Associations of genetic variations in pyroptosis related genes with acute adverse events in postoperative rectal cancer patients receiving concurrent chemoradiotherapy / 中华肿瘤杂志

Objective: This study aims to investigate the associations between genetic variations of pyroptosis pathway related key genes and adverse events (AEs) of postoperative chemoradiotherapy (CRT) in patients with rectal cancer. Methods: DNA was extracted from the peripheral blood which was collected from 347 patients before CRT. Sequenom MassARRAY was used to detect the genotypes of 43 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight pyroptosis genes, including absent in melanoma 2 (AIM2), caspase-1 (CASP1), caspase-4(CASP4), caspase-5 (CASP5), caspase-11 (CASP11), gasdermin D (GSDMD), gasdermin E (GSDME) and NLR family pyrin domain containing 3 (NLRP3). The associations between 43 htSNPs and AEs were evaluated by the odd ratios (ORs) and 95% confidence intervals (CIs) by unconditional logistic regression models, adjusted for sex, age, clinical stage, tumor grade, Karnofsky performance status (KPS), surgical procedure, and tumor location. Results: Among the 347 patients with rectal cancer underwent concurrent CRT with capecitabine after surgery, a total of 101(29.1%) occurred grade ≥ 2 leukopenia. rs11226565 (OR=0.41, 95% CI: 0.21-0.79, P=0.008), rs579408(OR=1.54, 95% CI: 1.03-2.29, P=0.034) and rs543923 (OR=0.63, 95% CI: 0.41-0.98, P=0.040) were significantly associated with the occurrence of grade ≥ 2 leukopenia. One hundred and fifty-six (45.0%) had grade ≥ 2 diarrhea, two SNPs were significantly associated with the occurrence of grade ≥ diarrhea, including CASP11 rs10880868 (OR=0.55, 95% CI: 0.33-0.91, P=0.020) and GSDME rs2954558 (OR=1.52, 95% CI: 1.01-2.31, P=0.050). In addition, sixty-six cases (19.0%) developed grade ≥2 dermatitis, three SNPs that significantly associated with the risk of grade ≥2 dermatitis included GSDME rs2237314 (OR=0.36, 95% CI: 0.16-0.83, P=0.017), GSDME rs12540919 (OR=0.52, 95% CI: 0.27-0.99, P=0.045) and NLRP3 rs3806268 (OR=1.51, 95% CI: 1.03-2.22, P=0.037). There was no significant difference in the association between other genetic variations and AEs of rectal cancer patients (all P>0.05). Surgical procedure and tumor location had great impacts on the occurrence of grade ≥2 diarrhea and dermatitis (all P<0.01). Conclusion: The genetic variants of CASP4, CASP11, GSDME and NLRP3 are associated with the occurrence of AEs in patients with rectal cancer who received postoperative CRT, suggesting they may be potential genetic markers in predicting the grade of AEs to achieve individualized treatment of rectal cancer.

Understanding cannabis use in Singapore: profile of users and drug progression

INTRODUCTION@#Cannabis has consistently been the third most commonly abused drug among drug arrestees in Singapore over the past few years. Accordingly, this study aimed to understand the profile of cannabis users in Singapore and explore the effects of cannabis use on drug progression.@*METHODS@#A total of 450 participants who had used cannabis at least once in their lifetime were recruited from the National Addictions Management Service, prisons, the Community Rehabilitation Centre and halfway houses from August 2017 to May 2018. A face-to-face questionnaire was administered and descriptive analyses were conducted.@*RESULTS@#The mean participant age was 40.9 ± 14.51 years, and 93.1% of them were male. The participants generally initiated cannabis use during adolescence, at a mean onset age of 16.5 ± 4.46 years. Most (89.6%) were introduced to cannabis by peers. Approximately half of them (46.9%) had used cannabis before other illicit drugs and 42.1% of them had used heroin as the succeeding drug.@*CONCLUSION@#In Singapore, cannabis use is often initiated during adolescence, largely under peer influence. Cannabis users may progress to other illicit drugs, particularly heroin, later in life.

