Identification of a six-gene signature to predict survival and immunotherapy effectiveness of gastric cancer.

Background: Gastric cancer (GC) ranks as the fifth most prevalent malignancy and the second leading cause of oncologic mortality globally. Despite staging guidelines and standard treatment protocols, significant heterogeneity exists in patient survival and response to therapy for GC. Thus, an increasing number of research have examined prognostic models recently for screening high-risk GC patients. Methods: We studied DEGs between GC tissues and adjacent non-tumor tissues in GEO and TCGA datasets. Then the candidate DEGs were further screened in TCGA cohort through univariate Cox regression analyses. Following this, LASSO regression was utilized to generate prognostic model of DEGs. We used the ROC curve, Kaplan-Meier curve, and risk score plot to evaluate the signature's performance and prognostic power. ESTIMATE, xCell, and TIDE algorithm were used to explore the relationship between the risk score and immune landscape relationship. As a final step, nomogram was developed in this study, utilizing both clinical characteristics and a prognostic model. Results: There were 3211 DEGs in TCGA, 2371 DEGs in GSE54129, 627 DEGs in GSE66229, and 329 DEGs in GSE64951 selected as candidate genes and intersected with to obtain DEGs. In total, the 208 DEGs were further screened in TCGA cohort through univariate Cox regression analyses. Following this, LASSO regression was utilized to generate prognostic model of 6 DEGs. External validation showed favorable predictive efficacy. We studied interaction between risk models, immunoscores, and immune cell infiltrate based on six-gene signature. The high-risk group exhibited significantly elevated ESTIMATE score, immunescore, and stromal score relative to low-risk group. The proportions of CD4+ memory T cells, CD8+ naive T cells, common lymphoid progenitor, plasmacytoid dentritic cell, gamma delta T cell, and B cell plasma were significantly enriched in low-risk group. According to TIDE, the TIDE scores, exclusion scores and dysfunction scores for low-risk group were lower than those for high-risk group. As a final step, nomogram was developed in this study, utilizing both clinical characteristics and a prognostic model. Conclusion: In conclusion, we discovered a 6 gene signature to forecast GC patients' OS. This risk signature proves to be a valuable clinical predictive tool for guiding clinical practice.

Radiomic model based on magnetic resonance imaging for predicting pathological complete response after neoadjuvant chemotherapy in breast cancer patients.

Purpose: To establish a model combining radiomic and clinicopathological factors based on magnetic resonance imaging to predict pathological complete response (pCR) after neoadjuvant chemotherapy in breast cancer patients. Method: MRI images and clinicopathologic data of 329 eligible breast cancer patients from the Affiliated Hospital of Qingdao University from August 2018 to August 2022 were included in this study. All patients received neoadjuvant chemotherapy (NAC), and imaging examinations were performed before and after NAC. A total of 329 patients were randomly allocated to a training set and a test set at a ratio of 7:3. We mainly studied the following three types of prediction models: radiomic models, clinical models, and clinical-radiomic models. All models were evaluated using subject operating characteristic curve analysis and area under the curve (AUC), decision curve analysis (DCA) and calibration curves. Results: The AUCs of the clinical prediction model, independent imaging model and clinical combined imaging model in the training set were 0.864 0.968 and 0.984, and those in the test set were 0.724, 0.754 and 0.877, respectively. According to DCA and calibration curves, the clinical-radiomic model showed good predictive performance in both the training set and the test set, and we found that we had developed a more concise clinical-radiomic nomogram. Conclusion: We have developed a clinical-radiomic model by integrating radiomic features and clinical factors to predict pCR after NAC in breast cancer patients, thereby contributing to the personalized treatment of patients.

The complete mitochondrial genome of Eastern Curlew Numenius madagascariensis (Charadriiformes, Scolopacidae).

The complete mitochondrial genome of Numenius madagascariensis Linnaeus, 1766 was sequenced in this study. The circular mitogenomes was 17,147 bp in length, containing 13 protein-coding genes, two ribosomal RNAs (12S rRNA and 16S rRNA), 22 transfer RNA genes, and a D-loop region. The overall nucleotide composition was A: 31.0%, T: 25.6%, C: 29.5%, and G: 13.9%. Twenty-eight genes were encoded on the heavy strand, while the remaining nine genes were encoded on the light strand. The common start codon was ATG, and three stop codons and an incomplete stop codon (T-) were used in PCGs. This study improves our comprehension of the mitogenomic characteristics and its phylogenetic relationships within Scolopacidae.

Pyroptosis in Cancer: Friend or Foe?

