OBJECTIVE: Cigarette smoking exacerbates the progression of pulmonary tuberculosis (TB). The role of tertiary lymphoid structures (TLS) in chronic lung diseases has gained attention; however, it remains unclear whether smoking-exacerbated lung damage in TB is associated with TLS. This study aimed to analyze the characteristics of pulmonary TLS in smokers with TB and to explore the possible role of TLS in smoking-related lung injury in TB. METHODS: Lung tissues from 36 male patients (18 smokers and 18 non-smokers) who underwent surgical resection for pulmonary TB were included in this study. Pathological and immunohistological analyses were conducted to evaluate the quantity of TLS, and chest computed tomography (CT) was used to assess the severity of lung lesions. The correlation between the TLS quantity and TB lesion severity scores was analyzed. The immune cells and chemokines involved in TLS formation were also evaluated and compared between smokers and non-smokers. RESULTS: Smoker patients with TB had significantly higher TLS than non-smokers ( P < 0.001). The TLS quantity in both the lung parenchyma and peribronchial regions correlated with TB lesion severity on chest CT (parenchyma: r = 0.5767; peribronchial: r = 0.7373; both P < 0.001). Immunohistochemical analysis showed increased B cells, T cells, and C-X-C motif chemokine ligand 13 (CXCL13) expression in smoker patients with TB ( P < 0.001). CONCLUSION Smoker TB patients exhibited increased pulmonary TLS, which was associated with exacerbated lung lesions on chest CT, suggesting that cigarette smoking may exacerbate lung damage by promoting TLS formation.
Humans ; Male ; Tuberculosis, Pulmonary/immunology* ; Middle Aged ; Tertiary Lymphoid Structures/pathology* ; Adult ; Lung/pathology* ; Smoking/adverse effects* ; Smokers ; Aged ; Tomography, X-Ray Computed

Objective:To explore the predictive value of intraoperative cerebral oxygen satu-ration(rSO2)combined with serum chitinase-3-like protein 1(CHI3L1)and CXC-chemokine ligand 16(CXCL16)for postoperative cognitive dysfunction(POCD)in colorectal cancer patients.Meth-ods:83 patients who developed POCD after colorectal cancer surgery in our hospital from Novem-ber 2021 to September 2023 were selected as the study group,another 83 patients without POCD who underwent colorectal cancer surgery were as control group.Spearman method was applied to analyze the correlation between serum CHI3L1,CXCL16 expression levels and MMSE score;re-ceiver operating characteristic(ROC)curve was applied to analyze the predictive value of intraopera-tive rSO2 combined with serum CHI3L1 and CXCL16 for postoperative POCD in colorectal cancer patients.Results:There was statistically difference in the postoperative MMSE scores between the study group and the control group(P＜0.05);there was no statistically difference in rSO2 level between the two groups at T0 and T1 time points(P＞0.05),while there was statistically difference in rSO2 level at T2,T3,T4,and T5 time points(P＜0.05),and the change rate of rSO2 in the study group was higher than that in the control group(P＜0.05);the expression levels of serum CHI3L1 and CXCL16 in the study group were higher than those in the control group(P＜0.05);the expres-sion levels of serum CHI3L1 and CXCL16,and the intraoperative change rate of rSO2 were nega-tively correlated with MMSE score(P＜0.05);the area under the curve(AUC)of serum CHI3L1,CXCL16 levels,and rSO2 change rate alone for predicting postoperative POCD in colorectal cancer patients was 0.790,0.754,and 0.870,respectively,however,the AUC predicted by the combina-tion of the three was 0.944,which was better than their individual predictions(Zcombination-CHI3L1=4.742,Zcombination-XCL16=5.081,Zcombination-rSO2 change rate=2.986,P＜0.05).Conclusion:The combination of intraop-erative rSO2 and serum CHI3L1 and CXCL16 expression have high predictive efficacy for postop-erative POCD in colorectal cancer patients.