The Association of Obstructive Sleep Apnea With Breast Cancer Incidence and Mortality: A Systematic Review and Meta-analysis / 한국유방암학회지

Purpose@#Emerging evidence from animal models suggests that intermittent hypoxia due to obstructive sleep apnea (OSA) is a risk factor for breast cancer. Despite their biological plausibility, human epidemiological studies have reported conflicting results. Therefore, we conducted a meta-analysis to delineate this relationship. @*Methods@#We searched the PubMed, Embase, Scopus, and Cochrane Library databases for eligible studies from inception until June 6, 2021. Two reviewers selected randomized trials or observational studies reporting the association between OSA and breast cancer incidence compared with those without OSA. Two reviewers extracted relevant data and assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework and Newcastle-Ottawa Scale (NOS). We pooled the maximally covariate-adjusted hazard ratios (HRs) using a random-effects inverse varianceweighted meta-analysis and performed pre-specified subgroup analyses. @*Results@#We included six studies out of 1,707 records, comprising a combined cohort of 5,165,200 patients. All studies used the International Classification of Diseases codes to classify OSA and breast cancer. OSA patients had a 36% increased breast cancer risk (HR, 1.36; 95% confidence interval [CI], 1.03–1.80; N = 6, I 2 = 96%) compared to those without OSA. Most studies adjusted for confounders, such as age, sex, obesity, diabetes mellitus, alcohol use, and hypertension. Subgroup analyses for studies with (1) multivariate adjustment and (2) at least five years of follow-up yielded HRs of 1.35 (95% CI, 0.98–1.87; N = 5, I 2 = 96%) and 1.57 (95% CI, 1.14–2.18; N = 4; I 2 = 90%), respectively. One Mendelian randomization study suggested a causal relationship, with a two-fold increase in the odds of breast cancer in patients with OSA. @*Conclusion@#This meta-analysis suggested that OSA is a risk factor for breast cancer. Future studies should explore the dose-response relationship between OSA and breast cancer, and whether treatment may mitigate breast cancer risk or progression.

Preliminary application and efficacy analysis of transumbilical single-incision plus one port robotic total mesorectal excision / 中华胃肠外科杂志

Objective: To investigate the feasibility of transumbilical single-incision plus one port (SIPOP) robotic total mesorectal excision. Methods: Clinical data of a 70-year-old male patient with BMI 22.1 kg/m(2) who successfully underwent transumbilical single-incision plus 1 port robotic total mesorectal resection of upper rectal cancer at the General Surgery Department of Daping Hospital of Army Military Medical University on September 18, 2019 were retrospectively analyzed. Preoperative colonoscopy revealed that the distance of upper rectal cancer to anal edge was 14 cm, and the tumor size was 2.5 cm×1.5 cm×1 cm. Pathological result confirmed rectal moderately differentiated adenocarcinoma. The preoperative abdominal CT showed thickened bowel-wall of upper rectum and the blurred perirectal fat, suggesting tumor infiltration. Results: The operation was successful. There were no conversion to laparotomy or abdominal auxiliary incision, and the mesorectum of the specimen was intact. The operation time was 165 minutes, the blood loss was about 20 ml, and there were no complications such as injury to peripheral organs. Postoperative pathology showed ulcerative moderately differentiated adenocarcinoma of the upper rectum with TNM stage IVA (T4N2b). The postoperative recovery was smooth. Patient ambulated on the 1st day, the catheter was removed on the 7th day, and discharged from the hospital on the 8th day. Conclusion: The transumbilical SIPOP robotic total mesorectal excision is safe, effective and feasible.

Simultaneous improvement to solubility and bioavailability of active natural compound isosteviol using cyclodextrin metal-organic frameworks

Cyclodextrin metal-organic framework (CD-MOF) as a highly porous supramolecular carrier could be one of the solutions to the insolubility of isosteviol (STV). The solubility of STV was lower than 20.00 ng/mL at pH 1.0 and pH 4.5, whilst its solubility increased to 20,074.30 ng/mL at pH 6.8 and 129.58 ng/mL in water with a significant pH-dependence. The

Effects of sodium arsenite and arsenic metabolites on the expression of linear and circular RNA of Nup107 in A549 cells / 中国职业医学

