Objective To explore the value of CT-enhanced portal venous phase radiomics combined with machine learning algo-rithms in assessing microvascular invasion(MVI)in hepatocellular carcinoma(HCC).Methods A retrospective analysis was con-ducted on imaging and clinical data of 132 HCC patients.The patients were randomly divided into training set and test set at a 7︰3 ratio.Independent influencing factors for predicting MVI status in HCC patients were identified through univariate and multivariate logistic regression analyses.Radiomics features were selected using the least absolute shrinkage and selection operator(LASSO)algorithm,and a Radiomics score(Radscore)was calculated to construct the final combined model.Four machine learning algorithms including-logistic regression(LR),naive Bayes(NB),support vector machine(SVM),and K-nearest neighbor(KNN)were applied to evaluate the model.The performance of each machine model was assessed using the receiver operating characteristic(ROC)curves and the area under the curve(AUC).Results Univariate and multivariate logistic regression analyses revealed that venous phase CT values were independentinfluencing factors,and six radiomics features were ultimately selected.After the Radscore was calculated,a combined model was constructed using Radscore and venous phase CT values.Machine learning algorithms showed that the combined model achieved the following AUC in the training set:0.895[95%confidence interval(CI)0.821-0.965]for LR,0.892(95%CI 0.831-0.963)for NB,0.644(95%CI 0.532-0.765)for SVM,and 0.855(95%CI 0.783-0.947)for KNN.In the test set,the respective AUC were 0.845(95%CI 0.712-0.961),0.840(95%CI 0.723-0.964),0.492(95%CI 0.311-0.687),and 0.716(95%CI 0.566-0.871).Conclusion Radiomics based on CT-enhanced portal venous phase combined with machine learning algorithms demonstrates high efficiency in preoperative evaluation of MVI in HCC,with the LR model showing the best performance.

The central amygdala (CeA) is a crucial modulator of emotional, behavioral, and autonomic functions, including cardiovascular responses. Despite its importance, the specific circuit by which the CeA modulates blood pressure remains insufficiently explored. Our investigations demonstrate that photostimulation of GABAergic neurons in the centromedial amygdala (CeM^GABA), as opposed to those in the centrolateral amygdala (CeL), produces a depressor response in both anesthetized and freely-moving mice. In addition, activation of CeM^GABA axonal terminals projecting to the nucleus tractus solitarius (NTS) significantly reduces blood pressure. These CeM^GABA neurons form synaptic connections with NTS neurons, allowing for the modulation of cardiovascular responses by influencing the caudal or rostral ventrolateral medulla. Furthermore, CeM^GABA neurons targeting the NTS receive dense inputs from the CeL. Consequently, stimulation of CeM^GABA neurons elicits hypotension through the CeM-NTS circuit, offering deeper insights into the cardiovascular responses associated with emotions and behaviors.
Animals ; GABAergic Neurons/physiology* ; Male ; Central Amygdaloid Nucleus/physiopathology* ; Hypotension/physiopathology* ; Mice ; Blood Pressure/physiology* ; Mice, Inbred C57BL ; Solitary Nucleus/physiology* ; Photic Stimulation ; Neural Pathways/physiology*

