Apparent diffusion coefficient and tissue stiffness are associated with different tumor microenvironment features of hepatocellular carcinoma.

OBJECTIVES: To investigate associations between tissue diffusion, stiffness, and different tumor microenvironment features in resected hepatocellular carcinoma (HCC). METHODS: Seventy-two patients were prospectively included for preoperative magnetic resonance (MR) diffusion-weighted imaging and MR elastography examination. The mean apparent diffusion coefficient (ADC) and stiffness value were measured on the central three slices of the tumor and peri-tumor area. Cell density, tumor-stroma ratio (TSR), lymphocyte-rich HCC (LR-HCC), and CD8 + T cell infiltration were estimated in resected tumors. The interobserver agreement of MRI measurements and subjective pathological evaluation was assessed. Variables influencing ADC and stiffness were screened with univariate analyses, and then identified with multivariable linear regression. The potential relationship between explored imaging biomarkers and histopathological features was assessed with linear regression after adjustment for other influencing factors. RESULTS: Seventy-two patients (male/female: 59/13, mean age: 56 ± 10.2 years) were included for analysis. Inter-reader agreement was good or excellent regarding MRI measurements and histopathological evaluation. No correlation between tumor ADC and tumor stiffness was found. Multivariable linear regression confirmed that cell density was the only factor associated with tumor ADC (Estimate = -0.03, p = 0.006), and tumor-stroma ratio was the only factor associated with tumor stiffness (Estimate = -0.18, p = 0.03). After adjustment for fibrosis stage (Estimate = 0.43, p < 0.001) and age (Estimate = 0.04, p < 0.001) in the multivariate linear regression, intra-tumoral CD8 + T cell infiltration remained a significant factor associated with peri-tumor stiffness (Estimate = 0.63, p = 0.02). CONCLUSIONS: Tumor ADC surpasses tumor stiffness as a biomarker of cellularity. Tumor stiffness is associated with tumor-stroma ratio and peri-tumor stiffness might be an imaging biomarker of intra-tumoral immune microenvironment. CLINICAL RELEVANCE STATEMENT: Tissue stiffness could potentially serve as an imaging biomarker of the intra-tumoral immune microenvironment of hepatocellular carcinoma and aid in patient selection for immunotherapy. KEY POINTS: Apparent diffusion coefficient reflects cellularity of hepatocellular carcinoma. Tumor stiffness reflects tumor-stroma ratio of hepatocellular carcinoma and is associated with tumor-infiltrating lymphocytes. Tumor and peri-tumor stiffness might serve as imaging biomarkers of intra-tumoral immune microenvironment.

Monocyte-Derived Macrophages Aggravate Cardiac Dysfunction After Ischemic Stroke in Mice.

BACKGROUND: Cardiac damage induced by ischemic stroke, such as arrhythmia, cardiac dysfunction, and even cardiac arrest, is referred to as cerebral-cardiac syndrome (CCS). Cardiac macrophages are reported to be closely associated with stroke-induced cardiac damage. However, the role of macrophage subsets in CCS is still unclear due to their heterogeneity. Sympathetic nerves play a significant role in regulating macrophages in cardiovascular disease. However, the role of macrophage subsets and sympathetic nerves in CCS is still unclear. METHODS AND RESULTS: In this study, a middle cerebral artery occlusion mouse model was used to simulate ischemic stroke. ECG and echocardiography were used to assess cardiac function. We used Cx3cr1GFPCcr2RFP mice and NLRP3-deficient mice in combination with Smart-seq2 RNA sequencing to confirm the role of macrophage subsets in CCS. We demonstrated that ischemic stroke-induced cardiac damage is characterized by severe cardiac dysfunction and robust infiltration of monocyte-derived macrophages into the heart. Subsequently, we identified that cardiac monocyte-derived macrophages displayed a proinflammatory profile. We also observed that cardiac dysfunction was rescued in ischemic stroke mice by blocking macrophage infiltration using a CCR2 antagonist and NLRP3-deficient mice. In addition, a cardiac sympathetic nerve retrograde tracer and a sympathectomy method were used to explore the relationship between sympathetic nerves and cardiac macrophages. We found that cardiac sympathetic nerves are significantly activated after ischemic stroke, which contributes to the infiltration of monocyte-derived macrophages and subsequent cardiac dysfunction. CONCLUSIONS: Our findings suggest a potential pathogenesis of CCS involving the cardiac sympathetic nerve-monocyte-derived macrophage axis.