OBJECTIVE: To explore the effect of sodium arsenite and arsenic metabolites monomethylarsenic acid(MMA) and dimethylarsenic acid(DMA)on the expression of linear and circularRNAs of nucleoporin 107(Nup107) in human lung adenocarcinoma A549 cells. METHODS: i) The A549 cells in logarithmic phase were treated with 0, 30, 60, 90 μmol/L sodium arsenite for 48 hours. ii)The A549 cells in logarithmic phase were treated with 90 μmol/L sodium arsenite, MMA and DMA for 48 hours, the control group received no treatment. After culturing, the relative expression of linear RNA and circular RNA(circRNA) of Nup107 was detected by real-time quantitative polymerase chain reaction. RESULTS: i) The relative expression of linear RNA of Nup107 decreased and four circRNA isomers such as hsa＿circ＿0003599, hsa＿circ＿0027477, hsa＿circ＿0027478 and hsa＿circ＿0027479 increased with the increase of sodium arsenite dose(all P<0.01), showing a dose-effect relationship. In the 90 μmol/L sodium arsenite stimulated group, the relative expression of linear RNA of Lin-Nup107 decreased, and the four circRNA isomers increased compared with the control group in the A549 cells(all P<0.01). ii) The relative expression of Lin-Nup107 increased in the MMA and DMA stimulated groups and decreased in the sodium arsenite stimulated group compared with the control group in the A549 cells(all P<0.05). The relative expression of Lin-Nup107 decreased in the sodium arsenite stimulated group compared with the MMA and DMA stimulated groups in the A549 cells(all P<0.05). The relative expressions of hsa＿circ＿0003599, hsa＿circ＿0027478, hsa＿circ＿0027479 in the sodium arsenite stimulated group were higher than that in the MMA and DMA stimulated groups as well as the control group(all P<0.05).The relative expressions of hsa＿circ＿0027479 in the DMA stimulated group was lower than that in the control group(P<0.05). CONCLUSION: Sodium arsenite can induce the down-regulation of linear RNA and the up-regulation of circRNA of Nup107 in a dose-dependent manner. The metabolites of arsenic MMA and DMA can induce the overexpression of linear RNA of Nup107, however, they had no obvious effect on the circRNA of Nup107 in A549 cells.

Effect of umbilical moxibustion on phlegm damp constitution and intestinal flora / 中国针灸

OBJECTIVE@#To observe the effect of umbilical moxibustion on phlegm damp constitution and intestinal flora, and explore the mechanism of umbilical moxibustion in improving phlegm damp constitution.@*METHODS@#A total of 60 subjects with phlegm damp constitution were randomly divided into an observation group and a control group, 30 cases in each group. The control group was given TCM health guidance, such as diet and exercise; on the basis of the control group, umbilical moxibustion was applied in the observation group, 7 moxa cones each time, 2 times a week for 8 weeks. Before and after intervention, the indexes (transformation score of phlegm damp constitution, body mass, body mass index [BMI], waist circumference, hip circumference, heart rate and blood pressure) related to phlegm damp constitution were recorded in the two groups. The intestinal flora was detected with 16S rDNA sequencing technology in the two groups.@*RESULTS@#After intervention, the transformation score of phlegm damp constitution, body mass, BMI, waist circumference and hip circumference were decreased compared before intervention in the observation group (@*CONCLUSION@#Umbilical moxibustion may reshape the intestinal flora by up-regulating the relative abundance of

Construction and Identification of Leukemia Cell Line Stably Expressing CD123 and CLL-1 / 中国实验血液学杂志

OBJECTIVE@#To construct an acute myeloid leukemia cell line stably expressing CD123-CLL1 so as to provide an "in vitro" model for studying the role of CD123 and CLL-1 in leukemia and the treatment targeting CD123 and CLL-1.@*METHODS@#The recombinant plasmid of lentivirus was constructed by synthesizing CD123 and CLL-1 sequences and PCR homologous recombination. The lentivirus vector was packaged by three-plasmid packaging system. After collecting the supernatant of lentivirus, the virus titer was determined by quantitative PCR. K562 leukemia cells were collected and transtected with virus supernatant. Leukemia cell line stably expressing the target gene were screened by purinomycin. The expression levels of CD123 and CLL-1 were detected by RT-PCR and flow cytometry.@*RESULTS@#The lentiviral vector was successfully constructed, and identified by agarose gel electrophoresis and gene sequencing, then the virus titer of the supernatant was up to 5.81×10@*CONCLUSION@#Lentiviral vector expressing CD123-CLL1 has been successfully constructed, and K562 leukemia cell line stably expressing CD123 and CLL-1 has been successfully obtained.

