Objective The objective of this study was to analyze the longitudinal trend of multidimensional treatment quality of breast cancer based on the latent growth mixture model(LGMM),identify potential change patterns and influencing factors,and pro-vide scientific basis for improving treatment quality and patient prognosis.Methods The quality monitoring data of breast cancer from four consecutive years were obtained in the National"Quality Monitoring System for Specific(single)Disease";Based on the item response theory(IRT),the treatment quality of breast cancer in the three dimensions of preoperative examination,treatment,and out-come was calculated;LGMM was constructed to analyze the independent and joint change trend of breast cancer treatment quality in all dimensions,and the optimal model was determined based on practical significance and statistical indicators.Results In the inde-pendent trend analysis,2 potential categories were identified for preoperative examination,treatment,and outcome dimensions.Among them,9%showed a rapid upward trend in the preoperative examination dimension,and 91%showed a relatively stable trend;The sta-ble growth accounted for 23%and slow decline accounted for 77%in the treatment dimension;13%of the outcome dimensions showed an upward trend,while 87%showed a downward trend.In the joint trend analysis of changes,2 potential categories were identified:the first category accounted for about 8%,and the preoperative examination dimension of this category had a good treatment quality,with mean intercepts and slopes of 3.326 and 3.367,respectively.The treatment quality in the treatment and outcome dimensions had steadily improved;The second category accounted for about 92%,and the treatment quality in this dimension was relatively good.Its mean intercept and slope were 0.548 and 0.018,respectively.There is still room for improvement in the treatment quality of the pre-operative examination and outcome dimensions;BMI and M stage in patient characteristics are important influencing factors on the trend of combined changes in treatment quality.Conclusion The treatment quality of breast cancer during this study period has im-proved to varying degrees in all dimensions of preoperative examination,treatment and outcome;In the joint trend analysis of the three dimensions,the improvement of treatment quality in the preoperative examination dimension can provide feasible references for subse-quent treatment and achieve the goal of reducing complications.

Objective Based on polynomial logistic regression model,this study aimed to analyze the optimal length of hospi-tal stay for patients with non-small cell lung cancer(NSCLC)at different stages to achieve the best treatment quality,providing refer-ence for improving treatment quality and formulating relevant policies.Methods The data of NSCLC cases were collected and 16 di-agnosis and treatment process indicators were selected.Patients were stratified according to the stage of lung cancer.A polynomial lo-gistic regression model was constructed,including patient characteristics to analyze the impact of first hospitalization days on the quali-ty of comprehensive treatment.Results A total of 10,053 patients with NSCLC were collected in this study,with a median compre-hensive treatment quality score of 0.60.According to the staging of lung cancer,patients were divided into the early stage group(stageⅠ-Ⅱ),locally advanced stage group(stage Ⅲ),and advanced stage group(stage Ⅳ).The first hospitalization days and treatment quality of each subgroup showed a non-linear relationship.The polynomial model results showed that after adjusting the characteristics of patients,the length of hospitalization day and the quadratic term of hospital stay had a statistically significant impact on treatment quality in each subgroup:early patients had a first hospital stay of 18 days,and locally advanced and advanced patients had a first hos-pital stay of 22 days,with the highest probability of achieving high treatment quality.Conclusion Patients in different stages have va-rying degrees of illness and treatment plans,resulting in different first hospitalization days corresponding to the highest probability of obtaining high-quality treatment.Hospitals can improve the treatment quality and medical efficiency by implementing standardized di-agnosis and treatment guidelines,strengthening the management of the diagnosis and treatment process,and reasonably controlling the first hospitalization time of patients in different stages.

