Endoscopic Submucosal Dissection Criteria for Differentiated-type Early Gastric Cancer Are Applicable to Mixed-type Differentiated Predominant.

BACKGROUND: There is a lack of sufficient evidence on whether mixed-type differentiated predominant early gastric cancer (MD-EGC) can be treated endoscopically by referring to the criteria for differentiated-type early gastric cancer (EGC). This study aims to evaluate the efficacy of endoscopic submucosal dissection (ESD) in MD-EGC. METHODS: Patients with differentiated-type EGC treated with ESD first from January 2015 to June 2021 were reviewed, including MD-EGC and pure differentiated-type EGC (PD-EGC). Clinical data, including the clinicopathological characteristics, resection outcomes of ESD, and recurrence and survival time, were collected, and the difference between MD-EGC and PD-EGC was tested. RESULTS: A total of 48 patients (48 lesions) with MD-EGC and 850 patients (890 lesions) with PD-EGC were included. Compared with PD-EGC, MD-EGC had a higher submucosal invasion rate (37.5% vs. 13.7%, P<0.001) and lymphatic invasion rate (10.4% vs. 0.4%, P<0.001). The rates of complete resection (70.8% vs. 92.5%, P<0.001) and curative resection (54.2% vs. 87.4%, P<0.001) in MD-EGC were lower than those of PD-EGC. Multivariate analysis revealed that MD-EGC (OR 4.26, 95% CI, 2.22-8.17, P<0.001) was an independent risk factor for noncurative resection. However, when curative resection was achieved, there was no significant difference in the rates of recurrence (P=0.424) between the 2 groups, whether local or metachronous recurrence. Similarly, the rates of survival(P=0.168) were no significant difference. CONCLUSIONS: Despite the greater malignancy and lower endoscopic curative resection rate of MD-EGC, patients who met curative resection had a favorable long-term prognosis.

Correlation of distribution characteristics and dynamic changes of gut microbiota with the efficacy of immunotherapy in EGFR-mutated non-small cell lung cancer.

BACKGROUND: The effects of gut microbiota and metabolites on the responses to immune checkpoint inhibitors (ICIs) in advanced epidermal growth factor receptor (EGFR) wild-type non-small cell lung cancer (NSCLC) have been studied. However, their effects on EGFR-mutated (EGFR +) NSCLC remain unknown. METHODS: We prospectively recorded the clinicopathological characteristics of patients with advanced EGFR + NSCLC and assessed potential associations between the use of antibiotics or probiotics and immunotherapy efficacy. Fecal samples were collected at baseline, early on-treatment, response and progression status and were subjected to metagenomic next-generation sequencing and ultra-high-performance liquid chromatography-mass spectrometry analyses to assess the effects of gut microbiota and metabolites on immunotherapy efficacy. RESULTS: The clinical data of 74 advanced EGFR + NSCLC patients were complete and 18 patients' fecal samples were dynamically collected. Patients that used antibiotics had shorter progression-free survival (PFS) (mPFS, 4.8 vs. 6.7 months; P = 0.037); probiotics had no impact on PFS. Two dynamic types of gut microbiota during immunotherapy were identified: one type showed the lowest relative abundance at the response time point, whereas the other type showed the highest abundance at the response time point. Metabolomics revealed significant differences in metabolites distribution between responders and non-responders. Deoxycholic acid, glycerol, and quinolinic acid were enriched in responders, whereas L-citrulline was enriched in non-responders. There was a significant correlation between gut microbiota and metabolites. CONCLUSIONS: The use of antibiotics weakens immunotherapy efficacy in patients with advanced EGFR + NSCLC. The distribution characteristics and dynamic changes of gut microbiota and metabolites may indicate the efficacy of immunotherapy in advanced EGFR + NSCLC.

Inhibition of ferroptosis by POLE2 in gastric cancer cells involves the activation of NRF2/GPX4 pathway.

