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.

Maternal exposure to hyperbaric oxygen at the preimplantation stages increases apoptosis and ectopic Cdx2 expression and decreases Oct4 expression in mouse blastocysts via Nrf2-Notch1 upregulation and Nf2 downregulation.

BACKGROUND: The environmental oxygen tension has been reported to impact the blastocyst quality and cell numbers in the inner cell mass (ICM) during human and murine embryogenesis. While the molecular mechanisms leading to increased ICM cell numbers and pluripotency gene expression under hypoxia have been deciphered, it remains unknown which regulatory pathways caused the underweight fetal body and overweight placenta after maternal exposure to hyperbaric oxygen (HBO). RESULTS: The blastocysts from the HBO-exposed pregnant mice revealed significantly increased signals of reactive oxygen species (ROS) and nuclear Nrf2 staining, decreased Nf2 and Oct4 expression, increased nuclear Tp53bp1 and active caspase-3 staining, and ectopic nuclear signals of Cdx2, Yap, and the Notch1 intracellular domain (N1ICD) in the ICM. In the ICM of the HBO-exposed blastocysts, both Nf2 cDNA microinjection and Nrf2 shRNA microinjection significantly decreased the ectopic nuclear expression of Cdx2, Tp53bp1, and Yap whereas increased Oct4 expression, while Nrf2 shRNA microinjection also significantly decreased Notch1 mRNA levels and nuclear expression of N1ICD and active caspase-3. CONCLUSION: We show for the first time that maternal exposure to HBO at the preimplantation stage induces apoptosis and impairs ICM cell specification via upregulating Nrf2-Notch1-Cdx2 expression and downregulating Nf2-Oct4 expression.

Body mass index, neck circumference, and hypertension: a prospective cohort study.

Objective: This study aimed to investigate the association between BMI combined with neck circumference and the risk of hypertension. Methods: We selected participants from the Kailuan study in 2014 who were normotensive as our research subjects. We compared the risk of hypertension among individuals in group 1 (non-obese with low neck circumference), group 2 (non-obese with high neck circumference), group 3 (obese with low neck circumference), and group 4 (obese with high neck circumference). Results: After a median observation period of 3.86 years, hypertension occurred in 13,383 participants. Subjects in Group 2, 3, and 4 had significantly higher risks of hypertension compared to Group 1, with hazard ratios (HRs) of 1.066 (95% CI: 1.025, 1.110), 1.322 (95% CI: 1.235, 1.415), and 1.422 (95% CI: 1.337, 1.512), respectively. Additionally, adding BMI to a conventional model had a greater incremental effect on predicting hypertension compared to adding neck circumference alone. However, considering both BMI and neck circumference together further improved the prediction of hypertension. Conclusion: Individuals with both high BMI and high neck circumference face a higher risk of hypertension. Moreover, BMI is a superior predictor of hypertension risk compared to neck circumference, but using both of these measures can further enhance the accuracy of hypertension risk prediction.

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.

Chronic high­salt intake induces cardiomyocyte autophagic vacuolization during left ventricular maladaptive remodeling in spontaneously hypertensive rats.

The role of autophagy in high-salt (HS) intake associated hypertensive left ventricular (LV) remodeling remains unclear. The present study investigated the LV autophagic change and its association with the hypertensive LV remodeling induced by chronic HS intake in spontaneously hypertensive rats (SHR). Wistar Kyoto (WKY) rats and SHR were fed low-salt (LS; 0.5% NaCl) and HS (8.0% NaCl) diets and were subjected to invasive LV hemodynamic analysis after 8, 12 and 16 weeks of dietary intervention. Reverse transcription-quantitative PCR and western blot analysis were performed to investigate the expression of autophagy-associated key components. The LV morphologic staining was performed at the end of the study. The rat H9c2 ventricular myoblast cell-associated experiments were performed to explore the mechanism of HS induced autophagic change. A global autophagy-associated key component, as well as increased cardiomyocyte autophagic vacuolization, was observed after 12 weeks of HS intake. During this period, the heart from HS-diet-fed SHR exhibited a transition from compensated LV hypertrophy to decompensation, as shown by progressive impairment of LV function and interstitial fibrosis. Myocardial extracellular [Na+] and the expression of tonicity-responsive enhancer binding protein (TonEBP) was significantly increased in HS-fed rats, indicating myocardial interstitial hypertonicity by chronic HS intake. The global autophagic change and overt deterioration of LV function were not observed in LS-fed SHR and HS-fed WKY rats. The study of rat H9c2 cardiomyocytes demonstrated a cytosolic [Na+] elevation-mediated, reactive oxygen species-dependent the autophagic change occurred when exposed to an increased extracellular [Na+]. The present findings demonstrated that a myocardial autophagic change participates in the maladaptive LV remodeling induced by chronic HS intake in SHR, which provides a possible target for future intervention studies on HS-induced hypertensive LV remodeling.

