[Antitumor effects of redox-responsive nanoparticles containing platinum（⠣）in ovarian cancer].

Objectives: To explore the antitumor effects of redox-responsive nanoparticles containing platinum(Ⅳ)-NP@Pt(Ⅳ) in ovarian cancer. Methods: Redox-responsive polymer carriers were synthesized. Polymer carriers and platinum(Ⅳ)-Pt(Ⅳ) can self-assemble into NP@Pt(Ⅳ). Inductively coupled plasma mass spectrometry was performed to detect the platinum release from NP@Pt(Ⅳ) in reducing environment and the platinum content in ovarian cancer cells ES2 treated with cisplatin, Pt(Ⅳ) and NP@Pt(Ⅳ). The proliferation ability of the ovarian cancer cells were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cellular apoptosis was assessed by flow cytometry. Collection of primary ovarian cancer tissues from patients with primary high-grade serous ovarian cancer who were surgically treated at the Cancer Hospital of the Chinese Academy of Medical Sciences from October to December 2022. The high-grade serous ovarian cancer patient-derived xenograft (PDX) mice were intravenously injected with Cy7.5 labeled NP@Pt(Ⅳ) followed by in vivo imaging system. Mice were treated with PBS, cisplatin and NP@Pt(Ⅳ). Tumor volume and weight were measured in each group. Necrosis, apoptosis and cell proliferation of tumor tissues were detected by hematoxylin-eosin (HE) staining, TUNEL fluorescence staining and Ki-67 immunohistochemistry staining. Body weight and HE staining of heart, liver, spleen, lung and kidney of mice in each group were measured. Results: The platinum release of NP@Pt(Ⅳ) after 48 hours in reducing environment was 76.29%, which was significantly higher than that of 26.82% in non-reducing environment (P<0.001). The platinum content in ES2 cells after 4 hours and 7 hours of treatment with NP@Pt(Ⅳ) (308.59, 553.15 ng/million cells) were significantly higher than those of Pt(Ⅳ) (100.21, 180.31 ng/million cells) and cisplatin (43.36, 50.36 ng/million cells, P＜0.05). The half inhibitory concentrations of NP@Pt(Ⅳ) in ovarian cancer cells ES2, A2780, A2780DDP were 1.39, 1.42 and 4.62 µmol/L, respectively, which were lower than those of Pt(IV) (2.89, 7.27, and 16.74 µmol/L) and cisplatin (5.21, 11.85, and 71.98 µmol/L). The apoptosis rate of ES2 cells treated with NP@Pt(Ⅳ) was (33.91±3.80)%, which was significantly higher than that of Pt(Ⅳ) [(16.28±2.41)%] and cisplatin [(15.01±1.17)%, P＜0.05]. In high-grade serous ovarian cancer PDX model, targeted accumulation of Cy7.5 labeled NP@Pt(Ⅳ) at tumor tissue could be observed. After the treatment, the tumor volume of mice in NP@Pt(IV) group was (130±98) mm3, which was significantly lower than those in control group [(1 349±161) mm3, P<0.001] and cisplatin group [(715±293) mm3, P=0.026]. The tumor weight of mice in NP@Pt(IV) group was (0.17±0.09)g, which was significantly lower than those in control group [(1.55±0.11)g, P<0.001] and cisplatin group [(0.82±0.38)g, P=0.029]. The areas of tumor necrosis and apoptosis in mice treated with NP@Pt(Ⅳ) were higher than those in mice treated with cisplatin. Immunohistochemical staining revealed that there were low expressions of Ki-67 at tumor tissues of mice treated with NP@Pt(Ⅳ) compared with cisplatin. The change in body weight of mice in NP@Pt(Ⅳ) group was not significantly different from that of the control group [(18.56±2.04)g vs.(20.87±0.79)g, P=0.063]. Moreover, the major organs of the heart, liver, spleen, lung, and kidney were also normal by HE staining. Conclusion: Redox-responsive NP@Pt(Ⅳ), produced in this study can enhance the accumulation of cisplatin in ovarian cancer cells and improve the efficacy of ovarian cancer chemotherapy.

[Establishment and validation of a prediction model for early-stage epithelial ovarian cancer based on LASSO regression].

Objective: To establish and validate a prediction model for early-stage epithelial ovarian cancer based on least absolute shrinkage and selection operator (LASSO) regression. Methods: A total of 509 cases ovarian mass patients who underwent surgical treatment in Tianjin Medical General Hospital from January 2018 to March 2023 were retrospectively analyzed. The patients were randomly divided into modeling group [n=356, M(Q1,Q3) for age were 43 (31, 61) years] and internal validation group [n=153, age 42 (31, 60) years] by 7∶3 ratio. In addition, 86 patients [age 44 (33, 61) years] who underwent surgical treatment for ovarian mass in Tianjin Medical University General Hospital from April to November 2023 were collected as external validation group. The variables were screened by LASSO regression. The nomogram model was established and plotted by multivariate logistic regression. Internal and external validation were then conducted. The model performance and clinical applicability were evaluated using receiver operating characteristic (ROC) curve, calibration curve and decision curve. Results: Five variables including age (OR=1.040,95%CI:1.000-1.050,P=0.002), carbohydrate antigen 125 (CA125) (OR=1.001, 95%CI: 1.000-1.010, P=0.017), human epididymis protein 4 (HE4) (OR=1.020, 95%CI: 1.000-1.030, P=0.002), carbohydrate antigen 199 (CA199) (OR=1.001, 95%CI:1.000-1.020, P=0.023) and lactate dehydrogenase (LDH) (OR=1.020, 95%CI: 1.010-1.022, P=0.001) were screened as risk factors for early-stage epithelial ovarian cancer. The nomogram model was constructed based on these above five risk factors to predict early-stage epithelial ovarian cancer. ROC curves showed the area under curve (AUC) were 0.915(95%CI:0.910-0.932)for modeling group, 0.891(95%CI:0.874-0.905) for internal validation group, and 0.924(95%CI:0.907-0.942) for external verification. The calibration curves and clinical decision curves showed the model exhibited good consistency and clinical practicability. Conclusions: The nomogram model built includes age, CA125, HE4, CA199, and LDH. It can effectively predict early-stage epithelial ovarian cancer and has strong clinical practicability.

