1.Risk factors for liver cancer in chronic hepatitis B patients and construction of a nomogram prediction model
Yichen ZHU ; Chunxia SHA ; Chunsun FAN ; Tiejun ZHANG
Journal of Clinical Hepatology 2024;40(12):2441-2449
ObjectiveTo investigate the risk factors for liver cancer in patients with chronic hepatitis B (CHB) in the Qidong Chronic Hepatitis B cohort, and to construct a nomogram model for predicting the risk of liver cancer in CHB patients. MethodsA structured questionnaire survey was conducted among the CHB patients, aged ≥18 years, who attended the outpatient service of Qidong Third People’s Hospital from January 1 to December 31, 2016. The onset of liver cancer was defined as the primary outcome, and the outcomes of the cohort were obtained from Qidong Cancer Registry. Baseline clinical features were compared ;between the liver cancer group and the non-liver cancer group. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The Cox regression model was used to analyze the risk factors for liver cancer in CHB patients and calculate their hazard ratio (HR) and 95% confidence interval (CI); the variables with statistical significance in the univariate Cox regression analysis were included in the LASSO regression analysis, and then the variables obtained were included in the multivariate Cox regression analysis to establish a predictive model. The nomogram was used to visualize the complex model. The receiver operating characteristic (ROC) curve, index of concordance (C-index), and the calibration curve were used to assess the predictive efficacy of the model, and the decision curve was used to evaluate the clinical practicability of the nomogram. ResultsA total of 1 479 CHB patients were selected, among whom 58 patients with a confirmed diagnosis of liver cancer, 15 with missing data on testing indicators, and 164 with missing data on important information in the questionnaire were excluded, and finally 1 242 subjects were included in the study. Up to December 31, 2023, there were 67 new cases of liver cancer after a median follow-up time of 7.71 years, and the incidence density of liver cancer was 729.78/100,000 person-years. There were significant differences between the liver cancer group and the non-liver cancer group in age, sex, educational level, liver cirrhosis, duration of liver cirrhosis, history of diabetes mellitus, albumin, total bilirubin (TBil), direct bilirubin, aspartate aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase (GGT), and alkaline phosphatase (all P<0.05). The multivariate Cox regression analysis showed that the increase in age (HR=1.07, 95%CI: 1.05 — 1.10, P<0.001), a relatively high level of TBil (HR=1.98, 95%CI: 1.15 — 3.42, P=0.014), a relatively high level of GGT (HR=2.41, 95%CI: 1.43 — 4.08, P=0.001), and a long duration of liver cirrhosis (HR=1.09, 95%CI: 1.02 — 1.15, P=0.009) were independent risk factors for liver cancer in CHB patients. A nomogram prediction model was constructed based on the above four indicators, with an area under the ROC curve of 0.790, 0.845, and 0.829, respectively, in predicting the risk of liver cancer in CHB patients at 1, 3, and 5 years, and the bootstrap resampling method was used for internal validation and showed a C-index of 0. 778. The calibration curve showed that the prediction model had good stability, and the decision curve showed that it had certain clinical practicability. ConclusionThe increase in age, relatively high levels of TBil and GGT, and a long duration of liver cirrhosis are independent risk factors for liver cancer in CHB patients, and the nomogram model constructed based on these factors has a good predictive value and can be used in clinical practice to help develop strategies for the long-term monitoring of liver cancer.
2.Analysis of resistance situation and resistance genes of clinical isolates of carbapenem-resistant Klebsiella pneumoniae and Escherichia coli
Yun HUANG ; Zhengyin ZHANG ; Ying JIN ; YiJing ZHENG ; Tiejun LI ; Lili SUN
Journal of Pharmaceutical Practice and Service 2024;42(10):439-444
Objective To analyze the current status of anti-bacterial activity of carbapenem-resistant Klebsiella pneumoniae and Escherichia coli clinically isolated from hospitalized patients,detect their related resistance genes,and provide reference for the clinical treatment of carbapenem resistant Enterobacteria(CRE)infections and the rational use of antibiotics.Methods A total of 400 non-repetitive isolates of Klebsiella pneumoniae and Escherichia coli isolated from clinical specimens of Punan Branch of Renji Hospital,Shanghai Jiao Tong University School of Medicine from January 2022 to December were collected.The minimum inhibitory concentrations of these strains against commonly used antibiotics were determined by the broth microdilution method.The carbapenemase and related resistance genes of CRE were detected by drug resistance phenotype testing and PCR.Results Among the 400 strains,51 strains were identified as CRE,accounting for 12.75%.Among these,49 strains produced carbapenemases,with 41 strains(80.39%)being CR Klebsiella pneumoniae and 10 strains(19.61%)being CR Escherichia coli.Among the CRE strains,34 strains(66.67%)carried blaKPC,13 strains(25.49%)carried blaNDM,and 2 strains(3.92%)carried blaOXA-48.Conclusion Compared with other commonly used antibiotics,colistin and tigecycline exhibited good in vitro antibacterial activity against carbapenemase-producing Klebsiella pneumoniae and Escherichia coli.In addition,there was good concordance between drug resistance phenotype testing and genotyping.Clinical microbiology laboratories could continuously monitor the drug resistance phenotype and genotype of CRE and develop appropriate treatment plans based on actual conditions.
3.Digital pathology-based artificial intelligence models for differential diagnosis and prognosis of sporadic odontogenic keratocysts
Cai XINJIA ; Zhang HEYU ; Wang YANJIN ; Zhang JIANYUN ; Li TIEJUN
International Journal of Oral Science 2024;16(2):349-358
Odontogenic keratocyst(OKC)is a common jaw cyst with a high recurrence rate.OKC combined with basal cell carcinoma as well as skeletal and other developmental abnormalities is thought to be associated with Gorlin syndrome.Moreover,OKC needs to be differentiated from orthokeratinized odontogenic cyst and other jaw cysts.Because of the different prognosis,differential diagnosis of several cysts can contribute to clinical management.We collected 519 cases,comprising a total of 2157 hematoxylin and eosin-stained images,to develop digital pathology-based artificial intelligence(AI)models for the diagnosis and prognosis of OKC.The Inception_v3 neural network was utilized to train and test models developed from patch-level images.Finally,whole slide image-level AI models were developed by integrating deep learning-generated pathology features with several machine learning algorithms.The AI models showed great performance in the diagnosis(AUC=0.935,95%CI:0.898-0.973)and prognosis(AUC=0.840,95%CI:0.751-0.930)of OKC.The advantages of multiple slides model for integrating of histopathological information are demonstrated through a comparison with the single slide model.Furthermore,the study investigates the correlation between AI features generated by deep learning and pathological findings,highlighting the interpretative potential of AI models in the pathology.Here,we have developed the robust diagnostic and prognostic models for OKC.The AI model that is based on digital pathology shows promise potential for applications in odontogenic diseases of the jaw.
4.Study on the risk for cerebrovascular disease among subtypes of middle-aged and elderly type 2 diabetes mellitus patients aged between 35‒74 years in Shanghai suburbs
Chengjun ZHANG ; Qiu XIAO ; Zhenqiu LIU ; Chen SUO ; Tiejun ZHANG ; Genming ZHAO ; Yanfeng JIANG ; Kelin XU ; Xingdong CHEN
Shanghai Journal of Preventive Medicine 2024;36(12):1148-1156
ObjectiveTo classify subtypes among middle-aged and elderly type 2 diabetes mellitus (T2DM) patients aged between 35‒74 years in Shanghai suburbs, to compare their characteristics and analyze incidence risk for cerebrovascular disease among these subtypes, so as to promote personalized and precise treatment of T2DM. MethodsA total of 7 792 patients with T2DM who completed a baseline survey from 2016 and 2019 were selected as the research subjects, based on the data from a natural population cohort and biobank in Shanghai suburbs. Patients were stratified by gender and clustered into subtypes using k-means method based on baseline parameters including the age at T2DM diagnosis, body mass index (BMI), fasting blood glucose, and triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C). Patients were followed up until March 31, 2023. Multivariate Cox regression models were used to analyze the association between subtypes and incidence risk for cerebrovascular disease, and those with cerebrovascular disease within 1 year of follow-up survey were excluded from sensitivity analysis. ResultsAmong the 7 792 patients with T2DM, 3 615 were males and 4 177 were females. Stratified by gender, 4 subgroups were identified through k-means clustering analysis, namely poor blood glucose control subgroup, severe insulin-resistant subgroup, younger onset subgroup, and older onset subgroup. The median follow-up time was 4.30 years, during which 1 960 cerebrovascular disease events were observed (844 in males, 1 116 in females). After adjusting for smoking, alcohol consumption, weekly exercise, family history of diabetes mellitus, and duration of diabetes mellitus, among male patients, the incidence risk for cerebrovascular disease was lower in the younger onset subgroup (HR=0.59, 95%CI: 0.48‒0.73, P<0.001), poor blood glucose control subgroup (HR=0.81, 95%CI: 0.65‒1.00, P=0.046), and severe insulin-resistant subgroup (HR=0.61, 95%CI: 0.50‒0.75, P<0.001), compared to the older onset subgroup. While among female patients, the incidence risk for cerebrovascular disease was also lower in the younger onset subgroup (HR=0.68, 95%CI: 0.57‒0.80, P<0.001), poor blood glucose control subgroup (HR=0.73, 95%CI: 0.60‒0.89, P=0.002), and severe insulin-resistant subgroup (HR=0.72, 95%CI: 0.61‒0.85, P<0.001), compared to the older onset subgroup. Results of the sensitivity analysis were consistent with the main findings. ConclusionAmong middle-aged and elderly T2DM patients in suburban Shanghai, both male and female patients have the highest incidence risk for cerebrovascular disease in the older onset subgroup. Subtyping of T2DM patients can help to identify the high-risk populations of cerebrovascular disease.
5.Clinical application of four-hook needle combined with holographic image in robot-assisted partial nephrectomy for completely intrarenal tumors
Qiubo XIE ; Yu ZHOU ; Lei GAO ; Zhong TU ; Jian SONG ; Renhao WANG ; Xiang LI ; Guan ZHANG ; Le ZHANG ; Tiejun PAN
Chinese Journal of Urology 2024;45(5):343-347
Objective:To investigate the safety and efficacy of four-hook needle combined with holographic image in robot-assisted partial nephrectomy for completely intrarenal tumors.Methods:The clinical data of 8 patients with completely intrarenal tumors treated by robot-assisted partial nephrectomy with four-hook needle combined with holographic image admitted to General Hospital of Central Theater Command from October 2023 to December 2023 were retrospectively analyzed. There were 6 males and 2 females, with average age of (44.5±12.0) years old. Tumors of 6 cases were in the left side and 2 cases in the right side. The maximum diameter of the tumor was (23.2±8.1) mm. The R. E.N.A.L. score was (9.0±1.4). The preoperative serum creatinine (Scr) was (73.1±14.7) μmol/L. CT-guided four-hook needle was used to locate the edge of completely intrarenal tumor before surgery. During the operation, the tumor was precisely resected under the guidance of hologram and four-hook needle. Perioperative data of patients were collected and analyzed.Results:All the tumor were successfully resected under the guidance of four-hook needle and hologram without conversion to radical nephrectomy or open surgery. The mean operative time was (117.0±14.5) min, the mean hot ischemia time was (20.2±5.1) min, the mean intraoperative blood loss was (75.0±17.3) ml, and the average hospitalization time was (9.5±1.3) days.The one week postoperative Scr was (73.2±14.8) μmol/L, which had no significant difference with that of before operation ( P=0.952). None of them received blood transfusion. The pathology results of 8 patients were clear cell renal cell carcinoma, and the surgical margins were negative. Conclusions:For completely intrarenal tumors, the four-hook needle combined with the hologram can guide the surgeon to quickly locate the tumor, accurately resect the tumor, reduce perioperative complications, and is safe and effective.
6.Genomic alterations in oral multiple primary cancers
Zhou XUAN ; Cai XINJIA ; Jing FENGYANG ; Li XUEFEN ; Zhang JIANYUN ; Zhang HEYU ; Li TIEJUN
International Journal of Oral Science 2024;16(1):145-153
Oral squamous cell carcinoma(OSCC)is the predominant type of oral cancer,while some patients may develop oral multiple primary cancers(MPCs)with unclear etiology.This study aimed to investigate the clinicopathological characteristics and genomic alterations of oral MPCs.Clinicopathological data from patients with oral single primary carcinoma(SPC,n=202)and oral MPCs(n=34)were collected and compared.Copy number alteration(CNA)analysis was conducted to identify chromosomal-instability differences among oral MPCs,recurrent OSCC cases,and OSCC patients with lymph node metastasis.Whole-exome sequencing was employed to identify potential unique gene mutations in oral MPCs patients.Additionally,CNA and phylogenetic tree analyses were used to gain preliminary insights into the molecular characteristics of different primary tumors within individual patients.Our findings revealed that,in contrast to oral SPC,females predominated the oral MPCs(70.59%),while smoking and alcohol use were not frequent in MPCs.Moreover,long-term survival outcomes were poorer in oral MPCs.From a CNA perspective,no significant differences were observed between oral MPCs patients and those with recurrence and lymph node metastasis.In addition to commonly mutated genes such as CASP8,TP53 and MUC16,in oral MPCs we also detected relatively rare mutations,such as HS3ST6 and RFPL4A.Furthermore,this study also demonstrated that most MPCs patients exhibited similarities in certain genomic regions within individuals,and distinct differences of the similarity degree were observed between synchronous and metachronous oral MPCs.