Pyroptosis is an inflammatory form of programmed cell death that is mediated by pore-forming proteins such as the gasdermin family (GSDMs), including GSDMA-E. Upon cleavage by activated caspases or granzyme proteases, the N-terminal of GSDMs oligomerizes in membranes to form pores, resulting in pyroptosis. Though all the gasdermin proteins have been studied in cancer, the role of pyroptosis in cancer remains mysterious, with conflicting findings. Numerous studies have shown that various stimuli, such as pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), and chemotherapeutic drugs, could trigger pyroptosis when the cells express GSDMs. However, it is not clear whether pyroptosis in cancer induced by chemotherapeutic drugs or CAR T cell therapy is beneficial or harmful for anti-tumor immunity. This review discusses the discovery of pyroptosis as well as its role in inflammatory diseases and cancer, with an emphasis on tumor immunity.

Frequent amplification of HDAC genes and efficacy of HDAC inhibitor chidamide and PD-1 blockade combination in soft tissue sarcoma.

BACKGROUND: The advent of immune checkpoint therapy has been a tremendous advance in cancer treatment. However, the responses are still insufficient in patients with soft tissue sarcoma (STS). We aimed to identify rational combinations to increase the response to immune checkpoint therapy and improve survival. METHODS: Whole-exome sequencing (WES) was performed in 11 patients with liposarcoma. Somatic copy number alterations (SCNAs) were analyzed at the gene level to identify obvious amplification patterns in drug-target genes. The expression and prognostic value of class I histone deacetylases (HDACs) was evaluated in 49 patients with sarcoma in our center and confirmed in 263 sarcoma samples from The Tumor Cancer Genome Atlas (TCGA) database. Q-PCR, flow cytometry and RNA-seq were performed to determine the correlations between class I HDACs, chidamide and PD-L1 in vitro and in vivo. The efficacy of combining chidamide with PD-1 blockade was explored in an immunocompetent murine model and a small cohort of patients with advanced sarcoma. Western blot, ChIP assay and dual luciferase assessment were applied in the mechanistic study. RESULTS: The HDAC gene family was frequently amplified in STS. SCNAs in the HDAC gene family were extensively amplified in 8 of 11 (73%) patients with liposarcoma, based on a drug-target gene set, and we verified amplification in 76.65% (197/257) of cases by analyzing TCGA sarcoma cohort. Class I HDAC expression is associated with a poor prognosis for patients with STS, and its inhibition is responsible for promoting apoptosis and upregulating of programmed cell death ligand 1 (PD-L1). The HDAC class I inhibitor chidamide significantly increases PD-L1 expression, increased the infiltration of CD8+ T cells and reduced the number of MDSCs in the tumor microenvironment. The combination of chidamide with an anti-PD-1 antibody significantly promotes tumor regression and improves survival in a murine model. Moreover, chidamide combined with the anti-PD-1 antibody toripalimab is effective in patients with advanced and metastatic sarcoma, and the side effects are tolerable. Mechanistically, chidamide increases histone acetylation at the PD-L1 gene through the activation of the transcriptional factor STAT1. CONCLUSIONS: The combination of chidamide and anti-programmed cell death 1 (PD-1) therapy represents a potentially important strategy for STS.

Time to Local Recurrence as a Predictor of Survival in Patients With Soft Tissue Sarcoma of the Extremity and Abdominothoracic Wall.

OBJECTIVE: The purpose of this retrospective study was to identify the prognostic significance of time to local recurrence (TLR) with regard to overall survival (OS) and survival after local recurrence (SAR) in patients with soft tissue sarcoma (STS) of the extremity and abdominothoracic wall. METHODS: We identified 477 patients who underwent R0 resection for localized STS of the extremity and abdominothoracic wall, from January 1995 to December 2016, of whom 190 patients developed local recurrence as their first recurrent event. Based on TLR, patients were divided into two groups: early local recurrence (ELR, <12 months) and late local recurrence (LLR, ≥12 months). The Kaplan-Meier method and Cox regression analysis were used to estimate the OS and SAR, and to identify factors associated with patient outcomes. RESULTS: The median follow-up time for the entire cohort was 118.4 months, and was 118.5 months for the 190 patients who developed local recurrence. Deep tumor location (HR 1.73, 95% CI 1.27-2.37, P = 0.001) and tumor grade ≥2 (G2 vs. G1: HR 1.75, 95% CI 1.21-2.53, G3 vs. G1: HR 2.57, 95% CI 1.66-3.98, P < 0.001) were associated with a higher rate of local recurrence. There were 99 patients in the ELR group and 91 in the LLR group, with a median TLR of 10.8 months for the entire cohort. Patients from the ELR group had a shorter OS and a lower 5-year OS rate than the LLR group. Univariate and multivariate analyses demonstrated TLR as an independent prognostic factor for SAR and OS, in addition to tumor grade. Also, surgical treatment and absence of metastasis after local recurrence were associated with longer SAR. CONCLUSIONS: In patients with STS of the extremity and abdominothoracic wall, ELR after R0 resection indicated a worse prognosis than those with LLR, and TLR can be considered an independent prognostic factor for OS and SAR. Furthermore, local recurrence was significantly influenced by the depth and the histopathological grading of the primary tumor, and reoperation after local recurrence could improve survival, which means salvage surgery may still be the preferred treatment when there are surgical indications after recurrence.

