1.Semiparametric analysis of nonparametric proportional hazards models with mixed dependent censored data
Shuying WANG ; Xinzhu JIANG ; Bo ZHAO ; He DONG
Journal of Southern Medical University 2024;44(4):689-696
Objective To construct a nonparametric proportional hazards (PH) model for mixed informative interval-censored failure time data for predicting the risks in heart transplantation surgeries. Methods Based on the complexity of mixed informative interval-censored failure time data, we considered the interdependent relationship between failure time process and observation time process, constructed a nonparametric proportional hazards (PH) model to describe the nonlinear relationship between the risk factors and heart transplant surgery risks and proposed a two-step sieve estimation maximum likelihood algorithm. An estimation equation was established to estimate frailty variables using the observation process model. I-spline and B-spline were used to approximate the unknown baseline hazard function and nonparametric function, respectively, to obtain the working likelihood function in the sieve space. The partial derivative of the model parameters was used to obtain the scoring equation. The maximum likelihood estimation of the parameters was obtained by solving the scoring equation, and a function curve of the impact of risk factors on the risk of heart transplantation surgery was drawn. Results Simulation experiment suggested that the estimated values obtained by the proposed method were consistent and asymptotically effective under various settings with good fitting effects. Analysis of heart transplant surgery data showed that the donor's age had a positive linear relationship with the surgical risk. The impact of the recipient's age at disease onset increased at first and then stabilized, but increased against at an older age. The donor-recipient age difference had a positive linear relationship with the surgical risk of heart transplantation. Conclusion The nonparametric PH model established in this study can be used for predicting the risks in heart transplantation surgery and exploring the functional relationship between the surgery risks and the risk factors.
2.Semiparametric analysis of nonparametric proportional hazards models with mixed dependent censored data
Shuying WANG ; Xinzhu JIANG ; Bo ZHAO ; He DONG
Journal of Southern Medical University 2024;44(4):689-696
Objective To construct a nonparametric proportional hazards (PH) model for mixed informative interval-censored failure time data for predicting the risks in heart transplantation surgeries. Methods Based on the complexity of mixed informative interval-censored failure time data, we considered the interdependent relationship between failure time process and observation time process, constructed a nonparametric proportional hazards (PH) model to describe the nonlinear relationship between the risk factors and heart transplant surgery risks and proposed a two-step sieve estimation maximum likelihood algorithm. An estimation equation was established to estimate frailty variables using the observation process model. I-spline and B-spline were used to approximate the unknown baseline hazard function and nonparametric function, respectively, to obtain the working likelihood function in the sieve space. The partial derivative of the model parameters was used to obtain the scoring equation. The maximum likelihood estimation of the parameters was obtained by solving the scoring equation, and a function curve of the impact of risk factors on the risk of heart transplantation surgery was drawn. Results Simulation experiment suggested that the estimated values obtained by the proposed method were consistent and asymptotically effective under various settings with good fitting effects. Analysis of heart transplant surgery data showed that the donor's age had a positive linear relationship with the surgical risk. The impact of the recipient's age at disease onset increased at first and then stabilized, but increased against at an older age. The donor-recipient age difference had a positive linear relationship with the surgical risk of heart transplantation. Conclusion The nonparametric PH model established in this study can be used for predicting the risks in heart transplantation surgery and exploring the functional relationship between the surgery risks and the risk factors.