Metformin inhibits pancreatic cancer metastasis caused by SMAD4 deficiency and consequent HNF4G upregulation

Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis due to limited therapeutic options. This study examines the roles of genome-wide association study identified PDAC-associated genes as therapeutic targets. We have identified HNF4G gene whose silencing most effectively repressed PDAC cell invasiveness. HNF4G overexpression is induced by the deficiency of transcriptional factor and tumor suppressor SMAD4. Increased HNF4G are correlated with SMAD4 deficiency in PDAC tumor samples and associated with metastasis and poor survival time in xenograft animal model and in patients with PDAC (log-rank P = 0.036; HR = 1.60, 95% CI = 1.03-2.47). We have found that Metformin suppresses HNF4G activity via AMPK-mediated phosphorylation-coupled ubiquitination degradation and inhibits in vitro invasion and in vivo metastasis of PDAC cells with SMAD4 deficiency. Furthermore, Metformin treatment significantly improve clinical outcomes and survival in patients with SMAD4-deficient PDAC (log-rank P = 0.022; HR = 0.31, 95% CI = 0.14-0.68) but not in patients with SMAD4-normal PDAC. Pathway analysis shows that HNF4G may act in PDAC through the cell-cell junction pathway. These results indicate that SMAD4 deficiency-induced overexpression of HNF4G plays a critical oncogenic role in PDAC progression and metastasis but may form a druggable target for Metformin treatment.

Genetic variation in DNA polymerase kappa gene is associated with the prognosis after platinum-based chemotherapy in small cell lung cancer patients / 中华肿瘤杂志

Objective@#To investigate the associations between genetic variations of DNA polymerase kappa (POLK) and treatment response to platinum-based chemotherapy of small cell lung cancer (SCLC), and to analyze the influencing factors on survival.@*Methods@#Five haplotype-tagging single nucleotide polymorphisms (htSNPs) of POLK were genotyped by Sequenom MassARRAY methods in 1 030 SCLC patients who received platinum-based chemotherapy, and had different response and survival time. The associations between SNPs and treatment response were analyzed by computing the odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression model. Cox regression was used for survival analysis between SNPs and overall survival by computing the hazard ratios (HRs) and 95% CIs.@*Results@#Among 1 030 cases, 558 (54.2%) cases received cis-platinum and etoposide treatment while others treated with carboplatin and etoposide. Seven hundred and eighty eight patients were chemotherapy responders in the study with a response rate of 76.5%. The median follow-up time of these patients was 22.0 months. Patients were followed up to get their survival information. The median survival time of these patients was 22.5 months. Six hundred and seventy three patients (65.3%) had died by the last date of follow-up to get their survival information (Dec 21, 2017). Five htSNPs of POLK were not associated with the chemotherapy response of SCLC patients who received platinum-based chemotherapy (all P>0.05). Multivariate Cox proportional hazards regression model analysis showed that, rs73120833 of POLK was significantly associated with the overall survival (OS) of SCLC patients, compared with POLK rs73120833 T allele, C allele can prolong OS (adjusted HR=0.87, 95% CI=0.77-0.97, P=0.021). The remaining 4 SNPS, including rs10077427, rs3756558, rs4549504 and rs5744545, were not significantly associated with overall survival. Age≤56, KPS> 80, limited-stage, chemotherapy response and radiation therapy can remarkably prolong OS (all P<0.05).@*Conclusion@#These results suggest that POLK genetic polymorphism rs73120833 plays an important role on the prognosis of SCLC patients, which can be potential genetic biomarker for SCLC personalized treatment.