Development of 3D printed electrospun vascular graft loaded with tetramethylpyrazine for reducing thrombosis and restraining aneurysmal dilatation.

Background: Small-diameter vascular grafts have become the focus of attention in tissue engineering. Thrombosis and aneurysmal dilatation are the two major complications of the loss of vascular access after surgery. Therefore, we focused on fabricating 3D printed electrospun vascular grafts loaded with tetramethylpyrazine (TMP) to overcome these limitations. Methods: Based on electrospinning and 3D printing, 3D-printed electrospun vascular grafts loaded with TMP were fabricated. The inner layer of the graft was composed of electrospun poly(L-lactic-co-caprolactone) (PLCL) nanofibers and the outer layer consisted of 3D printed polycaprolactone (PCL) microfibers. The characterization and mechanical properties were tested. The blood compatibility and in vitro cytocompatibility of the grafts were also evaluated. Additionally, rat abdominal aortas were replaced with these 3D-printed electrospun grafts to evaluate their biosafety. Results: Mechanical tests demonstrated that the addition of PCL microfibers could improve the mechanical properties. In vitro experimental data proved that the introduction of TMP effectively inhibited platelet adhesion. Afterwards, rat abdominal aorta was replaced with 3D-printed electrospun grafts. The 3D-printed electrospun graft loaded with TMP showed good biocompatibility and mechanical strength within 6 months and maintained substantial patency without the occurrence of acute thrombosis. Moreover, no obvious aneurysmal dilatation was observed. Conclusions: The study demonstrated that 3D-printed electrospun vascular grafts loaded with TMP may have the potential for injured vascular healing.

Construction of luciferase-expressing Neospora caninum and drug screening.

BACKGROUND: Neospora caninum is an apicomplexan parasite that is particularly responsible for abortions in cattle and neuromuscular disease in dogs. Due to the limited effectiveness of currently available drugs, there is an urgent need for new therapeutic approaches to control neosporosis. Luciferase-based assays are potentially powerful tools in the search for antiprotozoal compounds, permitting the development of faster and more automated assays. The aim of this study was to construct a luciferase-expressing N. caninum and evaluate anti-N. caninum drugs. METHODS: Luciferase-expressing N. caninum (Nc1-Luc) was constructed using clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR/Cas9). After testing the luciferase expression and phenotype of the Nc1-Luc strains, the drug sensitivity of Nc1-Luc strains was determined by treating them with known positive or negative drugs and calculating the half-maximal inhibitory concentration (IC50). The selective pan-rapidly accelerated fibrosarcoma (pan-RAF) inhibitor TAK-632 was then evaluated for anti-N. caninum effects using Nc1-Luc by luciferase activity reduction assay and other in vitro and in vivo studies. RESULTS: The phenotypes and drug sensitivity of Nc1-Luc strains were consistent with those of the parental strains Nc1, and Nc1-Luc strains can be used to determine the IC50 for anti-N. caninum drugs. Using the Nc1-Luc strains, TAK-632 showed promising activity against N. caninum, with an IC50 of 0.6131 µM and a selectivity index (SI) of 62.53. In vitro studies demonstrated that TAK-632 inhibited the invasion, proliferation, and division of N. caninum tachyzoites. In vivo studies showed that TAK-632 attenuated the virulence of N. caninum in mice and significantly reduced the parasite burden in the brain. CONCLUSIONS: In conclusion, a luciferase-expressing N. caninum strain was successfully constructed, which provides an effective tool for drug screening and related research on N. caninum. In addition, TAK-632 was found to inhibit the growth of N. caninum, which could be considered as a candidate lead compound for new therapeutics for neosporosis.

Iron Stress Affects the Growth and Differentiation of Toxoplasma gondii.

Iron is an indispensable nutrient for the survival of Toxoplasma gondii; however, excessive amounts can lead to toxicity. The parasite must overcome the host's "nutritional immunity" barrier and compete with the host for iron. Since T. gondii can infect most nucleated cells, it encounters increased iron stress during parasitism. This study assessed the impact of iron stress, encompassing both iron depletion and iron accumulation, on the growth of T. gondii. Iron accumulation disrupted the redox balance of T. gondii while enhancing the parasite's ability to adhere in high-iron environments. Conversely, iron depletion promoted the differentiation of tachyzoites into bradyzoites. Proteomic analysis further revealed proteins affected by iron depletion and identified the involvement of phosphotyrosyl phosphatase activator proteins in bradyzoite formation.