[Serum hepatitis B virus pregenomic RNA profiles in patients with chronic hepatitis B on long-term antiviral therapy].

Objective: To explore the clinical changes in levels of the new clinical marker serum hepatitis B virus (HBV) pregenomic RNA (pgRNA) in patients with chronic hepatitis B (CHB) with long-term antiviral therapy. Methods: 100 CHB cases who were initially treated with nucleos(t)ide analogues (NAs) at Peking University First Hospital were included. The levels of alanine aminotransferase (ALT), HBV DNA, hepatitis B e-antigen (HBeAg), and hepatitis B surface antigen (HBsAg) during the follow-up period were measured. The TaqMan-based real-time quantitative PCR method was used to detect serum HBV pgRNA levels. The independent sample t-test and Mann-Whitney U test were used to compare continuous variables between groups, while Pearson's χ (2) test and Fisher's exact test were used to compare categorical variables. Results: HBV pgRNA levels decreased significantly in patients who developed virological responses at 48 weeks (n = 54) during subsequent treatment compared to those who did not (n = 46). The HBV pgRNA level was lower in HBeAg-positive patients than in HBeAg-negative patients (P < 0.05 or P < 0.01). Patients with higher HBV DNA and HBeAg-positivity levels at baseline had a higher HBV pgRNA level following antiviral therapy. There was no statistically significant difference in HBV pgRNA levels in patients with different HBV pgRNA levels at baseline after antiviral therapy. There was no correlation between serum HBV pgRNA and HBsAg at baseline, but there was a correlation after long-term antiviral therapy, while there was a weak correlation between HBV pgRNA and HBsAg at the fifth and ninth years of antiviral therapy (r = 0.262, P = 0.031; r = 0.288, P = 0.008). Conclusion: HBV pgRNA levels were higher with higher HBV activity in CHB patients with long-term antiviral therapy.

[Clinical application of split liver transplantation: a single center report of 203 cases].

Objective: To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application. Methods: This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis. Results: The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group (χ2=5.560,P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group (χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion: SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

[Current status and progress of detection methods for common clinical toxicants].

With the progress of science and technology and the development of society, more and more chemical substances have been discovered and countless chemicals have been artificially synthesized, and the risk of exposure to some toxic chemicals by human beings has been greatly increased, resulting in the increasing incidence of acute poisoning, which has seriously endangered the public's physical health and life safety. As the poisoned patients are unconscious or refuse treatment when they are admitted to the hospital, it is difficult to understand the drug exposure history by asking the medical history, so the toxicity detection has become the key to the clinical diagnosis and treatment, and this paper briefly introduces some common toxicity detection methods in the clinic in the hope that it will bring help to the clinical doctors.

Development and validation of a prediction model for unsuccessful treatment outcomes in patients with multi-drug resistance tuberculosis.

BACKGROUND: The World Health Organization has reported that the treatment success rate of multi-drug resistance tuberculosis is approximately 57% globally. Although new drugs such as bedaquiline and linezolid is likely improve the treatment outcome, there are other factors associated with unsuccessful treatment outcome. The factors associated with unsuccessful treatment outcomes have been widely examined, but only a few studies have developed prediction models. We aimed to develop and validate a simple clinical prediction model for unsuccessful treatment outcomes in patients with multi-drug resistance pulmonary tuberculosis (MDR-PTB). METHODS: This retrospective cohort study was performed between January 2017 and December 2019 at a special hospital in Xi'an, China. A total of 446 patients with MDR-PTB were included. Least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were used to select prognostic factors for unsuccessful treatment outcomes. A nomogram was built based on four prognostic factors. Internal validation and leave-one-out cross-validation was used to assess the model. RESULTS: Of the 446 patients with MDR-PTB, 32.9% (147/446) cases had unsuccessful treatment outcomes, and 67.1% had successful outcomes. After LASSO regression and multivariate logistic analyses, no health education, advanced age, being male, and larger extent lung involvement were identified as prognostic factors. These four prognostic factors were used to build the prediction nomograms. The area under the curve of the model was 0.757 (95%CI 0.711 to 0.804), and the concordance index (C-index) was 0.75. For the bootstrap sampling validation, the corrected C-index was 0.747. In the leave-one-out cross-validation, the C-index was 0.765. The slope of the calibration curve was 0.968, which was approximately 1.0. This indicated that the model was accurate in predicting unsuccessful treatment outcomes. CONCLUSIONS: We built a predictive model and established a nomogram for unsuccessful treatment outcomes of multi-drug resistance pulmonary tuberculosis based on baseline characteristics. This predictive model showed good performance and could be used as a tool by clinicians to predict who among their patients will have an unsuccessful treatment outcome.

