Identification and immunological characterization of cuproptosis-related molecular clusters in idiopathic pulmonary fibrosis disease.

Background: Idiopathic pulmonary fibrosis (IPF) has attracted considerable attention worldwide and is challenging to diagnose. Cuproptosis is a new form of cell death that seems to be associated with various diseases. However, whether cuproptosis-related genes (CRGs) play a role in regulating IPF disease is unknown. This study aims to analyze the effect of CRGs on the progression of IPF and identify possible biomarkers. Methods: Based on the GSE38958 dataset, we systematically evaluated the differentially expressed CRGs and immune characteristics of IPF disease. We then explored the cuproptosis-related molecular clusters, the related immune cell infiltration, and the biological characteristics analysis. Subsequently, a weighted gene co-expression network analysis (WGCNA) was performed to identify cluster-specific differentially expressed genes. Lastly, the eXtreme Gradient Boosting (XGB) machine-learning model was chosen for the analysis of prediction and external datasets validated the predictive efficiency. Results: Nine differentially expressed CRGs were identified between healthy and IPF patients. IPF patients showed higher monocytes and monophages M0 infiltration and lower naive B cells and memory resting T CD4 cells infiltration than healthy individuals. A positive relationship was found between activated dendritic cells and CRGs of LIPT1, LIAS, GLS, and DBT. We also identified cuproptosis subtypes in IPF patients. Go and KEGG pathways analysis demonstrated that cluster-specific differentially expressed genes in Cluster 2 were closely related to monocyte aggregation, ubiquitin ligase complex, and ubiquitin-mediated proteolysis, among others. We also constructed an XGB machine model to diagnose IPF, presenting the best performance with a relatively lower residual and higher area under the curve (AUC= 0.700) and validated by external validation datasets (GSE33566, AUC = 0.700). The analysis of the nomogram model demonstrated that XKR6, MLLT3, CD40LG, and HK3 might be used to diagnose IPF disease. Further analysis revealed that CD40LG was significantly associated with IPF. Conclusion: Our study systematically illustrated the complicated relationship between cuproptosis and IPF disease, and constructed an effective model for the diagnosis of IPF disease patients.

Anti-tumor effect of coix seed based on the theory of medicinal and food homology.

Coix seed is a dry and mature seed of Coix lacryma-jobi L.var.ma-yuen (Roman.) Stapf in the Gramineae family. Coix seed has a sweet, light taste, and a cool nature. Coix seed enters the spleen, stomach, and lung meridians. It has the effects of promoting diuresis and dampness, strengthening the spleen to prevent diarrhea, removing arthralgia, expelling pus, and detoxifying and dispersing nodules. It is used for the treatment of edema, athlete's foot, poor urination, spleen deficiency and diarrhea, dampness and obstruction, lung carbuncle, intestinal carbuncle, verruca, and cancer. The medicinal and health value is high, and it has been included in the list of medicinal and food sources in China, which has a large development and application space. This article reviews the current research achievements in the processing methods and anti-tumor activities of Coix seed and provides examples of its clinical application in ancient and modern times, aiming to provide reference for further research on Coix seed and contribute to its clinical application and development. Through the analysis of the traditional Chinese patent medicines, and simple preparations and related health food of Coix seed queried by Yaozhi.com, the source, function, and dosage form of Coix seed were comprehensively analyzed, with a view of providing a reference for the development of Coix seed medicine and food.

High-altitude hypoxia-induced rat alveolar cell injury by increasing autophagy.

Autophagy has been implicated in the pathogenesis of various lung diseases. This study aimed to investigate the role of autophagy in lung injury induced by high-altitude hypoxia. Wistar rats were randomized into four groups for exposure to normal altitude or high altitude for 1, 7, 14 and 21 days with no treatment or with the treatment of 1 mg/kg rapamycin or 2 mg/kg 3-methyladenine (3-MA) for consecutive 21 days respectively. In control rats, the alveolar structure was intact with regularly arranged cells. However, inflammatory cell infiltration and shrunk alveoli were observed in rats exposed to hypoxia. Rapamycin treatment led to many shrunken alveoli with a large number of red blood cells in them. In contrast, 3-MA treatment led to almost intact alveoli or only a few shrunken alveoli. Compared to the control group exposure to high-altitude hypoxia for longer periods resulted in the aggravation of the lung injury, the formation of autophagosomes with a double-membrane structure and increased levels of Beclin-1 and LC3-II in alveolar tissues. Rapamycin treatment resulted in significant increase in Beclin-1 and LC3-II levels and further aggravation of alveolar tissue damage, while 3-MA treatment led to opposite effects. In conclusion, exposure to high-altitude hypoxia can induce autophagy of alveolar cells, which may be an important mechanism of high-altitude hypoxia-induced lung injury. The inhibition of autophagy may be a promising therapy strategy for high-altitude hypoxia-induced lung injury.