Evaluation of the effects of applying the ventricular care bundle (VCB) method for reducing ventilator-associated pneumonia (VAP) in the intensive care unit of a general Chinese tertiary hospital.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a severe complication that occurs within patients who must use ventilators in the intensive care unit (ICU). Ventilator care bundles (VCB) have been applied across many developed regions and have produced positive results in controlling VAP. In this study, we report on the implementation and effects of using VCBs to manage VAP in a general tertiary hospital in the Inner Mongolia Autonomous Region of China. METHODS: A targeted surveillance method was used to survey all the patients (n=4,716) in the ICU from June 1, 2017 to May 31, 2019. Patients from June 1, 2017 to May 31, 2018, and June 1, 2018, to May 31, 2019, were respectively divided into 2 groups: the control group (2,029 patients) and intervention group (2,687 patients). These dates were selected because VCB was implemented from June 1, 2018, in our institution. The variables that were associated with VCB and observed were the head-of-bed elevation, oral care, maintenance of the pressure for the cuff of the endotracheal tube, aspiration of subglottic secretion, daily sedation vacation protocol, daily extubation assessment results, and hand hygiene. After collecting the data, the compliance of VCB, ventilator use ratio, and the incidence rate of VAP in these 2 groups were compared. RESULTS: We observed that compliance with all of the intervention measures for VCB improved results in the intervention group compared to the control. Furthermore, the compliance rate of hand hygiene increased from 71.99% to 91.97%, and the head-of-bed elevation of 30°-45° increased from 62.02% to 85.96%. All differences between these two groups were statistically significant, according to the χ 2 -test. The ventilator use ratio was statistically and significantly lower in the intervention group (34.86%) compared to the control group (40.29%) (χ 2 =95.513, P<0.001). The incidence rate of VAP was statistically and significantly lower in the intervention group (13.70‰) compared to the control group (18.85‰) (χ 2 =5.471, P=0.019). CONCLUSIONS: Our results show that VCB prevents VAP. Therefore, personnel training, clinical supervision, and surveillance feedback could promote a reduction in intervention measures.

Drug resistance of healthcare-associated pathogenic bacteria and carbapenem-resistant Acinetobacter baumannii homology in the general intensive care unit.

BACKGROUND: The objective of this study was to understand the distribution and drug resistance of healthcare-associated infection (HAI) pathogens in an intensive care unit (ICU) of a general tertiary hospital in Inner Mongolia, and to classify carbapenem-resistant Acinetobacter baumannii (CR-AB) in ICU patients and environmental samples. Additionally, this study aimed to provide scientific evidence for the use of clinical antibiotics and effective prevention and control measures for CR-AB outbreak. METHODS: The distribution and drug resistance of pathogens isolated from patient's samples in the ICU of 12 Hospitals from January to May 2019 were retrospectively analyzed. Meanwhile, CR-AB isolated from patients and environmental samples were collected and classified by pulsed-field gel electrophoresis (PFGE). RESULTS: The pathogens isolated from ICU samples, mainly Gram-negative bacteria (63.07%), were CR-AB, Klebsiella pneumoniae, and Pseudomonas aeruginosa; the main Gram-positive bacteria (22.13%) were Enterococcus faecium and Staphylococcus aureus; and fungi accounted for the remaining (14.80%). The samples mainly came from sputum (41.09%). Among non-fermenting bacteria, the resistance rates of CRAB to piperacillin, piperacillin/tazobactam, and other treatments were higher than those of Pseudomonas aeruginosa (P<0.05). Meanwhile, the resistance rates to ampicillin/sulbactam and compound sulfamethoxazole were lower than those of Pseudomonas aeruginosa (P<0.05). The resistance rates of Klebsiella pneumoniae to piperacillin/tazobactam, ceftazidime, and others were higher than those of Escherichia coli (P<0.05). Among Gram-positive bacteria, the resistance rates of Enterococcus faecium to erythromycin, clindamycin, and other treatment were higher than those of Staphylococcus aureus (P<0.05). A total of 62 bands were obtained from 63 strains of CR-AB by electrophoresis. Also, 16 clusters (A-P) were obtained with a 74% similarity coefficient, among which K, L, and N types (more than 9 strains) were more common. CONCLUSIONS: Gram-negative bacteria were the primary pathogens of HAI in the ICU, and their drug resistance was serious. There is homology in the PFGE typing of CR-AB. Therefore, hospitals should strengthen the surveillance of drug-resistant pathogenic bacteria. Additionally, further cleaning and disinfection measures are needed to improve environmental hygiene and prevent outbreaks of HAI.