Characterization of adnexal lesions using photoacoustic imaging to improve sonographic O-RADS risk assessment.

OBJECTIVE: To assess the impact of photoacoustic imaging (PAI) on the assessment of ovarian/adnexal lesion(s) of different risk categories using the sonographic ovarian-adnexal imaging-reporting-data system (O-RADS) in women undergoing planned oophorectomy. METHOD: This prospective study enrolled women with ovarian/adnexal lesion(s) suggestive of malignancy referred for oophorectomy. Participants underwent clinical ultrasound (US) examination followed by coregistered US and PAI prior to oophorectomy. Each ovarian/adnexal lesion was graded by two radiologists using the US O-RADS scale. PAI was used to compute relative total hemoglobin concentration (rHbT) and blood oxygenation saturation (%sO2 ) colormaps in the region of interest. Lesions were categorized by histopathology into malignant ovarian/adnexal lesion, malignant Fallopian tube only and several benign categories, in order to assess the impact of incorporating PAI in the assessment of risk of malignancy with O-RADS. Malignant and benign histologic groups were compared with respect to rHbT and %sO2 and logistic regression models were developed based on tumor marker CA125 alone, US-based O-RADS alone, PAI-based rHbT with %sO2 , and the combination of CA125, O-RADS, rHbT and %sO2. Areas under the receiver-operating-characteristics curve (AUC) were used to compare the diagnostic performance of the models. RESULTS: There were 93 lesions identified on imaging among 68 women (mean age, 52 (range, 21-79) years). Surgical pathology revealed 14 patients with malignant ovarian/adnexal lesion, two with malignant Fallopian tube only and 52 with benign findings. rHbT was significantly higher in malignant compared with benign lesions. %sO2 was lower in malignant lesions, but the difference was not statistically significant for all benign categories. Feature analysis revealed that rHbT, CA125, O-RADS and %sO2 were the most important predictors of malignancy. Logistic regression models revealed an AUC of 0.789 (95% CI, 0.626-0.953) for CA125 alone, AUC of 0.857 (95% CI, 0.733-0.981) for O-RADS only, AUC of 0.883 (95% CI, 0.760-1) for CA125 and O-RADS and an AUC of 0.900 (95% CI, 0.815-0.985) for rHbT and %sO2 in the prediction of malignancy. A model utilizing all four predictors (CA125, O-RADS, rHbT and %sO2 ) achieved superior performance, with an AUC of 0.970 (95% CI, 0.932-1), sensitivity of 100% and specificity of 82%. CONCLUSIONS: Incorporating the additional information provided by PAI-derived rHbT and %sO2 improves significantly the performance of US-based O-RADS in the diagnosis of adnexal lesions. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Diagnostic performance of diffusion-weighted imaging and intravoxel incoherent motion for renal lesions: a meta-analysis.

AIM: To compare the diagnostic performance of diffusion-weighted imaging (DWI) and intravoxel incoherent motion (IVIM) parameters, specifically true diffusion coefficient (D), pseudo diffusion coefficient (D∗), and perfusion fraction (f) for quantitatively differentiating benign and malignant renal lesions. MATERIALS AND METHODS: A comprehensive search was conducted in the EMBASE and PubMed databases before September 2022 to identify studies in English investigating the diagnostic accuracy of DWI and IVIM in renal lesions. The quality of the included studies was assessed using the QUADAS-2 tool. Pooled sensitivity, specificity, and area under the curve (AUC) values were estimated for each parameter. RESULTS: A total of 19 studies involving 1,860 renal lesions (1,160 malignant and 700 benign), met the inclusion criteria. Among these studies, 15 assessed the apparent diffusion coefficient (ADC), four assessed IVIM, and three evaluated both ADC and IVIM. The pooled sensitivity, specificity, and AUC for ADC were 0.84 (95% confidence interval [Cl], 0.79-0.88), 0.82 (95% Cl, 0.72-0.89), and 0.89 (95% Cl, 0.86-0.92), respectively. The IVIM parameter with the highest diagnostic accuracy was D, with a pooled sensitivity, specificity, and AUC of 0.89 (95% Cl, 0.74-0.96), 0.96 (95% Cl, 0.85-0.99), and 0.98 (95% Cl, 0.96-0.99), respectively. The pooled sensitivity, specificity and AUC for f were 0.67 (95% Cl, 0.55-0.77), 0.81 (95% Cl, 0.30-0.98), and 0.73 (95% Cl, 0.69-0.77), respectively. The pooled sensitivity, specificity, and AUC for D∗ were 0.87 (95% Cl, 0.81-0.91), 0.59 (95% Cl, 0.48-0.70), and 0.82 (95% Cl, 0.78-0.85), respectively. CONCLUSION: This meta-analysis indicated that both IVIM and DWI had moderate to high diagnostic accuracy for differentiating benign and malignant renal lesions. Among the IVIM parameter, D exhibited the highest diagnostic accuracy, demonstrating higher sensitivity and specificity than ADC, D∗, and f.

