID-19). However, the objective and intelligent greasy coating and related diseases recognition methods are still lacking. The construction of the artificial intelligent tongue recognition models may provide important syndrome diagnosis and efficacy evaluation methods, and contribute to the understanding of ethnopharmacological mechanisms based on TCM theory. AIM OF THE STUDY: The present study aimed to develop an artificial intelligent model for greasy tongue coating recognition and explore its application in COVID-19. MATERIALS AND METHODS: Herein, we developed greasy tongue coating recognition networks (GreasyCoatNet) using convolutional neural network technique and a relatively large (N = 1486) set of tongue images from standard devices. Tests were performed using both cross-validation procedures and a new dataset (N = 50) captured by common cameras. Besides, the accuracy and time efficiency comparisons between the GreasyCoatNet and doctors were also conducted. Finally, the model was transferred to recognize the greasy coating level of COVID-19. RESULTS: The overall accuracy in 3-level greasy coating classification with cross-validation was 88.8% and accuracy on new dataset was 82.0%, indicating that GreasyCoatNet can obtain robust greasy coating estimates from diverse datasets. In addition, we conducted user study to confirm that our GreasyCoatNet outperforms TCM practitioners, yet only consuming roughly 1% of doctors' examination time. Critically, we demonstrated that GreasyCoatNet, along with transfer learning, can construct more proper classifier of COVID-19, compared to directly training classifier on patient versus control datasets. We, therefore, derived a disease-specific deep learning network by finetuning the generic GreasyCoatNet. CONCLUSIONS: Our framework may provide an important research paradigm for differentiating tongue characteristics, diagnosing TCM syndrome, tracking disease progression, and evaluating intervention efficacy, exhibiting its unique potential in clinical applications.

Constructing Co3O4/g-C3N4 Ultra-Thin Nanosheets with Z-Scheme Charge Transfer Pathway for Efficient Photocatalytic Water Splitting.

Photocatalytic water splitting for hydrogen generation is a significant pathway for sustainable energy conversion and production. The photocatalysts with a Z-scheme water splitting charge transfer pathway is superior due to the good separation and migration ability of photoexcited charge carriers. Herein, Co3O4/g-C3N4 photocatalysts with Z-scheme charge transfer pathway were successfully constructed by an electrostatic interaction-annealing method. The as-prepared Co3O4/g-C3N4 ultra-thin nanosheets were tested and analyzed by XRD, EA, ICP, SEM, TEM, AFM, XPS, UV-Vis DRS, PL and photoelectrochemical measurements. Moreover, the influences of fabrication parameters on performance of Co3O4/g-C3N4 catalysts were investigated, and 0.5% Co3O4/g-C3N4 exhibited the optimal activity. Based on the characterization and catalytic performance, the Z-scheme charge transfer pathway of Co3O4/g-C3N4 was established and put forward. To further improve the catalytic performance of Co3O4/g-C3N4, 0.5% Pt was added as a co-catalyst. The obtained Pt/0.5% Co3O4/g-C3N4 was recyclable and remained the original catalytic water splitting performance within 20 h. The modification of Co3O4 and Pt improved the separation and migration of e- and h+, and induced the increased hydrogen evolution rate of g-C3N4.