Beyond Occam's Razor: Concurrent Non-functional Pituitary Macroadenoma and Metastatic Hepatocellular Carcinoma in a Patient With Functional Cure of Hepatitis B.

Occam's razor, the principle of parsimony, is frequently employed in medicine to derive a single diagnosis from a patient's myriad symptoms. Conversely, Hickam's dictum, which embraces the principle of plenitude by considering multiple diagnoses for a patient's presentation, is often underutilized or not as widely recognized as Occam's razor. The application of Hickam's dictum is particularly crucial when evaluating nonspecific symptoms such as fatigue, which can manifest in various diseases. This report describes the case of a 72-year-old man with a history of functional cure for hepatitis B who presented with chronic fatigue and hyponatremia. Initially, he was diagnosed with non-functional pituitary macroadenoma and panhypopituitarism. Two months following pituitary surgery, the onset of dyspepsia and the recurrence of fatigue revealed metastatic tumors in the liver, stomach, pancreas, left adrenal gland, and peri-pancreatic lymph nodes. A liver biopsy confirmed the diagnosis of hepatocellular carcinoma. This case highlights the importance of considering multiple, potentially co-existing conditions based on the patient's symptoms and risk factors to complete the thorough diagnoses. Additionally, it emphasizes the need to remain vigilant regarding the risk of liver cancer in patients with a history of chronic hepatitis B infection, irrespective of a functional cure.

Design and Material Characterization of an Inflatable Vaginal Dilator.

There are more than 13,000 new cases of cervical cancer each year in the United States and approximately 245,000 survivors. External beam radiation and brachytherapy are the front-line treatment modalities, and 60% of patients develop vaginal damage and constriction, i.e., stenosis of the vaginal vault, greatly impeding sexual function. The incidence of vaginal stenosis (VS) following radiotherapy (RT) for anorectal cancer is 80%. VS causes serious quality of life (QoL) and psychological issues, and while standard treatment using self-administered plastic dilators is effective, acceptance and compliance are often insufficient. Based on published patient preferences, we have pursued the design of a soft inflatable dilator for treating radiotherapy-induced vaginal stenosis (VS). The critical component of the novel device is the dilator balloon wall material, which must be compliant yet able to exert therapeutic lateral force levels. We selected a commercially available silicone elastomer and characterized its stress-strain characteristics and hyperelastic properties. These parameters were quantified using uniaxial tensile testing and digital image correlation (DIC). Dilator inflation versus internal pressure was modeled and experimentally validated in order to characterize design parameters, particularly the dilator wall thickness. Our data suggest that an inflatable silicone elastomer-based vaginal dilator warrants further development in the context of a commercially available, well-tolerated, and effective device for the graded, controlled clinical management of radiotherapy-induced VS.

Case report: Heterozygous mutation in HTRA1 causing typical cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy.

Background: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is an autosomal recessive disorder characterized by baldness, recurrent ischemic stroke, lumbago, headache, and dementia which is closely related to homozygous mutations of the high-temperature requirement serine peptidase A1 (HTRA1) gene. Heterozygous mutations of HTRA1 are usually considered to be non-pathogenic. Although it has been revealed that only a few patients with heterozygous mutations could present some manifestations, their clinical symptoms were atypical, milder, and always with a lower frequency of extra-neurological features. Here, a rare patient with heterozygous mutation of HTRA1 who had all typical features of CARASIL as well as severe clinical symptoms and rapid progression was initially reported in our study. Case presentation: A 43-year-old female patient presented with a gradual onset of headache and cognitive decline. As time progressed, her headache intensified and symptoms of dementia began to manifest gradually. During her early years, she had thinning hair and subsequently experienced two occurrences of ischemic strokes in her thirties. Furthermore, she also had a history of lumbago and urinary retention before visiting our hospital. The patient's magnetic resonance imaging revealed the presence of widespread white matter lesions, infarctions, and microbleeds, in addition to lumbar disc herniation and degenerative lesions. The observed clinical characteristics had a strong correlation with CARASIL, and the patient was diagnosed with a heterozygous missense mutation of 905G>A (Arg302Gln) in the HTRA1 gene. The patient has been under continuous follow-up for a duration exceeding 3 years subsequent to her release from the hospital. She underwent cystostomy, and symptoms of bulbar paralysis developed in a progressive way. Currently, there has been a notable decrease in motor function and activities of daily living, resulting in the individual being confined to bed for a duration exceeding 1 year. Conclusion: This case suggests that patients carrying a heterozygous mutation in G905A may also have typical clinical features of CARASIL, which allows us to have a more comprehensive understanding of CARASIL.

Efficacy and safety of laparoscopic radical resection following neoadjuvant therapy for pancreatic ductal adenocarcinoma: A retrospective study.

BACKGROUND: Multiple studies have demonstrated that neoadjuvant chemotherapy (NACT) can prolong the overall survival of pancreatic ductal adenocarcinoma (PDAC) patients. However, most studies have focused on open surgery following NACT. AIM: To investigate the efficacy and safety of laparoscopic radical resection following NACT for PDAC. METHODS: We retrospectively analyzed the clinical data of 15 patients with pathologically confirmed PDAC who received NACT followed by laparoscopic radical surgery in our hospital from December 2019 to April 2022. All patients underwent abdominal contrast-enhanced computed tomography (CT) and positron emission tomography-CT before surgery to accurately assess tumor stage and exclude distant metastasis. RESULTS: All 15 patients with pancreatic cancer were successfully converted to surgical resection after NACT, including 8 patients with pancreatic head cancer and 7 patients with pancreatic body and tail cancer. Among them, 13 patients received the nab-paclitaxel plus gemcitabine regimen (gemcitabine 1000 mg/m2 plus nab-paclitaxel 125 mg/m2 on days 1, 8, and 15 every 4 wk) and 2 patients received the modified FOLFIRINOX regimen (intravenous oxaliplatin 68 mg/m2, irinotecan 135 mg/m2, and leucovorin 400 mg/m2 on day 1 and fluorouracil 400 mg/m2 on day 1, followed by 46-h continuous infusion of fluorouracil 2400 mg/m2). After each treatment cycle, abdominal CT, tumor markers, and circulating tumor cell counts were reviewed to evaluate the treatment efficacy. All 15 patients achieved partial remission. The surgical procedures included laparoscopic pancreaticoduodenectomy (LPD, n = 8) and laparoscopic radical antegrade modular pancreatosplenectomy (L-RAMPS, n = 7). None of them were converted to a laparotomy. One patient with pancreatic head carcinoma was found to have portal vein involvement during the operation, and LPD combined with vascular resection and reconstruction was performed. The amount of blood loss and operation times of L-RAMPS vs LPD were 435.71 ± 32.37 mL vs 343.75 ± 145.01 mL and 272.52 ± 49.14 min vs 444.38 ± 68.63 min, respectively. The number of dissected lymph nodes was 16.87 ± 4.10, and 3 patients had positive lymph nodes. One patient developed grade B postoperative pancreatic fistula (POPF) after L-RAMPS, and one patient experienced jaundice after LPD. None of the patients died after surgery. As of April 2022, progressive disease was noted in 4 patients, 2 patients had liver metastasis, and one had both liver metastasis and lymph node metastasis and died during the follow-up period. CONCLUSION: Laparoscopic radical resection of PDAC after NACT is safe and effective if it is performed by a surgeon with rich experience in LPD and in a large center of pancreatic surgery.

Comparison of Efficacy and Safety Between Laparoscopic and Open Radical Resection for Hilar Cholangiocarcinoma-A Propensity Score-Matching Analysis.

Background: Radical resection remains the most effective treatment for hilar cholangiocarcinoma (HCCA). However, due to the complex anatomy of the hilar region, the tumor is prone to invade portal vein and hepatic arteries, making the surgical treatment of HCCA particularly difficult. Successful laparoscopic radical resection of HCCA(IIIA, IIIB) requires excellent surgical skills and rich experience. Furthermore, the safety and effectiveness of this operation are still controversial. Aim: To retrospectively analyze and compare the efficacy and safety of laparoscopic and open surgery for patients with HCCA. Methods: Clinical imaging and postoperative pathological data of 89 patients diagnosed with HCCA (IIIA, IIIB) and undergoing radical resection in our center from January 2018 to March 2022 were retrospectively analyzed. Among them, 6 patients (4 were lost to follow-up and 2 were pathologically confirmed to have other diseases after surgery) were ruled out, and clinical data was collected from the remaining 83 patients for statistical analysis. These patients were divided into an open surgery group (n=62) and a laparoscopic surgery group (n=21) according to the surgical methods used, and after 1:2 propensity score matching (PSM), 32 and 16 patients respectively in the open surgery group and laparoscopic surgery group were remained. The demographic data, Bismuth type, perioperative data, intraoperative data, postoperative complications, pathological findings, and long-term survivals were compared between these two groups. Results: After 1:2 PSM, 32 patients in the open surgery group and 16 patients in the laparoscopic surgery group were included for further analysis. Baseline characteristics and pathological outcomes were comparable between the two groups. Statistically significant differences between the two groups were observed in intraoperative blood loss and operative time, as it were 400-800 mL vs 200-400 mL (P=0.012) and (407.97 ± 76.06) min vs (489.69 ± 79.17) min (P=0.001) in the open surgery group and laparoscopic surgery group, respectively. The R0 resection rate of the open group was 28 cases (87.5%), and the R0 resection rate of the laparoscopic group was 15 cases (93.75%). The two groups showed no significant difference in terms of surgical approach, intraoperative blood transfusion, incidence of postoperative complications, and short- and long-term efficacy (P>0.05). Conclusions: Laparoscopic radical resection of HCCA has comparable perioperative safety compared to open surgery group, as it has less bleeding and shorter operation time. Although it is a promising procedure with the improvement of surgical skills and further accumulation of experience, further investigations are warranted before its wider application.

Analysis of N6-Methyladenosine RNA Methylation Regulators in Diagnosis and Distinct Molecular Subtypes of Ankylosing Spondylitis.

The most frequent internal modification in eukaryotic mRNA is N6-methyladenosine (m6A). However, what we know about the m6A regulators in Ankylosing spondylitis (AS) is still limited. In our study, eight distinct m6A regulators were selected utilizing Differentially Expressed Gene (DEG) analysis of the Gene Expression Omnibus GSE73754 dataset for making comparisons between AS (Ankylosing spondylitis) and non-AS patients. The random forest model and the nomogram model were used to screen the eight candidate m6A regulators and evaluate their prediction accuracy for the occurrence of AS. Furthermore, based on the selected m6A regulators, the AS patients were divided into two subgroups, and we applied principal component analysis algorithms to calculate their m6A score and evaluate the m6A patterns. Our findings revealed that patients in cluster A were linked to activated CD4 T cell immunity and activated CD8 T cell immunity. With its major contributions in the area of immunology, our research in m6A patterns may benefit the future diagnosis and treatment strategies of AS.

Predictive modeling the probability of suffering from metabolic syndrome using machine learning: A population-based study.

Background: There is an increasing trend of Metabolic syndrome (MetS) prevalence, which has been considered as an important contributor for cardiovascular disease (CVD), cancers and diabetes. However, there is often a long asymptomatic phase of MetS, resulting in not diagnosed and intervened so timely as needed. It would be very helpful to explore tools to predict the probability of suffering from MetS in daily life or routinely clinical practice. Objective: To develop models that predict individuals' probability of suffering from MetS timely with high efficacy in general population. Methods: The present study enrolled 8964 individuals aged 40-75 years without severe diseases, which was a part of the REACTION study from October 2011 to February 2012. We developed three prediction models for different scenarios in hospital (Model 1, 2) or at home (Model 3) based on LightGBM (LGBM) technique and corresponding logistic regression (LR) models were also constructed for comparison. Model 1 included variables of laboratory tests, lifestyles and anthropometric measurements while model 2 was built with components of MetS excluded based on model 1, and model 3 was constructed with blood biochemical indexes removed based on model 2. Additionally, we also investigated the strength of association between the predictive factors and MetS, as well as that between the predictors and each component of MetS. Results: In this study, 2714 (30.3%) participants suffer from MetS accordingly. The performances of the LGBM models in predicting the probability of suffering from MetS produced good results and were presented as follows: model 1 had an area under the curve (AUC) value of 0.993 while model 2 indicated an AUC value of 0.885. Model 3 had an AUC value of 0.859, which is close to that of model 2. The AUC values of LR model 1 and 2 for the scenario in hospital and model 3 at home were 0.938, 0.839 and 0.820 respectively, which seemed lower than that of their corresponding machine learning models, respectively. In both LGBM and logistic models, gender, height and resting pulse rate (RPR) were predictors for MetS. Women had higher risk of MetS than men (OR 8.84, CI: 6.70-11.66), and each 1-cm increase in height indicated 3.8% higher risk of suffering from MetS in people over 58 years, whereas each 1- Beat Per Minute (bpm) increase in RPR showed 1.0% higher risk in individuals younger than 62 years. Conclusion: The present study showed that the prediction models developed by machine learning demonstrated effective in evaluating the probability of suffering from MetS, and presented prominent predicting efficacies and accuracies. Additionally, we found that women showed a higher risk of MetS than men, and height in individuals over 58 years was important factor in predicting the probability of suffering from MetS while RPR was of vital importance in people aged 40-62 years.

Knee Scores of Patients with Non-Lateral Compartmental Knee Osteoarthritis Undergoing Mobile, Fixed-Bearing Unicompartmental Knee and Total Knee Arthroplasties: A Randomized Controlled Trial.

OBJECTIVE: To evaluate knee scores and clinical efficacies of patients with non-lateral unicompartmental knee osteoarthritis (OA) who randomly underwent mobile-bearing (MB) unicompartmental knee arthroplasty (UKA), fixed-bearing (FB) UKA, and total knee arthroplasty (TKA). METHODS: From September 2015 to February 2017, a prospective, randomized, parallel, single-center trial of 180 patients (78 males and 102 females; 63.3 ± 6.9 years) with non-lateral compartmental knee OA was performed in the first author-affiliated hospital. The patients were randomly divided into three groups (each group included 60 patients) and received medial cemented Oxford phase 3 MB UKA, medial cemented Link FB UKA, or cemented DePuy Sigma PFC TKA, respectively. A similar perioperative management and fast-track surgery program was carried out for all patients. The knee scores at 3-year follow-up after operation and clinical efficacies of these three groups of patients were recorded, investigated, and compared. RESULTS: Primarily, compared to the TKA group, the UKA groups (MB UKA and FB UKA) had shorter operative time (median 63.2 < 67.1 min), less bleeding (8.6 < 30.0 mL), earlier resumption of walking without crutches (3.0 < 8.0 days) and walking up and down the stairs (5.0 < 10.0 days) (P < 0.001), higher FJS scores (78.0 > 74.5) (P = 0.007), better results in all knee scores (except VAS and KSS function scores) (P < 0.05), and a larger maximum flexion angle of the knee at the 3-year follow-up (123.0° > 96.0°) (P = 0.001). Secondarily, compared to the TKA group, the MB UKA group showed better results in the Western Ontario and McMaster Universities index (WOMAC) stiffness (83.6 > 79.6), WOMAC total (86.3 > 83.2), Oxford knee score (OKS) (20.0 < 23.0), Forgotten Joint Score (FJS) (78.5 > 74.5), and a larger maximum flexion angle of the knee (123.0 > 96.0) (P < 0.05). Moreover, the FB UKA group showed higher Hospital for Special Surgery Knee Score (HSS) (91.0 > 88.5), WOMAC stiffness (84.3 > 79.6), WOMAC function (85.2 > 81.7), WOMAC total scores (87.6 > 83.2), and a larger maximum flexion angle of the knee (119.0° > 96.0°) than the TKA group (P < 0.05). Overall, there was no significant difference in all knee scores and maximum flexion angles of the knee for the MB UKA and FB UKA groups (P > 0.05). There was one case with original bearing dislocation in MB UKA group. One patient with displacement of the femoral component caused by a fall injury, and another patient, who lost his life in a car accident, were involved in the FB UKA group. There was an infection case and an intermuscular vein thrombosis case in TKA group. CONCLUSION: UKA showed more advantages than TKA; however, there was no significant difference between the MB UKA and FB UKA groups for treatment of non-lateral compartmental knee OA.

Pseudolaric Acid B Attenuates High Salt Intake-Induced Hypertensive Left Ventricular Remodeling by Modulating Monocyte/Macrophage Phenotypes.

BACKGROUND Studies in ApoE knockout mice have shown that pseudolaric acid B (PB) can act as an immunomodulatory drug and attenuate atherosclerosis progression by modulating monocyte/macrophage phenotypes. Our previous study demonstrated that high salt intake could shift the phenotype of monocytes/macrophages to an inflammatory phenotype, and that this shift was related to hypertension and hypertensive left ventricular (LV) remodeling. However, no comprehensive assessment of the effects of PB on hypertensive LV remodeling has been conducted. MATERIAL AND METHODS In this study, RAW264.7 macrophages cultured with different concentrations of NaCl were used to investigate the modulating effects of PB on macrophage phenotype. Furthermore, N-nitro-L-arginine methyl ester hypertensive mice were used to investigate the modulating effects of PB on monocyte phenotype. LV remodeling was investigated by echocardiography. LV morphologic staining (for cardiomyocyte hypertrophy and collagen deposition) was performed at the time of sacrifice. RESULTS The results showed that PB significantly improved the viability of RAW264.7 cells, suppressed their phagocytic and migration abilities, and inhibited their phenotypic shift to M1 macrophages. In addition, the blood pressure of PB-treated mice was significantly decreased relative to that of control mice. Furthermore, after PB treatment, the percentage of Ly6Chi monocytes was significantly decreased while that of Ly6Clo monocytes was apparently increased. Moreover, PB preserved LV function and alleviated myocardial fibrosis and cardiomyocyte hypertrophy as measured at the end of the experimental period. The transfer of monocytes from PB-treated mice to hypertensive mice achieved the same effects. CONCLUSIONS Together, these findings indicate that PB exerts its protective effects on hypertensive LV remodeling by modulating monocyte/macrophage phenotypes and warrants further investigation.

Cystic duct dilation through endoscopic retrograde cholangiopancreatography for treatment of gallstones and choledocholithiasis: Six case reports and review of literature.

BACKGROUND: Choledocholithiasis removal via endoscopic retrograde cholangiopancreatography (ERCP) then followed by laparoscopic cholecystectomy (LC) has gradually become the principal method in the treatment of gallstones and choledocholithiasis. We use ERCP through the cystic duct to treat gallstones combined with choledocholithiasis, with the aim to preserve the normal function of the gallbladder while simultaneously decreasing risk of biliary tract injury. CASE SUMMARY: A total of six cases of patients diagnosed with gallstones and choledocholithiasis were treated with ERCP. The efficacy was evaluated via operation success rate, calculus removal rate, postoperative hospital stay and average hospitalization costs; the safety was evaluated through perioperative complication probability, gallbladder function detection and gallstones recrudesce. The calculus removal rate reached 100%, and patients had mild adverse events, including 1 case of postoperative acute cholecystitis and another of increased blood urinary amylase; both were relieved after corresponding treatment, the remaining cases had no complications. The average hospital stay and hospitalization costs were 6.16 ± 1.47 d and 5194 ± 696 dollars. The 3-11 mo follow-up revealed that gallbladder contracted well, without recurrence of gallstones. CONCLUSION: This is the first batch of case reports for the treatment of gallstones and choledocholithiasis through ERCP approached by natural cavity. The results and effects of six reported cases proved that the new strategy is safe and feasible and is worthy of further exploration and application.

Poor cardiovascular health status among Chinese women.

BACKGROUND: Systematic investigation and analysis of cardiovascular health status (CVHS) of Chinese women is rare. This study aimed to assess CVHS and atherosclerotic cardiovascular disease (ASCVD) burden in the Chinese women physicians (CWP) and community-based non-physician cohort (NPC). METHODS: In this prospective, multicenter, observational study, CVHS using the American Heart Association (AHA) defined 7 metrics (such as smoking and fasting glucose) and ASCVD risk factors including hypertension, hyperlipidemia and type-2 diabetes were evaluated in CWP compared with NPC. RESULTS: Of 5832 CWP with a mean age of 44 ± 7 years, only 1.2% achieved the ideal CVHS and 90.1% showed at least 1 of the 7 AHA CVHS metrics at a poor level. Total CVHS score was significantly decreased and ASCVD risk burden was increased in postmenopausal subjects in CWP although ideal CVHS was not significantly influenced by menopause. Compared to 2596 NPC, fewer CWP had ≥ 2 risk factors (8% vs. 27%, P < 0.001); CWP scored significantly higher on healthy factors, a composite of total cholesterol, blood pressure, fasting glucose (P < 0.001), but, poorly on healthy behaviors (P < 0.001), specifically in the physical activity component; CWP also showed significantly higher levels of awareness and rates of treatment for hypertension and hyperlipidemia, but, not for type-2 diabetes. CONCLUSION: Chinese women's cardiovascular health is far from ideal and risk intervention is sub-optimal. Women physicians had lower ASCVD burden, scored higher in healthy factors, but, took part in less physical activity than the non-physician cohort. These results call for population-specific early and improved risk intervention.

Experimental Study on the Effect of a Weifufang on Human Gastric Adenocarcinoma Cell Line BGC-823 Xenografts and PTEN Gene Expression in Nude Mice.

Background: This study aims at investigating the effect of the Weifufang, an effective prescription for the treatment of gastric cancer developed by the Traditional Chinese Medicine (TCM)/Combination of TCM and Western Medicine Department of the Hunan Cancer Hospital, on gastric cancer xenografts in nude mice and its effect on the PTEN gene; it also aims at exploring the possible tumor suppression mechanism. Methods: Nude mice with xenografts were treated with different concentrations of the Weifufang for 2 weeks, and changes in tumor volume were observed. The histopathology of the tumor was detected by hematoxylin and eosin staining; PTEN gene expression in tumor tissues was detected by immunohistochemistry (IHC) and western blot. Results: After 2 weeks of treatment, tumor inhibition rates in the 5-flourouracil (5-FU) group, and in the Weifufang low-, middle-, and high-dose groups were 30.67%, 19%, 49.52%, and 29.36%, respectively. The IOD of the PTEN gene was detected by IHC. The values in the water group, the 5-FU group, and the Weifufang low-, middle-, and high-dose groups were 0.013 ± 0.004, 0.085 ± 0.062, 0.041 ± 0.024, 0.128 ± 0.032, and 0.061 ± 0.052, respectively. Except for the 5-FU group, the differences between the gastric compound middle dose-group and the other groups were statistically significant (p < 0.05). Results of PTEN expression detection by western blot: The expression levels in the water group, 5-FU group, and the Weifufang low-, middle-, and high-dose groups were 0.2240 ± 0.0172, 0.4200 ± 0.0228, 0.2760 ± 0.0163, 0.3840 ± 0.0133, and 0.3040 ± 0.0211, respectively. Except for the 5-FU group, differences between the Weifufang middle-dose group and the other groups were statistically significant (p < 0.05). Conclusion: The Weifufang may inhibit the growth of gastric cancer xenografts by upregulating PTEN gene expression. The middle-dose group had the best effect.

A preliminary study of the clinical significance of folate receptor-positive circulating tumor cell in the management of hepatobiliary-pancreatic cancers.

BACKGROUND: Hepatobiliary-pancreatic cancers (HBPs) are highly lethal, partly because of their usually late diagnosis. This multi-center, observational study aimed to explore the clinical significance of folate receptor-positive circulating tumor cell (FR+CTC) as a liquid biopsy approach in the differential diagnosis and management of HBPs. METHODS: We recruited 119 patients suspicious for HBPs and 60 cancer-free healthy individuals in the present study. Patients without definitive pathological assessment or without pre-operative FR+CTC analysis were excluded. FR+CTC was tested prior to surgery or tissue biopsy using the CytoploRare® Detection Kit. Serum biomarkers, including CA 125, CA 19-9, and CEA, were tested in selected patients. Post-operative FR+CTC analysis was also performed in a subset of the patients receiving surgical resection. RESULTS: With 8.65 FU/3 mL as the cut-off value, the sensitivity and specificity of FR+CTC in differential diagnosis were 98.1% and 79.1%, respectively. The detection rate of FR+CTC was superior to conventional serum biomarkers (CA 19-9 > CA 125 > CEA). For the 16patients with matched post-operative FR+CTC analysis, FR+CTC levels significantly reduced after surgery (P=0.0084). CONCLUSIONS: Our results demonstrated that FR+CTC analysis could be an efficacious non-invasive biomarker in differential diagnosis and surveillance of HBPs, though further investigation with a larger sample size is required.

CAR-T 19 combined with reduced-dose PD-1 blockade therapy for treatment of refractory follicular lymphoma: A case report.

Anti-CD19 chimeric antigen receptor T cell (CAR-T) therapy has changed the typical outcomes of relapsed/refractory B-cell leukemia and lymphoma. However, treatment effectiveness for patients with relapsed/refractory B-cell non-Hodgkin lymphoma has been less satisfactory compared with patients with B-cell acute lymphoblastic leukemia. The present study described a case of refractory follicular lymphoma. A high expression of programmed cell death 1 (PD-1) was measured on CD3+ T cells (80.90%) in peripheral blood samples obtained from the patient enrolled in this study, indicating that treatment with autologous CAR-T 19 cell therapy may not be successful. Therefore, a therapy regimen consisting of CAR-T 19 cells in combination with a reduced dose of nivolumab (1.5 mg/kg) for PD-1 blockade was used. A low dose of PD-1 blockade therapy was used to reduce the adverse effects associated with the combination of a PD-1 inhibitor and CAR-T 19 cells. This salvage therapy resulted in remission that lasted for >10 months.

Identification of hepatitis B virus and liver cancer bridge molecules based on functional module network.

BACKGROUND: The potential role of chronic inflammation in the development of cancer has been widely recognized. However, there has been little research fully and thoroughly exploring the molecular link between hepatitis B virus (HBV) and hepatocellular carcinoma (HCC). AIM: To elucidate the molecular links between HBV and HCC through analyzing the molecular processes of HBV-HCC using a multidimensional approach. METHODS: First, maladjusted genes shared between HBV and HCC were identified by disease-related differentially expressed genes. Second, the protein-protein interaction network based on dysfunctional genes identified a series of dysfunctional modules and significant crosstalk between modules based on the hypergeometric test. In addition, key regulators were detected by pivot analysis. Finally, targeted drugs that have regulatory effects on diseases were predicted by modular methods and drug target information. RESULTS: The study found that 67 genes continued to increase in the HBV-HCC process. Moreover, 366 overlapping genes in the module network participated in multiple functional blocks. It could be presumed that these genes and their interactions play an important role in the relationship between inflammation and cancer. Correspondingly, significant crosstalk constructed a module level bridge for HBV-HCC molecular processes. On the other hand, a series of non-coding RNAs and transcription factors that have potential pivot regulatory effects on HBV and HCC were identified. Among them, some of the regulators also had persistent disorders in the process of HBV-HCC including microRNA-192, microRNA-215, and microRNA-874, and early growth response 2, FOS, and Kruppel-like factor 4. Therefore, the study concluded that these pivots are the key bridge molecules outside the module. Last but not least, a variety of drugs that may have some potential pharmacological or toxic side effects on HBV-induced HCC were predicted, but their mechanisms still need to be further explored. CONCLUSION: The results suggest that the persistent inflammatory environment of HBV can be utilized as an important risk factor to induce the occurrence of HCC, which is supported by molecular evidence.

The Dynamics of Circulating Monocyte Subsets and Intra-Plaque Proliferating Macrophages during the Development of Atherosclerosis in ApoE-/- Mice.

To detect the development of monocytes and proliferative macrophages in atherosclerosis of ApoE-/- mice, we randomly assigned 84 ApoE-/- mice fed western diet or chow diet. On weeks 2, 4, 6, 8, 10, and 12 after fed high-fat diet or normal chow diet, animals were euthanized (n = 7 for each group at each time point). Flow cytometry methods were used to analyze the proportions of circulation monocyte subsets. The macrophage and proliferative macrophage accumulation within atherosclerotic plaques was estimated by confocal florescence microscopy. Plasma levels of total cholesterol and triglyceride were measured by ELISA kit. The plaques of aortic sinus were stained with Oil Red O. The percent of Ly6Chi circulation monocyte, the density of proliferation macrophage, the total plasma cholesterol and triglyceride levels, the lesion area of ApoE-/- mice were consistently elevated in chow diet throughout the trial. The total plasma cholesterol and triglyceride levels, the lesion area were elevated in western diet group with age, and they were always higher than the chow diet group. The Ly6Chi monocytes and proliferative macrophages reached a plateau at 8 weeks and 6 weeks; despite continued high-triglyceride high-cholesterol diet the percent did not significantly change. Interestingly, the density of macrophage did not change significantly over age in western and chow diet groups. Our results provide a dynamic view of Ly6Chi monocyte subset, the density of macrophage and proliferation macrophage change during the development and progression of atherosclerosis, which is relevant for designing new treatment strategies targeting mononuclear phagocytes in this model.

Review of risk factors, treatment, and prevention of saphenous vein graft disease after coronary artery bypass grafting.

Saphenous vein graft disease (SVGD) is a type of vascular disease that may develop after coronary artery bypass grafting (CABG). SVGD seriously affects the short-term and long-term effects of CABG and increases the incidence of major adverse cardiovascular events. It is very important to identify patients at greatest risk and carry out prevention and treatment measures to determine the risk factors for SVGD. Many factors contribute to SVGD when the vein is grafted into an arterial environment, such as surgery-related factors, smoking, diabetes mellitus, hyperlipidemia, and others. In this review, we discuss the risk factors for SVGD, current surgical and pharmacologic therapies with which to manage SVGD, and the prevention of SVGD.

Readout-segmented echo-planar diffusion-weighted MR for the evaluation of aggressive characteristics of rectal cancer.

