Sepsis-induced lung injury is a common type of sepsis complicated with multiple organ dysfunction syndrome， whose uncontrolled inflammatory response and oxidative stress are the key pathological mechanisms. As an important pathway of anti-inflammatory and anti-oxidative stress， the nuclear factor-erythroid 2-related factor 2 （Nrf2） signaling pathway is very important in the occurrence and development of sepsis-induced lung injury. This review summarizes relevant research conducted over the past decade on the regulation of the Nrf2 signaling pathway by traditional Chinese medicine （TCM） to ameliorate sepsis- induced lung injury. It has been found that 14 kinds of TCM effective ingredients （including five types of compounds： flavonoids， terpenes， alkaloids， saponins， phenols） and 6 kinds of compound preparations （including three types of formulas： heat-clearing and detoxifying formulas， purgative formulas for promoting bowel movement， and formulas for reinforcing vital qi and consolidating the constitution） can inhibit inflammatory responses and oxidative stress by activating Nrf2 signaling pathway and intervening in related pathways such as those involving Kelch-like ECH-associated protein 1， heme oxygenase-1， antioxidant response element and AMP-activated protein kinase， thereby alleviating sepsis-induced lung injury.

Objective To explore the relationship between the polymorphism of excision repair cross-complementation group 1 (ERCC1) C8092A locus and the efficacy and prognosis of platinum-based chemotherapy for lung cancer (LC), and to provide a theoretical basis for precision treatment of LC. Methods From January 2014 to October 2017, 120 patients from two tertiary hospitals in Haikou City, and with pathologically confirmed lung cancer treated with platinum-based chemotherapy were selected as the research objects. After informed consent was obtained, peripheral blood samples were collected for DNA extraction, and the genotype of ERCC1 C8092A locus was detected by mass spectrometry. WHO's Response Evaluation Criteria in Solid Tumours (RECIST) was used to judge patients' chemotherapy efficacy and patients' survival status was obtained by telephone follow-up and other means. Results Among the 120 LC patients, the genotype frequencies of ERCC1 C8092A locus were 67 cases of CC wildtype (55.8%), 45 cases of CA heterozygous type (37.5%), and 8 cases of AA rare mutation type (6.7%), which conformed to Hardy-Weinberg equilibrium (χ2=0.140, P>0.05). The total effective rate of chemotherapy was 32.5%, with the highest effective rate in patients with the CA genotype (42.2%) at the ERCC1 C8092A locus and the lowest in patients with the CC genotype (25.4%). The overall one-year survival rate was 68.3% and the three-year survival rate was 35.8%. The patients with ERCC1 C8092A AA genotype had the lowest survival rate, with a one-year survival rate of 50.0% and three-year survival rate of only 25.0%. However, there were no statistical differences in the overall survival rate among the three genotypes of carriers of ERCC1 C8092A (χ2=0.328, P=0.849). Conclusions The polymorphism of ERCC1 C8092A locus is associated with the efficacy of platinum-based chemotherapy for LC, and patients with CA genotype have the highest efficacy. The one-year and three-year survival rates of patients with CC genotype are significantly higher than those of CA and AA genotypes.

