Microwave thermochemotherapy (MTC) has been applied to treat lip squamous cell carcinoma (LSCC), but a deeper understanding of its therapeutic mechanisms and molecular biology is needed. To address this, we used single-cell transcriptomics (scRNA-seq) and spatial transcriptomics (ST) to highlight the pivotal role of tumor-associated neutrophils (TANs) among tumor-infiltrating immune cells and their therapeutic response to MTC. MNDA⁺ TANs with anti-tumor activity (N1-phenotype) are found to be abundantly infiltrated by MTC with benefit of increased blood perfusion, and these TANs are characterized by enhanced cytotoxicity, ameliorated hypoxia, and upregulated IL1B, activating T&NK cells and fibroblasts via IL1B-IL1R. In this highly anti-tumor immunogenic and hypoxia-reversed microenvironment under MTC, fibroblasts accumulated in the tumor front (TF) can recruit N1-TANs via CXCL2-CXCR2 and clear N2-TANs (pro-tumor phenotype) via CXCL12-CXCR4, which results in the aggregation of N1-TANs and extracellular matrix (ECM) deposition. In addition, we construct an N1-TANs marker, MX2, which positively correlates with better prognosis in LSCC patients, and employ deep learning techniques to predict expression of MX2 from hematoxylin-eosin (H&E)-stained images so as to conveniently guide decision making in clinical practice. Collectively, our findings demonstrate that the N1-TANs/fibroblasts defense wall formed in response to MTC effectively combat LSCC.
Humans ; Neutrophils/metabolism* ; Single-Cell Analysis ; Lip Neoplasms/genetics* ; Hyperthermia, Induced/methods* ; Microwaves/therapeutic use* ; Transcriptome ; Carcinoma, Squamous Cell/immunology* ; Tumor Microenvironment

ObjectiveTo investigate the correlation between mild cognitive impairment (MCI) and traditional Chinese medicine (TCM) body constitution types in the elderly, and to provide an evidence for the control of cognitive impairment in the elderly. MethodsThe elderly aged 65 and above who participated in the community physical examinations in a community of Changning District, Shanghai were selected as the research subjects. The cognitive function was assessed by using the Clock Drawing Test combined with the Ascertain Dementia 8-item Questionnaire (AD8), the Montreal Cognitive Assessment (MoCA) and the Mini-mental State Examination (MMSE). The diagnostic criteria for MCI was identified based on the 2018 Chinese Guidelines for the Diagnosis and Treatment of Dementia and Cognitive Disorders, along with the assessment results and clinical history information. The current investigation method was used to collect the basic information and the prevalence of chronic disease of the subjects through questionnaire inquiries. The elderly subjects’ ability to take care of themselves was evaluated based on the Elderly Self⁃Care Ability Evaluation Scale, while the TCM body constitution types were determined based on the Chinese Medicine Health Care Management Service Specification. The association of the detection rate of MCI with gender, education level, history of chronic disease and TCM body constitution types were analyzed lastly. ResultsA total of 2 351 elderly people were investigated, including 1 037 males and 1 314 females, with an average age of (74.11±6.15) years. 174 subjects, accounting for 7.40%, were identified with MCI. The highest detection rate of MCI in the elderly are those with a Qi stagnation constitution (10.8%), followed by those with a dampness-heat constitution (9.1%) and a Qi deficiency constitution (8.4%). Multivariate logistic regression analysis showed that advanced age, lower educational level, a history of tuberculosis, and TCM constitutions such as dampness-heat, Qi stagnation, and Qi deficiency were the potential risk factors for MCI. ConclusionThere is a significant association between TCM constitution types such as dampness-heat, Qi stagnation, and Qi deficiency with MCI. TCM techniques can be integrated into the health management services for the elderly population, and targeted interventions can be provided to those with imbalanced constitution types so as to reduce the risk of MCI.