Efficacy and Prognostic Analysis of 315 Stage I-IVa Esophageal Cancer Patients Treated with Simultaneous Integrated Boost-Intensity-Modulated Radiation Therapy.

PURPOSE: Use of simulated integrated boost-intensity-modulated radiation therapy (SIB-IMRT) is rarely reported in the treatment of esophageal cancer. This study was performed to observe the curative effect and prognostic factors associated with concurrent chemoradiotherapy for esophageal cancer using modern radiotherapy (RT) techniques. PATIENTS AND METHODS: In total, 315 patients with esophageal squamous cell carcinoma who received SIB-IMRT between 2015 and 2018 were included in this retrospective study. Median doses were planning target volume (PTV) 5400 cGy, 30 times (180cGy/fraction); planning gross tumor volume (PGTV) 6000 cGy, 30 times (200 cGy/fraction), once a day and 5 times a week. The entire period of RT was 6 weeks. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse reactions were observed. Univariate analysis was performed, and factors with P<0.15 were included in multivariate analysis. Cox regression analysis was used for multivariate prognostic analysis. P<0.05 was considered statistically significant. The incidence of adverse reactions under single chemotherapy concurrent chemoradiotherapy (sCCRT) and double chemotherapy concurrent chemoradiotherapy (dCCRT) was analyzed. RESULTS: Two-year, 3-year OS and PFS of the entire group were 49.5%, 40.2% and 40.3%, 34.0%, and the median survival time was 23.5 months. Univariate and multivariate analyses showed that T-stage (P=0.049), N-stage (P=0.024), clinical stage (P=0.041), short-term efficacy (P<0.001), and use of concurrent chemotherapy (P<0.001) were the influencing factors for OS. ORR was 87.6%. Adverse reactions were significantly increased with increasing chemotherapy dose. CONCLUSION: The adverse reactions of SIB-IMRT in esophageal cancer can be tolerated. T-stage, N-stage, clinical stage, short-term curative effect, and concurrent chemotherapy are the prognostic factors affecting survival. Because it has lower toxicity and is as effective as dCCRT, sCCRT should be considered in the management of esophageal cancer.

Progress of clinical study on hypofractionated radiotherapy after breast-conserving surgery.

Whole-breast radiotherapy after breast-conserving surgery (BCS) can improve patient survival while reducing local tumor recurrence. Although standard breast radiotherapy can achieve good tumor control and cosmetic effects with low toxicity, the 5- to 7-week treatment time is relatively long for patients and can result in wasted medical resources. Therefore, there is a growing trend toward hypofractionated radiotherapy (HFRT), which accelerates partial-breast irradiation. Both short-course radiotherapy and conventional fractionated radiotherapy are safe and effective treatment modes, with similar survival and local tumor control effects as those of conventional radiotherapy (CRT), and adverse reactions can be tolerated. Compared with conventional fractionated radiotherapy, short-course radiotherapy saves medical resources and has a shorter total treatment time, reduced treatment costs, and an improved quality of life for patients.

MiR-629-3p-induced downregulation of SFTPC promotes cell proliferation and predicts poor survival in lung adenocarcinoma.