3.Classification of main pancreatic duct and treatment strategy after linear stapler closure of pancreatic neck in laparoscopic pancreaticoduodenectomy
Xiangtao WANG ; Jian KONG ; Jun GAO ; Xinliang KONG ; Shan KE ; Qiang WANG ; Shaohong WANG ; Chunmin NING ; Shigang GUO ; Shuying DONG ; Liqiang MI ; Wenxiao LI ; Shuangxi HAN ; Jinglong LI ; Wenbing SUN
International Journal of Surgery 2023;50(6):390-393
Objective:To investigate the classification of main pancreatic duct and treatment strategy after linear stapler closure of pancreatic neck in laparoscopic pancreaticoduodenectomy (LPD).Methods:The records of 51 consecutive patients with LPD who were treated by linear staple closure technique of pancreatic neck from February to December 2022 from Binzhou Second People′s Hospital, Shijingshan Campus, Beijing Chaoyang Hospital, Capital Medical University, Rizhao Hepatobiliary-Pancreatic-Splenic Surgery Research Institute, Chaoyang Central Hospital, Shandong Juxian People′s Hospital, Weihai Municipal Hospital, Binzhou Central Hospital, and Affiliated Hospital of Chifeng University were retrospectively reviewed. According to the visibility, position and diameter of the main pancreatic duct at the stump of the pancreas, the type of main pancreatic duct was divided into type I, type Ⅱ, type Ⅲa and type Ⅲb. The number of cases in each main pancreatic duct classification and the corresponding treatment strategies were examined.Results:A total of 51 cases of LPD were successfully completed. Of these patients, the males comprised 56.9%(29/51), and females comprised 43.1%(22/51), with age ranging from 31 to 88 years old. The type of the main pancreatic duct at the stump of the pancreas included 7 cases (13.7%) of type Ⅰ, 39 cases (76.5%) of type Ⅱ, 2 cases (3.9%) of type Ⅲa, and 3 cases (5.9%) of type Ⅲb. Corresponding treatment strategies were adopted according to different main pancreatic duct types, the main pancreatic duct was successfully found, and a support drainage tube was inserted.Conclusion:After linear stapler closure of pancreatic neck, corresponding treatment strategies should be adopted according to the classification of the main pancreatic duct, which would help to improve the success rate of finding the main pancreatic duct and placing a support drainage tube.
4.Radiation-induced GATA3 expression in lung epithelial cells and mechanism of RNA methylation
Junxuan YI ; Xiaodan DONG ; Wenxiang XUE ; Shuying GAO ; Naiwen XUE ; Shunzi JIN
Chinese Journal of Radiological Health 2023;32(3):223-229
Objective:
To investigate GATA3 expression and the regulatory mechanism of m6A modification in the re-
sponse of alveolar epithelial cells to radiation, and to provide a new therapeutic target for radiation-induced lung injury based on its pathogenesis.
Methods:
Human lung epithelial cell line (A549) and mouse lung epithelial cell line (MLE-12) were
exposed to X-ray irradiation with a single dose of 10 Gy (dose rate 1 Gy/min) and 6 Gy (dose rate 0.75 Gy/min), respect-
ively. The expression of VIRMA gene (RNA methylase) was inhibited by lipofection of A549 cells and MLE-12 cells with shRNA-VIRMA plasmid and siRNA-VIRMA interfering fragment, respectively. Quantification of m6A RNA methylation
was performed by colorimetry. Changes in the expression of mRNAs of VIRMA, GATA3, and epithelial-mesenchymal transition (EMT) markers in irradiated A549 and MLE-12 cells were determined by qRT-PCR. Changes in the expression of
VIRMA, GATA3, and EMT marker proteins in irradiated A549 and MLE-12 cells were determined by Western blot.
Results:
Radiation up-regulated the expression of methylase VIRMA in A549 and MLE-12 cells, which in turn enhanced
the m6A of total RNA and the expression of GATA3 gene and protein, resulting in EMT. Furthermore, in A549 and MLE-12
cells, interference of the VIRMA gene significantly reduced the expression of GATA3 gene and protein and the expression of EMT-related molecules.
Conclusion
Radiation induces m6A modification in alveolar epithelial cells, which up-regu-
lates the expression of GATA3 gene and induces EMT, thus playing an important role in the process of radiation-induced lung injury.