Objective The aim of this study was to estimate the causal effects of non-small cell lung cancer(NSCLC)treat-ment process on in-hospital mortality based on the double robust estimation(DR)method,and provide a reference basis for reducing in-hospital mortality of NSCLC.Methods According to the quality evaluation system of NSCLC treatment,the utilization rate of treatment process indicators was calculated,and patients were divided into the high-quality or low-quality groups based on the aver-age score of treatment process quality.In-hospital mortality was used as the outcome indicator,Kaplan-Meier method and Cox regres-sion adjusted for propensity score inverse probability of treatment weighting(IPTW)correction were used to analyze the impact of treat-ment process quality on in-hospital mortality in NSCLC.DR was combined to estimate the causal effects of the treatment process on in-hospital mortality.Results The median utilization rate of treatment process indicators was 66.88%,and the mean and standard de-viation of patients′ treatment process quality scores were 0.270±0.124,including 0.358±0.069 in the high-quality group,and 0.158±0.081 in the low-quality group.After the IPTW weighting,the standardized mean difference(SMD)of patients′baseline characteris-tics decreased;The difference in survival curves between the two groups of patients before and after ITPW was statistically significant(P<0.05),and the prognosis of patients in the high-quality group was better than that of patients in the low-quality group(pre-IPTW:HR=0.367,95%CI:0.275-0.491;post-IPTW:HR=0.228,95%CI:0.167-0.312).Compared with the low-quality group,the average causal effect of treatment process on in-hospital mortality was-0.026 in the high-quality group.Conclusion DR can compensate for the shortcomings of logistic or IPTW,avoid the risk of model error,and obtain for the causal effect of treatment process on in-hospital mortality.In medical practice,the utilization rate of treatment process indicators should be increased to improve patient prognosis;The study of causal effects suggests that besides the treatment process,other factors that affect in-hospital mortality cannot be ignored.

OBJECTIVE: To explore the genetic etiology and clinical outcome of a child with steroid-resistant nephrotic syndrome and diffuse mesangial sclerosis. METHODS: Genomic DNA was extracted from peripheral blood leukocytes of the proband and his parents. Targeted capture - next generation sequencing and Sanger sequencing were carried out. Candidate variant was verified by segregation analysis in his family. RESULTS: A heterozygous missense variant of the TRPC6 gene, namely c.325G>A (p.Gly109Ser), was detected in the proband. The same variant was not detected in either parent. According to the guidelines for the interpretation of sequence variants developed by American College of Medical Genetics and Genomics, the variant was predicted as pathogenic. CONCLUSION The missense variant of the TRPC6 gene probably underlay the diffuse mesangial sclerosis in this patient. Above finding has expanded the phenotypic spectrum of the TRPC6 gene.
Child ; Genomics ; Humans ; Mutation, Missense ; Nephrotic Syndrome/genetics* ; Sclerosis ; TRPC6 Cation Channel/genetics*

Objective:To explore the molecular pathogenesis of hereditary protein C (PC) deficiency due to a p. Gly86Asp variant of the PROC gene through in vitro expression experiment.Methods:Wild type and Gly86Asp mutant expression plasmids of PC were constructed and respectively transfected into HEK 293FT cells. Total RNA was extracted from the transfected cells, and the expression of PROC gene was determined by quantitative real-time PCR (qRT-PCR). PC antigen (PC: Ag) in the supernatant of cell culture and cell lysate was determined by enzyme-linked immunosorbent assay (ELISA), and the level of PC protein was detected by Western blotting. Results:qRT-PCR has detected no significant difference in the transcription level of wild-type and mutant-type PC. Compared with the wild type, the level of mutant PC: Ag in the supernatant and cell lysate were 81.3%±2.6% and 110.0%±2.8%, respectively. No difference was detected in the molecular weight between the wild-type and mutant-type PC by Western blotting. The PC content of mutant type was higher than wild-type in cell lysate, while the opposite was found with the cell culture supernatant.Conclusion:The impaired secretion by mutant PC may be the molecular mechanism of PC deficiency caused by the p.