Objective:To investigate the efficacy of fruquintinib in the treatment of advanced colorectal cancer, and to analyze the risk factors for all-cause death of fruquintinib.Methods:The clinical data of 82 patients with advanced colorectal cancer in the First Affiliated Hospital of Bengbu Medical College from December 2020 to April 2022 were retrospectively analyzed. The basic clinical data, efficacy and adverse reactions were recorded. The patients were followed up to October 2022, and all-cause death was recorded. Multivariate Logistic regression was used to analyze the risk factors of all-cause death in patients with advanced colorectal cancer treated with fruquintinib.Results:After treatment, partial remission was found in 9 cases, stable disease in 42 cases, disease progression in 31 cases. The objective remission rate was 10.98% (9/82), and the disease control rate was 62.20% (51/82). The incidence of adverse reactions was 75.61% (62/82), mainly hypertension and hand-foot syndrome. By the end of follow-up, 19 patients died and 63 survived. The incidences of body mass index (BMI)≥24 kg/m 2, lymph node metastasis, tumor located in the right colon and lactate dehydrogenase >200 U/L in all-cause death patients were significantly higher than those in survival patients: 36.51% (23/63) vs. 16/19, 39.68% (25/63) vs. 13/19, 44.44% (28/63) vs. 15/19 and 41.27% (26/63) vs. 14/19, and there were statistical differences ( P<0.01 or <0.05); there were no statistical differences in gender composition, age, smoking history, hypertension and postoperative complications between the two groups ( P>0.05). Multivariate Logistic regression analysis result showed that BMI≥24 kg/m 2, lymph node metastasis, tumor located in the right colon and lactate dehydrogenase >200 U/L were independent risk factors for all-cause death in patients with advanced colorectal cancer treated with fruquintinib ( OR = 9.275, 3.293, 4.687 and 3.985; 95% CI 2.440 to 35.265, 1.106 to 9.806, 1.398 to 15.715 and 1.277 to 12.430; P<0.01 or <0.05). Conclusions:Fruquintinib is effective in the treatment of advanced colorectal cancer. The BMI≥24 kg/m 2, lymph node metastasis, tumor located in the right colon and lactate dehydrogenase >200 U/L are independent risk factors for all-cause death in patients with advanced colorectal cancer treated with fruquintinib.

Objective:To investigate the clinical significance of cc-chemokine receptor 7 (CCR7) as a potential diagnostic or differential marker for chronic lymphocytic leukemia (CLL).Methods:A total number of 643 patients with B-cell chronic lymphoproliferative diseases (B-CLPD) admitted to the First Affiliated Hospital of Nanjing Medical University from January 2015 to December 2018 were enrolled. The patients included 327 cases of CLL, 58 cases of mantle cell lymphoma (MCL), 34 cases of follicular lymphoma (FL), 36 cases of marginal zone lymphoma (MZL), 10 cases of hair-cell leukemia or its variants (HCL/HCLV-v), 40 cases of Waldorf′s macroglobulinemia (WM), 48 cases of CD5 +B-cell chronic lymphoproliferative disease unclassified (B-CLPD-U) and 90 cases of CD5 -B-CLPD-U. At the same time, 20 samples from healthy people from the medical examination center of our hospital were used as normal controls. Flow cytometry was used to detect the immune-phenotype and CCR7 expression level in B-CLPD patients, and Fluorescence in situ hybridization (FISH) was used to analyze the genomic alterations: the ataxia telangiectasia mutant gene (ATM) deletion, the 13q14 deletion, the P53 deletion and trisomy 12. Sanger sequencing was used to analyze gene mutations of splicing factor 3B subunit 1 (SF3B1), NOTCH1, tumor protein 53 (TP53) and immunoglobulin heavy chain variable region (IGHV). Measurement data were compared by Mann-Whitney test, and the positive rates were compared by chi-square test. The diagnostic value and optimal positive cutoff value of CCR7 were calculated using receiver operating characteristic (ROC) curve. Results:The positive rates of CCR7 expression in typical CLL and atypical CLL were 90.8% (257/283) and 84.1% (37/44), respectively, and there was no significant difference of the positive rates (χ 2=1.228, P=0.268) between groups. The positive expression rates of CCR7 in CLL, MCL, CD5 +B-CLPD-U, CD5 -B-CLPD-U, FL, WM, HCL/HCL-v and MZL were 89.9% (294/327), 10.3% (6/58), 6.3% (3/48), 8.9% (8/90), 0, 0, 0 and 13.9% (5/36) respectively, and the median mean fluorescence intensity (MFI) was 278 (246, 307), 114 (106, 128), 112 (106, 117), 110 (104, 121), 108 (105, 119), 111 (105, 124), 112 (108, 115) and 109 (105, 120) respectively. Compared with CLL, the positive expression rates of CCR7 in other types of B-CLPDs were lower significantly (χ 2=181.3, 177.8, 232, 164.7, 180.8, 62.6, 129, P<0.01). In addition, the sensitivity, specificity and accuracy of CCR7 for distinguishing CLL from other types of B-CLPD were 89.9%, 93.0% and 92.3%, respectively. The positive expression rate of CD49d in CCR7 +CLL patients was 13.9%, which was significantly lower than that in CCR7 -CLL patients (42.1%) (χ 2=7.6, P=0.01). The coincidence rate of 13q14 deletion was 50.3% in CCR7 +CLL patients, which was significantly higher than that in CCR7 -CLL patients (20%) (χ 2=6.56, P=0.01). Conclusions:The CC-chemokine receptor 7 (CCR7) antigen is an effective marker for the diagnosis and identification of chronic lymphocytic leukemia (CLL). The expression level of CCR7 in clinical specimens can distinguish CLL from other pathological subtypes of B-CLPDs.