Objective:To evaluate the relationship between glutathione S-transferase μ1 (GSTM1) and the apoptosis signal-regulating kinase 1 (ASK1)-c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) signaling pathway during therapeutic hypothermia-induced reduction of cerebral ischemia-reperfusion injury (CIRI) in rats.Methods:One hundred clean-grade healthy male Sprague-Dawley rats, aged 8 weeks, weighing 260-280 g, were divided into 5 groups ( n=20 each) using a random number table method: sham operation group (S group), cerebral ischemia-reperfusion group (I/R group), therapeutic hypothermia group (H group), GSTM1 inhibitor+ therapeutic hypothermia group (IH group), and GSTM1 inhibitor + ASK1 inhibitor + therapeutic hypothermia group (IAH group). CIRI model was developed by occlusion of the left middle cerebral artery for 2 h, followed by restoration of the blood flow. A nylon thread was inserted into the internal carotid artery and advanced cephalad until resistance was met. The brain temperature was maintained at 36-37 ℃ during surgery. In H group, the head and neck were wiped with 75% alcohol immediately after reperfusion, and the brain temperature was maintained at 32-33℃ for 3 h, and the rest procedures were the same as those previously described in I/R group. In IH group, GSTM1 inhibitor itaconic acid 8.6 mg/kg was intraperitoneally injected at 24 and 1 h before developing the model, and the rest procedures were the same as those previously described in H group. In IAH group, ASK1 inhibitor selonsertib 10 mg/kg was given orally once a day for 4 consecutive days starting from 4 days before developing the model, and the rest procedures were the same as those previously described in IH group. Modified Neurological Severity Score (mNSS) was assessed at 24 h of reperfusion, then the rats were sacrificed and brains were harvested for microscopic examination of brain infarction, neuronal morphology (using HE staining) and for determination of the expression of GSTM1, ASK1, phosphorylated ASK1 (p-ASK1), JNK, phosphorylated JNK (p-JNK), p-38 MAPK and phosphorylated p-38 MAPK (p-p38 MAPK) (by Western blot) and neuronal apoptosis (by TUNEL assay). The percentage of the infarct size was calculated using TTC staining. The apoptosis rate was calculated. Results:Compared with S group, the mNSS, apoptosis rate of neurons, percentage of the cerebral infarct size, p-ASK1/ASK1 ratio, p-JNK/JNK ratio and p-p38 MAPK/p38 MAPK ratio were significantly increased, and the expression of GSTM1 was down-regulated in I/R group ( P<0.05). Compared with I/R group and IH group, the mNSS, apoptosis rate of neurons, percentage of the cerebral infarct size, p-ASK1/ASK1 ratio, p-JNK/JNK ratio and p-p38 MAPK/p38 MAPK ratio were significantly decreased, the expression of GSTM1 was up-regulated ( P<0.05), and the neuronal injury was significantly attenuated in H group. Compared with IH group, the mNSS, apoptosis rate of neurons, percentage of the cerebral infarct size, p-ASK1/ASK1 ratio, p-JNK/JNK ratio and p-p38 MAPK/p38 MAPK ratio were significantly decreased ( P<0.05), no significant change was found in GSTM1 expression ( P>0.05), and the neuronal damage was significantly attenuated in IAH group. Conclusions:The mechanism by which therapeutic hypothermia alleviates CIRI is related to up-regulating the expression of GSTM1 and inhibiting the activation of the ASK1-JNK-p38 MAPK signaling pathway in rats.

OBJECTIVE: To investigate the effects of the pre-shock state on the mortality of patients with sepsis. METHODS: We enrolled patients with sepsis admitted to the medical intensive care unit of a tertiary care university hospital. These patients were then classified into three groups: sepsis, pre-shock state, and septic shock. The primary outcome was the 28-day mortality rate. The secondary outcomes were the 90-day, 180-day, and 1-year mortality rates. RESULTS: A total of 303 patients (groups: sepsis 135 [44.6%]), pre-shock state (93 [30.7%]), and septic shock (75 [24.8%]) completed the 1-year follow-up. The mortality rates at 28 days, 90 days, and 180 days and 1 year were significantly higher in the pre-shock state group than those of the sepsis group, but significantly lower than those in the septic shock group, especially among older patients. When compared with the pre-shock state group, the sepsis group had significantly lower mortality risks at 28 days, 90 days, and 180 days and 1 year, whereas the sepsis shock group had higher mortality risks at these time points. CONCLUSION The mortality rates of patients in the pre-shock state were notably different from those of patients with sepsis or septic shock. The introduction of a modified sepsis severity classification, which includes sepsis, pre-shock state, and septic shock, could offer valuable additional prognostic information.
Humans ; Shock, Septic ; Retrospective Studies ; Sepsis ; Hospitalization ; Universities