Objective To evaluate the effects of chronic disease management on carotid atherosclerosis. Methods From May 2016 to October 2016, 500 subjects with carotid atherosclerosis diagnosed by ultrasound at the Physical examination center of the First Hospital of Jilin University were enrolled. The participants were aged 55?65(60.7±3.5) years. They were divided into the control group (n=250) and intervention group (n=250) using a random number table; a total of 20patients, 13 in the control group and 7 in the intervention group, were lost to follow-up at the end of the study. The control group only received anti-atherosclerosis treatment, while the intervention group underwent additional chronic disease management, and a 1-year follow-up study was conducted. The health of all the subjects was assessed at the beginning of the study and after the study, based on the health file. The chi-square test, two independent sample t-tests, and rank sum test were used to evaluate the effect of chronic disease management on carotid atherosclerosis. Results After 1 year of intervention, the proportion of patients with an unhealthy lifestyle (smoking, excessive drinking, high-salt diet intake, high-fat diet intake, lack of exercise, and overweight/obesity) decreased in the intervention group(10.3%, 13.1%, 7.8%, 8.6%, 6.2%, 28.0%, vs. 28.8%, 35.0%, 21.0%, 22.6%, 13.2%, 39.5%; χ2=26.49, 33.01, 17.09, 18.03, 6.80, 7.21; P<0.05), while the drug compliance increased(44.4% vs. 35.4%, χ2=4.15, P<0.05), and the total cholesterol (TC), triglyceride (TG), low density lipoproteincholesterol (LDL-C), fasting plasma glucose (FPG), uric acid (UA) and blood pressure (BP) compliance rate also increased (91.8%, 73.3%, 83.1%, 83.1%, 52.3%, 76.5%, 74.1%, 60.5%, vs. 67.5%,72.8%,28.0%,58.8%, respectively; χ2=26.86, 8.92, 15.97, 7.49, 29.81, 17.39, respectively; P<0.05); all indicators, except the drug compliance control rate, were better than those in the control group. After 1 year of intervention, the degree of carotid atherosclerosis in the intervention group was significantly reduced compared to that in the control group. Conclusions Chronic disease management could effectively interfere the control risk factors of atherosclerosis, such as smoking, drinking, obesity or overweight, BP, levels of FPG, blood lipids, and UA, improve drug compliance, delay the progression of atherosclerosis and provide a basis for the construction of the atherosclerosis management model.

Objective: To investigate the clinical characteristics and outcomes of ulcerative colitis (UC) with cytomegalovirus (CMV) infection. Methods: The related data of 300 patients with UC who were treated in the department of gastroenterology of the First Affiliated Hospital of Xiamen University from January 2013 to October 2017 were analyzed retrospectively. Eighty cases with CMV infection were included into the observation group while 220 cases without CMV infection were enrolled into the control group. The disease characteristics, clinical features, treatment and outcomes were compared between the two groups. Results: For disease characteristics, course of disease in observation group was significantly shorter than that in the control group (t=18.498, P<0.05). The previous application rates of glucocorticoid and immunosuppressant in the observation group were significantly higher than those in the control group (χ²=31.241, 10.381, P<0.05). The incidence rates of glucocorticoid dependence and glucocorticoid resistance in the observation group were significantly higher than those in the control group (χ²=17.513, 64.927, P<0.05). For clinical characteristics, the incidence rates of fever, abdominal pain and weight loss in the observation group were significantly higher than those in the control group (χ²=25.112, 20.633, 13.000, P<0.05). Colonoscopy showed that the ulcer rate in observation group was significantly higher than that in the control group (χ²=15.496, P<0.05). For outcomes, the improvement rate of the observation group was significantly lower than that of the control group (55.00% vs. 79.55%) (χ²=17.933, P<0.05). Conclusions The clinical symptoms of patients with UC and CMV infection are more obvious, the disease was more serious, the ulcer rate is higher and the clinical outcomes were worse than those of uninfected patients.

OBJECTIVE: To investigate the expression of apoptosis related protein cellular Fas associated death domain like interleukin 1 converting enzyme inhibitory protein (c-FLIP) in peripheral blood mononuclear cells (PBMCs) of patients with rheumatoid arthritis and its relation with extrinsic apoptotic pathway. METHODS: Sixty patients with rheumatoid arthritis were collected from Zhangzhou Affiliated Hospital of Fujian Medical University during January 2014 and June 2015, including 22 patients with low activities (DAS28<3.2), 20 patients with middle activities (3.2 ≤ DAS28 ≤ 5.1), and 18 patients with high activities (DAS28>5.1). And 25 healthy controls were also collected. The mRNA and protein expression levels of c-FLIP and the extrinsic apoptotic pathway related proteins Fas-associated protein with death domain (FADD), caspase-8 in PBMCs were detected by real-time RT-PCR and Western blot, respectively. Correlations between c-FLIP and FADD, caspase-8 in PBMCs were analyzed by pearson test. RESULTS: mRNA expression levels of c-FLIP, FADD and caspase-8 in PBMCs of patients with rheumatoid arthritis were all higher than those of healthy controls (all <0.05). mRNA expression levels of FADD and caspase-8 in patients with middle activities were significantly higher than those in patients with low activities (all <0.05), but the mRNA expression level of c-FLIP was not significantly higher than that in patients with low activities. mRNA expression level of c-FLIP in patients with high activities was higher than those in patients with middle or low activities (all <0.05), while the mRNA expression level of caspase-8 was lower than those in patients with middle or low activities (all <0.05). mRNA expression level of FADD in patients with high activities was higher than those in patients with low activities (<0.05). Pearson analysis showed that there was a positive correlation between c-FLIP and FADD mRNA expression (=0.323, <0.05), and negative correlation between c-FLIP and caspase-8 mRNA expression (-1.104, <0.05). The protein expression levels of c-FLIP and FADD in patients with middle activities were significantly higher than those in control group and patients with low or high activities (<0.05 or 0.01). The protein expression levels of caspase-8 in patients with middle and high activities were significantly higher than those in control group and patients with low activities (<0.05 or <0.01), and the protein expression level of caspase-8 in patients with high activities was higher than that in patients with middle activities (<0.05). CONCLUSIONS c-FLIP may be involved in the extrinsic apoptotic pathway in rheumatoid arthritis, and can provide reference for the evaluation of disease activities.
Apoptosis ; genetics ; Arthritis, Rheumatoid ; blood ; CASP8 and FADD-Like Apoptosis Regulating Protein ; genetics ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Leukocytes, Mononuclear ; metabolism