Healthcare-associated infection prevention and control management in a tertiary hospital and an overall evaluation.

BACKGROUND: Healthcare-associated infection (HAI) is a crucial factor influencing medical quality. Studies about HAI management situations are rare, especially for the Inner Mongolia region of China. Therefore, this study aimed to investigate management procedures and the overall evaluation of HAI in order to inform HAI management improvement more scientifically. METHODS: A questionnaire was used to investigate HAI-related prevention and control indicators in tertiary hospitals in the Inner Mongolia region from July 2018 to June 2019. RESULTS: The survey showed that the mean incidence rate of HAI was 3.79%. The mean rate of hand hygiene compliance of healthcare workers (HCWs), inpatient's antibiotics-use rate, and the detection of the antibiotic ratio before therapy was 54.34%, 34.33%, and 25.40%, respectively. The mean of the surgical site infection (SSI) rate of the level I incision and the preventive antibiotics-use ratio of the level I incision was 1.31% and 28.89%, respectively. The mean of the multi-drug resistant organism (MDRO) infection rate was 0.40% and the mean of the MDRO detection rate was 18.55%. The mean of the central line-associated bloodstream infection rate was 2.24%, the ventilator-associated pneumonia (VAP) rate was 11.17%, and the catheter-associated urinary tract infection (CAUTI) rate was 1.95‰. As for the overall evaluation, 19 (35.85%) hospitals had a bad grade, 18 (33.96%) hospitals had a medium grade, and 16 (30.19%) hospitals had a good grade. CONCLUSIONS: The incidence rate of HAI in tertiary hospitals in the Inner Mongolia region is higher than the national level. Also, the overall evaluation of bad-grade hospitals and their deficiencies should be used as an example to improve the HAI management level.

The prognostic role of the preoperative systemic immune-inflammation index and high-sensitivity modified Glasgow prognostic score in patients after radical operation for soft tissue sarcoma.

INTRODUCTION: The prognostic values of nutritional and immune-inflammatory indicators in non-metastatic soft tissue sarcoma (STS) patients are not clear. We investigated the utility of systemic immune-inflammation index (SII) and the high-sensitivity modified Glasgow prognostic score (Hs-mGPS) in the prediction of STS patient's prognosis. MATERIALS AND METHODS: Patients admitted between January 2000 and December 2016, who underwent R0 resection for STS at SYSUCC were carefully retrospectively reviewed, and 454 patients were enrolled. The laboratory data and clinical data were collected from the patient's record. ROC analysis is used to determine the optimal cutoff value. Survival curves were analysed by Kaplan-Meier method. Cox proportional hazard model was used to find out prognostic variables. RESULTS: Increased SII and Hs-mGPS values were significantly related to larger tumour size, deep tumour location, higher tumour grade and more advanced American Joint Committee on Cancer (AJCC) stage. Patients with an elevated SII had a shorter median survival time and a lower 5-year OS rate than those with a low SII. And patients with low Hs-mGPS had longer median OS and DFS. Multivariate analysis revealed that both the SII and the Hs-mGPS were independent predictive indicators for OS. And a joint model containing both the Hsm-GPS and the SII appeared to have the strongest predictive ability. CONCLUSION: Our findings indicated that malnutrition and systemic inflammation are risk factors for the survival of STS patients after operation, and early recognition and intervention of malnutrition and systemic inflammation may help to improve the survival of the patients.

Change of Pathological Type to Metaplastic Squamous Cell Carcinoma of the Breast During Disease Recurrence: Case Report and Literature Review.

