The present situation of environment polluted by phthalate esters,the main kinds of phthalate esters in the air samples and water samples and the pretreatment and analysis technology of phthalate esters in different environment were reviewed in the present article. In the air samples ,di(2-ethylhexy) phthalate(DEHP),di-n-butyl phthalate(DBP) and dioctyl phthalate(DOP) were included,while diethyl phthalate(DEP),di(2-ethylhexy) phthalate(DEHP),dipropyl phthalate(DPrP),butyl benzyl phthalate(BBP),dioctyl phthalate(DOP) and dimethyl phthalate(DMP) could be mainly detected in the water samples.

Objective To assess the association between NOD2 gene single nucleotide polymorphisms (SNPs) and leprosy in Chinese Yi population.Methods Whole blood samples were obtained from 300 patients with leprosy and 300 healthy human controls of Yi nationality in Sichuan province.Genomic DNA was extracted,and a SNaPshot assay was performed to determine the genotypes of four single nucleotide polymorphisms (SNPs) of the NOD2 gene,including rs9302752,rs7194886,rs8057341 and rs3135499.Chi-square test was conducted to compare allele frequency,and Hardy-Weinberg equilibrium was tested.Results The genotype distribution of all the four SNPs was consistent with Hardy-Weinberg equilibrium (all P ＞ 0.05).Significant differences were observed between the patients with leprosy and healthy controls in both genotype distribution and allele frequency of the SNP rs3135499 (both P ＜ 0.01),but not in those of the other three SNPs (all P ＞ 0.05).Conclusion The SNP rs3135499 of the NOD2 gene may be associated with the development of leprosy in Chinese Yi population.

Objective To investigate the risk factors for acute radiation esophagitis andpneumonitis after radiation therapy in esophageal cancer (EC) patients with diabetes or hypertension.Methods A total of 373 EC patients receiving three dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) were included in this study.Among these patients,42 showed concurrent with diabetes and 99 with hypertension.Radiation esophagitis or pneumonitis in patients with or without diabetes,and with or without hypertension were monitored in the 1-year follow up,respectively.Results The prevalence of grade 1,2,3 and 4 radiation esophagitis in diabetes and non-diabetes patients was 40.5％,38.1％,14.3％,4.8％ and 66.2％,27.8％,2.7％,1.8％,respectively,while that of the grade 1,2 and 3 radiation pneumonitis in diabetes and non-diabetes patients was 31.0％,16.7％,9.5％ and 30.8％,15.7％,1.2％,respectively.The prevalence of grade 3 or above radiation esophagitis and pneumonitis in patients with diabetes and was significantly higher than those with non-diabetes (x2 =13.573,12.279,P ＜ 0.05).The prevalence of grade 1,2,3 and 4 radiation esophagitis in hypertension and non-hypertension patients was 49.5％,38.4％,8.1％,3.0％ and 68.2％,25.5％,2.6％,1.8％,respectively,while that of the grade 1,2 and 3 radiation pneumonitis in hypertension and non-hypertension patients were 30.3％,18.2％,5.1％ and 31.0％,15.0％,1.1％,respectively.The prevalence of grade 3 or above radiation esophagitis and pneumonitis in patients with hypertension was significantly higher than those with non-hypertension (x2 =5.695、5.422,P ＜ 0.05).Diabetes is an independent risk factor for grade 3 or above acute radiation esophagitis and pneumonitis.Conclusions Diabetes or hypertension might be risk factors for severe radiation esophagitis and pneumonitis in EC patients receiving radiation therapy.

Cerebral small vessel disease is a group of heterogeneous diseases with stroke and cognitive impairment as the main clinical features.It can be divided into sporadic type and hereditary type.Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) belongs to hereditary cerebral small vessel disease.It has been reported in China,Japan,Spain,Greece,and other countries.The diagnosis mainly depends on characteristic clinical symptoms,imaging features,and genetic testing.CARASIL manifests as diffuse white matter abnormal signal and subcortical multiple infarcts on MRI,and it caused by HTRA1 gene mutation.

Medulla oblongata is precise in structure and the blood supply is complicated. After its infarction, it is easy to be misdiagnosed or missed because of its various clinical manifestations and lack of specificity. This article reviews the pathogenesis, clinical manifestations, and prognosis of medullary infarction in different sites.

Directed evolution strategy (error-prone PCR) was conducted to improve the activity of lipase from Rhizopus chinensis CCTCC M201021. Through two rounds of ep-PCR and pNPP top agar screening, two optimum mutant strains 1-11 and 2-28 were obtained with 2 and 4 fold of enzyme activity higher than that of parent strain, respectively. DNA sequencing of mutant lipase 2-28 revealed four amino acid substitutions: A129S, K161R, A230T, K322R. According to the simulated protein structure of Rhizopus chinensis lipase, A129S, K161R, A230T were located on the surface of the protein. A230T substitution improved the stability of the alpha-helix loop. K322R, near the catalytic center of lipase, located at a loop, formed a salt-bridge with a nearby aspartic acid (negative charged). Electrostatic force pulled the loop to the opposite direction of the substrate channel and made it easier for substrate to enter the lipase catalytic domain. Purified lipase was characterized and the result showed that Km of 2-28 lipase decreased by 10% compared with Km of the parent lipase, and Kcat was 2.75 fold improved than that of the original lipase.
Directed Molecular Evolution ; Lipase ; chemistry ; genetics ; Point Mutation ; Protein Engineering ; Rhizopus ; enzymology ; genetics