Objective: To compare the prognostic evaluation value of preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII) in rectal cancer patients. Nomogram survival prediction model based on inflammatory markers was constructed. Methods: The clinical and survival data of 585 patients with rectal cancer who underwent radical resection in the First Affiliated Hospital of Xi'an Jiao tong University from January 2013 to December 2016 were retrospectively analyzed. The optimal cut-off values of NLR, PLR, LMR, and SII were determined by the receiver operating characteristic (ROC) curve. The relationship between different NLR, PLR, LMR and SII levels and the clinic pathological characteristics of the rectal cancer patients were compared. Cox proportional risk model was used for univariate and multivariate regression analysis. Nomogram prediction models of overall survival (OS) and disease-free survival (DFS) of patients with rectal cancer were established by the R Language software. The internal validation and accuracy of the nomograms were determined by the calculation of concordance index (C-index). Calibration curve was used to evaluate nomograms' efficiency. Results: The optimal cut-off values of preoperative NLR, PLR, LMR and SII of OS for rectal cancer patients were 2.44, 134.88, 4.70 and 354.18, respectively. There was statistically significant difference in tumor differentiation degree between the low NLR group and the high NLR group (P<0.05), and there were statistically significant differences in T stage, N stage, TNM stage, tumor differentiation degree and preoperative carcinoembryonic antigen (CEA) level between the low PLR group and the high PLR group (P<0.05). There was statistically significant difference in tumor differentiation degree between the low LMR group and the high LMR group (P<0.05), and there were statistically significant differences in T stage, N stage, TNM stage, tumor differentiation degree and preoperative CEA level between the low SII group and the high SII group (P<0.05). The multivariate Cox regression analysis showed that the age (HR=2.221, 95%CI: 1.526-3.231), TNM stage (Ⅲ grade: HR=4.425, 95%CI: 1.848-10.596), grade of differentiation (HR=1.630, 95%CI: 1.074-2.474), SII level (HR=2.949, 95%CI: 1.799-4.835), and postoperative chemoradiotherapy (HR=2.123, 95%CI: 1.506-2.992) were independent risk factors for the OS of patients with rectal cancer. The age (HR=2.107, 95%CI: 1.535-2.893), TNM stage (Ⅲ grade, HR=2.850, 95%CI: 1.430-5.680), grade of differentiation (HR=1.681, 95%CI: 1.150-2.457), SII level (HR=2.309, 95%CI: 1.546-3.447), and postoperative chemoradiotherapy (HR=1.837, 95%CI: 1.369-2.464) were independent risk factors of the DFS of patients with rectal cancer. According to the OS and DFS nomograms predict models of rectal cancer patients established by multivariate COX regression analysis, the C-index were 0.786 and 0.746, respectively. The calibration curve of the nomograms showed high consistence of predict and actual curves. Conclusions: Preoperative NLR, PLR, LMR and SII levels are all correlated with the prognosis of rectal cancer patients, and the SII level is an independent prognostic risk factor for patients with rectal cancer. Preoperative SII level can complement with the age, TNM stage, differentiation degree and postoperative adjuvant chemoradiotherapy to accurately predict the prognosis of rectal cancer patients, which can provide reference and help for clinical decision.
Biomarkers, Tumor ; Carcinoembryonic Antigen ; Humans ; Inflammation/classification* ; Lymphocytes ; Neutrophils ; Nomograms ; Preoperative Period ; Prognosis ; Rectal Neoplasms/surgery* ; Retrospective Studies