Objective To explore the value of CT-enhanced portal venous phase radiomics combined with machine learning algo-rithms in assessing microvascular invasion(MVI)in hepatocellular carcinoma(HCC).Methods A retrospective analysis was con-ducted on imaging and clinical data of 132 HCC patients.The patients were randomly divided into training set and test set at a 7︰3 ratio.Independent influencing factors for predicting MVI status in HCC patients were identified through univariate and multivariate logistic regression analyses.Radiomics features were selected using the least absolute shrinkage and selection operator(LASSO)algorithm,and a Radiomics score(Radscore)was calculated to construct the final combined model.Four machine learning algorithms including-logistic regression(LR),naive Bayes(NB),support vector machine(SVM),and K-nearest neighbor(KNN)were applied to evaluate the model.The performance of each machine model was assessed using the receiver operating characteristic(ROC)curves and the area under the curve(AUC).Results Univariate and multivariate logistic regression analyses revealed that venous phase CT values were independentinfluencing factors,and six radiomics features were ultimately selected.After the Radscore was calculated,a combined model was constructed using Radscore and venous phase CT values.Machine learning algorithms showed that the combined model achieved the following AUC in the training set:0.895[95%confidence interval(CI)0.821-0.965]for LR,0.892(95%CI 0.831-0.963)for NB,0.644(95%CI 0.532-0.765)for SVM,and 0.855(95%CI 0.783-0.947)for KNN.In the test set,the respective AUC were 0.845(95%CI 0.712-0.961),0.840(95%CI 0.723-0.964),0.492(95%CI 0.311-0.687),and 0.716(95%CI 0.566-0.871).Conclusion Radiomics based on CT-enhanced portal venous phase combined with machine learning algorithms demonstrates high efficiency in preoperative evaluation of MVI in HCC,with the LR model showing the best performance.

Microcystin-leucine arginine (MC-LR), a potentially carcinogenic toxin, is produced by Cyanobacteria such as Microcystis and Ananabacteria during water bloom. Increasing evidence demonstrated that MC-LR induces male reproductive toxicity, mainly by inducing germ cell apoptosis, destroying cell cytoskeleton, interfering with DNA damage repair pathway, and damaging blood-testicular barrier (BTB), which eventually lead to male sterility. Testicular Sertoli cells are the somatic cells that directly contact with spermatogenic cells in seminiferous tubules. They not only regulate immune response to maintain testicular immune homeostasis by secreting a variety of cytokines and immunosuppressive factors, but also provide the protective effects of spermatogenic cells by forming BTB. MC-LR induces inflammation and apoptosis of Sertoli cells, and destroys the integrity of the BTB, and then causes spermatogenesis dysfunction.
Male ; Humans ; Sertoli Cells ; Leucine/pharmacology* ; Arginine/pharmacology* ; Microcystins/metabolism* ; Immunity

Objective: To explore the relationship between the change of blood cholesterol and prognosis in patients with sepsis. Methods: The clinical data of 236 patients with sepsis (observation group) admitted to Nanjing Hospital Affiliated to Nanjing Medical University from February 2014 to December 2018 were analyzed retrospectively.The general clinical data, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) of the two groups were compared with 236 patients without sepsis in the same period as the control group, high density lipoprotein cholesterol (HDL-C) and other biochemical indexes; sepsis patients were divided into survival group and death group according to the prognosis, and the related factors affecting the prognosis were analyzed by multi factor Logistic regression. Results: The survival rate of sepsis patients was 60.6% (143/236), the mortality rate was 39.4% (93/236), 143 cases in survival group and 93 cases in death group.Compared with control group, the levels of serum TC ((2.51±1.20) mmo/L vs.(3.42±1.33) mmo/L, t=6.385) and HDL-C ((1.62±0.91) mmo/L vs.(2.53±0.79) mmo/L, t=5.526) in observation group were significantly lower (all P<0.05), and that of LDL-C showed no statistically significant difference((1.95±0.93) mmo/L vs.(2.11±0.84) mmo/L, t=0.958, P>0.05). In observation group, the patients in death group were older than those of the survival group ((75.4±10.3) years vs.(64.3±16.0) years, t=4.984, P<0.05), serum creatinine (SCr) was higher than that of survival group((252.3±65.2) μmol/L vs.(168.3±47.8) μmol/L, t=5.604, P<0.05), the levels of serum TC ((2.20±1.46) mmo/L vs.(2.91±1.12) mmo/L, t=6.157, P<0.05), HDL-C ((1.41±0.51) mmo/L vs.(1.95±0.65) mmo/L, t=5.090, P<0.05) and LDL-C ((1.71±0.67) mmo/L vs.(2.02±0.84) mmo/L, t=4.525, P<0.05) were significantly lower than those of survival group.Logistic regression analysis showed that age was the risk factor of death in sepsis patients (OR=1.035, 95%CI 1.012-1.049, P=0.008), and TC was the protective factor on the prognosis of sepsis patients (OR=0.748, 95%CI 0.693-0.822, P=0.015). Conclusion TC and HDL-C were significantly decreased in sepsis patients, while those who died were further decreased than those who survived.As a protective factor TC can be an effective biochemical index to evaluate the prognosis of patients with sepsis.