Dexmedetomidine for adult cardiac surgery: a systematic review, meta-analysis and trial sequential analysis.

The effects of dexmedetomidine in adults undergoing cardiac surgery are inconsistent. We conducted a systematic review and meta-analysis to analyse the effects of peri-operative dexmedetomidine in adults undergoing cardiac surgery. We searched MEDLINE via Pubmed, EMBASE, Scopus and Cochrane for relevant randomised controlled trials between 1 January 1990 and 1 March 2022. We used the Joanna Briggs Institute methodology checklist to assess study quality and the GRADE approach to certainty of evidence. We assessed the sensitivity of results to false data. We used random-effects meta-analyses to analyse the primary outcomes: durations of intensive care and tracheal intubation. We included 48 trials of 6273 participants. Dexmedetomidine reduced the mean (95%CI) duration of intensive care by 5.0 (2.2-7.7) h, p = 0.001, and tracheal intubation by 1.6 (0.6-2.7) h, p = 0.003. The relative risk (95%CI) for postoperative delirium was 0.58 (0.43-0.78), p = 0.001; 0.76 (0.61-0.95) for atrial fibrillation, p = 0.015; and 0.49 (0.25-0.97) for short-term mortality, p = 0.041. Bradycardia and hypotension were not significantly affected. Trial sequential analysis was consistent with the primary meta-analysis. Adjustments for possible false data reduced the mean (95%CI) reduction in duration of intensive care and tracheal intubation by dexmedetomidine to 3.6 (1.8-5.4) h and 0.8 (0.2-1.4) h, respectively. Binary adjustment for methodological quality at a Joanna Briggs Institute score threshold of 10 did not alter the results significantly. In summary, peri-operative dexmedetomidine reduced the durations of intensive care and tracheal intubation and the incidence of short-term mortality after adult cardiac surgery. The reductions in intensive care stay and tracheal intubation may or may not be considered clinically useful, particularly after adjustment for possible false data.

[Development and validation of prognostic nomogram for malignant pleural mesothelioma].

Objective: To development the prognostic nomogram for malignant pleural mesothelioma (MPM). Methods: Two hundred and ten patients pathologically confirmed as MPM were enrolled in this retrospective study from 2007 to 2020 in the People's Hospital of Chuxiong Yi Autonomous Prefecture, the First and Third Affiliated Hospital of Kunming Medical University, and divided into training (n=112) and test (n=98) sets according to the admission time. The observation factors included demography, symptoms, history, clinical score and stage, blood cell and biochemistry, tumor markers, pathology and treatment. The Cox proportional risk model was used to analyze the prognostic factors of 112 patients in the training set. According to the results of multivariate Cox regression analysis, the prognostic prediction nomogram was established. C-Index and calibration curve were used to evaluate the model's discrimination and consistency in raining and test sets, respectively. Patients were stratified according to the median risk score of nomogram in the training set. Log rank test was performed to compare the survival differences between the high and low risk groups in the two sets. Results: The median overall survival (OS) of 210 MPM patients was 384 days (IQR=472 days), and the 6-month, 1-year, 2-year, and 3-year survival rates were 75.7%, 52.6%, 19.7%, and 13.0%, respectively. Cox multivariate regression analysis showed that residence (HR=2.127, 95% CI: 1.154-3.920), serum albumin (HR=1.583, 95% CI: 1.017-2.464), clinical stage (stage Ⅳ: HR=3.073, 95% CI: 1.366-6.910) and the chemotherapy (HR=0.476, 95% CI: 0.292-0.777) were independent prognostic factors for MPM patients. The C-index of the nomogram established based on the results of Cox multivariate regression analysis in the training and test sets were 0.662 and 0.613, respectively. Calibration curves for both the training and test sets showed moderate consistency between the predicted and actual survival probabilities of MPM patients at 6 months, 1 year, and 2 years. The low-risk group had better outcomes than the high-risk group in both training (P=0.001) and test (P=0.003) sets. Conclusion: The survival prediction nomogram established based on routine clinical indicators of MPM patients provides a reliable tool for prognostic prediction and risk stratification.

[Clinical characteristics of patients with rheumatic diseases and abnormal liver function].

