1.Clinical Characteristics and Prognosis of Primary Esophageal Small Cell Carcinoma
Min QUAN ; Jiayuan TANG ; Hong CHEN
Cancer Research on Prevention and Treatment 2024;51(12):1021-1027
Objective To investigate the clinical characteristics and prognostic factors of the limited-stage disease (LD) and extensive-stage disease (ED) of primary esophageal small cell carcinoma (PESCC). Methods The clinical data and follow-up information of 72 patients with PESCC were retrospectively analyzed. Chi-square test was used to compare the baseline data of patients with LD and ED, Kaplan-Meier method was employed to draw the survival curve of both groups, and Log-rank test was employed to compare survival rates between groups. Univariate and multivariate Cox regression methods were used to analyze the factors affecting the overall survival (OS) of patients with LD and ED. Results A total of 49 patients with LD and 23 patients with ED were included in this study. The median survival time of patients with LD was 18.300 months and that of patients with ED was 10.903 months (P=0.029). Total protein (TP) value (HR=0.890, 95%CI: 0.805−0.983, P=0.022) and chemotherapy cycle number (HR=0.388, 95%CI: 0.187−0.807, P=0.011) were independent prognostic factors of patients with LD. Systemic immune-inflammation index (SII) (HR=1.002, 95%CI: 1.000−1.004, P=0.007) and C-reactive protein (CRP) (HR=1.065, 95%CI: 1.021−1.111, P=0.004) were independent prognostic factors of patients with ED. Conclusion The malignant degree of PESCC is high, and prognosis is poor. Patients with LD and ED have different prognostic factors. Total protein value and chemotherapy cycle are independent prognostic factors of patients with LD. SII and CRP are independent prognostic factors of patients with ED.
2.Analysis of the causal relationship between human immune cells and hypertrophic scar using two-sample bidirectional Mendelian randomization method
Honglin WU ; Yongfei CHEN ; Shuting LI ; Hao YANG ; Xiaohui LI ; Bing TANG ; Jiayuan ZHU ; Zhicheng HU
Chinese Journal of Burns 2024;40(6):572-578
Objective:To explore the causal relationship between human immune cells and hypertrophic scar (HS) using two-sample bidirectional Mendelian randomization (MR) method.Methods:This study was based on two-sample MR method, and the datasets of 731 immune cells and HS were obtained from the genome-wide association study (GWAS) catalog database and Finngen database, respectively. A significance threshold was established to discern single nucleotide polymorphism (SNP) significantly correlated with immune cells or HS, thereby eliminating the impact of weak instrumental variable bias. The inverse variance weighted (IVW) method (meanwhile, the Benjamini-Hochberg (BH) procedure of false discovery rate (FDR) to adjust P values) was used for preliminary detection of the causal relationship between immune cells and HS and screen the immune cells that had a significant causal relationship with HS. Further, the causal relationship between the selected immune cells and HS was detected through five two-sample MR methods: IVW method, weighted median method, simple mode method, weighted mode method, and MR-Egger method, and the scatter plot was drawn. SNPs conformed to the hypothesis were subjected to Cochran Q test for heterogeneity assessment, MR-Egger regression coupled with MR-PRESSO to eliminate horizontal pleiotropic effects, and a leave-one-out analysis was also conducted to determine if significant results were driven by individual SNP. Finally, the IVW method contained in the two-sample MR analysis was utilized to inversely examine the causal relationship between HS and immune cells. Results:The number of SNPs in 731 immune cells reaching the significance threshold varied from 7 to 1 786, while in HS, 119 SNPs met the significance threshold, with the F values of all SNPs being greater than 10, suggesting a low likelihood of bias from weak instrumental variables. The IVW method revealed that 60 types of immune cells potentially had a causal relationship with HS (with all P values <0.05), and after adjustment using the BH method, only CD45RA and CD39 positive regulatory T cell (Treg) maintained a potentially strong causal relationship with HS ( PFDR<0.05). The IVW method (with odds ratio of 1.16 and 95% confidence interval of 1.08-1.24, P<0.05, PFDR<0.05), weighted median method (with odds ratio of 1.16 and 95% confidence interval of 1.05-1.28, P<0.05), weighted mode method (with odds ratio of 1.14 and 95% confidence interval of 1.02-1.27, P<0.05), and MR-Egger method (with odds ratio of 1.18 and 95% confidence interval of 1.07-1.30, P<0.05) of scatter plot all suggested a causal relationship between the 14 SNPs of CD45RA and CD39 positive Treg and risk of HS, only simple mode method of scatter plot suggested a not obvious relationship between the 14 SNPs of CD45RA and CD39 positive Treg and risk of HS ( P>0.05). Cochran Q test indicated no heterogeneity in the causal relationship between CD45RA on CD39 positive Treg and HS ( P>0.05). MR-Egger regression and MR-PRESSO analyses showed that there was no horizontal pleiotropy in the significant causal relationship between CD45RA and CD39 positive Treg and HS ( P>0.05). Leave-one-out analysis confirmed that the significant causal relationship between CD45RA and CD39 positive Treg and HS remained stable after sequentially removing individual SNP. Reverse two-sample MR analysis showed that HS had no potential causal relationship with any of the 731 types of immune cells ( P>0.05). Conclusions:From the perspective of genetics, it is revealed that immune cells CD45RA and CD39 positive Treg may increase the risk of HS.