BACKGROUND: Targeted therapy for patients with driver genes positive and immunotherapy for patients with driver gene-negative but high programmed death ligand 1 (PD-L1) expression are the standards of first-line treatment for patients with advanced non-small cell lung cancer (NSCLC). The treatment options for patients with driver gene positive and high PD-L1 expression are still worth exploring. METHODS: The characteristics of 315 patients with NSCLC were identified to analyze the clinicopathological characteristics of patients with driver gene positive and high PD-L1 expression, and the efficacy of targeted therapy. RESULTS: Among the 315 patients, the total positive rate of driver genes was 62.2%, and the high PD-L1 expression rate (≥50.0%) was 11.2%. The proportion of patients with driver gene positive and high PD-L1 expression was 10.7%. PD-L1 was highly expressed in patients with epidermal growth factor receptor (EGFR) mutation, KRAS mutation, ALK fusion, BRAF mutation, and MET 14 exon skip mutation, the proportions were 7.8% (11/141), 18.2% (4/22), and 23.1%, (3/13), 50.0% (2/4) and 100.0% (1/1) respectively. EGFR mutation positive with PD-L1 high expression was mainly in patients with stage IV lung adenocarcinoma. KRAS mutation positive with PD-L1 high expression was mainly in patients with a history of smoking. Among them, two patients were followed in detail for targeted therapy, who with ALK fusion-positive and PD-L1 high expression (90.0%), EGFR L858R mutation and PD-L1 high expression (70.0%) respectively. The total OS of the patients was 5 months, 2 months. CONCLUSIONS The high PD-L1 expression rate in NSCLC patients with different driver gene mutations was variable, which maybe correlated with distinct clinicopathological characteristics. Patients with sensitive mutations and high PD-L1 expression may be less benefit from targeted therapy and have poor prognosis.

BACKGROUND: Circulating tumor DNA (ctDNA) is a promising biomarker for non-invasive epidermal growth factor receptor mutations (EGFRm) detection in lung cancer patients, but existing methods have limitations in sensitivity and availability. In this study, we used the ΔCt value (mutant cycle threshold [Ct] value-internal control Ct value) generated during the polymerase chain reaction (PCR) assay to convert super-amplification-refractory mutation system (superARMS) from a qualitative method to a semi-quantitative method named reformed-superARMS (R-superARMS), and evaluated its performance in detecting EGFRm in plasma ctDNA in patients with advanced lung adenocarcinoma. METHODS: A total of 41 pairs of tissues and plasma samples were obtained from lung adenocarcinoma patients who had known EGFRm in tumor tissue and were previously untreated. EGFRm in ctDNA was identified by using superARMS. Through making use of ΔCt value generated during the detection process of superARMS, we indirectly transform this qualitative detection method into a semi-quantitative PCR detection method, named R-superARMS. Both qualitative and quantitative analyses of the data were performed. Kaplan-Meier analysis was performed to estimate the progression-free survival (PFS) and overall survival (OS). Fisher exact test was used for categorical variables. RESULTS: The concordance rate of EGFRm in tumor tissues and matched plasma samples was 68.3% (28/41). At baseline, EGFRm-positive patients were divided into two groups according to the cut-off ΔCt value of EGFRm set at 8.11. A significant difference in the median OS (mOS) between the two groups was observed (EGFRm ΔCt ≤8.11 vs. >8.11: not reached vs. 11.0 months; log-rank P = 0.024). Patients were divided into mutation clearance (MC) group and mutation incomplete clearance (MIC) group according to whether the ΔCt value of EGFRm test turned negative after 1 month of treatment. We found that there was also a significant difference in mOS (not reached vs. 10.4 months; log-rank P = 0.021) between MC group and MIC group. Although there was no significant difference in PFS between the two groups, the two curves were separated and the PFS of MC group tended to be higher than the MIC group (not reached vs. 27.5 months; log-rank P = 0.088). Furthermore, EGFRm-positive patients were divided into two groups according to the cut-off of the changes in ΔCt value of EGFRm after 1 month of treatment, which was set at 4.89. A significant difference in the mOS between the two groups was observed (change value of ΔCt >4.89 vs. ≤4.89: not reached vs. 11.0 months; log-rank P = 0.014). CONCLUSIONS Detecting EGFRm in ctDNA using R-superARMS can identify patients who are more likely sensitive to targeted therapy, reflect the molecular load of patients, and predict the therapeutic efficacy and clinical outcomes of patients.
Adenocarcinoma of Lung/genetics* ; Circulating Tumor DNA/genetics* ; ErbB Receptors/genetics* ; Humans ; Lung Neoplasms/genetics* ; Mutation/genetics* ; Protein Kinase Inhibitors

Phytochemical study of the aerial parts of Hypericum perforatum L. resulted in the isolation of an undescribed compound, which was identified as Rel-(2S,3R)-2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-2-methoxy-3-(2-oxopropyl)chroman-4-one (1) by spectroscopic methods including UV, IR, HR-ESI-MS, 1D and 2D NMR spectra. Compound 1 is a new 2,3-dioxo-flavone with an acetonyl moiety, rarely found in nature. In addition, a plausible biogenetic pathway of 1 was proposed in this article.