Adult-onset congenital intestinal malrotation: A case report and literature review.

BACKGROUND: Intestinal malrotation is an infrequent congenital anomaly primarily observed in neonates, and adult-onset cases are exceedingly rare. Studies on adult congenital intestinal malrotation are limited. METHODS: A case with congenital intestinal malrotation is reported in our study. The clinical data were collected and the treatment process and effect were evaluated. RESULTS: A 45-year-old female who had been experiencing vomiting for over 40 years was admitted to our hospital. According to the result of CT scan, intestinal volvulus accompanied by bowel obstruction was suspected. Then laparoscopic examination was applied to the patient and was ultimately diagnosed with adult congenital intestinal malrotation. We performed Ladd's procedure combined with gastrojejunostomy and Braun anastomosis. The patient recovered well and was successfully discharged from the hospital on the 13th day after surgery. After a 6-month follow-up, the symptom of vomiting was significantly alleviated and body weight was gained for 10 kg. She was very satisfied with the treatment. CONCLUSION: Adult congenital intestinal malrotation is a rare disease that is often misdiagnosed owing to nonspecific clinical manifestations. Therefore, awareness about this condition should be enhanced. Surgery remains the cornerstone of treatment for this disease. Combining gastrojejunostomy and Braun anastomosis with the traditional Ladd procedure can optimize surgical outcomes.

Distinguishing G-Quadruplexes Stabilizer and Chaperone for c-MYC Promoter G-Quadruplexes through Single-Molecule Manipulation.

G-quadruplex (G4) selective stabilizing ligands can regulate c-MYC gene expression, but the kinetic basis remains unclear. Determining the effects of ligands on c-MYC promoter G4s' folding/unfolding kinetics is challenging due to the polymorphic nature of G4s and the high energy barrier to unfold c-MYC promoter G4s. Here, we used single-molecule magnetic tweezers to manipulate a duplex hairpin containing a c-MYC promoter sequence to mimic the transiently denatured duplex during transcription. We measured the effects of six commonly used G4s binding ligands on the competition between quadruplex and duplex structures, as well as the folding/unfolding kinetics of G4s. Our results revealed two distinct roles for G4s selective stabilization: CX-5461 is mainly acting as c-MYC G4s stabilizer, reducing the unfolding rate (ku) of c-MYC G4s, whereas PDS and 360A also act as G4s chaperone, accelerating the folding rates (kf) of c-MYC G4s. qRT-PCR results obtained from CA46 and Raji cell lines demonstrated that G4s stabilizing ligands can downregulate c-MYC expression, while G4s stabilizer CX-5461 exhibited the strongest c-MYC gene suppression. These results shed light on the potential of manipulating G4s' folding/unfolding kinetics by ligands for precise regulation of promoter G4-associated biological activities.

MR Elastography: Practical Questions, From the AJR Special Series on Imaging of Fibrosis.

MR elastography (MRE), first described in 1995 and FDA-cleared in 2009, has emerged as an important tool for noninvasively detecting and staging liver fibrosis in patients with known or suspected chronic liver disease. This review focuses on a series of practical questions about the clinical use of MRE. Most head-to-head comparison studies with other laboratory and imaging-based tests have concluded that MRE has the highest diagnostic performance among tests for staging liver fibrosis. Limitations in the accuracy of biopsy as a standard of truth in staging liver fibrosis are increasingly being recognized. MRE-based measurements show promise as quantitative surrogates of disease severity and predictors of important clinical outcomes. The appropriate role of MRE in the management of patients with chronic liver disease is being actively incorporated into recognized clinical guidelines. Growing evidence shows that MRI measurement of elevated liver fat is the most important single biomarker for detecting nonalcoholic steatohepatitis (NASH) and that MRE-based liver stiffness is the most important single biomarker for detecting at-risk NASH (i.e., NASH with stage ≥ F2 fibrosis). Advances in MRE technology are offering higher precision and new biomarkers, which have potential to allow independent assessment of inflammation and other histologic processes in addition to fibrosis.

Technical Success and Reliability of Magnetic Resonance Elastography in Patients with Hepatic Iron Overload.