7.Correlation of HER2 expression and clinicopathological characteristics in patients with urothelial carcinoma in China
Shanshan WANG ; Dingwei YE ; Li YANG ; Fan CHENG ; Tiejun YANG ; Xiaoping ZHANG ; Zhixian YU ; Qingyun ZHANG ; Yong YANG
China Oncology 2024;34(11):1011-1019
Background and purpose:Human epidermal growth factor receptor 2(HER2)is closely associated with drug efficacy and prognosis in urothelial carcinoma(UC).HER2 is a significant biomarker and therapeutic target in various tumors.In recent years,anti-HER2 antibody-drug conjugates have shown significant clinical efficacy in UC patients with HER2 overexpression.Therefore,an in-depth understanding of HER2 expression and its characteristics in Chinese UC patients is crucial to guide treatment decision-making,optimize treatment strategies and achieve personalized therapy.This study aimed to thoroughly investigate correlation of HER2 expression and clinicopathological characteristics in Chinese patients with UC.Methods:This study was a multicenter study that retrospectively included UC patients from urology departments of 8 tertiary hospitals in 5 geographical regions of China(North China,East China,South China,Central China and Northwest)whose tissue samples were collected from January 2023 to March 2024.Inclusion criteria:① age above 18 years;② UC diagnosed by histopathological or cytological examination;③ complete results of HER2 expression detection using immunohistochemistry(IHC)in the primary tumor site were required.Exclusion criteria:① diagnosed patients with tumors in other parts of the body;② physicians evaluated other situations that were not suitable for inclusion in this study.IHC results for HER2 expression and clinicopathological data were collected.HER2 expression was determined according to the criteria outlined in"Clinical pathological expert consensus on HER2 testing in urothelial carcinoma in China",with HER2 2+and 3+defined as HER2 overexpression.The HER2 expression and clinicopathological features were analyzed.This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center(ethical number:2301268-12)and was registered at China Clinical Trial Registry(registration number:ChiCTR2300069746).Results:A total of 1054 patients with UC were included.Most of the tumors were bladder UC(n=807,76.6%).The mean age of patients was(66.8±10.5)years,and the majority were male(78.5%).The HER2 overexpression rate was 58.4%(n=616),with an additional 23%of patients having HER2 1+expression(n=242),and a small proportion exhibiting negative HER2 expression(n=196,18.6%).HER2 expression was significantly associated with various clinical and pathological characteristics such as Eastern Cooperative Oncology Group(ECOG)performance status,history of cardiovascular disease,history of metabolic disorders,smoking,UC disease location,differentiation grade,pathological type,and tumor stage.Conclusion:Retrospective analysis of multi-center data shows that HER2 expression is frequently observed in Chinese UC patients,with an overexpression rate of up to 58.4%.Furthermore,HER2 expression is closely associated with various clinical and pathological features of UC patients.This study underscores the critical importance of accurately assessing HER2 expression in UC patient to guide personalized therapies.
8.Prognostic values of tumor size and location in early stage endometrial cancer patients who received radiotherapy
Shuning JIAO ; Lichun WEI ; Lijuan ZOU ; Tiejun WANG ; Ke HU ; Fuquan ZHANG ; Xiaorong HOU
Journal of Gynecologic Oncology 2024;35(6):e84-
Objective:
To investigate the correlation between tumor size, tumor location, and prognosis in patients with early-stage endometrial cancer (EC) receiving adjuvant radiotherapy.
Methods:
Data of patients who had been treated for stage I–II EC from March 1999 to September 2017 in 13 tertiary hospitals in China was screened. Cox regression analysis was performed to investigate associations between tumor size, tumor location, and other clinical or pathological factors with cancer-specific survival (CSS) and distant metastasis failurefree survival (DMFS). The relationship between tumor size as a continuous variable and prognosis was demonstrated by restricted cubic splines. Prognostic models were constructed as nomograms and evaluated by Harrell’s C-index, calibration curves and receiver operating characteristic (ROC) curves.