The long-term prognosis of patients with lung cancer remains poor and thus it is imminent to further elucidate the molecular mechanism for the oncogenesis of lung cancer. In this study, we observed that surfactant protein C (SFTPC) expression was downregulated in human lung adenocarcinoma tissues and cell lines, and low SFTPC expression correlated with poor overall survival of lung adenocarcinoma patients. Moreover, we found that overexpression of SFTPC could inhibit lung cancer cell proliferation in vitro and in vivo, but downregulation of SFTPC showed the opposite results. Besides, it was observed that miR-629-3p expression was upregulated in human lung adenocarcinoma tissues and cell lines. More importantly, we found that miR-629-3p could downregulate SFTPC expression by directly binding to the SFTPC 3'-UTR and inhibit the regulatory effect of SFTPC on lung adenocarcinoma cell proliferation. In conclusion, these data suggested that miR-629-3p-meditated downregulation of SFTPC may promote lung adenocarcinoma progression.

Impact of high body mass index on surgical outcomes and long-term survival among patients undergoing esophagectomy: A meta-analysis.

BACKGROUND: The impact of high body mass index (BMI, >23/25 kg/m) on surgical outcomes and prognosis in patients with esophageal carcinoma (EC) after undergoing esophagectomy remains controversial. We herein conducted a systematic review and meta-analysis to determine the relationship between high BMI and surgical outcomes and prognosis in patients undergoing esophagectomy for EC. METHODS: The study search was conducted by retrieving publications from the PubMed, Embase, Web of Science, and CNKI (up to September 8, 2017). Nineteen studies with 13,756 patients were included in this meta-analysis. RESULTS: We found that high BMI was closely associated with a higher incidence of wound infection (odds ratio [OR]: 1.41, 95% confidence interval [CI]: 1.02-1.97, P = .04), cardiovascular complications (OR: 2.51, 95% CI, 1.65-3.81, P < .0001), and anastomotic leakage (OR: 1.50, 95% CI, 1.21-1.84, P = .0002), but a lower incidence of chylous leakage (OR: 0.59, 95% CI, 0.40-0.88, P = .01) when compared with normal BMI. The high BMI group was not associated with better or worse overall survival (OS) (hazard ratio [HR]: 0.95, 95% CI, 0.85-1.07, P = .4) and disease-free survival (HR: 0.95, 95% CI, 0.72-1.25, P = .72) than the normal BMI group. However, in the subgroup analysis, the pooled result of HRs generated from multivariate analyses suggested that high BMI could improve OS in EC patients (HR: 0.84, 95% CI, 0.76-0.93, P < .01). CONCLUSIONS: Overweight patients with EC should not be denied surgical treatment, but intraoperative prevention and careful postoperative monitoring for several surgical complications must be stressed for this population. Besides, high BMI might be a prognostic predictor in EC patients; further studies are warranted.

Randomised phase III trial of concurrent chemoradiotherapy with extended nodal irradiation and erlotinib in patients with inoperable oesophageal squamous cell cancer.

BACKGROUND: This randomised phase III study was conducted to investigate the efficacy of extended nodal irradiation (ENI) and/or erlotinib in inoperable oesophageal squamous cell cancer (ESCC). PATIENTS AND METHODS: Patients with histologically confirmed locally advanced ESCC or medically inoperable disease were randomly assigned (ratio 1:1:1:1) to one of four treatment groups: group A, radiotherapy adoption of ENI with two cycles of concurrent TP chemotherapy (paclitaxel 135 mg/m2 day 1 and cisplatin 20 mg/m2 days 1-3, every 4 weeks) plus erlotinib (150 mg per day during chemoradiotherapy); group B, radiotherapy adoption of ENI with two cycles of concurrent TP; group C, radiotherapy adoption of conventional field irradiation (CFI) with two cycles of concurrent TP plus erlotinib; group D, radiotherapy adoption of CFI with two cycles of concurrent TP. RESULTS: A total of 352 patients (88 assigned to each treatment group) were enrolled. The 2-year overall survival rates of group A, B, C and D were 57.8%, 49.9%, 44.9% and 38.7%, respectively (P = 0.015). Group A significantly improved 2-year overall survival compared with group D. The ENI significantly improved overall survival in patients with inoperable ESCC (P = 0.014). The addition of erlotinib significantly decreased loco-regional recurrence (P = 0.042). Aside from rash and radiation oesophagitis, the incidence of grade 3 or greater toxicities did not differ among 4 groups. CONCLUSION: Chemoradiotherapy with ENI and erlotinib might represent a substantial improvement on the standard of care for inoperable ESCC. ENI alone should be adopted in concurrent chemoradiotherapy for ESCC patients.