RATIONALE AND OBJECTIVES: This study aimed to evaluate the technical success rate and stiffness measurement reliability of two specific hepatic magnetic resonance elastography (MRE) sequences dedicated to solving susceptibility artifacts in patients with various degrees of hepatic iron overload. MATERIALS AND METHODS: Thirty-seven patients with iron-overloaded liver confirmed by R2* value measurement who underwent two-dimensional (2D) spin-echo (SE) MRE and 2D SE-echo-planar-imaging (EPI) MRE were reviewed retrospectively. According to four categories based on R2* value (mild, moderate, severe elevation, and extremely severe iron overload), we compared the success rate, quality score, and liver stiffness of the two sequences. In addition, Spearman's correlation was performed to evaluate the relationship between the R2* value and liver stiffness. RESULTS: The overall success rates of SE MRE and SE-EPI MRE in patients with hepatic iron overload were 91.89% and 78.38%, respectively, and 100% and 78.57%, respectively, for severe elevation iron overload. In all patients, the MRE quality scores were 54 and 48 for SE MRE and SE-EPI MRE, respectively (P = 0.107). There were no significant differences in liver stiffness measurements between the two MRE methods in patients with mild, moderate, and severe elevation iron-overloaded livers (P > 0.6 for all), respectively. For both MRE methods, R2* value had no significant effect on the liver stiffness measurements (correlation coefficient <0.1, P >0.6 for both). CONCLUSION: In the mild and moderate elevation iron-overloaded liver, both SE MRE and fast SE-EPI MRE can provide successful and reliable liver stiffness measurement. In severe elevation iron-overloaded livers, SE MRE may be a better choice than SE-EPI MRE.

Endothelium-Mimicking Bilayer Vascular Grafts with Dual-Releasing of NO/H2S for Anti-Inflammation and Anticalcification.

Vascular complications caused by diabetes impair the activities of endothelial nitric oxide synthase (eNOS) and cystathionine γ-lyase (CSE), resulting in decreased physiological levels of nitric oxide (NO) and hydrogen sulfide (H2S). The low bioavailability of NO and H2S hinders the endothelialization of vascular grafts. In this study, endothelium-mimicking bilayer vascular grafts were designed with spatiotemporally controlled dual releases of NO and H2S for in situ endothelialization and angiogenesis. Keratin-based H2S donor was synthesized and electrospun with poly(l-lactide-co-ε-caprolactone) (PLCL) as the outer layer of the graft to release H2S. Hyaluronic acid, one of the major glycosaminoglycans in endothelial glycocalyx, was complexed with Cu ions as the inner layer to mimic glutathione peroxidase (GPx) and maintain long-term physiological NO flux. The synergistic effects of NO and H2S of bilayer grafts selectively promoted the regeneration and migration of human umbilical vascular endothelial cells (HUVECs), while inhibiting the overproliferation of human umbilical artery smooth muscle cells (HUASMCs). Bilayer grafts could effectively prevent vascular calcification, reduce inflammation, and alleviate endothelial dysfunction. The in vivo study in a rat abdominal aorta replacement model for 1 month showed that the graft had a good patency rate and had potential for vascular remodeling in situ.

The molecular mechanism of neutrophil extracellular traps and its role in bone and joint disease.

As the body's first line of defense, neutrophils play an important role in the early stages of infection. Neutrophil extracellular traps (NETs), a novel way to kill pathogens, are released from activated neutrophils to trap and kill microorganisms and protect the body from invasion. However, studies have shown that NETs not only play a role in self-defense in vivo but also participate in some pathological processes. Current studies have found that excessive or abnormally activated NETs play a pathogenic role in a variety of diseases. NETs, in addition to killing pathogens during the pathology of sepsis, affect on coagulation function, and blood endothelium. Additionally, NETs have a wide range of effects in other inflammatory, immune, and other related diseases. NETs are involved in the pathology of atherosclerosis. NETs also play a role in systemic lupus erythematosus, diabetes mellitus, Alzheimer's disease, and tumors, but there are relatively few NETs studies on bone and joint diseases. This article discusses NETs, their formation, and their association with bone and joint disorders. New targets for the effective treatment of joint diseases may be identified by studying the relationship between NETs and bone and joint diseases.

Colorectal motility patterns and psychiatric traits in functional constipation and constipation-predominant irritable bowel syndrome: A study from China.