5.Analysis of clinical characteristics and risk factors of sarcopenia in elderly patients with chronic kidney disease stage 3-4
Qian WANG ; Jing GUO ; Bing LI ; Ling DONG ; Xiangya ZHAO ; Yi YANG ; Shengnan YANG ; Shuying LI ; Rui TIAN
Chinese Journal of Nephrology 2023;39(7):485-490
Objective:To explore the clinical characteristics and risk factors of sarcopenia in elderly patients with chronic kidney disease (CKD) stage 3-4.Methods:It was a single-center, retrospective observational study. CKD stage 3-4 patients aged ≥60 years old from March 2019 to March 2022 in the Geriatrics Department of the First Affiliated Hospital of Zhengzhou University were enrolled in the study. General data of the patients were collected, and laboratory indicators, muscle strength, physical function and appendicular muscle mass index (ASMI) were measured. According to the diagnostic criteria of sarcopenia, the patients were divided into no sarcopenia CKD group and sarcopenia CKD group. Baseline data between these two groups were compared. Logistic regression analysis was used to analyze the related factors of sarcopenia in elderly CKD stage 3-4 patients.Results:A total of 162 CKD stage 3-4 patients were enrolled in this study, with 89 males (54.9%) and a median age of 75 (69, 82) years. Sarcopenia was diagnosed in 40 cases, and the prevalence was 24.7% (95% CI 18.1%-31.3%). Compared with no sarcopenia CKD group, age, proportion of dementia, cystatin C, urea nitrogen, C-reactive protein (CRP) and ratio of urine protein to creatinine were higher (all P<0.05), while body mass index (BMI), hemoglobin, carbon dioxide combining power, estimated glomerular filtration rate (eGFR), serum albumin and the proportion of regular exercise and using α-ketones were lower in sarcopenia CKD group (all P<0.05). Meanwhile, grip strength, walking speed, short physical performance battery score and ASMI were lower in sarcopenia CKD group (all P<0.05). Multivariable logistic regression analysis results showed that low eGFR ( OR=0.824, 95% CI 0.687-0.987, P=0.036), low BMI ( OR=0.463, 95% CI 0.304-0.704, P<0.001), low serum albumin ( OR=0.459, 95% CI 0.263-0.802, P=0.006) and high CRP ( OR=2.754, 95% CI 1.708-4.439, P<0.001) were the independent related factors of sarcopenia in elderly CKD patients. Conclusions:The prevalence of sarcopenia in elderly CKD stage 3-4 patients is high. Low eGFR, low BMI, low serum albumin and high CRP are the independent risk factors for sarcopenia in elderly CKD stage 3-4 patients.
6.Molecular epidemiological characteristics of human rhinovirus in adults with upper respiratory tract infection in Nanjing
Hongming DONG ; Limin HUANG ; Yanqing YANG ; Na LI ; Shuying LI ; Jun HAN
Chinese Journal of Microbiology and Immunology 2023;43(4):279-284
Objective:To analyze the clinical and epidemiological features of human rhinovirus (HRV) infection in adult patients with upper respiratory tract infection (URTI) in Nanjing.Methods:Epidemiological data of adult patients with URTI in Nanjing from October 2021 to September 2022 were collected. Clinical specimens were collected and subjected to quantitative reverse transcription polymerase chain reaction (qRT-PCR) for the detection of 14 common respiratory viruses. The VP4/VP2 genes in HRV-positive samples were amplified and sequenced. Then a phylogenetic tree was constructed.Results:A total of 399 pharyngeal swabs were collected from patients with URTI. The overall positive rate of respiratory viruses was 28.07% (112/399) with HRV accounting for most at 9.52% (38/399). Thirty-seven VP4/VP2 sequences were successfully obtained from the 38 HRV-positive specimens. Three genotypes involving 25 serotypes were identified with 13 strains belonging to HRV-A, 14 belonging to HRV-B, and 10 belonging to HRV-C. The three genotypes of HRV showed alternate prevalence or co-prevalence.Conclusions:HRV was the main pathogen causing URTI in adult patients in Nanjing from October 2021 to September 2022, and three genotypes of HRV-A, B and C were prevalent alternatively or together.
7.The effect of improving moderate and severe benign prostatic hyperplasia with lower urinary tract symptoms on renal function in elderly patients aged 80 years and over
Qian WANG ; Bin ZHANG ; Shengnan YANG ; Xiangya ZHAO ; Yi YANG ; Ling DONG ; Shuying LI ; Rui TIAN
Chinese Journal of Geriatrics 2022;41(12):1494-1497
Objective:To investigate the effect of improving moderate and severe benign prostatic hyperplasia(BPH)with lower urinary tract symptoms(LUTS)on renal function in elderly patients aged 80 years and over.Methods:A total of 129 inpatients with moderate and severe BPH and its associated LUTS(BPH/LUTS)who took tamsulosin combined with finasteride aged 80 years old and over in Geriatric Department of the First Affiliated Hospital of Zhengzhou University were enrolled in the retrospective study from July 2018 to July 2020.Patients were divided into normal blood pressure group(n=51)and hypertension group(n=78)and divided into normal renal function group(n=77)and CKD3a stage group(n=52).Serum creatinine, estimated glomerular filtration rate(eGFR), prostate volume(PV)and post-void residual urine volume(PVR), and International Prostate Symptom Score(IPSS)were compared before versus after 1, 3 and 6 months of treatment.Multivariable linear regression analysis was performed to evaluate the influence of the most relevant factors on renal function in patients with BPH/LUTS.Results:After 1, 3 and 6 months of tamsulosin combined with finastide treatment, the lower urinary tract symptoms of elderly patients with BPH/LUTS were improved, IPSS score and PVR were decreased, and the differences were statistically significant(all P<0.01).PV, serum creatinine and eGFR were not changed after 6 months of treatment(all P>0.05).However, further subgroup analysis showed that serum creatinine level in hypertension group and CKD3a stage group was increased compared with that before treatment, while eGFR in CKD3a stage group was decreased before treatment, and the difference was statistically significant(all P<0.05).Compared with before treatment, serum creatinine and eGFR in hypertensive group improved after 3 months of treatment, and CKD3a group improved after 1 month of treatment, and the differences were statistically significant(all P<0.05).There were no significant changes in serum creatinine and eGFR in normal blood pressure group and normal renal function group after 6 months of treatment(all P>0.05).Multiple linear regression analysis showed that hypertension( β=2.06, P<0.05)and CKD3a stage( β=17.16, P<0.01)were independent risk factors for creatinine changes before and after treatment.Hypertension( β=-2.27, P<0.01), CKD3a stage( β=-11.93, P<0.01)and CKD3A stage( β=-2.27, P<0.01)were independent risk factors for creatinine changes before and after treatment. P<0.01)and PV before treatment( β=-0.11, P<0.05)were independent risk factors for the change of eGFR before and after treatment. Conclusions:Treatment for moderate and severe BPH/LUTS can improve renal function in elderly patients with hypertension or CKD3a.
8.Circular BANP knockdown inhibits the malignant progression of residual hepatocellular carcinoma after insufficient radiofrequency ablation
Guoming LI ; Jian KONG ; Shuying DONG ; Haigang NIU ; Shilun WU ; Wenbing SUN
Chinese Medical Journal 2022;135(13):1578-1587
Background::Circular RNAs (circRNAs) are endogenous non-coding RNAs, some of which have pathological roles. The current study aimed to explore the role of circRNA BTG3-associated nuclear protein (circ-BANP) binding with let-7f-5p and its regulation of the toll-like receptor 4 (TLR4)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in residual hepatocellular carcinoma (HCC) after insufficient radiofrequency ablation (RFA).Methods::Circ-BANP, let-7f-5p, and TLR4 expressions in HCC samples were assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Bioinformatics prediction, RNA pull-down assay, and dual luciferase reporter gene assay were used to analyze the relationships among circ-BANP, let-7f-5p, and TLR4. Huh7 cells were used to generate an in vitro model of residual HCC, defined as Huh7-H cells, which were transfected with either a plasmid or the sequence of circ-BANP, let-7f-5p, or TLR4. Expression of circ-BANP, let-7f-5p, and TLR4 mRNA was determined by RT-qPCR. TLR4, STAT3, p-STAT3, vascular endothelial growth factor A, vascular endothelial growth factor receptor-2, and epithelial-mesenchymal transformation (EMT)-related factors proteins were determined by Western blotting. Cell proliferation was determined by cell counting kit-8 and 5-Ethynyl-2’-deoxyuridine (EdU) assay and cell migration and invasion by Transwell assay. Animal studies were performed by inducing xenograft tumors in nude mice. Results::Circ-BANP and TLR4 mRNAs were upregulated in HCC tissues (the fold change for circ-BANP was 1.958 and that for TLR4 was 1.736 relative to para-tumors) and expression further increased following insufficient RFA (fold change for circ-BANP was 2.407 and that of TLR4 was 2.224 relative to para-tumors). Expression of let-7f-5p showed an opposite tendency (fold change for let-7f-5p in HCC tissues was 0.491 and that in tumors after insufficient RFA was 0.300 relative to para-tumors). Competitive binding of circ-BANP to let-7f-5p was demonstrated and TLR4 was identified as a target of let-7f-5p (P < 0.01). Knockdown of circ-BANP or elevation of let-7f-5p expression inhibited the TLR4/STAT3 signaling pathway, proliferation, invasion, migration, angiogenesis, and EMT in Huh7 and Huh7-H cells ( P < 0.01). The effects induced by circ-BANP knockdown were reversed by let-7f-5p inhibition. Overexpression of TLR4 reversed the impact of let-7f-5p upregulation on the cells ( P < 0.01). Silencing of circ-BANP inhibited the in vivo growth of residual HCC cells after insufficient RFA ( P < 0.01). Conclusions::Knockdown of circ-BANP upregulated let-7f-5p to inhibit proliferation, migration, and EMT formation in residual HCC remaining after insufficient RFA. Effects occur via regulation of the TLR4/STAT3 signaling pathway.
9.Translation and assessment about the Sexual Interest and Desire Inventory-Female
Chenchen LIU ; Guangling GUO ; Chao ZHANG ; Qinqin GONG ; Sirui DONG ; Shuying ZHAO ; Fan ZOU ; Yuqian XIONG
Chinese Journal of Practical Nursing 2021;37(36):2807-2813
Objective:To translate the English version of Sexual Interest and Desire Inventory-Female (SIDI-F) into Chinese, evaluate its reliability, validity and the proper cut-off point of diagnosis of hypoactive sexual desire disorder (HSDD) in China.Methods:Chinese version of SIDI-F was developed and 96 healthy women from January 1, 2019 to December 31, 2019 in Taihe Hospital, Shiyan City, Hubei Province were selected to fill in the Chinese version of SIDI-F and the Female Sexual Function Index (FSFI). Next, analyzed the reliability, validity and the cut-off point of diagnosis of HSDD of the SIDI-F.Results:The Cronbach coefficient of the Chinese version of SIDI-F was 0.931, split-half reliability was 0.922, the intra-group correlation coefficient was 0.805. Analysis of content validity of the SIDI-F indicated that the average of scale-level content validity index was 1.00, the item-level content validity index was 1.00, and the Pearson correlation coefficient between the score of SIDI-F and the erotica score of the FSFI (FSFI-D) was 0.802. Factor analysis of the Chinese version of SIDI-F showed good construct validity. The area under ROC was 0.835. With the SIDI-F score and the best cut-off point of 26.5, Youden index was the largest, at 0.635. The validity indicators were 76.7% for sensitivity, 86.8% for specificity, 5.95 for positive likelihood ratio.Conclusions:The Chinese version of SIDI-F has high reliability and validity in Chinese population, and these show 26.5 point can be used as the best cut-off value of diagnose HSDD.
10.Evaluation of therapeutic efficacy of radiofrequency ablation on hepatic cancer: a preliminary study using superb microvascular imaging
Zipeng HE ; Hua TANG ; Pengcheng JIANG ; Hongyan ZHAO ; Shuying DONG
Chinese Journal of Hepatobiliary Surgery 2021;27(9):663-666
Objective:To study the predictive value of superb microvascular imaging(SMI) in evaluating therapeutic efficacy of hepatic cancer treated by percutaneous radiofrequency ablation(PRFA).Methods:From Feb 2017 to Feb 2018, 55 patients (male: 31, female: 24, age range: 37-68 years, mean age: 56years) with 72 hepatic carcinoma lesions (length: 21.3-45.6 mm, average: 31.2 mm) were detected by SMI and contrast-enhanced CT(CECT)before PRFA. One month after treatment, more than two imaging examinations (CECT, CEMR, ultrasonic imaging) were used as the "gold standard" to evaluate the complete ablation rates. Consistency between the SMI grading and the arterial phase enhancement of CECT was analyzed by the Kappa-test.Results:Before PRFA, SMI showed 12 lesions (16.7%) to be in grade Ⅰ, 28 lesions (38.9%) in grade Ⅱ and 32 lesions (44.4%) in grade Ⅲ. The arterial phase of CECT showed 37 lesions (51.4%) to have no obvious enhancement and 35 lesions (48.6%) to have obvious enhancement. Consistency analysis showed that there was a high consistency between SMI and CECT(Kappa=0.861, P<0.001). The higher the SMI grading, the more obvious the enhancement on CECT. The complete ablation rates of the grade Ⅰ, grade Ⅱ and grade Ⅲ lesions were 100%(12/12), 92.9%(26/28) and 71.9%(23/32), respectively. The complete ablation rate of the lesions in grade Ⅲ was significantly lower than that in grade Ⅰ and grade Ⅱ (both P<0.05). Conclusion:SMI showed a good consistency with CECT in evaluating the blood flow signals of hepatic cancer, SMI grading could be used in predicting the therapeutic efficacy of hepatic cancer treated by PRFA.

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