Objective:To evaluate the effect of sodium sivelestat on the expression of specialized pro-resolving mediators (SPMs) synthesis enzymes in mice with lipopolysaccharide (LPS)-induced acute lung injury (ALI).Methods:Eighteen SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 3 groups ( n=6 each) using a random number table method: control group (C group), LPS-induced ALI group (ALI group), and LPS-induced ALI + sodium sivelestat group (ALI+ SV group). ALI was induced by intravenous injection of LPS 15 mg/kg through the tail vein. Sodium sivelestat 50 mg/kg was intraperitoneally injected at 1 h after LPS administration. At 12 h after LPS administration, blood samples were collected from the eyeballs for routine blood tests, and the remaining blood was processed for serum extraction. The mice were sacrificed after anesthesia, and lung tissues were collected to determine the wet/dry weight (W/D) ratio, serum concentrations of interleukin-1beta (IL-1β) and IL-10 (by enzyme-linked immunosorbent assay), expression of neutrophil elastase (NE) and SPMs synthesis enzymes 5-lipoxygenase (5-LOX), 12-lipoxygenase (12-LOX), and 15-lipoxygenase (15-LOX) in lung tissues (by Western blot) and to examine the pathological changes of lung tissues which were scored. Results:Compared with C group, the lung injury scores, W/D ratio, white blood cell counts, percentage of neutrophil, and serum IL-1β and IL-10 concentrations were significantly increased, the expression of NE was up-regulated, and the expression of 5-LOX, 12-LOX and 15-LOX was down-regulated in ALI group ( P<0.05). Compared with ALI group, the lung injury scores, W/D ratio, white blood cell counts, percentage of neutrophil, and serum IL-1β concentration were significantly decreased, the serum IL-10 concentration was increased, the expression of NE was down-regulated, and the expression of 5-LOX, 12-LOX and 15-LOX was up-regulated in ALI+ SV group ( P<0.05). Conclusions:The mechanism by which sodium sivelestat alleviates LPS-induced ALI may be related to up-regulating the expression of SPMs synthesis enzyme and promoting the resolution of pulmonary inflammation in mice.

ObjectiveTo investigate effect of conducting training of autism spectrum disorder （ASD） early screening skill on improving the ability to early identify ASD of medical staffs in primary care hospitals. MethodsIn September 2021， the training of ASD early screening skills was carried out for medical staffs from 20 primary care hospitals in Chengdu. After training， the training effect was evaluated. The numbers of referrals from primary care hospitals to superior hospitals， confirmed ASD as well as their average diagnostic age of children with ASD before and after training were used as evaluation indicators. ResultsAfter training， the number of children with suspected ASD referred by primary care hospitals was more than that before training ［（16.65±11.60） vs. （3.40±2.23）， t=5.431， P<0.01］， the number of children diagnosed with ASD was more than that before training［（6.85±4.93） vs. （2.45±1.67）， t=4.171， P<0.01］， and the differences were statistically significant. As for the diagnosed age of ASD children， after training， the average age was lower than that before training ［（34.95±11.67） vs. （42.2±14.64）， t=-2.553， P=0.019］. ConclusionTraining of ASD early screening skills for medical staffs in primary care hospitals may help to improve their ability to early screening ASD children.