Results:
The study cohort comprised 805 patients with a median follow-up of 61 months and a median tumor size of 3.0 cm (range 0.2–15.0 cm). Lower uterine segment involvement (LUSI) was found in 243 patients (30.2%). Tumor size and LUSI were identified to be independent prognostic factors for CSS. Further, tumor size was an independent predictor of DMFS. A broadly positive relationship between poor survival and tumor size as a continuous variable was visualized in terms of hazard ratios. Nomograms constructed and evaluated for CSS and DMFS had satisfactory calibration curves and C-indexes of 0.847 and 0.716, respectively. The area under the ROC curves for 3- and 5-year ROC ranged from 0.718 to 0.890.
Conclusion
Tumor size and LUSI are independent prognostic factors in early-stage EC patients who have received radiotherapy. Integrating these variables into prognostic models would improve predictive ability.
9.Prognostic values of tumor size and location in early stage endometrial cancer patients who received radiotherapy
Shuning JIAO ; Lichun WEI ; Lijuan ZOU ; Tiejun WANG ; Ke HU ; Fuquan ZHANG ; Xiaorong HOU
Journal of Gynecologic Oncology 2024;35(6):e84-
Objective:
To investigate the correlation between tumor size, tumor location, and prognosis in patients with early-stage endometrial cancer (EC) receiving adjuvant radiotherapy.
Methods:
Data of patients who had been treated for stage I–II EC from March 1999 to September 2017 in 13 tertiary hospitals in China was screened. Cox regression analysis was performed to investigate associations between tumor size, tumor location, and other clinical or pathological factors with cancer-specific survival (CSS) and distant metastasis failurefree survival (DMFS). The relationship between tumor size as a continuous variable and prognosis was demonstrated by restricted cubic splines. Prognostic models were constructed as nomograms and evaluated by Harrell’s C-index, calibration curves and receiver operating characteristic (ROC) curves.
Results:
The study cohort comprised 805 patients with a median follow-up of 61 months and a median tumor size of 3.0 cm (range 0.2–15.0 cm). Lower uterine segment involvement (LUSI) was found in 243 patients (30.2%). Tumor size and LUSI were identified to be independent prognostic factors for CSS. Further, tumor size was an independent predictor of DMFS. A broadly positive relationship between poor survival and tumor size as a continuous variable was visualized in terms of hazard ratios. Nomograms constructed and evaluated for CSS and DMFS had satisfactory calibration curves and C-indexes of 0.847 and 0.716, respectively. The area under the ROC curves for 3- and 5-year ROC ranged from 0.718 to 0.890.
Conclusion
Tumor size and LUSI are independent prognostic factors in early-stage EC patients who have received radiotherapy. Integrating these variables into prognostic models would improve predictive ability.
10.Prognostic values of tumor size and location in early stage endometrial cancer patients who received radiotherapy
Shuning JIAO ; Lichun WEI ; Lijuan ZOU ; Tiejun WANG ; Ke HU ; Fuquan ZHANG ; Xiaorong HOU
Journal of Gynecologic Oncology 2024;35(6):e84-
Objective:
To investigate the correlation between tumor size, tumor location, and prognosis in patients with early-stage endometrial cancer (EC) receiving adjuvant radiotherapy.
Methods:
Data of patients who had been treated for stage I–II EC from March 1999 to September 2017 in 13 tertiary hospitals in China was screened. Cox regression analysis was performed to investigate associations between tumor size, tumor location, and other clinical or pathological factors with cancer-specific survival (CSS) and distant metastasis failurefree survival (DMFS). The relationship between tumor size as a continuous variable and prognosis was demonstrated by restricted cubic splines. Prognostic models were constructed as nomograms and evaluated by Harrell’s C-index, calibration curves and receiver operating characteristic (ROC) curves.
Results:
The study cohort comprised 805 patients with a median follow-up of 61 months and a median tumor size of 3.0 cm (range 0.2–15.0 cm). Lower uterine segment involvement (LUSI) was found in 243 patients (30.2%). Tumor size and LUSI were identified to be independent prognostic factors for CSS. Further, tumor size was an independent predictor of DMFS. A broadly positive relationship between poor survival and tumor size as a continuous variable was visualized in terms of hazard ratios. Nomograms constructed and evaluated for CSS and DMFS had satisfactory calibration curves and C-indexes of 0.847 and 0.716, respectively. The area under the ROC curves for 3- and 5-year ROC ranged from 0.718 to 0.890.
Conclusion
Tumor size and LUSI are independent prognostic factors in early-stage EC patients who have received radiotherapy. Integrating these variables into prognostic models would improve predictive ability.

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