Associations of Genetic Variations in Mismatch Repair Genes MSH3 and PMS1 with Acute Adverse Events and Survival in Patients with Rectal Cancer Receiving Postoperative Chemoradiotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Mismatch repair (MMR) deficiency plays a critical role in rectal cancer. This study aimed to explore the associations between genetic variations in seven MMR genes and adverse events (AEs) and survival of patients with rectal cancer treated with postoperative chemoradiotherapy (CRT). MATERIALS AND METHODS: Fifty single nucleotide polymorphisms in seven MMR (MLH1, MLH3, MSH2, MSH3, MSH6, PMS1 and PMS2) genes were genotyped by Sequenom MassARRAY method in 365 patients with locally advanced rectal cancer receiving postoperative CRT. The associations between genotypes and AEs were measured by odds ratios and 95% confidence intervals (CIs) by unconditional logistic regression model. The associations between genetic variations and survival were computed by the hazard ratios and 95% CIs by Cox proportional regression model. RESULTS: The most common grade ≥ 2 AEs in those 365 patients, in decreasing order, were diarrhea (44.1%), leukopenia (29.6%), and dermatitis (18.9%). Except 38 cases missing, 61 patients (18.7%) died during the follow-up period. We found MSH3 rs12513549, rs33013 and rs6151627 significantly associated with the risk of grade ≥ 2 diarrhea. PMS1 rs1233255 had an impact on the occurrence of grade ≥2 dermatitis. Meanwhile, PMS1 rs4920657, rs5743030, and rs5743100 were associated with overall survival (OS) time of rectal cancer. CONCLUSION: These results suggest that MSH3 and PMS1 polymorphisms may play important roles in AEs prediction and prognosis of rectal cancer patients receiving postoperative CRT, which can be potential genetic biomarkers for rectal cancer personalized treatment.

Transcriptome analysis on symbiotic molecular mechanism of Armillaria mellea and Gastrodia elata / 中草药

Objective In this study, Armillaria mellea and Zhaotong Gastrodia elata vegetative stems were used as the experimental material to reveal the symbiosis molecular mechanism of A. mellea infecting G. elata through comparative transcriptome sequencing analysis. Methods Trizor reason (invitrogen) was used to extract RNA from vegetative propagation stem samples, and the sequencing library was established and sequenced. Results The results showed that 38 838 sequences were annotated when G. elata symbiosis with A. mellea. Under false discovery rate (FDR) 1 screening conditions, there were significant differences in expression levels among the 23 333 genes, in which 1 595 genes up-regulated and 21 738 down-regulated expression. Based on the transcriptome analysis, unigenes associated with the extracellular enzyme gene cellulase, xylanase, laccase, and polygalacturonase genes were 21, 6, 39, and 6 genes, respectively, in which the number of corresponding differentially expressed genes were 9, 3, 23, and 4, respectively. The expression of all these unigenes were down-regulated except for one cellulase genes. The number of unigenes related to anti-oxidant enzymes superoxide dismutase, peroxidase, and catalase were 13, 7, and 17, respectively. The differentially expressed genes respectively were 6, 7, and 7, all of which were down-regulated. In addition, these genes were selectively confirmed by real-time PCR. Conclusion The life activites of A. mellea which infect and symbiosis with G. elata declined, meanwhile G. elata did not produce biological stress for A. mellea. This study provides a lot of valuable genetic resources for further studying the symbiosis molecular mechanism of A. mellea and G. elata.

Genetic variations in MLH3 and MSH2 genes are associated with the sensitivity and prognosis in locally advanced rectal cancer patients receiving preoperative chemoradiotherapy / 中华肿瘤杂志