Objective: To investigate the clinical characteristics of patients with rheumatic diseases and abnormal liver function, as well as determine the proportion and severity of liver function abnormalities. Methods: Cross-sectional study. Data were collected from patients registered in the Chinese Rheumatism Date Center from 2011 to 2021. The rheumatic diseases analyzed in this study were rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren syndrome (SS), ankylosing spondylitis (AS), and gout. Patient data, including demographic characteristics [ such as age, sex, body mass index,(BMI), and smoking history], liver function test results [including alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase(ALP), and total bilirubin], and use of anti-rheumatic immune drugs and liver-protective drugs, were collected and compared between groups with normal and abnormal liver functions. In addition, the proportions of abnormal liver function were compared between sex and age groups. Results: A total of 116 308 patients were included in this study, including 49 659 with RA, 17 597 with SLE, 9 039 with SS, 11 321 with AS, and 28 692 with gout. The lowest proportion of liver function abnormalities was observed in patients with RA[11.02% (5 470/49 659)], followed by those with SS[17.97% (1 624/9 039)] and AS [18.22% (2 063/11 321) ], whereas patients with SLE [21.14% (3 720/17 597) ] and gout [28.73% (8 242/28 692)] exhibited the highest proportion of these abnormalities. Elevated ALT, mostly classified as grade 1, was the most commonly noted liver function abnormality, whereas elevated ALP was the least common. Some patients who took liver-protective drugs had normal liver function, with the lowest percentage observed in patients with gout [7.45% (36/483) ] and ranging from 21.7% to 30.34% in patients with RA, SLE, SS, and AS. The proportion of liver function abnormalities was higher in males than in females for all disease types [RA: 13.8%(1 368/9 906) vs. 10.3%(4 102/39 753); SLE: 33.6% (479/1 424) vs. 20.0% (3 241/16 173); SS: 25.4%(111/437) vs. 17.6%(1 513/8 602); AS: 20.1%(1 629/8 119) vs. 13.6% (434/3 202); and gout: 29.3% (8 033/27 394) vs. 16.1% (209/1 298)]. In RA, SLE, and AS, the proportions of liver function abnormalities were similar across all age groups. In SS, the proportion of liver function abnormalities increased with age [<40 years: 14.9%(294/1 979); 40-59 years: 18.1%(858/4 741); ≥60 years: 20.4%(472/2 319)], whereas a reversal of this trend was observed in gout [<40 years: 34.9%(4 294/12 320); 40-59 years: 25.5%(2 905/11 398);≥60 years: 21.0%(1 042/4 971)]. Conclusions: The proportions of combined liver function abnormalities in patients with rheumatologic diseases were high, and the utilization rates of liver-protective drugs were low. It is necessary to pay more attention to monitoring patients' liver function, timely administer liver-protective drugs, and optimize liver-protective regimens during the treatment of rheumatic diseases.

[Value of radiomics models based on MRI diffusion weighted imaging and apparent diffusion coefficient in differentiating benign and malignant thyroid nodules].

Objective: To investigate the value of radiomics models based on magnetic resonance imaging (MRI) diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps in distinguishing benign and malignant thyroid nodules. Methods: A cross-sectional study. Clinical data of 148 thyroid nodules (50 benign, 98 malignant) from 140 patients who underwent thyroid MRI examination in Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences between January 2019 and December 2022 were retrospectively analyzed. The nodules were used as the study units, and a leave-one-out method was used to randomly divide the nodules into a training set and a test set at a 7∶3 ratio. Region of interest was segmented and radiomics features were extracted from the DWI and ADC images. In the training set, feature selection was performed using inter-observer agreement analysis, U-test, least absolute shrinkage and selection operator algorithm, and correlation analysis. Four classifiers, including support vector machine (SVM), random forest (RF), k-nearest neighbors (KNN) and logistic regression (LR) were used to build models with the selected features, including the DWI models, ADC models, and combined models. The models were independently tested in the test set. The performance of the radiomics models in distinguishing benign and malignant thyroid nodules was evaluated using the receiver operating characteristic (ROC) curve, with pathological results as the gold standard. Results: Of the 140 patients, there were 40 males and 100 females, with a mean age of (38.4±12.2) years. After feature selection, 11 DWI features and 11 ADC features were used to build the models. In the training set, the AUC values of the combined models were higher than those of the corresponding DWI and ADC models. In the test set, the SVM combined model showed the best predictive performance, with an AUC of 0.873 (95%CI:0.740-0.954), accuracy of 75.6%, sensitivity of 46.7%, specificity of 90.0%, positive predictive value (PPV) of 70.0% and negative predictive value (NPV) of 77.1%, while the RF combined model had an AUC of 0.836 (95%CI:0.695-0.929), accuracy of 77.8%, sensitivity of 40.0%, specificity of 96.7%, PPV of 85.7% and NPV of 76.3%, the KNN combined model had an AUC of 0.832 (95%CI:0.691-0.927), accuracy of 77.8%, sensitivity of 33.3%, specificity of 100%, PPV of 100% and NPV of 75.0%, the LR combined model had an AUC of 0.813 (95%CI:0.669-0.914), accuracy of 77.8%, sensitivity of 60.0%, specificity of 86.7%, PPV of 69.2% and NPV of 81.3%. Conclusions: Radiomics models based on DWI and ADC image features can effectively distinguish benign and malignant thyroid nodules. The SVM combined model had the best prediction performance.

TFP5, a Peptide Derived from Cdk5 Activator p35, Protects Pancreatic ß Cells from Glucose Toxicity.

We studied the effect of TFP5 on MIN6 cells (cultured mouse islet ß cells) treated with different concentrations of glucose (5 or 25 mM). The results were verified in C57BL/6J mice (control; n=12) and db/db mice with type 2 diabetes mellitus (n=12). To synthesize TFP5, peptide p5 (a derivative of p35 protein, activator of cyclin-dependent kinase 5, Cdk5) was conjugated with a FITC tag at the N-terminus and an 11-amino acid TAT protein transduction domain at the C-terminus. TFP5 was employed to inhibit Cdk5 activity and then to evaluate its efficiency in treating experimental type 2 diabetes mellitus. TFP5 effectively inhibited the pathological hyperactivity of Cdk5, enhanced insulin secretion, and protected pancreatic ß cells from apoptosis in vitro and in vivo. In addition, TFP5 inhibited inflammation in pancreatic islets by reducing the expression of inflammatory cytokines TGF-ß1, TNFα, and IL-1ß. These novel data indicates that TFP5 is a promising candidate for treatment of type 2 diabetes mellitus.