Objective:To investigate the short-term efficacy of hip arthroscopy for different types of femoroacetabular impingement syndrome (FAI).Methods:A retrospective analysis was conducted of the 85 FAI patients who had been treated by hip arthroscopy at Department of Orthopaedic Surgery, General Hospital of Southern Theater Command of PLA from January 2016 to December 2018. They were 52 males and 33 females, aged from 19 to 59 years (average, 36.9 years). According to the anatomical morphology of the acetabulum and proximal femur, there were 26 cases of cam type, 16 cases of pincer type and 43 cases of mixed type. Routine hip arthroscopy was performed to remove the proliferative synovium. Femoral head and neck plasty was conducted for the cases of cam type, resection of the overly covered acetabulum followed by labral suture for those of pincer type, and resection of overly covered acetabulum and labral suture followed by femoral head and neck plasty for those of mixed type. Hip function was assessed one year after surgery using the modified Harris hip score (mHHS), nonarthritic hip score(NAHS), and hip outcome score activity of daily living scale (HOS-ADL); the alpha angle and central edge(CE) angle were measured after CT reconstruction.Results:The 85 patients were successfully followed up for an average of 21 months (range, from 12 to 48 months). The mHHS, NAHS and HOS-ADL for all the patients were improved significantly from preoperative 63.1±7.9, 62.5±7.5 and 62.3±7.9 to 83.4±8.7, 82.9±8.2 and 83.6±8.8 one year after surgery, respectively (all P<0.05) while the mHHS, NAHS and HOS-ADL for the patients of cam, pincer and mixed types were all significantly improved compared to their preoperative values (all P<0.05). The preoperative alpha angles for the cam and mixed types (67.3°±5.2° and 64.2°±5.2°) were significantly reduced to 50.3°±2.9° and 49.6°±2.8° one year postoperatively ( P<0.05); the preoperative CE angles for the pincer and mixed types (52.9°±4.6° and 50.9°±3.6°) were significantly reduced to 33.1°±4.5° and 31.3°±4.3° one year postoperatively ( P<0.05). Conclusion:Hip arthroscopy can effectively treat FAI of cam, pincer and mixed types, leading to good short-term efficacy.

Objective: To explore the value of quantitative CT radiomics features in predicting the anaplastic lymphoma kinase (ALK) mutation status in lung adenocarcinoma patients. Methods: This retrospective study reviewed one hundred and ninety-five lung adenocarcinoma patients (including 60 patients with ALK mutation) whose ALK genetic test results were available from Nov 2015 to May 2018 in PUMCH. VOIs were labeled by an automatic pulmonary nodule detection and segmentation algorithm and were later revised and confirmed by two senior radiologists. The PyRadiomics tools were used to resample the labeled regions, followed by image pre-processing (Wavelet filter or Laplacian of Gaussian (LoG) filter) and feature extraction. Normalized features were selected based on their representativeness on Dr. Wise research platform. Multivariate logistic regression was performed to develop prediction models of ALK mutation gene based on different image pre-processing techniques and different radiomics feature types. The results were validated by ten runs of five-fold cross validation. ROC curve analysis and Delong test were used to compare the predictive performance among models. Results: Fifteen radiomics features with the highest representativeness were selected from the original 1 232 features. The prediction model based on these radiomics features showed good performance (AUC=0.88 in the training set and 0.78 in the validation set) and was not significantly different from the prediction models based on radiomics features of different pre-processing images (AUC=0.76, P=0.1, original CT images; AUC=0.75, P=0.3, Wavelet-filtered images; AUC=0.76, P=0.2, LoG-filtered images). Among the models built with radiomics features of different types, the one based on GLCM feature (a subtype of texture feature) showed the best performance in predicting ALK genetic status (AUC=0.83, accuracy=0.74, sensitivity=0.85 and specificity=0.69). The model based on first-order statistic features had an AUC of 0.80. Conclusion Quantitative CT radiomics features have a good potential to anticipate the expression of ALK fused gene in patients with lung adenocarcinoma.

Objective To investigate the effect of quercetin on suppressing the proliferation,migration and invasion of A549 cells via the signal transducer and activator of transcription 3(STAT3)signaling pathway. Methods The A549 cells were cultured in vitro and treated with quercetin at various concentrations(0,7.5,15,30,60 and 120μmol/L)for 24 h,48 h and 72 h. The proliferation of A549 and the 50%inhibitory concentration(IC50)were measured by the cell counting kit-8(CCK-8). The A549 cells treated for 24 h were randomly divided into 4 groups:the blank control,15 and 30 μmol/L quercetin,and 3 μg/ml cisplatin(the positive control) groups. The effect of quercetin on adhesion rate was detected by the cell adhesion assay;the cell migration ability was evaluated by the wound healing assay;the cell invasion ability was evaluated by the Transwell chamber assay;the expression of STAT3 and phosphory?lated-STAT3(p-STAT3)proteins were detected by Western blot assay. Results Quercetin inhibited A549 cell growth dose-depend?ently. Compared with the blank control group,quercetin could significantly inhibit the adhesion rate,migration ability and invasion of A549 cells(P<0.05 or P<0.01);compared with the blank control group,quercetin significantly inhibited STAT3 and p-STAT3 ex?pression level(P<0.05 or P<0.01). Conclusion Quercetin could inhibit the proliferation,migration and invasion of A549 cells, and the mechanism is libely related to the STAT3 signal pathway.