3.Bidirectional relationship between type 2 diabetes mellitus and coronary artery disease: Prospective cohort study and genetic analyses
Wenqiang ZHANG ; Li ZHANG ; Chenghan XIAO ; Xueyao WU ; Huijie CUI ; Chao YANG ; Peijing YAN ; Mingshuang TANG ; Yutong WANG ; Lin CHEN ; Yunjie LIU ; Yanqiu ZOU ; Ling ZHANG ; Chunxia YANG ; Yuqin YAO ; Jiayuan LI ; Zhenmi LIU ; Xia JIANG ; Ben ZHANG
Chinese Medical Journal 2024;137(5):577-587
Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.
4.Effects and mechanisms of allogeneic epidermal stem cells on the survival of allogeneic full-thickness skin grafts in nude mice with full-thickness skin defect wounds
Shaobin HUANG ; Zhicheng HU ; Yi ZHANG ; Bing TANG ; Peng WANG ; Hailin XU ; Zhiyong WANG ; Yunxian DONG ; Pu CHENG ; Yanchao RONG ; Jun WU ; Jiayuan ZHU
Chinese Journal of Burns 2021;37(11):1061-1069
Objective:To investigate the effects and mechanisms of allogeneic epidermal stem cells (ESCs) on the survival of allogeneic full-thickness skin grafts in nude mice with full-thickness skin defect wounds.Methods:Experimental research methods were applied. Primary ESCs that appeared paving stone-like after being cultured for 7 d were obtained by enzymatic digestion method from one 4-week-old male BALB/c-NU nude mouse (the same strain, age, and sex below). The cells of third passage were identified by flow cytometry to positively express ESC marker CD44 and negatively express CD45, meanwhile, the positive expression of ESC markers of p63 and integrin 6α, and negative expression of CD71 were identified by immunofluorescence method. The ESCs of third passage in the logarithmic growth phase were used for the following experiments. Twenty-six nude mice were equally divided into phosphate buffered saline (PBS) group and ESCs group according to the random number table. A full-thickness skin defect wound was made on the back of each nude mouse, and then the wounds of the two groups were sprayed with equal volumes of PBS and ESCs, respectively. The wounds were transplanted with full-thickness skin grafts cut from the backs of 4 other nude mice. Each ten nude mice from the two groups were selected, the wound healing and skin survival on post surgery day (PSD) 0 (immediately), 3, 7, 14, and 21 were observed, and the survival ratio and shrinkage rate of skin grafts on PSD 3, 7, 14, and 21 were calculated (the number of sample was the number of surviving skin grafts at each time point); the blood perfusion in the skin grafts on PSD 3, 7, and 14 was detected by the laser speckle blood flow imager, and the blood flow ratio of nude mice skin grafts in ESCs group to PBS group at each time point was calculated (the number of sample was the pair number of surviving skin grafts in group pairing at each time point). The skin graft tissue of each 3 nude mice remained in the two groups were collected on PSD 7, and the mRNA expressions and protein expressions of tumor necrosis factor α (TNF-α), interleukin 8 (IL-8), IL-10, type Ⅰ collagen, type Ⅲ collagen, and matrix metalloproteinase 9 (MMP-9) in the tissue were detected by real-time fluorescent quantitative reverse transcription polymerase chain reaction and Western blotting, respectively. Data were statistically analyzed with Log-rank test, analysis of variance for repeated measurement, one-way analysis of variance, independent sample t test, and Bonferroni correction. Results:Taking the condition on PSD 0 as a reference, the wounds of nude mice in the two groups healed gradually on PSD 3, 7, 14, and 21, and the shrinkage of skin grafts was gradually obvious. Among them, the shrinkage healing of wound of nude mice in PBS group was more significant than that in ESCs group. On PSD 3, the skin graft of 1 nude mouse failed in ESCs group, while the skin graft of 3 nude mice failed in PBS group. On PSD 7, the skin graft of another nude mouse failed in PBS group. The survival ratio of skin grafts of nude mice in the two groups was similar on PSD 3, 7, 14, and 21 ( P>0.05). On PSD 3, 7, 14, and 21, the shrinkage rates of skin grafts of nude mice in ESCs group were (9.2±0.4)%, (19.7±1.2)%, (53.6±3.5)%, and (62.2±5.1)%, respectively, which was significantly lower than (11.0±0.9)%, (47.8±2.8)%, (86.1±7.1)%, and (89.7±9.0)% in PBS group ( t=5.719, 26.650, 11.940, 7.617, P<0.01). On PSD 3, 7, and 14, blood perfusion signals were observed in the skin grafts of nude mice in the two groups. The average blood perfusion ratios of the skin grafts of nude mice in ESCs group to PBS group were greater than 1, and there was no