Objective:To explore the correlation of CD49d expression patterns with molecular genetics and hotspot gene mutants in patients with chronic lymphocytic leukemia.Methods:The expression of CD49d was detected by flow cytometry and grouped into homogeneous, bimodal, negative and positive expression. Panel fluorescence in situ hybridization (FISH) was used for molecular genetics analysis and next-generation sequencing (NGS) was conducted for gene mutation detection.Results:There were 43 patients (23.89% ) with positive CD49d expression, 137 patients (76.11% ) with negative CD49d expression, 96 patients (53.33% ) with homogeneous CD49d expression and 84 patients (46.67% ) with bimodal CD49d expression. Compared with patients in the CD49d negative group, patients in the CD49d positive group had higher Rai stage ( P=0.048) and higher proportion of spleen enlargement ( P=0.030) . Compared with patients with homogeneous expression of CD49d, patients with bimodal expression of CD49d had a higher proportion of spleen enlargement ( P=0.009) . The expression rate of 11q22- in bimodal CD49d - group was significantly higher than that in homogeneous CD49d - group (24.29% vs 10.45% , P=0.043) . The incidence of +12 in homogeneous CD49d group was higher than that in bimodal CD49d group (16.67% vs 5.95% , P=0.035) . The incidence of +12 in homogeneous CD49d + group was higher than that in bimodal CD49d - group (17.24% vs 4.29% , P=0.045) . The incidence of +12 in homogeneous CD49d - group was higher than that in bimodal CD49d - group (16.42% vs 4.29% , P=0.024) . BIRC3 mutation rate in CD49d positive group was higher than that in CD49d negative group (11.63% vs 2.92% , P=0.037) . Conclusion:There were significant correlations between CD49d and 11q22-, +12 and BIRC3 gene mutation. Patients with bimodal CD49d were more correlated with poor prognosis indexes.

Objective:To analyze the differences in immunophenotype, cytogenetics, and molecular biology between typical and atypical immunophenotype chronic lymphocytic leukemia (CLL) , and explore the correlation of cytogenetic anomalies with gene mutations.Methods:This study included 488 patients diagnosed in the First Affiliated Hospital of Nanjing Medical University between November 2014 and May 2021. Of these, 382 patients scored 4-5 points, which was typical CLL (tCLL) , and 106 scored 3 points, which was atypical CLL (aCLL) as per the Royal Marsden Hospital Immunomarker Integral System. Peripheral blood cells were collected for immunophenotype by multiparameter flow cytometry in 488 patients, fluorescence in situ hybridization (FISH) was employed to detect cytogenetic anomalies in 359 patients, and gene mutations were detected by next-generation sequencing (NGS) in 330 patients.Results:The positive rates of CD10, CD22, CD49d, CD81, and FMC7 were significantly higher in the aCLL compared with the tCLL group ( P=0.020, P<0.001, P<0.001, P=0.027, and P<0.001, respectively) , while the positive rates of CD5, CD23, CD148, and CD200 were lower in the former compared to the latter ( P<0.001, P=0.017, P=0.041, and P<0.001, respectively) . aCLL exhibited a higher frequency of trisomy 12 and lower frequency of del (13q14) compared to the tCLL group ( P<0.001 and P<0.001, respectively) . Moreover, aCLL patients also showed a higher incidence of NOTCH1 mutations than the tCLL patients ( P=0.038) , while no statistically significant differences in other gene mutations occurred between the two groups. No significant differences in overall survival (OS) and treatment-free survival (TFS) occurred between aCLL and tCLL using Kaplan-Meier analysis ( P>0.05) . Conclusion:aCLL has characteristic immunophenotype, cytogenetic, and somatic mutation that differ from tCLL, and this can provide reliable information for the diagnosis and differential diagnosis between the two groups.