BACKGROUND: Functional constipation (FC) and constipation-predominant irritable bowel syndrome (IBS-C) represent a spectrum of constipation disorders. However, the majority of previous clinical investigations have focused on Western populations, with limited data originating from China. AIM: To determine and compare the colorectal motility and psychiatric features of FC and IBS-C in an Eastern Chinese population. METHODS: Consecutive chronic constipation patients referred to our motility clinic from December 2019 to February 2023 were enrolled. FC and IBS-C diagnoses were established using ROME IV criteria, and patients underwent high-resolution anorectal manometry (ARM) and a colonic transmit test using the Sitz marker study. Constipation-related symptoms were obtained through questionnaires. Anxiety and depression were assessed by the Hamilton anxiety rating scale and the Hamilton Depression Rating Scale-21. The clinical characteristics and colorectal motility patterns of FC and IBS-C patients were compared. RESULTS: No significant differences in sex, age or abdominal discomfort symptoms were observed between IBS-C and FC patients (all P > 0.05). The proportion of IBS-C patients with delayed colonic transit was higher than that of patients with FC (36.63% vs 15.91%, P < 0.05), while rectosigmoid accumulation of radiopaque markers was more common in the FC group than in the IBS-C group (50% vs 26.73%, P < 0.05). Diverse proportions of these dyssynergic patterns were noted within both the FC and IBS-C groups by ARM. IBS-C patients were found to have a higher prevalence of depression than FC patients (66.30% vs 42.42%, P < 0.05). The scores for feelings of guilt, suicide, psychomotor agitation, diurnal variation, obsessive/compulsive disorder, hopelessness, self-abasedment and gastrointestinal symptoms were significantly higher in IBS-C patients than that in FC patients (P < 0.05). For IBS-C (χ2 = 5.438, P < 0.05) but not FC, patients with normal colon transit time were significantly more likely to have anxiety than those with slow colon transit time. For IBS-C patients but not FC patients, the threshold of first constant sensation, desire to defecate and sustained urgency were all weakly correlated with the degree of anxiety (r = 0.414, r = 0.404, and r = 0.418, respectively, P < 0.05). The proportion of patients with a low threshold of desire to defecate among IBS-C patients with depression was lower than that in those without depression (69.6% vs 41.9%, χ2 = 4.054, P < 0.05). CONCLUSION: Our findings highlight both overlapping and distinctive patterns of colon transit, dyssynergic patterns, anorectal sensation, psychological distress, and associations of psychiatric and colorectal motility characteristics in FC and IBS-C patients in an Eastern Chinese population, providing valuable insights into the pathophysiological underpinnings of these disorders.

Synthesis and anticancer activity of podophyllotoxin derivatives with nitrogen-containing heterocycles.

Three series of podophyllotoxin derivatives with various nitrogen-containing heterocycles were designed and synthesized. The antitumor activity of these podophyllotoxin derivatives was evaluated in vitro against a panel of human tumor cell lines. The results showed that podophyllotoxin-imidazolium salts and podophyllotoxin-1,2,4-triazolium salts a1-a20 exhibited excellent cytotoxic activity. Among them, a6 was the most potent cytotoxic compound with IC50 values of 0.04-0.29 µM. Podophyllotoxin-1,2,3-triazole derivatives b1-b5 displayed medium cytotoxic activity, and podophyllotoxin-amine compounds c1-c3 has good cytotoxic activity with IC50 value of 0.04-0.58 µM. Furthermore, cell cycle and apoptosis experiments of compound a6 were carried out and the results exhibited that a6 could induce G2/M cell cycle arrest and apoptosis in HCT-116 cells.

A diagnostic test of three-dimensional magnetic resonance elastography imaging for preoperative prediction of microvascular invasion in patients with T1 stage clear cell renal carcinoma.