statistically significant difference in the overall comparison of 3 time points ( P>0.05). On PSD 7, compared with those of PBS group, the mRNA and protein expressions of TNF-α, IL-8, type Ⅰ collagen, and type Ⅲ collagen in the skin graft tissue of nude mice in ESCs group were significantly reduced, while the mRNA and protein expressions of IL-10 and MMP-9 in the skin graft tissue of nude mice in ESCs group were significantly increased (in mRNA comparison, t=2.823, 2.934, 2.845, 2.860, 3.877, 2.916, P<0.05). Conclusions:Allogeneic ESCs can reduce the shrinkage of allogeneic full-thickness skin grafts transplanted on full-thickness skin defect wounds in nude mice, promote the formation of new blood vessels between the skin graft and the wound, reduce inflammation and collagen protein expression, and promote the expression of MMP-9, thus improving the survival quality of skin grafts.
5.Clinical observation of vacuum sealing drainage in osteomyelitis of sternum after cardio-thoracic surgery operation
Bin CHEN ; Jiayuan ZHU ; Bin ZHU ; Bing TANG ; Zhicheng HU ; Kai ZHANG ; Xiaohui LI
Chinese Journal of Primary Medicine and Pharmacy 2012;(23):3550-3551
Objective To explore detection value of vacuum sealing drainage in osteomyelitis of sternum after cardio-thoracic surgery operation.Methods 132 cases of osteomyelitis of sternum after cardio-thoracic surgery operation were randomly divided into two groups(research group and control group).The research group had 72 cases)and the control group had 60 cases.The control group was treated with conventional treatment.The research group was treated with vacuum sealing drainage.The average healing time and clinical therapeutic effect of the two groups were observed.Results The patients'age and the sternum of osteomyelitis was significantly related,with OR=1.153 and P<0.05.After treatment,the average healing time of the research group was(3.1±0.8)months.The average healing time of the control group was(7.2±1.5)months.The average healing time of the two groups had significant difference(P<0.05).Conclusion Vacuum sealing drainage in osteomyelitis of sternum after cardio-thoracic surgery operation has sure curative effect.It can change chronic wounds for acute tissue effectively,shorten the healing time.It has high application value in the first phase of treatment and the second phase of repair.
6.Construction and identification of recombinant replication- defective adenovirus vector containing interleukin-10 in a rat
Shuana LI ; Renqang SONG ; Bing TANG ; Bin ZHU ; Xuhong ZHU ; Jiayuan ZHU ; Liangkuan BI
Chinese Journal of Tissue Engineering Research 2009;13(7):1397-1400
BACKGROUND: Construction of recombinant adenovirus plasmid plays a central role in preparation of recombinant adenovirus.However, conventionally intracellular homologous recombination method is limited by complex procedures, low successful ratio,and long experimental cycle.OBJECTIVE: To construct the recombinant replication-defective adenovirus vector containing interleukin-10 (Ad.dL-10) in a SD rat, and to provide experimental evidences for eukaryotic expression and animat model studying.DESIGN, TIME AND SEI-FING: Opening study was conducted in the First Affiliated Hospital of Sun Yat-sen University from July 2005 to April 2006.MATERIALS: A SD rat, AdEasy system (USA), ThermoscdptTMRT kit & Tdzol (USA), and HEK-293 (Guangzhou, China) were used in this study. The primer of rlL-10 gene of clone rat was synthesized and sequenced in Shanghai, China.METHODS: rlL-10 gene was cloned from total RNA of healthy SD rat spleen tissue with RT-PCR, and then recombinant adenovirus plasmid named pAd.rlL-10 was obtained by homologous recombination within E.ColiBJ5183 carded with AdEasy-1 system. Last, the recombinant adenovirus was packaged, proliferated by HEK-293 cells and purified.MAIN OUTCOME MEASURES: The Ad.rlL-10 was identified using Western blot and RT-PCR methods.RESULTS: rlL-10 gene was successfully cloned from fresh spleen tissue of a SD rat and incorporated into recombinant adenovirus plasmid pad in order to obtain the Ad.rlL-10. Western blot and RT-PCR showed the rlL-10 gene and protein expressions in the cells. Finally, the rlL-10 recombinant adenovirus was obtained with the titers of 1.0x1014 pfu/mL after amplification and purification.CONCLUSION: AdEasy-1 system characterizing by simple operation and reliable results is commonly used to obtain enough quantity and quality adenovirus after homologous recombination, and HEK-293-induced package, amplification, and purification.