Background: Metaplastic squamous cell carcinoma (SCC) of the breast is a rare and heterogeneous group of primary breast malignancies. The etiology, pathogenesis, and proper treatment for this kind rare breast cancer are still unclear. Case presentation: We reported a case of a 55-year-old woman with a palpable lump in the inner quadrant of the right breast. She underwent a right breast mass resection and sentinel lymph node biopsy, which revealed that the tumor was an invasive ductal carcinoma, followed by four cycles of doxorubicin plus cyclophosphamide and four cycles of docetaxel as adjuvant chemotherapy, and then simultaneous integrated boost intensity modulated radiotherapy to the whole right breast. After 2 years' follow-up, she had biopsy-proven disease recurrence in the right breast, which revealed SCC, and a mammogram showed abnormalities in the lower inner quadrant of the right breast and left axillary lymph nodes. Then we performed bilateral breast modified radical mastectomy, which confirmed that the recurrent tumors were metaplastic SCC, followed by adjuvant chemotherapy and adjuvant radiotherapy of the left supraclavicular and apical axillary regions. There has been no recurrent or metastatic evidence in the 16 months' follow-up since the second surgery. Conclusion: This case report shows that evolution of pathology type in recurrent breast cancer after initial treatment is possible. Detailed pathologic and immunohistochemical analyses are needed for identification of this change. Surgery and adjuvant radiation and chemotherapy are appropriate treatments for recurrent primary SCC of the breast.

The Impact of Unplanned Excision on the Outcomes of Patients With Soft Tissue Sarcoma of the Trunk and Extremity: A Propensity Score Matching Analysis.

BACKGROUND: Unplanned excision (UPE) of soft tissue sarcoma (STS) is often chosen in the early phase by general physicians without any radiological evaluation. PURPOSE: The present study aimed to evaluate the impact of UPE on the clinical outcomes of patients with STS of the trunk and extremity. MATERIALS AND METHODS: Patients with STS of the trunk and extremity who underwent R0 resection between 1998 and 2016 were included and divided into the UPE and planned excision (PE) groups. Propensity score matching (PSM) was used to control the selection bias. The endpoints were disease-specific survival (DSS), local recurrence-free survival (LRFS), and metastasis-free survival (MFS). RESULTS: In total, 458 patients (277 males, 181 females; median age: 43 years) were included: 329 (71.8%) in the PE group and 129 (28.2%) in the UPE group. The follow-up time ranged from 7.1 to 313.78 months, with a median of 112.18 months. UPE patients were more likely to have a smaller or superficial lesion and were more frequently administered adjuvant therapy. After PSM, compared with the PE group, the UPE group had a longer LRFS (P=0.015), but there was no difference between the two groups regarding DSS and MFS. Residual disease was observed in 77.5% of the re-resected specimens in the UPE group and was a risk factor for DSS (P = 0.046) and MFS (P = 0.029) but was not associated with local recurrence (LR) (P=0.475) or LRFS (P=0.334). Moreover, we found no difference in DSS, LRFS or MFS according to the interval from UPE to definitive resection. CONCLUSION: STS treated with UPE had distinct characteristics. Patients who undergo UPE followed by an additional wide R0 resection have similar oncological survival compared to patients who undergo an initial PE, although the high incidence of residual tumor in the UPE group leads to an unfavorable clinical course.

Active surveillance of ventilator-associated pneumonia in the intensive care unit and establishment of the risk grading system and effect evaluation.

BACKGROUND: To discuss ventilator-associated pneumonia (VAP) patient's clinical characteristic and related factors in the intensive care unit (ICU), and to establish a risk grading system for VAP patients in the ICU in order to provide a reference for VAP prevention. METHODS: A total of 1,513 patients in eight ICUs who received mechanical ventilation between June 2015 and June 2018 were randomized and into two groups, with 908 patients in the model group and 605 patients in the verification group. The model group was used to analyze the influencing factors of VAP and establish a risk grading system, while the verification group was used to verify the risk grading system. A receiver operating characteristic (ROC) curve was used to evaluate the predictive effect of the grading system. RESULTS: During the 3-year study period, of the 1,513 total patients, 188 patients were infected with VAP, leading to an incidence rate of 12.43% (188/1,513) and an infection rate of 15.23‰ (188/12,347). ICU length of stay, mechanical ventilation days, frequency of oral care, unused subglottic secretion drainage, tracheotomy, APACHE II score, and combined antibiotics use were risk factors of VAP infection for patients who received mechanical ventilation in the modeling group (P<0.05). In a VAP risk-grading system established based on risk factors, the high, medium and low-grade patients had a statistically significantly different VAP infection rate in the model group, and patients with a high grade had a higher risk of VAP infection. Patients' data in the model and verification groups were used to draw a ROC curve which showed a good predictive effect. CONCLUSIONS: This study establishes and verifies the VAP risk grading system for patients who receive mechanical ventilation. It is helpful in high-risk patient surveillance and in reducing and preventing VAP infection.