Patterns of failure after involved field radiotherapy for locally advanced esophageal squamous cell carcinoma.

PURPOSE: To retrospectively analyze the patterns of failure and the treatment effects of involved-field irradiation (IFI) on patients treated with locally advanced esophageal squamous cell carcinoma (ESCC) and to determine whether IFI is practicable in these patients. METHODS: A total of 79 patients with locally advanced ESCC underwent three dimensional conformal (3D)CRT) or intensity modulated radiotherapy (IMRT) using IFI or elective nodal irradiation (ENI) according to the target volume. The patterns of failure were defined as local/regional, in-field, out)of)field regional lymph node (LN) and distant failure. With a median follow)up of 32.0 months, failures were observed in 66 (83.6%) patients. RESULTS: The cumulative incidence of local/regional failure (55.8 vs 52.8%) and in)field regional lymph node failure (25.6 vs 19.4%) showed no statistically significant difference between the IFI and the ENI group (p=0.526 and 0.215, respectively). Out)of)field nodal relapse rate of only 7.0% was seen in the IFI group. Three)year survival rates for the ENI and IFI group were 22.2 and 18.6%, respectively (p=0.240), and 3)year distant metastasis rates were 27.8 and 32.6%, respectively (p=0.180). The lung V10, V20, V30 and mean lung dose of the ENI group were greater than those of the IFI group, while the mean lung dose and V10 had statistically significant difference. CONCLUSIONS: The patterns of failure and survival rates in the IFI group were similar as in the ENI group; the regional recurrence and distant metastasis are the main cause of treatment failure. IFI is feasible for locally advanced ESCC. Further investigation is needed to increase local control and decrease distant metastasis in these patients.

[Effect of Qingfei Quyu Decoction in Prevention of Radiation Pneumonitis Induced by Concurrent Chemoradiotherapy for Esophageal Carcinoma Patients].

OBJECTIVE: To assess the effect of Qingfei Quyu Decoction (QQD) in preventing radiation pneumonitis in esophageal carcinoma patients by concurrent using it with chemoradiotherapy. METHODS: A total of 120 patients with mid-late stage esophageal carcinoma were randomly assigned to the treatment group (60 cases) and the control group (60 cases). All patients received concurrent radiochemotherapy. Patients in the treatment group additionally took QQD, one dose per day for 8 successive weeks. The incidence of radiation pneunonitis was compared between the two groups. The improvement rates of short-term benefit rate, Karnofsky performance scale (KPS), and body weight (BW) improvement rate were calculated between the two groups. The 1-and 2-year overall survival rates were compared between the two groups. RESULTS: The incidence of radiation pneunonitis was 8.93% (15/56) in the treatment group and 18.64% (11/59) in the control group (P < 0.05). The short-term benefit rate was 92.86% (52/56) in the treatment group and 69.49% (41/59) in the control group (P < 0.05). Besides, the KPS and BW improvement rate were higher in the treatment group [89.29% (50/56) and 83.05% (49/59) ] than in the control group [80.36% (45/56) and 66.10% (39/59)] (P < 0.05). The 1-and 2-year overall survival rate were 66.07% and 35.71% in the treatment group, higher than those of the control group (61.02% and 30.51%; P > 0.05). CONCLUSION: Concurrent using QQD with chemoradiotherapy for treating esophageal carcinoma patients could lower the incidence of radiation pneumonitis, attenuate the degree of radiation induced lung injury, improve clinical benefit rate, and elevate their QOL.

[Curative Effect of Jiedu Shengji Recipe in Preventing and Treating Acute Radiation Esophagitis in Radiotherapy Induced Esophageal Carcinoma Patients].