[Hereditary pulmonary hypertension family with BMPR2 gene variation: a case report and literature review].

Objective: To describe the clinical characteristics, diagnosis, genetic features and treatment of hereditary pulmonary hypertension complicated with suspected hereditary hemorrhagic telangiectasia (HHT). Methods: Firstly, we summarized and analyzed the clinical data of two cases of suspected HHT admitted to the Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University. Secondly, the genes of peripheral blood of patients and their families were completely sequenced and sanger sequencing was performed to verify the variation sites, and then the mRNA deletion caused by the variation was further verified. Thirdly, "HHT" "FPAH" and "BMPR2 gene variation" were used as keywords,and the related literatures of Wanfang database and PubMed database from January 2000 to November 2021 were searched and reviewed. Results: We found two patients in a family from Yiyang, Hunan province, who had symptoms of hemoptysis or pulmonary hypertension without epistaxis or other clinical features of HHT. However, both patients had pulmonary vascular abnormalities and pulmonary hypertension in their lungs. We found that BMPR2 gene variation (NM_001204.7:c.1128+1G>T) was positive and ENG, ACVRL1 and SMAD4 genes were negative. Family analysis and Sanger verification were carried out on 16 individuals in 4 generations of the family (7 of whom were found to carry the mutant gene), and then transcriptional level mRNA sequencing further confirmed that the variation resulted in the deletion of exon 8 and exon 9, and amino acid sequence estimation revealed that the amino acids of the protein from 323 to 425 were deleted. We thought that the incomplete translation of BMPR2 gene could lead to BMPRⅡ dysfunction. Therefore, it was diagnosed as hereditary pulmonary hypertension with suspected HHT. Both patients were suggested to reduce the pulmonary artery pressure, and at the same time, the whole-body imaging examination should be performed to screen other arteriovenous malformations, and the annual cardiac color Doppler ultrasound should be reviewed to evaluate the changes of pulmonary artery pressure. Conclusions: Hereditary pulmonary hypertension (HPAH) is a group of diseases with increasing pulmonary vascular resistance caused by genetic factors, including familial PAH and simple PAH. Variation in the BMPR2 gene is an important pathogenic factor of HPAH. Therefore, we should pay attention to the inquiry of family history when we clinically encounter young patients with pulmonary hypertension. If the cause is unknown, genetic testing is recommended. HHT is a rare autosomal dominant genetic disease. The possibility of this disease should be considered in clinical manifestations such as familial pulmonary vascular abnormality, pulmonary hypertension and recurrent epistaxis. There is no effective specific treatment for HPAH and HHT, which are treated symptomatically (including blood pressure reduction and hemostasis, etc.). It is suggested for these patients that pulmonary artery pressure should be dynamically monitored and have genetic counseling before giving birth.

[Analysis of the characteristics of retracted scientific papers in the field of global liver diseases published by Chinese scholars].

Objective: To analyze the characteristics of scientific papers in the field of global liver diseases published by Chinese scholars that were retracted for diverse reasons from the Retraction Watch database, so as to provide a reference to publishing-related papers. Methods: The Retraction Watch database was retrieved for retracted papers in the field of global liver disease published by Chinese scholars from March 1, 2008 to January 28, 2021. The regional distribution, source journals, reasons for retraction, publication and retraction times, and others were analyzed. Results: A total of 101 retracted papers that were distributed across 21 provinces/cities were retrieved. Zhejiang area (n = 17) had the most retracted papers, followed by Shanghai (n = 14), and Beijing (n = 11). The vast majority were research papers (n = 95). The journal PLoS One had the highest number of retracted papers. In terms of time distribution, 2019 (n = 36) had the most retracted papers. 23 papers, accounting for 8.3% of all retractions, were retracted owing to journal or publisher concerns. Liver cancer (34%), liver transplantation (16%), hepatitis (14%), and others were the main areas of retracted papers. Conclusion: Chinese scholars have a large number of retracted articles in the field of global liver diseases. A journal or publisher chooses to retract a manuscript after investigating and discovering more flawed problems, which, however, require further support, revision, and supervision from the editorial and academic circles.

[Impact of COVID-19 on primary percutaneous coronary intervention in patients with acute ST segment elevation myocardial infarction in Beijing].