Objective To analyze the common causes of fatty liver in Chinese adults.Methods The CNKI, WANFANG database and VIP database were searched by computer , and the etiology of fatty liver was published from January 2008 to December 2017.Meta-analysis of pre-valence, influencing factors, and blood biochemical indicators were per-formed using R software and Stata software .Results Twenty-four stu-dies were finally included,with a total of 49,275 cases.Meta-analysis showed that the prevalence of fatty liver in the population were : total prevalence 19.31%, male prevalence 26.44%, female prevalence 15.31%.The prevalence rates at different ages were :＜30 years old 13.20%, 31-40 years old 16.73%, 41-50 years old 20.98%, 51-60 years old 21.85%,＞60 years old 17.46%.The risk ratio of influen-cing factors in patients with fatty liver compared with normal population was: high cholesterol 2.03, high triglyceride 3.02, aspartate transaminas increased 3.70, alanine transaminase increased 4.55, hyperglycemia 2.54, obesity 10.73 , greasy food 3.93, alcohol consumption 2.85, hy-pertension 2.06, quality index fat 2.52.The differences in mean blood biochemical results between patients with and without fatty liver were as follows: total cholestero 1.23,triglyceride 1.18,high-density lipoprotein -0.55,low-density lipoprotein 0.28, aspartate transaminase 1.09, alanine transaminase 1.45,total bilirubin 1.09, fasting blood glucose 1.16.Conclusion The preva-lence of fatty liver in Chinese men is higher than that in females ; common factors are high cholesterol , high triglycerides, elevated aspartate transaminase, elevated alanine transaminase, hyperglycemia, obesity, greasy food, hypertension, body mass index; patients with fatty liver fatty biochemical indicators than the normal population were abnormal.

BackgroundRecent advances in extracorporeal membrane oxygenation (ECMO) have led to increasing interest in its use during cardiopulmonary resuscitation (CPR). However, decisions regarding extracorporeal CPR (ECPR) in children are difficult as a result of limited studies, especially in Asia Pacific. The objective of this study was to investigate trends in survival and demographic details for children with ECPR in Asia Pacific recorded in the Extracorporeal Life Support Organization (ELSO) registry from 1999 to 2016 and identify the risk factors associated with in-hospital mortality.

MethodsThe data of children younger than 18 years of age who received ECPR over the past 18 years in Asia Pacific were retrospectively analyzed. The data were extracted from the ELSO registry and divided into two 9-year groups (Group 1: 1999-2007 and Group 2: 2008-2016) to assess temporal changes using univariate analysis. Then, univariate and multiple logistic regression analyses were performed between survivors and nonsurvivors to identify factors independently associated with in-hospital mortality.

ResultsA total of 321 children were included in final analysis, with an overall survival rate of 50.8%. Although survival rates were similar between Group 1 and Group 2 (43.1% vs. 52.5%, χ = 1.67, P = 0.196), the median age (1.7 [0.3, 19.2] months for Group 1 vs. 5.6 [0.8, 64.9] months for Group 2, t = -2.93, P = 0.003) and weight (3.7 [3.0, 11.5] kg for Group 1 vs. 6.0 [3.4, 20.3] kg for Group 2, t = -3.14, P = 0.002) of children increased over time, while the proportion of congenital heart disease (75.9% for Group 1 vs. 57.8% for Group 2, χ = 6.52, P = 0.011) and cardiogenic shock (36.2% for Group 1 vs. 7.2% for Group 2, χ = 36.59, P < 0.001) decreased. Patient conditions before ECMO were worse, while ECMO complications decreased across time periods, especially renal complications. Multiple logistic regression analysis of ECMO complications showed that disseminated intravascular coagulation (DIC), myocardial stunning, and neurological complications were independently associated with increased odds of hospital mortality.

ConclusionsThe broader indications and decreased complication rates make EPCR to be applicated more and more extensive in children in Asia Pacific region. ECMO complications such as myocardial stunning are independently associated with decreased survival.

Asia ; Cardiopulmonary Resuscitation ; methods ; Child ; Child, Preschool ; Extracorporeal Membrane Oxygenation ; methods ; Female ; Humans ; Infant ; Infant, Newborn ; Logistic Models ; Male ; Registries ; Retrospective Studies ; Risk Factors ; Survival Rate ; Time Factors