To evaluate whether aggressive characteristics of rectal cancer can be predicted by the apparent diffusion coefficient (ADC) obtained using readout-segmented echo-planar imaging (rs-EPI) diffusion-weighted magnetic resonance. We enrolled one hundred and fifteen patients. The image quality of ADC maps by rs-EPI was compared with that by traditional single-shot echo-planar imaging (ss-EPI), and ADC measurement was performed on the rs-EPI based ADC maps. Differences in ADC values of tumors grouped according to differentiation grade, clinical T stage and plasmatic carcinoembryonic antigen (CEA) level were tested. The correlation between each aggressive characteristic and the corresponding ADC values was evaluated. The image quality of ADC maps obtained by rs-EPI was superior toss-EPI (P < 0.05). The ADC values of tumor were categorized based on the following differentiation grades: poor (0.89 ± 0.12 × 10-3 mm2/s), moderate (1.13 ± 0.25 × 10-3 mm2/s), and good (1.31 ± 0.19 × 10-3 mm2/s); P < 0.001. Tumors with lower differentiation grades corresponded to lower ADC values (r = 0.59, P < 0.001). However, ADC differences were not observed in different clinical T stage (P = 0.22) and plasmatic CEA level (P = 0.38). Rs-EPI sequence-based ADC values represent a potential imaging marker for the aggressive rectal cancer characteristics.

Association between proprotein convertase subtilisin/kexin type 9 and late saphenous vein graft disease after coronary artery bypass grafting: a cross-sectional study.

OBJECTIVE: The study aims to explore the association between serum proprotein convertase subtilisin/kexin type 9 (PCSK9) level and saphenous vein grafts disease (SVGD) after coronary artery bypass grafting (CABG). DESIGN: A cross-sectional study. SETTING: A secondary hospital in Tianjin City, China. PARTICIPANTS: A total of 231 participants were included in the study. Inclusion criteria were as follows: age ≥18 years, previous CABG surgery at least 12 months ago, at least one SVG for bypass during CABG, abnormal non-invasive test results or recurrent stable angina pectoris by coronary angiography indications, and willing to participate and sign informed consent. Participants with any of the following were excluded from the study: congenital valvular disease, decompensated heart failure, anaemia defined as a haemoglobin level of <12 g/dL in women or <13 g/dL in men, malignant neoplasms, renal failure, severe hepatic disease, thyroid disease, acute or chronic inflammatory disease and chronic obstructive lung disease. PRIMARY OUTCOME MEASURE: SVGD was defined as at least one SVG with significant stenosis (≥50%). Circulating PCSK9 levels were measured using commercial ELISA kits according to the manufacturer's instructions. RESULTS: The mean PCSK9 level in the SVGD group was significantly higher than that in the patent group (275.2±38.6 vs 249.3±37.7, p<0.01). The multivariate logistic regression model revealed a significant association between serum PCSK9 and SVGD (OR 2.08, 95% CI 1.46-2.95) per 1 SD increase in serum PCSK9. CONCLUSIONS: The present study is the first to identify an independent association between PCSK9 and late SVGD after adjustment for established cardiovascular risk factors. A multicentre prospective cohort study with large sample size should be conducted in the future to further research this relationship.

MicroRNA-23a-5p regulates osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by targeting mitogen-activated protein kinase-13.

The molecular mechanisms of osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) remain to be fully elucidated. MicroRNAs (miRs) serve vital roles in the process of regulating osteogenic differentiation of BMSCs. The present study aimed to investigate the role of miR­23a­5p in osteogenic differentiation of human (h)BMSCs, and the underlying molecular mechanism. The results of reverse transcription­quantitative polymerase chain reaction demonstrated that miR­23a­5p was significantly downregulated in the process of osteogenic differentiation. Upregulation of miR­23a­5p inhibited osteogenic differentiation of hBMSCs, and down­regulated expression of miR­23a­5p enhanced this process, which was confirmed by alkaline phosphatase (ALP) and Alizarin Red S staining. A dual­luciferase reporter assay confirmed that mitogen­activated protein kinase 13 (MAPK13) was a direct target of miR­23a­5p. In addition, knockdown of MAPK13 inhibited osteogenic differentiation of hBMSCs, similar to the effect of upregulation of miR­23a­5p. Finally, the knockdown of MAPK13 also blocked the effect of miR­23a­5p in osteogenic differentiation of hBMSCs, which was also confirmed by ALP and Alizarin Red S staining. These results indicated that by targeting MAPK13, miR­23a­5p serves a vital role in osteogenic differentiation of hBMSCs, which may provide novel clinical treatments for bone injury however, further studies are required.