Objective@#To investigate the associations between genetic variations in DNA mismatch repair genes and sensitivity as well as prognosis to preoperative chemoradiotherapy in patients with locally advanced rectal cancer.@*Methods@#Fourteen haplotype-tagging single nucleotide polymorphisms (htSNPs) of MLH1, MLH3 and MSH2 genes were genotyped by Sequenom MassARRAY method in 146 patients with locally advanced rectal cancer who received preoperative chemoradiotherapy. The associations between genotypes and response to capecitabine-based neoadjuvant chemoradiotherapy (nCRT) were measured by odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for sex, age, clinical stages and karnofsky performance score (KPS) by unconditional logistic regression model. The survival analyses were performed by the hazard ratios (HRs) and 95% CIs by Cox proportional regression model.@*Results@#Among 146 cases, 64 patients were nCRT responders with a response rate of 43.8%. MLH3 rs175057 C>T and MSH2 rs13019654 G>T loci were associated with the sensitivity to preoperative chemoradiotherapy. Compared with the rs175057 CC genotype, the adjusted OR for patients with CT and TT genotypes was 0.42 (95% CI: 0.19-0.91; P=0.029). Moreover, for rs13019654, the adjusted OR for patients with the GT or TT genotypes was 0.49 (95% CI: 0.24-0.98; P=0.047) than those with GG genotype. The remaining 12 SNPs, including rs1540354, rs4026175, rs1981929, rs2042649, rs2303428, rs3771273, rs4608577, rs4952887, rs6544991, rs6544997, rs10188090 and rs10191478, were not significantly associated with therapeutic response to preoperative chemoradiotherapy. Meanwhile, MLH3 rs175057 C>T locus was also associated with longer overall survival time in locally advanced rectal cancer (HR=0.44, 95% CI: 0.20-0.96, P=0.038), whereas MSH2 rs3771273 T>A, rs10188090 A>G and rs10191478 T>G loci were associated with shorter overall survival time (HR=1.74, 95% CI: 1.06-2.84, P=0.028; HR=1.64, 95% CI: 1.01-2.66, P=0.046; HR=1.71, 95% CI: 1.01-2.91, P=0.047, respectively). The remaining 10 SNPs, including rs1540354, rs4026175, rs1981929, rs2042649, rs2303428, rs4608577, rs4952887, rs6544991, rs6544997 and rs13019654, were not significantly associated with prognosis.@*Conclusions@#Genetic polymorphisms of MLH3 rs175057 and MSH2 rs13019654 loci can predict the nCRT response, while MLH3 rs175057 as well as MSH2 rs3771273, rs10188090 and rs10191478 may predict prognosis in patients with locally advanced rectal cancer who received preoperative chemoradiotherapy. Therefore, these SNPs could be used as potential genetic markers in the personalized therapy of rectal cancer.

Analysis on Adverse Drug Reactions of 43 Cases of Lentinan Injectionon and Discussion on Safety Medication / 中国中医药信息杂志

Objective To study the features and patterns of adverse drug reactions (ADR) induced by lentinan injection; To provide references for rational medication. Methods By using the method of retrospective analysis from 1994 to 2015, publicly reported 22 of lentinan injection ADR case report were analyzed. Results Clinical manifestations of lentinan injection ADR could be involved in a variety of organs, also could cause systemic damage. ADR associated with patient age at the same time, inappropriate drug dosage, solvent selection are factors that lead to adverse reactions. Conclusion When using lentinan injection, attention should be paid to the supervision of special population, medication should be strict according to the instructions and medication education should be strengthened, so as to reduce the occurrence of ADR and improve the satisfaction of patients.

Analysis of the impact of county medical alliance on patient flows under the NRCMS: A case study of Dingyuan county of Anhui Province / 中国卫生政策研究

Objective:This study is conducted to analyze the impact of county medical alliance on patient flows under the NRCMS in Dingyuan county of Anhui province. Methods: data on patient-flow were collected through the NRCMS information platform and related policy documents for 2015-2016, and interviews were conducted to study the main reform practices in the county medical alliance. Results: The patient flow under the NRCMS varied in the way of 1) the total number of inpatients seeking treatment outside of the county decreased by 3.31%;2) the treat-ment volume of county-level hospitals and township health centers were increasing,and the latter one is growing faster than the former,meanwhile,the treatment volume of the village clinics declined,and 3) the hospitalization expenses per inpatient for patients who seek treatment outside the county are much higher than the expenses incurred within the county. Conclusions:the development of county-level medical alliance has influence on patients with common disea-ses who used to seek treatment by helping to reduce the number of inpatients outside the county and reduce the pres-sure of the new rural cooperative fund. However, significant problems still exist such as shortage of talented practi-tioners,and lagging development of information technology system.