OBJECTIVE: To observe the curative effect of Jiedu Shengji Recipe (JSR) in preventing and treating acute radiation esophagitis in radiotherapy induced esophageal carcinoma patients. METHODS: Totally 86 mid-late stage esophageal carcinoma patients were assigned to the treatment group and the control group according to random digit table, 43 in each group. All patients received concurrent radiochemotherapy. Patients in the treatment group took JSR from starting the radiotherapy, one dose per day for 8 successive weeks, while those in the control group took mixture of dexamethasone, lido- caine, and gentamicin, 10 mL each time, taken before radiation and within 30 min after radiation, discontinued till the end of radiation. The occurrence time of acute radiation esophagitis and, duration of symptoms, esophageal radioactive damage degree, curative effect, improvement rate of Karnofsky performance scale (KPS) , and the incidence of adverse reactions were observed in the two groups. RESULTS: Compared with the control group, the occurrence time of acute radiation esophagitis was prolonged (15. 46±3. 37 days vs 10.23±2.46 days) , and duration of symptoms was shortened (20.18±4.56 days vs 26. 17±3. 26 days) in the treatment group, with statistical difference (P <0. 01). In the treatment group the occurrence rate of mid and high level (degree II to degree IV) acute radiation esophagitis was lower than that of the control group (Z =3. 34, P <0. 01). The total effective rate was 95. 35% (41/43) in the treatment group and 67. 44% (29/43) in the control group, with statistical difference between the two groups (X² =11.06, P<0.01 ). The improvement rate of KPS were higher in the treatment group than in the control group [65. 12% (28/43) vs 27.91% (12/43) ; X² =11.97, P <0. 01]. The incidence of adverse reactions were lower in the treatment group than in the control group with statistical difference [9.30% (4/43) vs 34. 88% (15/43) ; X²=8.17, P <0. 01]. CONCLUSION: JSR had better effect for preventing and treating moderate and severe acute radiation esophagitis in concurrent chemoradiotherapy induced esophageal carcinoma patients.

Misdiagnosis of a small cell lung cancer resulting from inaccurate pathology.

Currently, a biopsy provides the most reliable evidence for diagnosing a disease, and the majority of doctors do not question the diagnosis made by a pathologist. However, an inaccurate diagnosis may lead to serious consequences; for example, a benign tumor may be misdiagnosed as a malignancy, or a malignancy may be deemed to be benign. How to avoid these types of mistakes is a continuing issue of concern to all doctors. Here, we report a case of small cell lung cancer misdiagnosed as an inflammatory myofibroblastic tumor. Fortunately, we performed a mediastinoscopy on the patient and discovered the actual pathologic condition. This case is presented to caution against the possibility of the misdiagnosis of uncommon diseases in clinical practice.

[Expression pattern of tumor-associated antigen MG7-Ag in gastric cancer: difference between Tibetans and Hans].

OBJECTIVE: To investigate the difference of the expression pattern of tumor-associated antigen MG(7)-Ag in gastric carcinoma between Hans and Tibetans. METHODS: Avidin-biotin peroxidase complex immunohistochemical methods were adapted to examine the expression pattern of MG(7)-Ag in 200 patients with gastric carcinoma, including 100 Tibetan patients and 100 Hans patients, 10 patients with chronic artrophic gastritis, 18 with gastric mucosal dysphasia and 10 subjects with normal gastric mucosa served as control. RESULTS: The positive rate for MG(7)-Ag was 92.4% and 88.7% in Tibetan and Han gastric carcinoma patients, 55.6% and 38.9% in Tibetan and Han gastric mucosal dysplasia patients, 20.0% and 10.0% in Tibetan and Han chronic atrophic gastritis patients, respectively. There was no positive expression in normal gastric mucosa of both Hans and Tibetans. >From normal gastric mucosa, chronic artrophic gastritis and gastric mucosal dysplasia to gastric carcinoma, expression of MG(7)-Ag showed an ascending tendency in the same group of subjects or patients (P < 0.01). However between Hans and Tibetans there was no significantly different expression of MG(7)-Ag. In gastric carcinoma, the expression pattern of MG(7)-Ag was not related to tumor cell differentiation and metastasis of lymph nodes in Hans and Tibetans (P > 0.05), but in the same group the expression of MG(7)-Ag was related to metastasis of lymph nodes. CONCLUSIONS: The expression pattern of MG(7)-Ag displayed no significant difference between Hans and Tibetans, The tumor associated antigen MG(7)-Ag in gastric carcinoma can be used in Tibetans as a reliable marker to predict early gastric cancer.