Background: Detection of microvascular invasion (MVI) of kidney tumors is important for selecting the optimal therapeutic strategy. Currently, the prediction of MVI lacks an accurate imaging biomarker. This study evaluated the performance of three-dimensional (3D) magnetic resonance elastography (MRE) imaging in predicting microvascular invasion (MVI) of T1 stage clear cell renal carcinoma (ccRCC). Methods: In this prospective study, we conducted pre-surgical imaging with a clinical 3.0 T magnetic resonance imaging (MRI) system. Firstly, 83 consecutive patients were enrolled in this study. A 3D MRE stiffness map was generated and transferred to a post-processing workstation. Contrast-enhanced computed tomography (CT) was conducted to calculate the tumor enhancement ratio. The presence of MVI was evaluated by histopathological analysis and graded according to the risk stratification based upon the number and distribution. The mean stiffness and CT tumor enhancement ratio was calculated for tumors with or without MVI. The diagnostic performance [sensitivity, specificity, positive predictive value, negative predictive value, area under the curve (AUC)] and independent predicting factors for MVI were investigated. Results: Finally, A total of 80 patients (aged 46.7±13.2 years) were enrolled, including 22 cases of tumors with MVI. The mean MRE stiffness of kidney parenchyma and kidney tumors was 4.8±0.2 and 4.5±0.7 kPa, respectively. There was significant difference in the mean MRE stiffness between tumors with MVI (5.4±0.6 kPa) and tumors without MVI (4.1±0.3 kPa) (P<0.05). The sensitivity, specificity, positive predictive value, negative predictive value, and the AUC for mean stiffness in the prediction of MVI were 100%, 75%, 63%, 96%, and 0.87 [95% confidence interval (CI): 0.72, 0.94], respectively. The corresponding values for the CT tumor enhancement ratio were 90%, 80%, 63%, 96%, and 0.88 (95% CI: 0.71, 0.93), respectively. The odds ratio (OR) value for MRE tumor stiffness and CT kidney tumor enhancement ratio in the prediction of MVI was 2.9 (95% CI: 1.8, 3.7) and 1.2 (95% CI: 1.0, 1.7), respectively (P>0.05). Conclusions: 3D MRE imaging has promising diagnostic performance for predicting MVI in T1 stage ccRCC, which may improve the reliability of surgical strategy selection with T1 stage ccRCC.

Head-to-head comparison of magnetic resonance elastography-based liver stiffness, fat fraction, and T1 relaxation time in identifying at-risk NASH.

BACKGROUND AND AIMS: The presence of at-risk NASH is associated with an increased risk of cirrhosis and complications. Therefore, noninvasive identification of at-risk NASH with an accurate biomarker is a critical need for pharmacologic therapy. We aim to explore the performance of several magnetic resonance (MR)-based imaging parameters in diagnosing at-risk NASH. APPROACH AND RESULTS: This prospective clinical trial (NCT02565446) includes 104 paired MR examinations and liver biopsies performed in patients with suspected or diagnosed NAFLD. Magnetic resonance elastography-assessed liver stiffness (LS), 6-point Dixon-derived proton density fat fraction (PDFF), and single-point saturation-recovery acquisition-calculated T1 relaxation time were explored. Among all predictors, LS showed the significantly highest accuracy in diagnosing at-risk NASH [AUC LS : 0.89 (0.82, 0.95), AUC PDFF : 0.70 (0.58, 0.81), AUC T1 : 0.72 (0.61, 0.82), z -score test z >1.96 for LS vs any of others]. The optimal cutoff value of LS to identify at-risk NASH patients was 3.3 kPa (sensitivity: 79%, specificity: 82%, negative predictive value: 91%), whereas the optimal cutoff value of T1 was 850 ms (sensitivity: 75%, specificity: 63%, and negative predictive value: 87%). PDFF had the highest performance in diagnosing NASH with any fibrosis stage [AUC PDFF : 0.82 (0.72, 0.91), AUC LS : 0.73 (0.63, 0.84), AUC T1 : 0.72 (0.61, 0.83), |z| <1.96 for all]. CONCLUSION: Magnetic resonance elastography-assessed LS alone outperformed PDFF, and T1 in identifying patients with at-risk NASH for therapeutic trials.

[Value of Baseline Calcitonin for Differential Diagnosis of Medullary Thyroid Cancer].

Objective: To analyze the efficacy of using baseline calcitonin (bCtn) for auxiliary diagnosis of medullary thyroid cancer (MTC) in the hypercalcitoninemic population with thyroid nodules and to explore the relationship between preoperative levels of bCtn and carcinoembryonic antigen (CEA) and MTC staging. Methods: The clinical, pathological, imaging, and lab test data of 58 MTC patients and 84 non-MTC patients were retrospectively reviewed in the study. The patients were hospitalized at West China Hosptal, Sichuan University between 2011 and 2020. Receiver operating characteristic (ROC) curves were constructed to calculate the MTC diagnostic efficacy of bCtn and CEA. The differences in the preoperative bCtn and CEA levels of MTC patients with different primary tumor sites and regional lymph node involvement were compared. Results: The bCtn cutoff values were 31.54 pg/mL for men and 22.60 pg/mL for women for diagnosing MTC in the hypercalcitoninemic population with thyroid nodules. There were statistical differences in preoperative bCtn levels ( H=16.166, P=0.001) and in preoperative CEA levels ( H=9.447, P=0.024) in MTC patients of different T stages. There were statistical differences in preoperative bCtn levels ( H=7.919, P=0.019) and in preoperative CEA levels ( H=7.934, P=0.019) in MTC patients of different N stages. Conclusion: The best bCtn cutoff values for the diagnosis of MTC in the hypercalcitoninemic population with thyroid nodules and are 31.54 pg/mL for men and 22.60 pg/mL for women.