Objective To investigate the efficacy of hypofractionated radiotherapy(HFRT)com-bined with programmed cell death protein-1/programmed cell death ligand-1(PD-1/PD-L1)inhibitors in sequential with granulocyte-macrophage colony-stimulating factor(GM-CSF)and interleukin-2(IL-2)for the treatment of advanced metastatic solid tumors.Methods A prospective single-center single-arm study was designed for patients failed standard treatments for advanced refractory solid tumors in the Department of Radiotherapy of Jiangyin Hospital affiliated to Nantong University,and eli-gible patients were given quadruple therapy:HFRT(5 to 8 Gy × 2 to 3 f)once every 21 days for at least 2 cycles;200 μg GM-CSF from the 1st to 7 th day of radiotherapy,and 2 million IU IL-2 from the 8thto 14th day.Within 1 week after the completion of HFRT,PD-1/PD-L1 inhibitors were used for treatment.The above treatment strategy was repeated.GM-CSF and IL-2 were treated for 6 cycles,fol-lowed by maintenance with PD-1/PD-L1 inhibitors until disease progression(PD)or intolerable toxici-ty occurred.Objective response rate(ORR)and treatment-related adverse events were analyzed.Results From January 9,2021 to June 15,2023,totally 40 patients were enrolled,with follow-up of 2.8 to 31.0 months and a median follow-up of 9.9 months,and 39 patients(97.5％)completed at least one time tumorsite evaluation within the non-radiotherapy target area.97.5％of patients had canc-ers,2.5％had soft tissue sarcomas,and 20.0％had received immune checkpoint inhibitors(ICIs)at baseline check.The ORR was 30.8％,and the disease control rate(DCR)was 71.8％;the ORR for non-small cell lung cancer(NSCLC)was 28.6％,and the DCR was 57.1％;the ORR for colorectal cancer was 14.3％,and the DCR was 71.4％;the ORR for gastric cancer was 16.7％,and the DCR was 66.7％;28 patients(70.0％)had treatment-related adverse events(TRAE),4 patients(10％)had TRAE≥level 3,and the most common types of TRAE were fatigue,fever and hypothyroidism.Conclusion The treatment of HFRT combined with immune checkpoint inhibitors in sequential with GM-CSF and IL-2 is well tolerated and toxicity accepted in patients with advanced metastatic solid tumors,which may provide a new method for salvage treatment of patients with ad-vanced metastatic solid tumors.

Objective To investigate the efficacy of hypofractionated radiotherapy(HFRT)com-bined with programmed cell death protein-1/programmed cell death ligand-1(PD-1/PD-L1)inhibitors in sequential with granulocyte-macrophage colony-stimulating factor(GM-CSF)and interleukin-2(IL-2)for the treatment of advanced metastatic solid tumors.Methods A prospective single-center single-arm study was designed for patients failed standard treatments for advanced refractory solid tumors in the Department of Radiotherapy of Jiangyin Hospital affiliated to Nantong University,and eli-gible patients were given quadruple therapy:HFRT(5 to 8 Gy × 2 to 3 f)once every 21 days for at least 2 cycles;200 μg GM-CSF from the 1st to 7 th day of radiotherapy,and 2 million IU IL-2 from the 8thto 14th day.Within 1 week after the completion of HFRT,PD-1/PD-L1 inhibitors were used for treatment.The above treatment strategy was repeated.GM-CSF and IL-2 were treated for 6 cycles,fol-lowed by maintenance with PD-1/PD-L1 inhibitors until disease progression(PD)or intolerable toxici-ty occurred.Objective response rate(ORR)and treatment-related adverse events were analyzed.Results From January 9,2021 to June 15,2023,totally 40 patients were enrolled,with follow-up of 2.8 to 31.0 months and a median follow-up of 9.9 months,and 39 patients(97.5％)completed at least one time tumorsite evaluation within the non-radiotherapy target area.97.5％of patients had canc-ers,2.5％had soft tissue sarcomas,and 20.0％had received immune checkpoint inhibitors(ICIs)at baseline check.The ORR was 30.8％,and the disease control rate(DCR)was 71.8％;the ORR for non-small cell lung cancer(NSCLC)was 28.6％,and the DCR was 57.1％;the ORR for colorectal cancer was 14.3％,and the DCR was 71.4％;the ORR for gastric cancer was 16.7％,and the DCR was 66.7％;28 patients(70.0％)had treatment-related adverse events(TRAE),4 patients(10％)had TRAE≥level 3,and the most common types of TRAE were fatigue,fever and hypothyroidism.Conclusion The treatment of HFRT combined with immune checkpoint inhibitors in sequential with GM-CSF and IL-2 is well tolerated and toxicity accepted in patients with advanced metastatic solid tumors,which may provide a new method for salvage treatment of patients with ad-vanced metastatic solid tumors.

AIM:To determine the biological feature of circulating endothelial cells (CECs) in acute promye-locytic leukemia ( APL) patients before and after treatment , and to analyze the relationship between CECs and the clinical characteristics .METHODS: The CECs were sorted from peripheral blood by magnetic-activated cell sorting and then counted by 3-color flow cytometry.The cells were identified by immunofluorescence staining for the expression of CD 146, CD31, CD144, VEGFR-2, CD45 and CD133.The CECs were cultured in vitro, and the tube formation and colony-forming rate were determined .RESULTS:Increased quantity of CECs was observed in CD 34 positive group and group with WBC >10 ×109/L (P<0.05).The quantity of CECs had a significant difference among low risk , medium risk and high risk groups (P<0.05).The positive rate of CD133 and quantity of CECs significantly reduced in 32 APL patients when they gain complete remission after treatment (P<0.05).The amount of tube formation and colony-forming rate were significant-ly reduced after treatment (P<0.05).The ratio of CECs quantity from APL patients after treatment to that before treatment had a negative correlation with arsenic concentration in urine on day 7 during As2O3 treatment (P<0.05).CONCLU-SION:Accurately counting CECs may be helpful for evaluating prognosis and designing treatment strategy .

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.