Objective To explore the relationship between different types of female reproductive system dysplasia and age of visit, clinical manifestations, common types of combined malformations and endometriosis. Methods The patient′s medical records in the Second Hospital of Hebei Medical University from December 2002 to June 2016 were collected and retrospectively analyzed. Results Among 924 cases of genital tract dysplasia, uterine dysplasia (65.3%, 824/1 261) was the most common, followed by vaginal dysplasia (28.3%, 357/1 261), hymen atresia and urogenital fistula (3.7%, 47/1 261), and cervical dysplasia (2.6%, 33/1 261). (1) The youngest age was in patients with hymen atresia and urogenital fistula, with a median of 14.5 years old, while the older age were in patients with uterine, vaginal and cervical dysplasia, with median age of 25.0, 24.0 and 23.0 years old, respectively. (2) The clinical manifestations were lack of specificity, mainly abnormal findings of physical examination or accessory examination, primary amenorrhea, lower abdominal pain, infertility, adverse pregnancy history. (3) About other systemic malformations, urological malformations were the most common (4.8%, 44/924), followed by spinal malformations (0.5%, 5/924), inguinal hernia (0.4%, 4/924), heart malformations (0.2%, 2/924), cleft lip and palate (0.2%, 2/924). Oblique vaginal septal syndrome and MRKH syndrome were the most likely to be associated with other system malformations. (4) About combination with endometriosis, there was no significant difference between obstructive genital tract malformations (2.3%, 9/385) and non obstructive genital tract malformations (1.7%, 9/539; P=0.469). Conclusions Female reproductive system dysplasia is the most common in uterine dysplasia, followed by vaginal dysplasia, hymen atresia and urogenital fistula, and cervical dysplasia. The age of visit is generally older, often found by abnormal findings of physical examination or accessory examination, primary amenorrhea, lower abdominal pain, infertility, adverse pregnancy history;and could be combined with a variety of other system malformations, most seen by urinary system malformations,there is also the risk of endometriosis.

Objective: To create and validate a scoring system for predicting clinical prognosis in patients with cardiac resynchronization therapy (CRT). Methods: A cohort of 367 consecutive patients received CRT in our hospital from 2010-01 to 2015-12 were enrolled. The endpoint follow-up events were all-cause death including heart transplantation and heart failure re-admission. The patients were randomly categorized into 2 groups: Modeling group, to develop HEAL scoring system,n=300 and Veriifcation group, to validate HEAL model,n=67. HEAL system was established by Cox proportional hazards regression model, discrimination between HEAL and EARRN scoring systems was evaluated by AUC of ROC, HEAL calibration was assessed by Hosmer-Lemeshow test and clinical endpoint evaluation by 2 scoring systems were compared by Kaplan-Meier method. Results: Modeling group analysis indicated that hs-CRP (HR=1.137, 95% CI 1.072-1.205,P<0.001), big endothelin-1 (HR=1.934, 95% CI 1.066-3.507,P=0.03), left atrial diameter (HR=1.045, 95% CI 1.007-1.084,P=0.02) and NYHA IV (HR=2.583, 95% CI 1.331-5.013,P=0.005) were the independent risk factors of adverse prognosis in CRT patients. Based on β partial regression coefifcient, HEAL scoring system was established to classify the patient's risk levels: low risk<4, moderate risk 4-10 and high risk>10. AUC for risk classification in Modeling group and Verification group were 0.719(95% CI 0.629-0.809) and 0.708 (95% CI 0.539-0.878), HEAL can well distinguish clinical prognosis in patients at different risk levels (log-rank test showed in Modeling groupP<0.001 and in Veriifcation groupP=0.002); Hosmer-Lemeshow test presented good calibration,P=0.952. All 367 patients were respectively evaluated by HEAL and EARRN scoring systems, HEAL had the better discrimination than EARRN as AUC 0.763 (95% CI 0.692-0.833) vs AUC 0.602 (95% CI 0.517-0.687). Conclusion: HEAL scoring system can effectively predict adverse prognosis in CRT patients, it had the better discrimination than EARRN system and was valuable to distinguish high risk patients in clinical practice.