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.

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.

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.

The relationship between high-normal blood pressure in the first half of pregnancy and the risk of hypertensive disease of pregnancy.

Early warning of hypertensive disorder in pregnancy (HDP) can improve maternal and infant outcomes. However, few studies had evaluated the warning value of high-normal blood pressure (BP) before the onset of HDP. This was a prospective cohort study to investigate the relationship between high-normal BP in the first half of pregnancy and the risk of HDP. According to the maximum BP measured before 20+6  weeks of gestation, the cohort was divided into three groups: optimal BP (SBP < 120 mmHg and DBP < 80 mmHg), normal BP (120 mmHg ≤ SBP < 130 mmHg or 80 mmHg ≤ DBP < 85 mmHg), and high-normal BP (130 mmHg ≤ SBP < 140 mmHg or 85 mmHg ≤ DBP < 90 mmHg). The relationship between different BP levels in the first half of pregnancy and HDP risk was assessed by general linear models. Ten thousand one hundred and ninety-three normotensive pregnant women with complete information were finally included for data analysis. Among them, 532 pregnant women were diagnosed with HDP, with a total HDP incidence of 5.2%. The incidences in the optimal, normal, and high-normal BP groups were 2.4%, 6.0%, and 21.8%, respectively. Compared to women with optimal BP in the first half of pregnancy, women with high-normal BP had a 445% increased risk of HDP (aRR: 5.45, 95% CI: 4.24-7.00), and even women with normal BP had a 107% increased risk of HDP (aRR: 2.07, 95% CI: 1.68-2.56). This study demonstrated that among low-risk healthy women, women with high-normal BP in the first half of pregnancy had a significantly higher risk of HDP.

Vanadium oxides obtained by chimie douce reactions: The influences of transition metal species on crystal structures and electrochemical behaviors in zinc-ion batteries.

Rechargeable aqueous zinc-ion batteries (RAZIBs) have received increasing attention due to cost-effectiveness and inherent safety. A wide variety of advanced cathode materials have been revealed with promising performance in RAZIBs. However, these materials usually require sophisticated procedures at high temperatures, which greatly limit further practical application. Herein, a chimie douce approach is adopted to prepare vanadium oxides from V2O5 suspension with the addition of various transition metal cations (Mn2+, Zn2+, Ag+, and Fe3+) by simple liquid-solid mixing under ambient conditions. For the cases of Mn2+ and Zn2+, the dissolution-recrystallization process takes place leading to layered Mn0.31V3O7·1.40H2O (MnVO) and Zn0.32V3O7·1.52H2O (ZnVO). The use of Ag+ forms tunneled Ag0.33V2O5 (AgVO), and the present of Fe3+ stays mainly unreacted V2O5. The underlying reaction chemistries are proposed, for which the pH values of precursor solutions are found to be a key factor. Among the prepared materials, layered vanadium oxides exhibit promising battery performance. Particularly, MnVO delivers 340 and 217 mAh g-1 at 1 and 8 A g-1, respectively. A specific capacity of 164 mAh g-1 can be retained after 500 cycles at 1 A g-1. By contrast, AgVO and FeVO demonstrate inferior performance with retaining only 89 and 20 mAh g-1 after 500 cycles.

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.

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.

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.

Association of Plasma Connective Tissue Growth Factor Levels with Hyperthyroid Heart Disease.

Hyperthyroid heart disease (HHD) is one of the most severe complications of overt hyperthyroidism and increases the risk of mortality in affected patients. Early identification of patients at a higher risk of developing HHD can improve clinical outcomes through active surveillance and management. Connective tissue growth factor (CTGF), a secreted extracellular protein, plays a significant role in cardiac remodeling and dysfunction. We aimed to investigate the association between plasma CTGF level and the risk of HHD in this study. A total of 142 overt hyperthyroid patients without HHD and 99 patients with HHD were included. The plasma CTGF levels were measured using ELISA kits. Routine clinical medical data and echocardiography parameters were recorded for analysis. The plasma CTGF level was significantly higher in patients with HHD than in those without HHD (P=0.002). The plasma CTGF level was positively correlated with free triiodothyronin, tryrotropin receptor antibody, troponin I and lactate dehydrogenase levels and the left atrium diameters, right atrium diameters, and right ventricular end-diastolic diameters (all P<0.05). Logistic regression analysis showed that quartiles 3 and 4 of plasma CTGF levels were significantly associated with the increased risk of HHD (crude OR: 2.529; 95% CI: 1.188-5.387). However, after adjustment for the potentially confounding variables, quartile 4 alone was significantly associated with the higher risk of HHD relative to quartile 1. Hyperthyroid patients with HHD display higher plasma CTGF levels. Furthermore, CTGF is an independent risk factor for HHD. Therefore, the plasma CTGF level may be a potential biomarker for the risk of HHD.