Objective: To investigate the impact of COVID-19 on treatment of patients with acute ST segment elevation myocardial infarction(STEMI) undergoing primary percutaneous coronary intervention(PPCI). Methods: This was a multicenter retrospective study. STEMI patients undergoing PPCI from January 1, 2019 to December 31, 2021 were selected, based on the data of Xinnaolvsetongdao App. Clinical data and treatment time indicators, including symptom to first medical contact (S-FMC), symptom to door (StoD), first medical contact to ECG (FMC-ECG), first medical contact to guide wire (FMC-W), door to balloon (DtoB) and total ischemic time in 2019, 2020 and 2021 were compared. STEMI patients aged<60 years were sub-grouped as the young and middle-aged group, and STEMI patients aged≥60 years were sub-grouped as the elderly group. Results: A total of 7 435 (3 305 in 2019, 1 796 in 2020 and 2 334 in 2021) STEMI patients aged (59.6±12.6) years undergoing PPCI were included in this analysis. There were 5 990 males. For STEMI patients with PPCI in 2019, 2020 and 2021, FMC-ECG was 3 (1, 5) min, 3(1, 7) min and 4 (1, 7) min. FMC-W was 73 (56, 87) min, 78 (62, 95) min and 77 (62, 87) min. DtoB was 73 (56, 85) min, 78 (62, 95) min and 77 (62, 86) min. Total ischemic time was 189 (130, 273) min, 196 (138, 295) min and 209 (143, 276) min. FMC-ECG, FMC-W, DtoB and total ischemic time were longer in 2020 and 2021 than in 2019 (all P<0.05). The proportions of patients with FMC-ECG≤10 min (88.4% (1 588/1 796) vs. 92.7% (3 064/3 305), P<0.05), FMC-W≤120 min (87.9% (1 579/1796) vs. 91.7% (3 030/3 305), P<0.05) and DtoB≤90 min (72.3% (1 298/1 796) vs. 80.8% (2 672/3 305), P<0.05) were lower in 2020 than in 2019, whereas no differences were observed in the proportions of patients with FMC-ECG≤10 min (91.3% (2 131/2 334) vs. 92.7% (3 064/3 305), P=0.054), FMC-W≤120 min (92.0% (2 148/2 334) vs. 91.7% (3 030/3 305), P=0.635) and DtoB≤90 min (80.0% (1 867/2 334) vs. 80.8% (2 672/3 305), P=0.424) in 2021 compared with 2019. In the subgroup analysis, the proportions of patients with FMC-ECG≤10 min, FMC-W≤120 min and DtoB≤90 min were lower in the elderly group than in young and middle-aged group in 2019 (all P<0.05). The proportions of patients with FMC-W≤120 min and DtoB≤90 min were lower in the elderly group than in young and middle-aged group in 2021(all P<0.05). No differences were observed in the proportions of patients with FMC-ECG≤10 min, FMC-W≤120 min and DtoB≤90 min between the two group in 2020 (all P>0.05). Conclusions: Affected by the COVID-19, there is a reduction in the number of PPCI cases and treatment delays in STEMI patients, especially in the elderly. After adjusting the treatment strategy and widely applying the Xinnaolvsetongdao APP, the above indicators are significantly improved in 2021 as compared with 2020.

[Effects of specimen preservation and transportation on blood paraquat concentration in rats].

Objective: To investigate the effects of duration, temperature and shake on paraquat (PQ) concentration in the blood of PQ-exposed rats during the specinen preservation and transportation. Methods: In March 2021, 60 SD male rats of Specific Pathogen Free class were randomly divided into low-dose group (10 mg/kg PQ) and high-dose group (80 mg/kg PQ). Each group was divided into 5 subgroups (normal temperature group, cold storage group, 37 ℃ storage group, shaking on normal temperature group and shaking on 37 ℃ group), six rats in each subgroup. The rats were given intraperitoneal injection of PQ, 1 h after exposure, the blood samples were obtained by cardiac extraction. After different interventions, the concentrations of PQ were detected and compared before and after the intervention in each subgroup. Results: In the shaking on 37 ℃ group, the results of PQ concentrations in PQ-exposed rats were significantly lower than those before the intervention (P<0.05). In the other subgroups, the results were not significantly different compared with before intervention (P>0.05) . Conclusion: The concentration of PQ in the blood of rats exposed to PQ was decreased by shaking for 4 hours at 37 ℃.

Development and validation of an individualized nomogram for predicting the high-volume (> 5) central lymph node metastasis in papillary thyroid microcarcinoma.

PURPOSE: Papillary thyroid microcarcinoma (PTMC) frequently presents a favorable clinical outcome, while aggressive invasiveness can also be found in some of this population. Identifying the risk clinical factors of high-volume (> 5) central lymph node metastasis (CLNM) in PTMC patients could help oncologists make a better-individualized clinical decision. METHODS: We retrospectively reviewed the clinical characteristics of adult patients with PTC in the Surveillance, Epidemiology, and End Results (SEER) database between Jan 2010 and Dec 2015 and in one medical center affiliated to Chongqing Medical University between Jan 2018 and Oct 2020. Univariate and multivariate logistic regression analyses were used to determine the risk factors for high volume of CLNM in PTMC patients. RESULTS: The male gender (OR = 2.02, 95% CI 1.46-2.81), larger tumor size (> 5 mm, OR = 1.64, 95% CI 1.13-2.38), multifocality (OR = 1.87, 95% CI 1.40-2.51), and extrathyroidal invasion (OR = 3.67; 95% CI 2.64-5.10) were independent risk factors in promoting high-volume of CLNM in PTMC patients. By contrast, elderly age (≥ 55 years) at diagnosis (OR = 0.57, 95% CI 0.40-0.81) and PTMC-follicular variate (OR = 0.60, 95% CI 0.42-0.87) were determined as the protective factors. Based on these indicators, a nomogram was further constructed with a good concordance index (C-index) of 0.702, supported by an external validating cohort with a promising C-index of 0.811. CONCLUSION: A nomogram was successfully established and validated with six clinical indicators. This model could help surgeons to make a better-individualized clinical decision on the management of PTMC patients, especially in terms of whether prophylactic central lymph node dissection and postoperative radiotherapy should be warranted.