Gastric cancer results in great cancer mortality worldwide, and inducing ferroptosis dramatically improves the malignant phenotypes of gastric cancer. DNA polymerase epsilon subunit 2 (POLE2) plays indispensable roles in tumorigenesis; however, its involvement and molecular basis in ferroptosis and gastric cancer are not clear. Human gastric cancer cells were infected with lentiviral vectors to knock down or overexpress POLE2, and cell ferroptosis was detected. To further validate the involvement of nuclear factor erythroid 2-related factor 2 (NRF2) and glutathione peroxidase 4 (GPX4), lentiviral vectors were used. POLE2 expression was elevated in human gastric cancer cells and tissues and closely correlated with clinicopathological features in gastric cancer patients. POLE2 knockdown was induced, while POLE2 overexpression inhibited ferroptosis of human gastric cancer cells, thereby modulating the malignant phenotypes of gastric cancer. Mechanistic studies revealed that POLE2 overexpression elevated NRF2 expression and activity and subsequently activated GPX4, which then prevented lipid peroxidation and ferroptosis in human gastric cancer cells. In contrast, either NRF2 or GPX4 silence significantly prevented POLE2 overexpression-mediated inductions of cell proliferation, migration, invasion and inhibition of ferroptosis. POLE2 overexpression inhibits ferroptosis in human gastric cancer cells through activating NRF2/GPX4 pathway, and inhibiting POLE2 may be a crucial strategy to treat gastric cancer.

The association of growth differentiation factor 5 rs143383 gene polymorphism with osteoarthritis: a systematic review and meta-analysis.

BACKGROUND: Osteoarthritis (OA) is caused by a complex set of pathophysiological factors. The genetic factors involved in the occurrence and progress of the disease have been widely discussed by scholars. It was found that growth differentiation factor 5 (GDF5) gene polymorphisms may be linked to OA susceptibility, which has been controversial and needs to be further confirmed by an updated meta-analysis. OBJECTIVES: We examined the association between GDF5 rs143383 single nucleotide polymorphism (SNP) and OA susceptibility. METHODS: All relevant articles that met the criteria are retrieved and included, and the search deadline is June 2022. The allele frequencies and different genotype frequencies of GDF5 rs143383 loci in each study were extracted and statistically analyzed by R4.1.3 software, and the different genetic models were analyzed based on their odds ratio (OR) and 95% confidence interval (CI). RESULTS: The meta-analysis explained that GDF5 rs143383 SNP was crucial correlated with OA in all patients with OA of knee, hip and hand. The codominant gene model in the whole crowd (OR = 1.17, 95% CI 1.07-1.27, P < 0.01) enlightened that OA was vitally associated with GDF5 gene polymorphism. At the same time, we did a subgroup analysis based on ethnicity. The codominant gene model (OR = 1.31, 95% CI 1.12-1.53, P < 0.01) in Asian population, the codominant homozygote model (OR = 1.28, 95% CI 1.14-1.43), codominant heterozygote gene model (OR = 1.12, 95% CI 1.01-1.23, P = 0.02), and dominant gene model (OR = 1.19, 95% CI 1.09-1.31, P < 0.01) in Caucasian are analyzed by subgroup analysis. It means that there is a momentous relationship between the GDF5rs143383 gene polymorphism and OA, especially among Caucasians. In addition, we also discussed different types of OA separately and discover that the GDF5rs143383 gene polymorphism was relevant for knee osteoarthritis (KOA) and hand osteoarthritis, and it was more significant in the Caucasian population. But due to the high heterogeneity in hip osteoarthritis, it could not be accurately concluded. Furthermore, we also analyzed the osteoarthritis of different genders and found that the GDF5 rs143383 SNP was associated with both men and women and was still significant in the Caucasian population. CONCLUSION: We found a close association between osteoarthritis and GDF5rs143383SNP in this study. From the analysis of each group, we got the same conclusion in KOA and hand OA, but which need further verification in hip OA. Considering gender, we found a close relationship between GDF5 rs143383 SNP and OA of the knee, hip and hand, both for men and women. This conclusion is more obvious in Caucasian people.

CNIH4 governs cervical cancer progression through reducing ferroptosis.