7.Clinical Distribution and Drug Resistance of Non-fermentative Bacilli in Surgery
Bing TANG ; Yingpeng CUI ; Bin ZHU ; Jiayuan ZHU ; Yang LIU
Chinese Journal of Nosocomiology 2006;0(09):-
OBJECTIVE To investigate the clinical distribution and drug resistance of non-fermentative bacilli isolated from department of surgery so as to guide the rational use of antibiotics.METHODS VITEK-60 AMS system and Kirby-Bauer method were used to identify the pathogenic bacilli and examine the antibiotic resistance.RESULTS A total of 463 strains of nonfermentative bacteria were isolated from Jan 2002 to Dec 2004,the most common pathogen was Pseudomonas aeruginosa(55.07%),the next were Acinetobacter baumannii(20.52%) and Stenotrophomonas maltophilia(11.88%).The samples were mainly sputum(31.97%),drainage(13.39%),and wound secretion(12.31%).Isolation rate from SICU,departments of organ transplantation and burn were 28.08%,17.28% and 12.10%,respectively.P.aeruginosa,A.baumannii and S.maltophilia had high and multi-drug resistance.CONCLUSIONS Infections of respiratory tract and wound caused by non-fermentative bacilli are common in surgical department,and drug resistance is serious.The drugs should be chosen according to the results of the antimicrobial susceptibility tests.
8.Identification of scar animal models with method of picric-sirius red polarized light
Bin ZHU ; Jiayuan ZHU ; Tao ZHANG ; Bing TANG ; Xinqiang LI ; Shusen ZHENG ; Dong CHEN ; Wei ZHANG ; Shuang LI
Chinese Journal of Tissue Engineering Research 2006;10(12):182-183,插5
BACKGROUND: Stable reliable experimental animal models are needed urgently in scar research.OBJECTIVE: Scar animal models of nude mice are evaluated with histological method to define optimal opportunity for using.DESIGN: Randomizly controlled and repetitively measured design.SETTING: Department of Burn, First Affiliated Hospital, Sun Yat-sen University.MATERIALS: The experiment was conducted at the Center for Animal Experiment, Medical College, Sun Yat-sen University between January 2004 and March 2004. Fifteen nude mice aged 4-6 weeks were provided by Center for Animal Experiment, Medical College, Sun Yat-sen University (of either gender with body mass of 15-25 g). Hyperplastic scar was gained from samples of exairesis in patients with burn after healing which is hyperplastic scar for half a year.METHODS: Human hyperplastic scar was grafted at dorsa of nude mice to establish scar animal models. After graft for four weeks, 5 experimental animals were killed every week, and grafts were gained. 100 g/L formalin was used to fix samples for 3 weeks. Picric-sirius red polarized light method was used to detect the graft and clinical materials, and histological feature was observed.MAIN OUTCOME MEASURES: ①Results of film reading of picric-sirius red polarized light method. ②Analytic result of computer image.RESULTS: ①Results of film reading of picric-sirius red polarized light method: The grafts showed the same feature of diffused distribution of mainly yellow and red thick fiber with thin-mesh green fiber under polarized light in every time segment group. ②Analytic result of computer image: In clinicopathological hyperplastic scar, type Ⅰ collagen was about 74%; type Ⅲ collagen accounted for about 26%. In the graft from 4-6 weeks, the contents of type Ⅰ collagen were (74.52 ±0.47)% , (74.43 ±0.53)% ,(74.69±0.63)%, respectively; The contents of type Ⅲ were (25.48±0.47)%, (25.57±0.53)%, (25.31±0.63)%, respectively, which had insignificant difference (P > 0.05 ).CONCLUSION: In the time segment designed by experiment, the feature of graft and clinical material is coincident, which is accorded with the characteristics of hyperplastic scar. The detection of collagen of scar tissue with picric-sirius red polarized light method is a simple effective method for assessing the tissue of hyperplastic scar. Establishing scar models with nude mice is effective and stable.

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