Objective: To explore the impact of atrial fibrillation (AF) on clinical outcomes in patients with cardiac resynchronization therapy (CRT). Methods: A total of 258 arrhythmia patients who received CRT in our hospital from 2010-01 to 2014-12 were retrospectively enrolled. According to AF occurrence, the patients were divided into 2 groups: AF group,n=42 and Non-AF group,n=216. The end point events were deifned by heart failure (HF) re-admission and all-cause death (including heart transplantation). Survival curve was drawn by Kaplan-Meier method, clinical prognosis was comparedbetween 2 groups with log-rank test and the impact of AF on end point prediction was analyzed by uni- and multivariate Cox proportional-hazards regression models. Results: There were 16.3% (42/258) patients combining AF. The following indexes were statistically different between AF group and Non-AF group: patients' age, the ratios of male gender and left bundle branch block (LBBB), eGFR, blood levels of creatinine, uric acid, big endothelin-1, left atrial diameter and application of amiodarone. With the median of 22 months follow-up study, there were 33/258 (12.8%) patients died, 5 (1.9%) received heart transplantation and 72 (27.9%) with HF re-admission. Survival analysisindicated that HF re-admission rate in AF group was higher than Non-AF group (χ2=6.651,P=0.010), all cause mortality was similar between 2 groups (χ2=0.528,P=0.468). Univariate Cox proportional-hazards regression analysis showed that AF, LBBB, higher blood levels of creatinine, big endothelin-1 and large left atrium were the suspiciousrisk factors for HF re-admission; increased blood levels of creatinine, big endothelin-1 and large left atrium were thesuspiciousrisk factors for all cause death. Multivariate Cox proportional-hazards regression analysis presented that AF was not the independent risk factor for HF re-admission and all-cause death, while largeleft atrium was the independent risk factor for HF re-admission (HR=1.041, 95% CI 1.007-1.075,P=0.018); large left atrium and increased serum creatinine were the independent risk factors for all cause death (HR=1.045, 95% CI 1.001-1.091,P=0.048) and (HR=1.008, 95% CI 1.001-1.015,P=0.035) respectively. Conclusion: AF was associated with the higher rate of HF re-admission in CRT patients; while no clear evidencesupported that AF was the independent risk factor for HF re-admission and all cause death in CRT patients.