Dosimetric differences between volumetric modulated arc therapy plans with different arc numbers for cervical cancer / 医疗卫生装备

Object To study the effects of the number of arcs in the treatment of cervical cancer with volumetric modulated arc therapy (VMAT) on the treatment plan, and to provide reference for the selection of the number of arcs in the clinical application.Methods CT images of 10 patients with cervical cancer were selected, it's the radiation therapist that delineated the target area and organs, the prescribed dose was 5040 cGy per 28 times to the target area, and single arc (Arc1), double arc (Arc2) and three (Arc3) plan were designed by RayStation planning system to compare the differences with the dosimetry characteristics of target and organs. The time required for planning optimization was recorded, and the difference between the monitor unit and the delivery time in the three plans was analyzed. A dose validation tool for PTW was used to verify the dose to analyze the influence of the number of arc on the passing rate of gamma verification.Results Single arc plan (Arc1), double arc plan (Arc2) and three arc plan (Arc3) for 10 cases of cervical cancer all proved to meet the clinical requirements. With the increase of arc number, the target area distribution got improved, V40, V45 and Dmean in the organs at risk of rectum, bladder, and femoral head gradually decreased in case of doses of 40 and 45 Gy, and V35, V40 and V45 in the normal tissue were lowered in case of the doses of 35, 40 and 45 Gy. With the increase of the arc number, the optimization time and the delivery time of the plan increased, while the difference between the monitor unit of the three plans was smaller. The passing rate of the three plans was more than 99.5％, and the difference was small.Conclusion Cervical cancer VMAT plan has the target dose distribution and the protection of organs at risk enhanced with the increase of the number of arcs, while the treatment time and cost increased. Therefore, it is necessary to take comprehensive considerations on the number of VMAT plan arcs.

Protectin DX Exhibits Protective Effects in Mouse Model of Lipopolysaccharide-Induced Acute Lung Injury / 中华医学杂志(英文版)

<p><b>Background</b>Acute lung injury (ALI) is a severe disease with high mortality and poor prognosis. Protectin DX (PDX), a pro-resolving lipid mediator, exhibits protective effects in ALI. Our experiment aimed to explore the effects and related mechanisms of PDX in mice with ALI induced by lipopolysaccharide (LPS).</p><p><b>Methods</b>BALB/c mice were randomly divided into five groups: sham, LPS, LPS plus 1 ng of PDX (LPS + PDX-1 ng), LPS plus 10 ng of PDX (LPS + PDX-10 ng), and LPS plus 100 ng of PDX (LPS + PDX-100 ng). Bronchoalveolar lavage fluids (BALFs) were collected after 24 h, and total cells, polymorphonuclear leukocytes, monocyte-macrophages, and lymphocytes in BALF were enumerated. The concentration of interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), macrophage inflammatory protein (MIP)-1α, and MIP-2 in BALF was determined, and histopathological changes of the lung were observed. The concentration of protein in BALF and lung wet/dry weight ratios were detected to evaluate pulmonary edema. After determining the optimal dose of PDX, neutrophil-platelet interactions in whole blood were evaluated by flow cytometry.</p><p><b>Results</b>The highest dose of PDX (100 ng/mouse) failed to provide pulmonary protective effects, whereas lower doses of PDX (1 ng/mouse and 10 ng/mouse), especially 1 ng PDX, alleviated pulmonary histopathological changes, mitigated LPS-induced ALI and pulmonary edema, inhibited neutrophil infiltration, and reduced pro-inflammatory mediator (IL-1β, IL-6, TNF-α, and MIP-1α) levels. Meanwhile, 1 ng PDX exhibited pro-resolving functions in ALI including upregulation of monocyte-macrophage numbers and anti-inflammatory mediator IL-10 levels. The flow cytometry results showed that PDX could inhibit neutrophil-platelet interactions in ALI.</p><p><b>Conclusion</b>PDX exerts protective effects in LPS-induced ALI by mitigating pulmonary inflammation and abrogating neutrophil-platelet interactions.</p>

CCGD-ESCC: A Comprehensive Database for Genetic Variants Associated with Esophageal Squamous Cell Carcinoma in Chinese Population / 基因组蛋白质组与生物信息学报·英文版