Objective To study the feasibility and early efficacy of matrix?induced autologous chondrocyte implantation repairing knee joint cartilage injury. Methods The Matrix?induced autologous chondrocyte implantation was used to repair knee joint cartilage injury in 13 cases (11 males and 2 females) with knee joint cartilage injury from April 2012 to March 2013. The av?erage age was 27.5 years old. All cases were suffering from unilateral focal cartilage defect of knee joint with International Carti?lage Repair Society (ICRS) chondral defect classification system grade III or IV, visual analogue scale (VAS)>3, and all of which had corresponding pain symptoms. The average defect area was 4.2 cm2. Standardized rehabilitation exercise was carried out after matrix?induced autologous chondrocyte implantation. Patients were followed up for 1 years, and knee injury and use osteoarthritis outcome score(KOOS), International Knee Documentation Committee (IKDC), subjective knee form and Lysholm score were col?lected to assess the function. Meanwhile, magnetic resonance observation of cartilage repair tissue (MOCART) score was used to assess the magnetic resonance imaging. Results All patients had been followed?up for 1 year. One patient had meniscus repair under arthroscopy for the meniscus injury caused by downstairs sprain in 6.5 months postoperative, so the score of 12 months post?operative was excluded. The knee range of motion was decreased in 3 months postoperative (123.1°±8.0°) compared to preopera?tive one (135.4°±5.7°), and has no difference in 6 months (136.1°±6.1°) and 12 months postoperative (135.1°±3.6°) compared to preoperative one. The 5 subsets of KOOS score were decreased in 3 months compared to preoperative one, and were significantly increased in 6 months and 12 months. The IKDC has no difference in 3 months (26.1±3.9) compared to preoperative one (43.5± 6.5), and were significantly increased in 6 months (53.3±5.8) and 12 months (62.8±7.2) compared to preoperative one. The magnet?ic resonance observation of cartilage repair tissue (MOCART) score was increased in 12 month(73.3±17.9)compared to preopera?tive one(51.5 ± 12.6). Conclusion MACI is a good technology for knee joint cartilage injury. It has a good clinical effect on re? pairing cartilage injury effectively and restoring the function of knee joint.

Objective To observe the effects of capsaicin on PGE2 concentration of IL-1β-induced human large cell carcinoma NCI-H460 cells,and further observe its effect on COX-2 and mPGES-1 so as to explore the possible mechanisms against non-small cell lung cancer.Methods NCI-H460 cells were cultured in vitro ;the effect of capsaicin in inhibiting NCI-H460 cells proliferation was observed.The 50% inhibitory concentration (IC50 ) was measured by MTT assay.IL-1βstimulation method was used to construct inflammation model,and the effects of capsaicin on COX-2 activity and PGE2 concentration in NCI-H460 cells were measured by ELISA.The effects of capsaicin on COX-2 and mPGES-1 protein level in NCI-H460 cells were analyzed by Western blot;the effects of capsaicin on COX-2 mRNA and mPGES-1 mRNA expressions in NCI-H460 cells were analyzed by Real-time PCR. Results MTT assay results showed that the growth of NCI-H460 cells treated with capsaicin was significantly inhibited compared with the control group (P <0.05 or P <0.01 ).Capsaicin could significantly decrease COX-2 activity and PGE2 concentration in NCI-H460 cells,and significantly decrease COX-2,mPGES-1 protein levels as well as COX-2,mPGES-1 mRNA expressions in NCI-H460 cells in a dose-dependent manner compared with the control group (P < 0.05 ).Conclusion Capsaicin inhibits the release of PGE2 by downregulating COX-2 and mPGES-1 mRNA expressions in NCI-H460 cells,which may be one mechanism of its effect against non-small cell lung cancer.