Objective To explore the association between the C46T polymorphism of coagulation factor Ⅻ (FⅫ) gene and the involvement of FⅫ activity (FⅫ:C) in patients with unexplained recurrent spontaneous abortion (URSA), and to elucidate its role in the pathogenesis of URSA. Methods This study included 203 patients with URSA (URSA group) and 171 healthy women with at least one child and no history of infertility or miscarriage (control group) in the southern area of Zhejiang Province. The C 46T polymorphism of the FⅫ gene was analyzed with matrix-assisted laser desorption/ionization time of flight-mass spectrometry (MALDI-TOF-MS) in all subjects. The values of prothrombin time, activated partial thromboplastin time (APTT), fibrinogen, FⅫ:C and other coagulant parameters were determined. The frequency distribution of the wild-type (CC), heterozygote (CT), homozygote (TT) genotypes and C and T alleles were compared between the patients and controls. A comprehensive analysis of association was conducted between C46T genotypes and the FⅫ:C levels in URSA patients. Results The CC, CT, TT genotypes of the FⅫgene were observed in 7 (3.4%, 7/203), 83 (40.9%, 83/203) and 113 (55.7%, 113/203) patients with URSA versus 7 (4.1%, 7/171), 46 (26.9%, 46/171) and 118 (69.0%, 118/171) controls. The frequency of CT in the patients with URSA was significantly higher than that in controls, but the frequency of TT in the patients was lower than that in controls (χ2=7.939, OR=1.884, 95%CI:1.210-2.935, P<0.05). The frequencies of allele C and allele T were observed in 97 (23.9%, 97/406) and 309 (76.1%, 309/406) patients with URSA versus 60 (17.5%, 60/342) and 282 (82.5%, 282/342) controls. The distribution frequency of allele T in URSA group was lower than that in control group (χ2=4.510, OR=1.475, 95%CI:1.029-2.115, P<0.05). The FⅫ:C levels in the patients were (102±13)%in CC genotype, (78±11)%in CT genotype and (59± 9)%in TT genotype, respectively. The differences of the FⅫ:C levels between the CC and CT, CT and TT, CC and TT genotypes in the patients were significant (all P<0.05). Conclusions The low level of FⅫ:C maybe result from the T allele of the FⅫgene in URSA patients. The CT genotype might be relative to the pathogenesis of URSA in a Chinese Han female population from the southern area of Zhejiang province.

Polyethylene glycol (PEG) is extensively used to increasing the in vivo and in vitro stability of liposomes. However, PEGylated liposomes also produce some negative effects with further research, such as low cellular uptake, poor "endosomal escape" of pH sensitive liposome (PSL) and accelerated blood clearance (ABC) phenomenon, and this situation is referred as the "PEG dilemma". "PEG dilemma" posed severe challenges for the targeted delivery of PEGylated liposomes-loaded anticancer drugs, effective intracellular release of PEGylated PSL-encapsulated gene and protein drugs, and repeated administration of PEGylated liposomes. Therefore, it is urgent to solve the "PEG dilemma". This review focused on the definition, classification of "PEG dilemma", and discussed several possible approaches to overcome "PEG dilemma".