Esophageal squamous-cell carcinoma (ESCC) is one of the most lethal malignancies in the world and occurs at particularly higher frequency in China. While several genome-wide association studies (GWAS) of germline variants and whole-genome or whole-exome sequencing studies of somatic mutations in ESCC have been published, there is no comprehensive database publically available for this cancer. Here, we developed the Chinese Cancer Genomic Database-Esophageal Squamous Cell Carcinoma (CCGD-ESCC) database, which contains the associations of 69,593 single nucleotide polymorphisms (SNPs) with ESCC risk in 2022 cases and 2039 controls, survival time of 1006 ESCC patients (survival GWAS) and gene expression (expression quantitative trait loci, eQTL) in 94 ESCC patients. Moreover, this database also provides the associations between 8833 somatic mutations and survival time in 675 ESCC patients. Our user-friendly database is a resource useful for biologists and oncologists not only in identifying the associations of genetic variants or somatic mutations with the development and progression of ESCC but also in studying the underlying mechanisms for tumorigenesis of the cancer. CCGD-ESCC is freely accessible at http://db.cbi.pku.edu.cn/ccgd/ESCCdb.

Correlations between genetic variations of glutathione synthetase gene and the response to platinum-based chemotherapy and prognosis of small cell lung cancer patients / 中华肿瘤杂志

Objective@#To explore the associations between genetic variations of glutathione synthetase gene (GSS) and response to platinum-based chemotherapy of small cell lung cancer(SCLC), and to analyze the influencing factors on survival.@*Methods@#Four haplotype-tagging single nucleotide polymorphisms (htSNPs) of GSS were genotyped by Sequenom MassARRAY methods in 903 SCLC patients who received platinum-based chemotherapy, and had different response and survival time. The associations between genotypes and platinum-based chemotherapy response were measured by odds ratios (OR) and 95% confidence intervals (CI), adjusted for sex, age, smoking, KPS, staging and chemotherapy regiments, by unconditional logistic regression model. The hazard ratios (HR) were estimated by Cox proportional hazards regression model.@*Results@#Among the 903 patients, 462(51.2%) cases received cis-platinum and etoposide treatment while others were treated with carboplatin and etoposide. 656 patients were chemotherapy responders in the study with a response rate of 72.6%. Patients were followed up to get their survival information. The median survival time (MST) of these patients was 25.0 months.We found that rs725521 located in the 3′ near gene region of GSS was significantly associated with chemotherapy response. Compared with the T allele, patients with C allele had a worse chemotherapy response and an increased risk of no-responders (P=0.027). Rs7265992 and rs725521 of GSS were associated with the overall survival (OS) of SCLC patients who received platinum-based chemotherapy (HR=1.16, 95% CI=1.02-1.33, P=0.027; HR=1.17, 95% CI=1.05-1.31, P=0.006, respectively). The patients carrying 1 or 2 risk alleles and the patients carrying 3 or 4 risk alleles had worse MST than the patients without the rs7265992A and rs725521C risk alleles (24.0 and 22.0 versus 30.0 months), with the HR for death being 1.26 (95% CI=1.04-1.54) and with the HR of 1.52 (95%CI=1.18-1.97, P=0.001). Rs2025096 and rs2273684 were not associated with the OS of SCLC patients who received platinum-based chemotherapy. Age ≤ 56, KPS> 80, limited-stage, chemotherapy response and radiation therapy had a remarkably prolonged OS (all P<0.05).@*Conclusions@#These results suggest that GSS genetic polymorphism rs725521 plays an important role in the response to platinum-based chemotherapy, while rs7265992 and rs725521 have important effect on the prognosis of SCLC patients, which may be potential genetic biomarkers for personalized treatment of SCLC.

Novel dry powder inhalation carrier:drug-carried lactose microparticles with flower shape and nanoporous structure / 药学学报

This work was designed to study a novel dry powder inhalation (DPI) carrier for drug loading and release of tiotropium bromide (asthma medicine). The synthesized lactose drug-carrier with a flower shape was crystalline. The carrier with a micro-meso-macroporous structure had advantages of high pore surface area, high capacity of drug loading and fast release of drug. In the study of loading tiotropium bromide, the drug was distributed at the core of carrier using the solution-based method, while the morphology was changed a little and the amount of loaded drug was 5% (w/w). Using the crystallization-based method, the drug was distributed at the shell of carrier, while the morphology was changed a lot and the amount of loaded drug was 49% (w/w). In addition, with the impact of carrier structure, the drug release rate was increased first and then decreased thereafter using the solution-based method, while the drug release rate was decreased first and then increased thereafter using the crystallization-based method. Thus, the lactose microparticles can be used as a novel drug carrier for dry powder inhalation.