Genetic analyses of blood ß-hydroxybutyrate predicted from milk infrared spectra and its association with longevity and female reproductive traits in Holstein cattle.

Ketosis is one of the most prevalent and complex metabolic disorders in high-producing dairy cows and usually detected through analyses of ß-hydroxybutyrate (BHB) concentration in blood. Our main objectives were to evaluate genetic parameters for blood BHB predicted based on Fourier-transform mid-infrared spectra from 5 to 305 d in milk, and estimate the genetic relationships of blood BHB with 7 reproduction traits and 6 longevity traits in Holstein cattle. Predicted blood BHB records of 11,609 Holstein cows (after quality control) were collected from 2016 to 2019 and used to derive 4 traits based on parity number, including predicted blood BHB in all parities (BHBp), parity 1 (BHB1), parity 2 (BHB2), and parity 3+ (BHB3). Single- and multitrait repeatability models were used for estimating genetic parameters for the 4 BHB traits. Random regression test-day models implemented via Bayesian inference were used to evaluate the daily genetic feature of BHB variability. In addition, genetic correlations were calculated for the 4 BHB traits with reproduction and longevity traits. The heritability estimates of BHBp, BHB1, BHB2, and BHB3 ranged from 0.100 ± 0.026 (± standard error) to 0.131 ± 0.023. The BHB in parities 1 to 3+ were highly genetically correlated and ranged from 0.788 (BHB1 and BHB2) to 0.911 (BHB1 and BHB3). The daily heritability of BHBp ranged from 0.069 to 0.195, higher for the early and lower for the later lactation periods. A similar trend was observed for BHB1, BHB2, and BHB3. There are low direct genetic correlations between BHBp and selected reproductive performance and longevity traits, which ranged from -0.168 ± 0.019 (BHBp and production life) to 0.157 ± 0.019 (BHBp and age at first calving) for the early lactation stage (5 to 65 d). These direct genetic correlations indicate that cows with higher BHBp (greater likelihood of having ketosis) in blood usually have shorter production life (-0.168 ± 0.019). Cows with higher fertility and postpartum recovery, such as younger age at first calving (0.157 ± 0.019) and shorter interval from calving to first insemination in heifer (0.111 ± 0.006), usually have lower BHB concentration in the blood. Furthermore, the direct genetic correlations change across parity and lactation stage. In general, our results suggest that selection for lower predicted BHB in early lactation could be an efficient strategy for reducing the incidence of ketosis as well as indirectly improving reproductive and longevity performance in Holstein cattle.

[Inhibition of GAS5 promoted invasion, migration and epithelial-mesenchymal transition of colorectal cancer cells via miR-21/PTEN/Akt axis].

Objective: To explore the effect of growth arrest-specific5 (GAS5) inhibition on the proliferation, colony formation, invasion, migration andepithelial-mesenchymal transition(EMT), cancer cell stem of HCT-116 and its mechanism. Methods: The colorectal carcinoma (CRC) cell HCT116 was divided into blank control, negative control (NC), si-GAS5 and si-GAS5+ miR-21 inhibitor groups. The quantitative real-time polymerase chain reaction (qRT-PCR) was used to test the expressions of miR-21 and GAS5 at 48 h after transfection. The binding site of GAS5 and miR-21 was determined by luciferase reporter array. Cell proliferation ability was detected by CCK-8 assay. Cell colony ability was detected by colony formation assay. Cell invasion and migration abilities were detected by Transwell assay. Cell cycle and apoptosis were examined by flow cytometer (FCM). The protein levels of EMT associated factors including Snail, N-cadherin, vimentin, E-cadherin, stem cell related factors including CD44, SOX2, Oct2, and PTEN/Akt signal pathway associated factors were examined by western blotting. Results: The expression levels of miR-21 in blank, NC, si-GAS5 group were 1.00±0.10, 1.00±0.10, 1.80±0.20, the absorbance values were 0.51±0.02, 0.50±0.01 and 0.65±0.01, the cell clones were 90±4, 91±5, 200±8, the invaded cells were 118±3, 119±3, 150±4, the migrated cells were 110±2, 108±2, 127±2, the cell ratios in G(1) phase were (49.3±2.1)%, (50.1±2.0)% and (42.2±1.1)%, the cell ratios in S phase were (19.2±1.2)%, (20.2±1.1)% and (28.3±2.2)%, the cell apoptotic ratios were (14.4±2.2)%, (14.5±2.1)% and (7.2±1.3)%. These results indicated that inhibition of GAS5 up regulated the expression level of miR-21, promoted cell proliferation, invasion and migration, decreased G(1)-phase cells and increased S-phase cells, and suppressed cell apoptosis (P<0.05). Moreover, inhibition of GAS5 up regulated the expressions of Snail, N-cadherin, vimentin, Sox2, CD44, Oct2 and p-Akt in HCT-116 cells (P<0.05), while down regulated the expressions of E-cadherin and PTEN (P<0.05). Inhibition of miR-21 reversed the impact of GAS5 knockdown on PTEN/Akt signaling pathway (P<0.05). Conclusion: GAS5 can act as a competing endogenous RNA for miR-21, and down regulation of GAS5 can promote the development of CRC by activating the miR-21/PTEN/Akt signaling pathway and promoting the acquisition of EMT and tumor cell stemness.