Analysis on Incidence and Mortality Trends and Age-Period-Cohort of Breast Cancer in Chinese Women from 1990 to 2019.

AIMS: To analyze the incidence and mortality trends of breast cancer among women in China from 1990 to 2019 and explore the effects of age, period, and cohort on the incidence and mortality of breast cancer. METHODS: We performed a Joinpoint regression model to describe trends in breast cancer incidence and mortality. We used an age-period-cohort analysis model to estimate the impact of age, period, and cohort on breast cancer incidence and mortality. We collected breast cancer incidence and mortality among women aged 20-89 in China (1990-2019) from the Global Health Data Exchange (GHDx) database. RESULTS: The crude incidence and mortality of breast cancer from 1990 to 2019 in Chinese women showed an increasing trend, with an average annual increase percentage (AAPC) of 4.69% and 2.18%, respectively. The analysis on the age-period-cohort model revealed that the risk of incidence increased first and then decreased with age and peaked at 55-59 years old, whereas the risk of mortality increased by approximately 60.34 times from 20 to 89 years old. The risk of incidence and mortality increased by 2.64 and 1.49 times with the passage of time, respectively. The later the birth cohort is, the lower the risk of incidence and mortality will be. CONCLUSION: From 1990 to 2019, the incidence and mortality of breast cancer among Chinese women showed an increasing trend, and the prevention and control situation of breast cancer was still grim. Therefore, visual examination and palpation examination should be actively carried out in adult women with breast cancer, and the conventional population after 40 years of age, the high-risk population carrying hereditary breast cancer gene and the elderly population should be assisted with imaging examination along with palpation examination. When treating patients suffering from breast cancer, in order to reduce the death rate, a personalized treatment plan should be developed based on the characteristics of different patients.

Longitudinal Changes in MR Elastography-based Biomarkers in Obese Patients Treated with Bariatric Surgery.

Obesity-related chronic inflammation contributes to nonalcoholic fatty liver disease (NAFLD) progression in obese patients (body mass index [BMI] >30 kg/m2).1 The early detection of inflammation with noninvasive imaging technology may help identify individuals with a high risk of developing NAFLD.

Early diagnosis of hepatic inflammation in Japanese nonalcoholic fatty liver disease patients using 3D MR elastography.

BACKGROUND: The damping ratio (DR) and the loss modulus (G″) obtained by 3D MR elastography complex modulus analysis has been reported recently to reflect early intrahepatic inflammation, and is expected to be a noninvasive biomarker of inflammation in nonalcoholic fatty liver disease (NAFLD). However, the role of the DR and the G″ in Japanese NAFLD patients remains unclear. METHODS: We enrolled 39 Japanese patients with NAFLD who underwent liver biopsy and 3D MR elastography within 1 month and analyzed the association between DR, G″, and histological activity. RESULTS: Regarding DR, no evident correlation was observed between the DR and histological activity (p = 0.14) when patients with all fibrosis stages were included. However, when patients were restricted up to stage F2 fibrosis, the association of the DR and inflammation became significant, the DR increasing with the degree of activity (p = 0.02). Among the constituents of fibrosis activity, ballooning correlated with the DR (p < 0.01) while lobular inflammation did not. Regarding G″, it was correlated with histological activity (p < 0.01), ballooning (p < 0.01), and lobular inflammation (p < 0.01) in patients with all fibrosis stages and in patients up to F2 fibrosis (p = 0.03 for activity and p = 0.04 for ballooning). The best cutoff value of DR for hepatitis activity in patients within the F2 stage was 0.094 (area under the receiver operating characteristic curve 0.775, 95% CI: 0.529-1.000) and G″ was 0.402 (area under the receiver operating characteristic curve 0.825, 95% CI: 0.628-1.000). CONCLUSIONS: The DR and G″ reflected the histological activity in Japanese patients with NAFLD during the early stage, indicating these values for noninvasive diagnosis of inflammation in Japanese patients with NAFLD.