The objectification of facial diagnosis has been developed through recent years and has become a multidisciplinary research topic.However,many studies are still limited to the adjustment of algorithms and the design of data collection environment and equipments,few studies focus on facial diagnosis zoning.The purpose of this paper is to discuss the problems in the current research literature on machine learning-based intelligent TCM facial diagnosis zoning to build a foundation for subsequent related research.The study uses bibliometric methods and text analysis to clarify and analyze the current intelligent TCM facial diagnosis zoning methods,which mainly include facial feature point-based,facial feature block-based and complete face-based method;then by analyzing the influencing factors of facial diagnosis zoning research and summarizing the common machine learning algorithms,the advantages and disadvantages of different machine learning algorithms and the corresponding common facial diagnosis zoning methods are obtained;Finally,we discuss three aspects of the current phase of facial diagnosis zoning research:dataset construction,advantages of deep learning,and embodiment of facial diagnosis theory.

N1-methyladenosine(m1A)RNA methylation is critical for regulating mRNA translation;however,its role in the development,progression,and immunotherapy response of head and neck squamous cell carcinoma(HNSCC)remains largely unknown.Using Tgfbr1 and Pten conditional knockout(2cKO)mice,we found the neoplastic transformation of oral mucosa was accompanied by increased m1A modification levels.Analysis of m1A-associated genes identified TRMT61A as a key m1A writer linked to cancer progression and poor prognosis.Mechanistically,TRMT61A-mediated tRNA-m1A modification promotes MYC protein synthesis,upregulating programmed death-ligand 1(PD-L1)expression.Moreover,m1A modification levels were also elevated in tumors treated with oncolytic herpes simplex virus(oHSV),contributing to reactive PD-L1 upregulation.Therapeutic m1A inhibition sustained oHSV-induced antitumor immunity and reduced tumor growth,representing a promising strategy to alleviate resistance.These findings indicate that m1A inhibition can prevent immune escape after oHSV therapy by reducing PD-L1 expression,providing a mutually reinforcing combination immunotherapy approach.

Pulse recognition is an important part of the objectification and intelligence of TCM.This non-invasive and fast diagnostic method has great clinical value,however,data imbalance and cumbersome feature extraction are still challenging problems.The feature vectors were extracted from the one-dimensional pulse signal obtained after the Butterworth bandpass filter using the tsfresh library.And 9 columns of medical auxiliary features selected by exploratory data analysis were added.The feature filtering is performed jointly to derive 21 columns of feature vectors,which are used as input to the weighted soft voting fusion model.The data imbalance problem is solved by Borderline SMOTE algorithm.Construct a weighted soft-voting fusion model based on four types of machine learning:XGBoost,RF,LGBM,and GBDT.Eventually,the models will output specific pulse categories and demonstrate the performance by evaluating the metrics accuracy,precision,recall and F1 score.The experimental results show that the screened 21 feature vectors for a total of six types of pulse signal test sets achieve an accuracy of 90.04%in the five-fold cross-validation and take only 65.9466 seconds.It can provide a more accurate and intelligent auxiliary reference for pulse signal recognition,with lower operational complexity and higher accuracy compared to commonly used pulse recognition methods.The shorter training time also makes it more clinically useful in the recognition of multiple pulse signals.

Cancer stem cell-like cells (CSCs) play an integral role in the heterogeneity, metastasis, and treatment resistance of head and neck squamous cell carcinoma (HNSCC) due to their high tumor initiation capacity and plasticity. Here, we identified a candidate gene named LIMP-2 as a novel therapeutic target regulating HNSCC progression and CSC properties. The high expression of LIMP-2 in HNSCC patients suggested a poor prognosis and potential immunotherapy resistance. Functionally, LIMP-2 can facilitate autolysosome formation to promote autophagic flux. LIMP-2 knockdown inhibits autophagic flux and reduces the tumorigenic ability of HNSCC. Further mechanistic studies suggest that enhanced autophagy helps HNSCC maintain stemness and promotes degradation of GSK3β, which in turn facilitates nuclear translocation of β-catenin and transcription of downstream target genes. In conclusion, this study reveals LIMP-2 as a novel prospective therapeutic target for HNSCC and provides evidence for a link between autophagy, CSC, and immunotherapy resistance.
Humans ; Autophagy ; Carcinoma, Squamous Cell/pathology* ; Cell Line, Tumor ; Glycogen Synthase Kinase 3 beta/metabolism* ; Head and Neck Neoplasms/pathology* ; Neoplastic Stem Cells/pathology* ; Squamous Cell Carcinoma of Head and Neck/pathology* ; Lysosome-Associated Membrane Glycoproteins

The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death (ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment (ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin (DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels (DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful anti-tumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.

Objective:To observe the efficacy of apatinib combined with first-line chemotherapy and maintenance therapy of only apatinib in patients with extensive small-cell lung cancer.Methods:The clinical data of 56 newly diagnosed patients with extensive small-cell lung cancer in the Fifth People′s Hospital of Dalian City from January 2018 to June 2019 were retrospectively analyzed. Among them, 27 patients (experimental group) were treated with first-line chemotherapy combined with apatinib, and 29 patients (control group) were treated with first-line chemotherapy alone. In experimental group, the expression levels of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR)-2 1 day before chemotherapy and 1 day after chemotherapy were detected by enzyme linked immunosorbent assay method. Response evaluation criteria in solid tumor (RECIST) was used to evaluate the efficacy. The occurrence of adverse reaction was recorded. The patients were followed up for 12 to 24 months, and progression-free survival and 1-year survival were recorded.Results:The objective response rate, median progression-free survival time and 1-year survival rate in experimental group were significantly higher than those in control group: 81.5% (22/27) vs. 55.2% (16/29), 10.5 months vs. 8.5 months and 81.5% (22/27) vs. 55.2% (16/29), and there were statistical differences ( P<0.05); there was no statistical difference in disease control rate between 2 groups ( P>0.05). In experimental group, the patients with complete response and partial response after chemotherapy were classified as effective subgroup (22 cases), and the patients with stationary disease and progressive disease were classified as ineffective subgroup (5 cases). There were no statistical difference in VEGF and VEGFR-2 before chemotherapy between 2 subgroups ( P>0.05). The VEGF and VEGFR-2 in effective subgroup were significantly lower than those in ineffective subgroup: (275.34 ± 16.15) ng/L vs. (330.24 ± 23.21) ng/L and (89.35 ± 4.34) ng/L vs. (112.34 ± 5.45) ng/L, and there were statistical differences ( P<0.01). There were no uncontrollable adverse reactions in 2 groups, and there was no statistical difference in the incidence of adverse reactions between 2 groups ( P>0.05). Conclusions:Application of apatinib in first-line therapy and maintenance therapy for patients with extensive small-cell lung cancer can improve clinical efficacy and survival benefit with controllable adverse reactions.

Objective:To investigate the factors associated with delay in anticoagulant therapy in patients with cerebral venous sinus thrombosis (CVST) and its effect on outcome.Methods:Patients with CVST admitted to Changhai Hospital, Naval Medical University from January 2010 to August 2021 were retrospectively enrolled. Patients were divided into early anticoagulation group and late anticoagulation group by the median time interval from first symptom to initiation of anticoagulation. The modified Rankin Scale was used for outcome assessment at 90 d after onset. 0-2 scores were defined as good outcome and 3-6 were defined as poor outcome. Demographic and clinical data were compared for the early versus late anticoagulation group and for the good versus poor outcome groups. Multivariable logistic regression was used to identify independent influencing factors of delay in anticoagulation and the correlation of delay in anticoagulation with poor outcome. Results:A total of 131 patients were included, their age was 40.07±15.11 years old, and 68 (51.91%) were male. Of these, 65 patients (49.62%) were in the early anticoagulation group and 14 (10.69%) were in the poor outcome group. Compared with the late anticoagulation group, the early anticoagulation group had a significantly higher proportion of patients with seizures and brain parenchymal damage as well as higher D-dimer levels on admission, while the proportion of patients with visual impairment/papilloedema was significantly lower (all P<0.05). Compared with the good outcome group, the poor outcome group had significantly higher proportions of patients with seizures, dyskinesia, impaired consciousness, low Glasgow Coma Scale score, and brain parenchymal damage as well as higher D-dimer, total cholesterol and low density lipoprotein cholesterol levels, sites of thrombus involvement were more common in the superior sagittal and straight sinuses, and significantly lower proportions of patients with headache and lower albumin levels on admission (all P<0.05). Multivariate logistic regression analysis showed that visual impairment/papilloedema (odds ratio [ OR] 0.119, 95% confidence interval [ CI] 0.030-0.473; P=0.002) and brain parenchymal damage ( OR 1.341, 95% CI 1.042-1.727; P=0.023) were independently associated with a delay in anticoagulation treatment, and a delay in anticoagulation treatment ( OR 6.102, 95% CI 1.185-30.504; P=0.030) and D-dimer level on admission ( OR 1.299, 95% CI 1.141-1.480; P<0.001) were the independent predictors of poor outcome in patients with CVST. Conclusions:Visual impairment/papilloedema and absence of brain parenchymal damage on cranial imaging are the independent risk factors for delay in anticoagulation in patients with CVST. The delay in anticoagulation is strongly associated with the poor outcome in patients with CVST.

Objective To study the immunomodulatory effect of polysaccharides (CRPS25-Ⅱ) derived from Chroogomphus rutilus on mouse mononuclear macrophages, RAW264.7 cells. Methods RAW264.7 cells were resuspended and cultured, cell suspension was prepared. The blank control group and CRPS25-Ⅱ groups with different mass concentrations (1, 20, 40, 80 and 160 μg/ml) were set up. MTT assay was used to determine the cytotoxicity of CRPS25-Ⅱ on RAW264.7 cells. RT-PCR was used to detect the effects of CRPS25-Ⅱ on the secretion of immune regulatory factors IL-6 and TNF-α from RAW264.7 cells. Western blot was used to detect the effects of CRPS25-Ⅱ on the expression of p-P65 protein in NF-κB pathway of RAW264.7 cells. Results The results showed that CRPS25-Ⅱ (1−160 μg/ml) had no obvious cytotoxicity. CRPS25-Ⅱ (1−160 μg/ml) increased the secretion of cytokines, and thus promoted the mRNA expression of IL-6 and TNF-α. CRPS25-Ⅱ increased the phosphorylation of p-P65 protein and activated the NF-κB signaling pathway, and thus promoted the immune regulation of cells. CRPS25-Ⅱ (1−160 μg/ml) could increase the p-P65 protein, and the promoting effects of CRPS25-Ⅱshowed an upward trend in the concentration range of 1−40 μg/ml and gradually weakened in the concentration range of 40−160 μg/ml. Conclusion Polysaccharides derived from chroogomphus rutilus had no cytotoxicity to mouse macrophages, and could promote the secretion of inflammatory factors IL-6 and TNF-α and activate the NF-κB signaling pathway, thus playing an immunomodulatory role.

Objective:To investigate the effect of pidotimod in reducing pulmonary infection in patients with lung cancer undergoing chemotherapy.Methods:One hundred and twenty patients with lung cancer in the Fifth People′s Hospital of Dalian City from July 2017 to July 2018 were selected. The patients were divided into control group and pidotimod group by random digits table method with 60 cases each. The patients were treated with standard two drugs chemotherapy containing platinum drug according to the pathological type, and the patients in pidotimod group were combined with pidotimod. The number of pulmonary infections during chemotherapy, number of completed scheduled chemotherapy and adverse reaction were observed. The correlation between pulmonary infection and pidotimod was analyzed by multivariate orderly Logistic regression.Results:The incidence of pulmonary infection in pidotimod group was significantly lower than that in control group: 18.33% (11/60) vs. 40.00% (24/60), and there was statistical difference ( χ2 = 6.845, P<0.01). The rate of completed scheduled chemotherapy in pidotimod group was significantly higher than that in control group: 55.00% (33/60) vs. 36.67% (22/60), and there was statistical difference ( χ2 = 4.062, P<0.05). Multivariate orderly Logistic regression analysis result showed that pidotimod could reduce the risk of pulmonary infection ( OR = 0.210, 95% CI 0.072 to 0.606, P = 0.004), and help to complete the scheduled chemotherapy ( OR = 2.323, 95% CI 1.080 to 5.003, P = 0.031). In pidotimod group, no obvious adverse reaction related to pidotimod application was detected, and chemotherapy was not affected. Conclusions:Application of pidotimod can reduce the chance of pulmonary infection in patients with lung cancer undergoing chemotherapy and help patients complete scheduled chemotherapy.