Cervical cancer is one of the most leading causes of cancer death worldwide, and ferroptosis is implicated in the progression of cervical cancer. Cornichon family AMPA receptor auxiliary protein 4 (CNIH4) is involved in the progression of various human cancers; however, its function in cervical cancer remains unclear. The present study aims to investigate the role and mechanism of CNIH4 in cervical cancer using gain- and loss-of-function studies in vitro. SiHa and CaSki cells were infected with lentiviral vectors to manipulate the expression of CNIH4 in vitro, and cell viability, migration, invasion as well as ferroptosis were evaluated. Transcriptome sequencing analysis was performed to further validate the mechanism through which CNIH4 regulated the progression of cervical cancer. The expression of CNIH4 was upregulated in human cervical cancer tissues and cells, and strongly correlated with the decreases in overall survival and disease free survival rates of cervical cancer patients. CNIH4 silence inhibited, while CNIH4 overexpression facilitated the survival of human cervical cancer cells. Mechanistically, CNIH4 elevated solute carrier family 7 member 11 (SLC7A11)-mediated cystine import, and subsequently increased intracellular glutathione synthesis and glutathione peroxidase 4 activity, thereby inhibiting ferroptosis of human cervical cancer cells. SLC7A11 silence significantly abolished CNIH4-mediated inhibition of ferroptosis in cervical cancer cells in vitro. Our study for the first time reveals that CNIH4 inhibits ferroptosis of human cervical cancer cells through upregulating SLC7A11, defining CNIH4 as an attractive therapeutic and prognostic target for cervical cancer.

ANGPTL2 aggravates LPS-induced septic cardiomyopathy via NLRP3-mediated inflammasome in a DUSP1-dependent pathway.

Angiopoietin-like protein 2 (ANGPTL2) was implicated in various cardiovascular diseases; however, its role in lipopolysaccharide (LPS)-related septic cardiomyopathy remains unclear. Herein, mice were exposed to LPS to generate septic cardiomyopathy, and adeno-associated viral vector was employed to overexpress ANGPTL2 in the myocardium. Besides, mice were treated with adenoviral vector to knock down ANGPTL2 in hearts. ANGPTL2 expressions in hearts and cardiomyocytes were upregulated by LPS challenge. ANGPTL2 overexpression aggravated, while ANGPTL2 silence ameliorated LPS-associated cardiac impairment and inflammation. Mechanically, we found that ANGPTL2 activated NLRP3 inflammasome via suppressing DUSP1 signaling, and NLRP3 knockdown abrogated the detrimental role of ANGPTL2 in aggravating LPS-induced cardiac inflammation. Furthermore, DUSP1 overexpression significantly inhibited ANGPTL2-mediated NLRP3 activation, and subsequently improved LPS-related cardiac dysfunction. In summary, ANGPTL2 exacerbated septic cardiomyopathy via activating NLRP3-mediated inflammation in a DUSP1-dependent manner, and our study uncovered a promising therapeutic target in preventing septic cardiomyopathy.

Duration of SARS-CoV-2 Serum-Neutralizing Antibodies Against SARS-CoV-2 Dependent on the Individual.

We investigated the persistence of SARS-CoV-2-specific neutralizing antibodies in serum (CoV-2-SNAb) against the "WH-Human 1" coronavirus in 57 convalescent persons from January 2020 to January 2021. The CoV-2-SNAb response against authentic "WH-Human 1" showed a significant (p < 0.01) neutralizing high effect (≥95%) in the following manner: by 94.7% neutralization for up to 6 months, by 73.1% for up to 8 months, and by 31.7% for up to 10 months in correlation with a significant decrease in the concentration of the virus determined by SARS-CoV-2 spike protein extracellular domain and spike-receptor-binding domain (S-RBD). There was neutralizing effect (<95%) when the S-RBD optical density (OD) value was more than 1.0, showing a suitable threshold of S-RBD = 1.0 (antibody-tittering, OD). However, in some convalescent persons, no neutralizing effect (<95%) was observed although the SARS-CoV-2-specific neutralizing antibodies were bound to the S-RBD (OD >1.0). The neutralization of the virus in these cases may not involve S-RBD, but rather B- and T cell memory responses in overall immunity, using the threshold value (OD = 1.0) of S-RBD as a simple and effective method to determine the neutralization effect of the antibody efficacy and use of vaccination in combination with a standard pseudovirus neutralizing assay. We suggest that convalescent persons should contact their physicians 6-month postinfection to test the function of their serum neutralizing antibodies and determine whether administering a SARS-CoV-2 vaccine is necessary to prevent the development of severe illness in the future.

A Prediction Model Based on the Risk Factors Associated with Pathological Upgrading in Patients with Early-Stage Gastric Neoplasms Diagnosed by Endoscopic Forceps Biopsy.

Background/Aims: The discrepancies between the diagnosis of preoperative endoscopic forceps biopsy (EFB) and endoscopic submucosal dissection (ESD) in patients with early gastric neoplasm (EGN) exist objectively. Among them, pathological upgrading directly influences the accuracy and appropriateness of clinical decisions. The aims of this study were to investigate the risk factors for the discrepancies, with a particular focus on pathological upgrading and to establish a prediction model for estimating the risk of pathological upgrading after EFB. Methods: We retrospectively collected the records of 978 patients who underwent ESD from December 1, 2017 to July 31, 2021 and who had a final histopathology determination of EGN. A nomogram to predict the risk of pathological upgrading was constructed after analyzing subgroup differences among the 901 lesions enrolled. Results: The ratio of pathological upgrading was 510 of 953 (53.5%). Clinical, laboratorial and endoscopic characteristics were analyzed using univariable and binary multivariable logistic regression analyses. A nomogram was constructed by including age, history of chronic atrophic gastritis, symptoms of digestive system, blood high density lipoprotein concentration, macroscopic type, pathological diagnosis of EFB, uneven surface, remarkable redness, and lesion size. The C-statistics were 0.804 (95% confidence interval, 0.774 to 0.834) and 0.748 (95% confidence interval, 0.664 to 0.832) in the training and validation set, respectively. We also built an online webserver based on the proposed nomogram for convenient clinical use. Conclusions: The clinical value of identifying the preoperative diagnosis of EGN lesions is limited when using EFB separately. We have developed a nomogram that can predict the probability of pathological upgrading with good calibration and discrimination value.

A Prediction Model Based on the Risk Factors Associated with Pathological Upgrading in Patients with Early-Stage Gastric Neoplasms Diagnosed by Endoscopic Forceps Biopsy

Background/Aims@#The discrepancies between the diagnosis of preoperative endoscopic forceps biopsy (EFB) and endoscopic submucosal dissection (ESD) in patients with early gastric neoplasm (EGN) exist objectively. Among them, pathological upgrading directly influences the accuracy and appropriateness of clinical decisions. The aims of this study were to investigate the risk factors for the discrepancies, with a particular focus on pathological upgrading and to establish a prediction model for estimating the risk of pathological upgrading after EFB. @*Methods@#We retrospectively collected the records of 978 patients who underwent ESD from December 1, 2017 to July 31, 2021 and who had a final histopathology determination of EGN. A nomogram to predict the risk of pathological upgrading was constructed after analyzing subgroup differences among the 901 lesions enrolled. @*Results@#The ratio of pathological upgrading was 510 of 953 (53.5%). Clinical, laboratorial and endoscopic characteristics were analyzed using univariable and binary multivariable logistic regression analyses. A nomogram was constructed by including age, history of chronic atrophic gastritis, symptoms of digestive system, blood high density lipoprotein concentration, macroscopic type, pathological diagnosis of EFB, uneven surface, remarkable redness, and lesion size. The C-statistics were 0.804 (95% confidence interval, 0.774 to 0.834) and 0.748 (95% confidence interval, 0.664 to 0.832) in the training and validation set, respectively. We also built an online webserver based on the proposed nomogram for convenient clinical use. @*Conclusions@#The clinical value of identifying the preoperative diagnosis of EGN lesions is limited when using EFB separately. We have developed a nomogram that can predict the probability of pathological upgrading with good calibration and discrimination value.

Copper-Catalyzed, N-Directed Distal C(sp3)-H Functionalization toward Azepanes.

We herein report a copper-catalyzed formal [5 + 2] aza-annulation of N-fluorosulfonamides and 1,3-dienes/1,3-enynes for synthesis of structurally diverse alkene/alkyne-containing azepanes. The reaction features selective functionalization of distal unactivated C(sp3)-H bonds and a broad substrate scope, thus allowing the late-stage modification of pharmaceuticals and natural products. A radical mechanism involving 1,5-hydrogen atom transfer of N-radicals, facile coupling of alkyl radicals with 1,3-dienes/1,3-enynes, and the construction of azepane motifs via C-N bond formation is proposed.

Clinical Features Analysis and Survival Nomogram of Primary Small Intestinal Diffuse Large B-Cell Lymphoma.

Purpose: This study aimed to analyze the clinical features and survival of primary small intestinal diffuse large B-cell lymphoma (PsI-DLBCL), and establish and independently validate a prognostic nomogram for individual risk prediction. Patients and methods: Data for 24 patients from the Renmin Hospital of Wuhan University were used as an independent validation cohort, data for 1144 patients with PsI-DLBCL from the SEER database were randomly assigned to training (N=817) and internal validation (N=327) sets. The survival nomogram was constructed with the most significant factors associated with OS using Univariate and multivariate analyses on the training set. Decision curve analysis (DCA) was conducted. Internal validation was SEER validation set. Our cancer center cohort was used as an external validation set to further verify the survival nomogram. Results: Five clinicopathological feature factors associated with OS of the training set yielded (age, marital status, Ann Arbor stage, surgery for primary site and chemotherapy), which were used to create a survival nomogram. Additionally, the calibration curves of the prognostic nomogram revealed good agreement between the predicted survival probabilities and the ground truth values. The stability of our survival nomogram was explained by internal and external validation data. Conclusion: Our nomogram proposes the clinical and therapeutic factors affecting OS for patients with PsI-DLBCL. It shows that chemotherapy and surgery are beneficial to patients in the choice of treatment options. These results suggest that a survival nomogram may be better at predicting OS for PsI-DLBCL patients.

Licochalcone A inhibits cell growth through the downregulation of the Hippo pathway via PES1 in cholangiocarcinoma cells.

Overexpression or activation of Yes-associated protein (YAP) is common in cancer cells. Thus, targeting YAP may be a strategy for cancer therapy. Licochalcone A (LicA) is a primary active compound of licorice root and is known to have medicinal effects, such as antioxidant, antibacterial, antiviral, and anticancer effects. However, the anticancer pharmacological mechanism of LicA has not been investigated in cholangiocarcinoma. In this study, we investigated the antiproliferative effect of LicA and the underlying molecular mechanism in HCCC-9810 and RBE human cholangiocarcinoma cells. Our experiments indicated that LicA suppressed the growth of cholangiocarcinoma cells through inactivation of the Hippo pathway. Pescadillo ribosomal biogenesis factor 1 (PES1) was notably upregulated and related to carcinogenesis. We also found that LicA suppressed the expression and nuclear localization of PES1, which was associated with the inhibition of YAP expression and transcriptional activity.

Diagnostic value of serum TIM-3 in patients with liver cancer / 国际肿瘤学杂志

Objective:To analyze the changes of T cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3) in serum of patients with liver cancer and its diagnostic value.Methods:From March 2021 to May 2021, 37 patients with viral hepatitis type B (hepatitis B group) , 44 patients with liver cirrhosis (liver cirrhosis group) and 27 patients with liver cancer (liver cancer group) were selected in the Second Affiliated Hospital of Air Force Medical University, and 35 healthy subjects who underwent physical examination during the same period were selected as the healthy control group. The serum alpha fetoprotein (AFP) , liver function indexes and TIM-3 levels were detected, and the differences among groups were analyzed. The correlations between TIM-3 and AFP and liver function indexes were analyzed by Spearman correlation. Receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of TIM-3 in liver cancer.Results:There was a statistically significant difference in AFP among the hepatitis B group, liver cirrhosis group and liver cancer group ( χ2=11.75, P=0.003) . There were statistically significant differences in total bilirubin ( χ2=22.85, P<0.001) , direct bilirubin ( χ2=25.90, P<0.001) , indirect bilirubin ( χ2=19.92, P<0.001) , alanine aminotransferase ( χ2=36.64, P<0.001) , aspertate aminotransferase ( χ2=26.26, P<0.001) , aspertate aminotransferase/alanine aminotransferase ( χ2=34.67, P<0.001) and total bile acid ( χ2=13.10, P<0.001) among the hepatitis B group, liver cirrhosis group and liver cancer group. The serum levels of TIM-3 in the healthy control group, hepatitis B group, liver cirrhosis group and liver cancer group were 11.1 (4.2, 14.4) ng/ml, 12.7 (4.3, 23.9) ng/ml, 11.4 (3.4, 17.0) ng/ml and 15.7 (10.5, 21.2) ng/ml, with a statistically significant difference ( χ2=11.85, P=0.008) . There were statistically significant differences between the liver cancer group and healthy control group and liver cirrhosis group (both P<0.05) . Spearman correlation analysis showed that TIM-3 had no correlation with AFP in the four groups ( r=0.05, P=0.791; r=0.18, P=0.497; r=0.03, P=0.883; r=0.24, P=0.396) . There were correlations between serum TIM-3 and total protein in the healthy control group ( r=0.36, P=0.036) , serum TIM-3 and globulin in the hepatitis B group ( r=0.35, P=0.034) , and serum TIM-3 and total bile acid in the liver cancer group ( r=0.46, P=0.017) . ROC curve analysis showed that the sensitivity of serum TIM-3 for the diagnosis of liver cancer was 48.10%, and the specificity was 91.43%, when taking healthy subjects as the control group. The sensitivity of serum TIM-3 for the diagnosis of liver cancer was 96.30%, and the specificity was 41.77%, when taking healthy subjects and liver cirrhosis patients as the control group. The sensitivity of serum TIM-3 for the diagnosis of liver cancer was 96.30%, and the specificity was 40.52%, when taking healthy subjects, hepatitis B patients and liver cirrhosis patients as the control group. Conclusion:The serum level of TIM-3 in patients with liver cancer is significantly increased, which has certain diagnostic value for liver cancer, and can be used as a diagnostic marker and potential therapeutic target for liver cancer patients.

Current status and prospect of biomarker research for schizophrenia / 中华检验医学杂志

Schizophrenia is a serious mental disease. The diagnosis of schizophrenia so far relies heavily on subjective evidence, including self-reported experiences by patients, manifestations described by relatives, and abnormal behaviors assessed by psychiatrists. The diagnosis, monitoring of the disease progression and therapy efficacy assessment are challenging due to the lack of established laboratory biomarkers. Based on the current literature, clinical consensus, guidelines, and expert recommendations, this review highlighted evidence-based potential laboratory biomarkers for the diagnosis of schizophrenia, including genetic biomarkers, neurotransmitters, neurodevelopmental-related proteins, and intestinal flora, and discussed the potential future directions for the application of these biomarkers in this field, aiming to provide an objective basis for the use of these biomarkers in the early and accurate diagnosis, treatment, and prognosis and rehabilitation assessment of schizophrenia.

Routine blood test results of Tibetan children and adolescents in plateau areas / 中国学校卫生

Objective@#To investigate routine blood test results and secular changes among Tibetan children and adolescents aged from 3 to 19 in the plateau, and to provide the basis for reference range of routine blood test for this population.@*Methods@#A total of 1 568 Tibetan children and adolescents aged from 3 to 19 living in Shigatse, Tibet were selected by cluster random sampling method. Routine blood test results and its secular trends were compared by age and gender.@*Results@#Significantly differences were found in red blood cell(RBC), hemoglobin(HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin(MCH), white blood cell(WBC), neutrophil(NEU), neutrophil percentage (NEU%), lymphocyte(LYM), lymphocyte percentage(LYM%)，monocyte percentage(MON%)，eosinophil percentage(EOS%),basophil percentage(BAS%) and platelet(PLT) among the four age groups of 3-5, 6-12, 13-15, and 16-19 years ( F/H =60.22, 179.41, 249.45, 115.03, 74.90, 14.33 , 33.46, 78.90, 49.20, 97.29, 24.45,24.28,42.65,20.10, P <0.05). Among red blood cell indexes, RBC, HGB, HCT,MCH increased with age in boys( F =148.77, 493.04, 623.14, 249.92, P <0.05), but there was no similar trend in girls( F =1.37, 0.15, 2.94, 0.11, P >0.05). HCT showed significant sex differences among the four age groups of 3-5 years, 6-12 years, 13-15 years, and 16-19 years [(41.33±2.31)% vs (41.98±2.40)%; (43.28±2.60)% vs ( 43.75 ±2.36)%; (46.20±3.11)% vs (44.83±2.67)%; (51.10±4.15)% vs (43.61±4.70)%, t =-2.10, -2.88, 3.50, 10.82, P <0.05]. WBC, NEU, NEU%, LYM, LYM%, monocyte(MON), and MON% increased significantly with age in both boys and girls ( P <0.05). From the age of 12 to 13, RBC, HGB and HCT in Tibetan male and female adolescents showed an opposite trend and widened gradually.@*Conclusion@#Red blood cell index shows significantly different trends among Tibetan adolescents and children of different ages and genders. Regional nationality, age, gender, and other factors should be considered when developing the reference value range of blood routine index.

Routine blood test results of Tibetan children and adolescents in plateau areas / 中国学校卫生

Objective@#To investigate routine blood test results and secular changes among Tibetan children and adolescents aged from 3 to 19 in the plateau, and to provide the basis for reference range of routine blood test for this population.@*Methods@#A total of 1 568 Tibetan children and adolescents aged from 3 to 19 living in Shigatse, Tibet were selected by cluster random sampling method. Routine blood test results and its secular trends were compared by age and gender.@*Results@#Significantly differences were found in red blood cell(RBC), hemoglobin(HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin(MCH), white blood cell(WBC), neutrophil(NEU), neutrophil percentage (NEU%), lymphocyte(LYM), lymphocyte percentage(LYM%)，monocyte percentage(MON%)，eosinophil percentage(EOS%),basophil percentage(BAS%) and platelet(PLT) among the four age groups of 3-5, 6-12, 13-15, and 16-19 years ( F/H =60.22, 179.41, 249.45, 115.03, 74.90, 14.33 , 33.46, 78.90, 49.20, 97.29, 24.45,24.28,42.65,20.10, P <0.05). Among red blood cell indexes, RBC, HGB, HCT,MCH increased with age in boys( F =148.77, 493.04, 623.14, 249.92, P <0.05), but there was no similar trend in girls( F =1.37, 0.15, 2.94, 0.11, P >0.05). HCT showed significant sex differences among the four age groups of 3-5 years, 6-12 years, 13-15 years, and 16-19 years [(41.33±2.31)% vs (41.98±2.40)%; (43.28±2.60)% vs ( 43.75 ±2.36)%; (46.20±3.11)% vs (44.83±2.67)%; (51.10±4.15)% vs (43.61±4.70)%, t =-2.10, -2.88, 3.50, 10.82, P <0.05]. WBC, NEU, NEU%, LYM, LYM%, monocyte(MON), and MON% increased significantly with age in both boys and girls ( P <0.05). From the age of 12 to 13, RBC, HGB and HCT in Tibetan male and female adolescents showed an opposite trend and widened gradually.@*Conclusion@#Red blood cell index shows significantly different trends among Tibetan adolescents and children of different ages and genders. Regional nationality, age, gender, and other factors should be considered when developing the reference value range of blood routine index.

How to Choose a Survival Period? The Impact of Antibiotic Use on OS or PFS in NSCLC Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

BACKGROUND: The development of immunotherapy has dramatically changed the treatment of non-small-cell lung cancer. The negative association of antibiotics on the clinical activity of immune checkpoint inhibitors in patients with NSCLC is well known. METHODS: PubMed, Embase, and Medline databases were searched until January 11, 2020. We included retrospective studies of ICIs (e.g., PD-1, PD-L1, and CTLA-4). The clinical outcomes were progression-free survival (PFS) and overall survival (OS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated, and subgroup and sensitivity analyses were performed. RESULTS: Our results indicated that the use of antibiotics reduced the survival of NSCLC patients treated with ICIs. The pooled HRs of PFS and OS were HR = 1.41 (95% CI = 1.23-1.61; P < 0.001) and HR = 2.16 (95% CI = 1.79-2.60; P < 0.001). We divided the studies into 5 subgroups according to antibiotic exposure time. Subgroup analysis showed that the patients that were administered antibiotics [-60 days; 0 days] or [-30 days; 0 days] before the initiation of ICIs treatment had a poorer OS rate, whereas those patients that were administered antibiotics [0 days; 30 days] after the initiation of ICIs treatment had a poorer PFS rate. In summary, ATB treatment in patients [-60 days; +30 days] near the initiation of ICIs treatment significantly reduced the survival in NSCLC patients. CONCLUSION: Our results indicated that ATB use is negatively associated with survival in NSCLC patients treated with ICIs immunotherapy. Similar studies involving a larger sample of cases are still being published. This meta-analysis identified that the timing of ATB treatment in NSCLC patients receiving ICIs immunotherapy has different effects on the OS and PFS of these patients. ATB treatment prior to the initiation of ICIs treatment affects OS, whereas ATB treatment after the initiation of ICIs treatment affects PFS.

Bioenergy from dairy manure: technologies, challenges and opportunities.

Dairy manure (DM) is a kind of cheap cellulosic biomass resource which includes lignocellulose and mineral nutrients. Random stacks not only leads damage to the environment, but also results in waste of natural resources. The traditional ways to use DM include returning it to the soil or acting as a fertilizer, which could reduce environmental pollution to some extent. However, the resource utilization rate is not high and socio-economic performance is not utilized. To expand the application of DM, more and more attention has been paid to explore its potential as bioenergy or bio-chemicals production. This article presented a comprehensive review of different types of bioenergy production from DM and provided a general overview for bioenergy production. Importantly, this paper discussed potentials of DM as candidate feedstocks not only for biogas, bioethanol, biohydrogen, microbial fuel cell, lactic acid, and fumaric acid production by microbial technology, but also for bio-oil and biochar production through apyrolysis process. Additionally, the use of manure for replacing freshwater or nutrients for algae cultivation and cellulase production were also discussed. Overall, DM could be a novel suitable material for future biorefinery. Importantly, considerable efforts and further extensive research on overcoming technical bottlenecks like pretreatment, the effective release of fermentable sugars, the absence of robust organisms for fermentation, energy balance, and life cycle assessment should be needed to develop a comprehensive biorefinery model.

Effects of Artesunate Combined with Arsenious Acid on Proliferation and Apoptosis of Multiple Myeloma Cells via PI3K/AKT Signaling Pathway / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of artesunate and arsenous acid and their combination on the proliferation and apoptosis of human multiple myeloma cells and their mechanism.@*METHODS@#Human multiple myeloma cell line RPMI 8226 cells were cultured and treated with 0, 1, 2, 4, 8 nmol/L arsenous acid and 0, 40, 80, 160, 320 μmol/L artesunate, respectively. The inhibition of cell growth was detected by CCK-8 assay. The apoptosis rate was detected by flow cytometry. QPCR was used to detect the mRNA expression of cell proliferation and apoptosis-related factors. The expression of cell proliferation, apoptosis-related factors and PI3K/AKT pathway protein were detected by Western blot.@*RESULTS@#CCK-8 assay showed that the growth of multiple myeloma cells was inhibited by arsenous acid and artesunate. The IC@*CONCLUSION@#Artesunate combined with arsenous acid inhibits proliferation and promotes apoptosis of tumor cells through PI3K/AKT signaling pathway, and is superior to the effect of two drugs alone.