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.

Evaluating angiotensin-converting enzyme 2-mediated SARS-CoV-2 entry across species.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic represents a global threat, and the interaction between the virus and angiotensin-converting enzyme 2 (ACE2), the primary entry receptor for SARS-CoV-2, is a key determinant of the range of hosts that can be infected by the virus. However, the mechanisms underpinning ACE2-mediated viral entry across species remains unclear. Using infection assay, we evaluated SARS-CoV-2 entry mediated by ACE2 of 11 different animal species. We discovered that ACE2 of Rhinolophus sinicus (Chinese rufous horseshoe bat), Felis catus (domestic cat), Canis lupus familiaris (dog), Sus scrofa (wild pig), Capra hircus (goat), and Manis javanica (Malayan pangolin) facilitated SARS-CoV-2 entry into nonsusceptible cells. Moreover, ACE2 of the pangolin also mediated SARS-CoV-2 entry, adding credence to the hypothesis that SARS-CoV-2 may have originated from pangolins. However, the ACE2 proteins of Rhinolophus ferrumequinum (greater horseshoe bat), Gallus gallus (red junglefowl), Notechis scutatus (mainland tiger snake), or Mus musculus (house mouse) did not facilitate SARS-CoV-2 entry. In addition, a natural isoform of the ACE2 protein of Macaca mulatta (rhesus monkey) with the Y217N mutation was resistant to SARS-CoV-2 infection, highlighting the possible impact of this ACE2 mutation on SARS-CoV-2 studies in rhesus monkeys. We further demonstrated that the Y217 residue of ACE2 is a critical determinant for the ability of ACE2 to mediate SARS-CoV-2 entry. Overall, these results clarify that SARS-CoV-2 can use the ACE2 receptors of multiple animal species and show that tracking the natural reservoirs and intermediate hosts of SARS-CoV-2 is complex.

Xiaoyaosan Exerts Therapeutic Effects on the Colon of Chronic Restraint Stress Model Rats via the Regulation of Immunoinflammatory Activation Induced by the TLR4/NLRP3 Inflammasome Signaling Pathway.

Depression is the neurological manifestation most commonly associated with gastrointestinal diseases. The release of inflammatory cytokines mediated by TLR4/NLRP3 inflammasome signaling-induced immunoinflammatory activation may represent a common pathogenic process underlying the development of gastrointestinal diseases and depression. Clinical studies have indicated that Xiaoyaosan (XYS) can relieve depressive behavior by improving gastrointestinal symptoms. We previously demonstrated that XYS can reduce colonic inflammation in a rat model of chronic unpredictable mild stress; however, the precise anti-inflammatory mechanisms involved remain unclear. Here, we investigated whether XYS can ameliorate depressive behavior through regulating the TLR4/NLRP3 inflammasome signaling pathway, thereby inhibiting immunoinflammatory activation and reducing colonic proinflammatory cytokine levels. Fifty-two healthy male Sprague-Dawley rats were randomly divided into four groups (control, model, XYS, and fluoxetine). The latter three groups were subjected to 21 days of chronic restraint stress to generate a model of stress-induced depression. XYS and fluoxetine were administered intragastrically. Behavioral changes in the rats were assessed after 21 days. Serum and colon samples were collected, and the relative levels of the inflammation indicators IL-6, IL-1ß, and TNF-α were determined by ELISA. Pathological changes in colon tissue were assessed by hematoxylin and eosin staining. The levels of TLR4, MyD88, NF-κB-p65, TAK1, IRAK1, and TRAF6 were detected by immunohistochemistry, while the gene and protein expression levels of TLR4, MyD88, NF-κB-p65, TAK1, IRAK1, TRAF6, NLRP3, ASC, and caspase-1 were detected by quantitative polymerase chain reaction (qPCR) and Western blotting. The results indicated that XYS could improve the depressive-like behavior and the weight loss of rats with stress-induced depression. Furthermore, depressed rats treated with XYS exhibited decreased expression levels of TLR4, MyD88, NF-κB-p65, TAK1, IRAK1, TRAF6, NLRP3, ASC, and caspase-1 in colonic tissue; reduced colon and serum concentrations of the inflammatory factors IL-6, IL-1ß, and TNF-α; and lowered levels of colonic inflammation.

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.

Retraction Note: Prognostic value of heart failure in hemodialysis-dependent end-stage renal disease patients with myocardial fibrosis quantification by extracellular volume on cardiac magnetic resonance imaging.

An amendment to this paper has been published and can be accessed via the original article.