Objective:To explore the role of parental origin verification in chromosomal microarray analysis (CMA) on the determination of the clinical significance of copy number variations (CNVs).Methods:This retrospective study collected clinical information from 73 core families who underwent prenatal diagnosis at Peking University First Hospital from November 2017 to December 2019. Indications for prenatal diagnosis included ultrasound abnormality in 54 cases (including 12 with thickened nuchal translucency (≥2.5 mm), four with fetal growth restriction, seven with abnormal pregnancy history, and 31 with isolated ultrasound abnormality), NIPT indicated high-risk in four cases, advanced age in nine cases, abnormal pregnancy history alone in three cases, intrauterine death in two cases and one with maternal mental retardation. Genomic DNA of amniotic fluid sample, chorionic villi, cord blood, fetal tissues, and fetal heart blood were extracted using genomic DNA extraction kit. The CNVs of prenatal samples in 73 subjects were analyzed using array-based comparative genomic hybridization (array-CGH) analysis and single nucleotide polymorphism array (SNP-array). Peripheral blood DNA of the couples, and relevant families if necessary, were collected and analyzed in the same way. The results of parental origin detection in CMA were summarized.Results:A total of 76 CNVs were detected in these 73 samples, out of which nine were pathogenic and parental origin detection revealed that six were de novo, two were maternally, and one was paternally inherited; six CNVs were likely pathogenic, including three de novo, two maternally inherited and one paternally inherited; 20 CNVs were variants of uncertain significance, including five paternally inherited, three maternally inherited and 12 de novo; 41 CNVs were likely benign, among which 38 were inherited from parents with normal phenotype. Conclusions:Parental origin verification plays an important role in explaining the clinical significance of detected fetal CNVs and thereby can help to analyze its clinical effect and reproductive risk.

Objective:To investigate the effects of Notch1 signaling on histone acetylation of Foxp3 gene and its roles in regulating regulatory T (Treg) cells in children with acute B-cell precursor lymphoblastic leukemia (BCP-ALL).Methods:Blood samples were collected form 38 children with BCP-ALL before treatment and 15 age-matched healthy children (control group). Flow cytometry was performed to detect the proportion of peripheral blood CD4 + CD25 hiFoxp3 + Treg cells and the expression of Foxp3, cytotoxic lymphocyte antigen 4 (CTLA4), glucocorticoid-induced tumor necrosis factor receptor (GITR), CD39 and Notch1 at protein level. Histone 4 acetylation (H4Ac) at Foxp3 gene promoter and the binding abilities of Foxp3 gene promoter to NICD1 and p300 in CD4 + T cells were measured by chromatin immunoprecipitation. Quantitative real-time PCR was performed to detect the expression of Foxp3, presenilin 1 (PSEN1), mastermind-like transcriptional coactivator 1 (MAML1), SKI-interacting protein (SKIP), F-box and WD40 domain protein 7 (FBXW7), glycogen synthase kinase-3 beta (GSK3β) and IKAROS at mRNA level in CD4 + T cells. The concentrations of TGF-β and IL-10 in plasma were evaluated by ELISA. Results:(1) The proportion of peripheral blood CD4 + CD25 hiFoxp3 + Treg cells, the expression of differentiation- and function-associated molecules (Foxp3, CTLA4, GITR and CD39) and the concentrations of TGF-β and IL-10 in plasma were higher in the BCP-ALL group than in the control group ( P<0.05). (2) In children with acute BCP-ALL, H4Ac at Foxp3 promoter and the binding abilities of Foxp3 gene promoter to NICD1 and p300 were significantly increased as compared with those in control group( P<0.05). The binding abilities of Foxp3 gene promoter to NICD1 and p300 were positively correlated with the expression of Foxp3 at mRNA level ( r=0.58 and 0.46, both P<0.05). After competitive inhibition, the three aforementioned indexes in the acute BCP-ALL group were significantly lower than those in untreated group ( P<0.05); the binding ability of Foxp3 gene promoter to NICD1 in the control group was also significantly lower than that in untreated control group ( P<0.05), but no statistical differences in the other two indexes were found between the control groups with or without treatment ( P>0.05). ⑶ Compared with the control group, the expression of Notch1, PSEN1, MAML1 and SKIP in CD4 + T cells were elevated significantly ( P<0.05), while the transcription level of negative regulatory factor FBXW7 was decreased remarkably in children with acute BCP-ALL ( P<0.05). No statistical differences in the expression of GSK3β or IKAROS were found between the two groups ( P>0.05). Conclusions:Overactivation of Notch1 signaling caused by low expression of FBXW7 might be the key factor resulting in histone 4 hyperacetylation at foxp3 gene promoter and Treg cell dysfunction in children with acute BCP-ALL.

Objective:To survey the application of an intelligent consultation system for common eye diseases and evaluate its applicational effectiveness on an internet hospital platform.Methods:A cross-sectional study was performed in Zhongshan Ophthalmic Centre of Sun Yat-sen University.Natural language processing technology was applied to develop the intelligent consultation system for common eye diseases.Its efficiency and quality were evaluated.The survey data were collected from February 1 to 29, 2020 to analyze the demographic information, consultation time, consultation category, consultation content, service satisfaction.This study protocal was approved by an Ethic Committee of Zhongshan Ophthalmic Centre of Sun Yat-sen University(2020KYPJ095).Results:The intelligent consultation system for common eye diseases was developed and successfully deployed in Internet Hospital of Zhongshan Ophthalmic Center.The repeatability and accuracy of the intelligent consultation system were 100.0% and 99.8%, respectively.During February 1 to 29, 2020, the intelligent consultation system served 6 462 patients, including 3 082 males(47.7%) and 3 380 females(52.3%). The average age of patients was 32.3 years old.Total of 1 135(17.6%) patients used the intelligent guidance consultation, and 5 375(82.4%) patients used the intelligent outpatient consultation.The intelligence consultation system was applied by 223 patients per day with a maximum of 74 patients per hour.The survey showed that 25.6% and 36.4% of the patients felt very satisfied and relatively satisfied with the efficiency of the intelligent consultation service, respectively; 24.3% and 37.8% of the patients were very satisfied and relatively satisfied with the quality of the intelligent consultation service, respectively.Conclusions:Intelligent consultation system for common eye diseases can meet the needs of patients because of its high repeatability and accuracy.Patients are satisfied with the service efficiency and quality of the intelligent consultation system, which avoids the risk of cross infection and releases the burden of medical staff.

Objective To explore the spatial description of Keshan disease(KD)and to provide a basis for reasonable allocation of health resources and for making precision prevention and control strategies. Methods In 2013 and 2014, the KD's condition, prevention and control measures and their effects were investigated in the diseased affected counties in the provinces through combination of case search and key survey. Results A total of 16(100.0%,16/16)diseased provinces,315(96.0%,315/328)diseased counties were surveyed,and 1 562 people with KD were detected in 281 000 residents, the detection rate was 55.6/10 000. Chronic and latent KD detection rates were 8.9/10 000(250)and 46.7/10 000(1 312),respectively.There were 261(82.9%)diseased counties that had reached the control standards of KD,and 54(17.1%)did not meet the control standards,which mainly distributed in the provinces of Henan, Inner Mongolia, Gansu and Shanxi. Conclusions The detection rate of KD has been at a low level, but in Henan, Inner Mongolia, Gansu, and Shanxi, there are prevalent KD areas that have not yet reached the control level.This part of the areas should be treated as key prevention and control areas of KD.