Objective: To assess the relationship between serum albumin level and clinical outcome in heart failure (HF) patients receiving cardiac resynchronization therapy (CRT). Methods: In this retrospective cohort study, 357 consecutive chronic heart failure patients receiving CRT between January 2010 and December 2015 were enrolled and divided into two groups based on pre-CRT serum albumin (albumin≥40 g/L, n=244; albumin<40 g/L, n=113). Clinical outcomes were defined as all-cause mortality (including heart transplantation) and rehospitalization due to worsening HF.Baseline characteristics were compared and all-cause mortality (including heart transplantation) and rehospitalization due to worsening heart failure (HF) were analyzed using Kaplan-Meier curves.Prognostic value of albumin level was evaluated in Cox proportional-hazards regression models. Results: Over a median follow-up time of 21 months, 45 patients (12.6%) died, 4 patients (1.1%) underwent heart transplantation and 100 patients (28.0%) were rehospitalized due to worsening HF. HF patients with pre-CRT albumin<40 g/L were related with worse NYHA function class, lower HDL-C level and ACEI/ARB use compared to HF patients with pre-CRT albumin≥40 g/L. Kaplan-Meier analyses evidenced lower survival rate in HF patients (log-rank test: P=0.000 4, χ²=12.60) and higher rehospitalization rate due to worsening HF (log-rank test: P=0.009, χ²=6.82) in HF patients with pre-CRT albumin<40 g/L.Multivariate Cox analyses indicated that serum pre-CRT albumin <40 g/L was an independent risk factor for all-cause mortality (HR=2.019, 95%CI 1.125-3.622, P=0.018) and HF rehospitalization (HR=1.517, 95%CI 1.014-2.270, P=0.043). Conclusion Pre-CRT serum albumin level is associated with the severity of heart failure in CRT recipients.Patients with lower pre-CRT albumin level face increased risk of all-cause mortality and HF rehospitalization in chronic heart failure patients receiving cardiac resynchronization.

BACKGROUNDDyslipidemia caused by liver injury is a significant risk factor for cardiovascular complications. Previous studies have shown that hydrogen sulfide (H2S) protects against multiple cardiovascular disease states in a similar manner as nitric oxide (NO), and NO/endothelial nitric oxide synthase (eNOS) pathway is the key route of NO production. The purpose of this study was to investigate whether H2S can ameliorate the high blood pressure and plasma lipid profile in Nw-nitro-L-argininemethyl ester (L-NAME)-induced hypertensive rats by NO/eNOS pathway.

METHODSThirty-six 4-week old Sprague-Dawley (SD) male rats were randomly assigned to 6 groups (n = 6): control group, L-NAME group, control + glibenclamide group, control + NaHS group, L-NAME + NaHS group, and L-NAME + NaHS + glibenclamide group. Measurements were made of plasma triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (CHO), glutamic-pyruvic transaminase (ALT) levels after 5 weeks. Then measurements of NO level and proteins expression of eNOS, P-eNOS, AKT, P-AKT were made in liver tissue.

RESULTSAfter 5 weeks of L-NAME treatment, the blood pressure, plasma TG ((1.22±0.12) mmol/L in L-NAME group vs. (0.68±0.09) mmol/L in control group; P < 0.05) and LDL ((0.54±0.04) mmol/L in L-NAME group vs. (0.28±0.02) mmol/L in control group; P < 0.05) concentration were significantly increased, and the plasma HDL ((0.26±0.02) mmol/L in L-NAME group vs. (0.69±0.07) mmol/L in control group; P < 0.05) concentration significantly decreased. Meanwhile the rats treated with L-NAME exhibit dysfunctional eNOS, diminished NO levels ((1.36±0.09) mmol/g protein in L-NAME group vs. (2.34±0.06) mmol/g protein in control group; P < 0.05) and pathological changes of the liver. H2S therapy can markedly decrease the blood pressure ((37.25±4.46) mmHg at the fifth week; P < 0.05), and ameliorate the plasma TG ((0.59±0.06) mmHg), LDL ((0.32±0.04) mmHg), and HDL ((0.46±0.03) mmHg) concentration in L-NAME + NaHS group (all P < 0.05). H2S therapy can also restore eNOS function and NO bioavailability and attenuate the pathological changes in the liver in L-NAME-induced hypertensive rats.

CONCLUSIONH2S protects the L-NAME-induced hypertensive rats against liver injury via NO/ eNOS pathway, therefore decreases the cardiovascular risk.

Animals ; Cardiovascular Diseases ; metabolism ; prevention & control ; Hydrogen Sulfide ; therapeutic use ; Hypertension ; chemically induced ; drug therapy ; Liver ; drug effects ; metabolism ; Male ; NG-Nitroarginine Methyl Ester ; toxicity ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type III ; metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects