Two three-dimensional coordination polymers as fluorescence probes for the detection of nitrobenzene, tetracycline, fluazinam and their application in green pepper.

Two coordination polymers (CPs), [Zn5(L)2(phen)5](1) and [Cd2(HL)(2,2-bpy)(H2O)3](2), were synthesized by using 2',3,3',5,5'-Diphenyl ether pentacarboxylic acid (H5L), phenanthroline (phen), and 2,2'-bipyridine (2,2'-bpy) under hydrothermal conditions. The L5- ligand adopts the µ6-к2: к2: к1: к1: к1: к1 mode in 1 and the µ5-к2: к2: к2: к2: к1 mode in 2. Sensing experiments show that 1 and 2 are fluorescence probes with high sensitivity and rapid detection of nitro explosives, antibiotics, and pesticides. In order to verify the ability of 2 to detect FLU in actual samples, we performed a spiked recovery experiment in green pepper water. The spiked recoveries were 97.77-101.18 %. Interestingly, because H5L is not completely deprotonated in 2, there is abundant hydrogen bonding, which makes the fluorescence quenching rate higher and the detection limit lower. The possible fluorescence quenching mechanism of 1 and 2 can be explained by their UV-VIS absorption spectra and orbital energy levels.

Clinical follow-up investigation on thickness changes in the peripapillary retinal nerve fibre layer of patients with Leber hereditary optic neuropathy.

BACKGROUND: To investigate the peripapillary retinal nerve fibre layer (RNFL) thickness changes and analyse factors associated with visual recovery of G11778A Leber hereditary optic neuropathy (LHON) patients. METHODS: Patients diagnosed with G11778A LHON between July 2017 and December 2020 in Tongji hospital were included in this follow-up study. Patients were grouped according to disease duration. Variations in the RNFL thickness in each quadrant at different disease stages were characterised using optical coherence tomography. According to the absence or presence of significant visual acuity improvements, LHON patients of disease duration ≥ 6 months were divided into two groups. A bivariate logistic regression model was constructed to analyse the potential factors associated with spontaneous visual recovery. RESULTS: This study included 56 G11778A LHON patients (112 eyes) and 25 healthy controls (50 eyes), with a mean follow-up of 5.25 ± 1.42 months. All quadrants and mean RNFL thicknesses of LHON patients first increased and then decreased, except for the temporal RNFL. As the disease progressed, RNFL thinning slowed; however, gradual RNFL thinning occurred. Logistic regression revealed that baseline best corrected visual acuity was related to spontaneous visual recovery of LHON patients with disease duration ≥ 6 months. CONCLUSION: The pattern of RNFL involvement could be helpful in the differential diagnosis of LHON and other optic neuropathies. LHON patients with better vision are more likely to experience some degree of spontaneous visual acuity recovery after the subacute phase.

Etiologies of Persistent Aminotransferase Elevations in Chronic Hepatitis B Patients Treated with Nucleos(t)ide Analogs.

Background/Aims: Recent studies revealed that patients with persistent aminotransferase elevations after antiviral treatment had higher risk of hepatic events; yet its underlying causes remain unclear. Our study aimed to investigate the etiologies of persistent aminotransferase elevations in patients treated with nucleos(t)ide analogs (NAs). Materials and Methods: A retrospective study was conducted on chronic hepatitis B (CHB) patients who had been receiving NA treatment for over a year and had an aminotransferase level greater than 40 IU/mL (more than twice, with a 3-month interval) and subsequently underwent a liver biopsy. Results: The study group included 46 patients (34 males) with a mean age of 44.8 ± 20.3 years (range: 24-71 years).The average dura- tion of NA therapy was 3.7 years (1.1-10.6 years). The etiologies of persistant transaminase elevation were categorized into 4 groups: patients with low hepatitis B virus (HBV) viral load (LVL, n = 11); concurrent non-alcoholic fatty liver disease (NAFLD, n = 12); concurrent other liver diseases (OLD, n = 12); and unknown liver dysfunction (ULD, n = 11). The proportion of G ≥ 2 inflammation was significantly higher in the LVL group (90.9%) compared to NAFLD (33.3%), OLD (50%), and ULD (27.2%) groups (P = .012). The hepatitis B e-antigen (HBeAg)-positive group exhibited a younger age (34.5 ± 10.2 vs. 48.1 ± 9.4 years, P < .001), a lower proportion of fibrosis F ≥ 2 (36.3% vs. 77.1%, P = .012), and a higher prevalence of detectable HBV DNA (54.5% vs.14.2%, P = .00632) compared to the HBeAg-negative group. Conclusion: The etiology of persistent aminotransferase elevations in CHB patients undergoing NAs treatment warrants investigation. Besides the commonly observed NAFLD and low HBV viral load, concurrent presence of other liver diseases requires elucidation.The proportion of G≥2 inflammation was higher in the LVL group.

Nab-paclitaxel plus S-1 versus nab-paclitaxel plus gemcitabine in patients with advanced pancreatic cancer: a multicenter, randomized, phase II study.

BACKGROUND: Encouraging antitumor activity of nab-paclitaxel plus S-1 (AS) has been shown in several small-scale studies. This study compared the efficacy and safety of AS versus standard-of-care nab-paclitaxel plus gemcitabine (AG) as a first-line treatment for advanced pancreatic cancer (PC). METHODS: In this multicenter, randomized, phase II trial, eligible patients with unresectable, locally advanced, or metastatic PC were recruited and randomly assigned (1:1) to receive AS (nab-paclitaxel 125 mg/m2 on days 1 and 8; S-1 twice daily on days 1 through 14) or AG (nab-paclitaxel 125 mg/m2 on days 1 and 8; gemcitabine 1000 mg/m2 on days 1 and 8) for 6 cycles. The primary endpoint was progression-free survival (PFS). RESULTS: Between July 16, 2019, and September 9, 2022, 62 patients (AS, n = 32; AG, n = 30) were treated and evaluated. With a median follow-up of 8.36 months at preplanned interim analysis (data cutoff, March 24, 2023), the median PFS (8.48 vs 4.47 months; hazard ratio [HR], 0.402; P = .002) and overall survival (OS; 13.73 vs 9.59 months; HR, 0.226; P < .001) in the AS group were significantly longer compared to the AG group. More patients had objective response in the AS group than AG group (37.50% vs 6.67%; P = .005). The most common grade 3-4 adverse events were neutropenia and leucopenia in both groups, and gamma glutamyl transferase increase was observed only in the AG group. CONCLUSION: The first-line AS regimen significantly extended both PFS and OS of Chinese patients with advanced PC when compared with the AG regimen, with a comparable safety profile. (ClinicalTrials.gov Identifier: NCT03636308).

Structural basis of tolvaptan binding to the vasopressin V2 receptor.

The vasopressin V2 receptor (V2R) is a validated therapeutic target for autosomal dominant polycystic kidney disease (ADPKD), with tolvaptan being the first FDA-approved antagonist. Herein, we used Gaussian accelerated molecular dynamics simulations to investigate the spontaneous binding of tolvaptan to both active and inactive V2R conformations at the atomic-level. Overall, the binding process consists of two stages. Tolvaptan binds initially to extracellular loops 2 and 3 (ECL2/3) before overcoming an energy barrier to enter the pocket. Our simulations result highlighted key residues (e.g., R181, Y205, F287, F178) involved in this process, which were experimentally confirmed by site-directed mutagenesis. This work provides structural insights into tolvaptan-V2R interactions, potentially aiding the design of novel antagonists for V2R and other G protein-coupled receptors.

Patient with suspected co-infection of hemorrhagic fever with renal syndrome and malaria: a case report.

Background: Hemorrhagic fever with renal syndrome (HFRS) is a natural epidemic disease that can be caused by the Hantaan virus (HTNV). Malaria is caused by plasmodium and can be transmitted by a mosquito bite. The similar manifestations shared by these disorders pose a challenge for clinicians in differential diagnosis, in particular, coupled with a false-positive serological test. Case presentation: A 46-year-old man was admitted for fever and chills for over 10 days and was suspected of being co-infected with HFRS and malaria due to a history of travel to malaria-endemic areas and a positive HTNV-immunoglobulin M (IgM) test. Although leukocytosis, thrombocytopenia, renal injury, lymphocytosis, overexpression of interleukin-6, and procalcitonin were observed during the hospitalization, the hypotensive, oliguria, and polyuria phases of the HFRS course were not observed. Instead, typical symptoms of malaria were found, including a progressive decrease in erythrocytes and hemoglobin levels with signs of anemia. Furthermore, because the patient had no history of exposure to HFRS endemic areas, exposure to an HTNV-infected rodent, or a positive HTNV-IgG test, and false serological tests of IgM can be caused by various factors, the HFRS coinfection with malaria was ruled out. Conclusion: Misdiagnosis can be easily induced by a false serological test, in particular the IgM test which can be influenced by various factors. A combination of health history, epidemiology, physical examination, precise application of specific examinations involving tests of conventional laboratory parameters as well as well-accepted methods such as the immunochromatographic (ICG) test, real-time reverse transcription-polymerase chain reaction (PCR), and Western blot (WB), and acquaintance with disorders with similar manifestations will contribute to the precise diagnosis in clinical treatment.

Multiomics analyses provide insights into the genomic basis of differentiation among four sweet osmanthus groups.

Sweet osmanthus (Osmanthus fragrans) is famous in China for its flowers and contains four groups: Albus, Luteus, Aurantiacus, and Asiaticus. Understanding the relationships among these groups and the genetic mechanisms of flower color and aroma biosynthesis are of tremendous interest. In this study, we sequenced representative varieties from two of the four sweet osmanthus groups. Multiomics and phylogenetic analyses of varieties from each of the four groups showed that Asiaticus split first within the species, followed by Aurantiacus and the sister groups Albus and Luteus. We show that the difference in flower color between Aurantiacus and the other three groups was caused by a 4-bp deletion in the promoter region of carotenoid cleavage dioxygenase 4 (OfCCD4) that leads to expression decrease. In addition, we identified 44 gene pairs exhibiting significant structural differences between the multiseasonal flowering variety "Rixianggui" in the Asiaticus group and other autumn-flowering varieties. Through correlation analysis between intermediate products of aromatic components and gene expression, we identified eight genes associated with the linalool and α- and ß-ionone biosynthesis pathways. Overall, our study offers valuable genetic resources for sweet osmanthus, while also providing genetic clues for improving the flower color and multiseasonal flowering of osmanthus and other flowers.

IAIH-PG consensus for histological criteria of AIH: Multicentre validation with focus on chronic liver diseases in China.

BACKGROUND AND AIMS: The International AIH Pathology Group (IAIH-PG) put forward the new histological criteria of autoimmune hepatitis (AIH) in 2022, which have not undergone adequate verification. In this study, we verified the applicability of the new histological criteria in the population of Chinese patients with chronic liver disease, comparing it with the simplified criteria. METHODS: The gold standard for diagnosis in all patients was based on histological findings, combined with clinical manifestations and laboratory tests and determined after a follow-up period of at least 3 years. A total of 640 patients with various chronic liver diseases from multiple centres underwent scoring using the new histological criteria and the simplified criteria, comparing their diagnostic performance. RESULTS: In this study, the new histological criteria showed a sensitivity of 73.6% and 100% for likely and possible AIH, with specificities of 100% and 69.0% respectively. The coincidence rates of possible AIH for the new histological criteria, simplified histological criteria and simplified score were 81.7%, 72.8% and 69.7% respectively. For likely AIH, the rates were 89.2%, 75.9% and 65.6% respectively. Based on the new histological criteria, all patients with AIH were correctly diagnosed. Specifically, 73.6% were diagnosed with likely AIH and 26.4% were possible AIH. Additionally, the simplified histological criteria achieved a diagnosis rate of 98.6% for AIH, while the simplified score could only diagnose 53.8% of AIH. CONCLUSIONS: Compared with the simplified score and simplified histological criteria, the sensitivity and specificity of the new histological criteria for AIH were significantly improved. The results indicate that the new histological criteria exhibit high sensitivity and specificity for diagnosing AIH in China.

Precirrhotic Primary Biliary Cholangitis with Portal Hypertension: Bile Duct Injury Correlate.

Background/Aims: The histological characteristics and natural history of precirrhotic primary biliary cholangitis (PBC) with portal hypertension (PH) are unclear. Our aim was to clarify the prevalence, risk factors, and histological characteristics of precirrhotic PBC patients with PH. Methods: This retrospective study compared the clinical features, histological characteristics, and response to ursodeoxycholic acid (UDCA) between the PH and non-PH groups of precirrhotic PBC patients. Results: Out of 165 precirrhotic PBC patients, 40 (24.2%) also had PH. According to histological stage 1, 2 and 3 disease, 5.3% (1/19), 17.3% (17/98), and 45.8% (22/48) of patients also had PH, respectively. Precirrhotic PBC with PH was significantly positively correlated with bile duct loss, degree of cytokeratin 7 positivity, and degree of fibrosis in the portal area, but significantly negatively correlated with lymphoid follicular aggregation. Compared to the non-PH group, patients in the PH group showed a higher prevalence of obliterative portal venopathy, incomplete septal fibrosis, portal tract abnormalities and non-zonal sinusoidal dilatation (p<0.05). In addition, patients with PH were more likely to present with symptoms of jaundice, ascites, epigastric discomfort, a poorer response to UDCA, and more decompensation events (p<0.05). High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values were risk factors for precirrhotic PBC with PH. Conclusions: Approximately 24.2% of precirrhotic PBC patients have PH, which is histologically related to the injury of bile ducts. High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values are associated with increased risk of precirrhotic PBC with PH.

Characteristics of the Hantaan virus complicated with SARS-CoV2 infection: A case series report.

Background: Coinfection poses a persistent threat to global public health due to its severe effect on individual-level infection risk and disease outcome. Coinfection of SARS-CoV2 with one or more pathogens has been documented. Nevertheless, this virus co-infected with the Hantaan virus (HTNV) is rarely reported. Case summary: Here, we presented three cases of HTNV complicated with SARS-CoV2 infection. Not only the conditions including general clinical manifestations, immune and inflammation parameters fluctuation presented in the single infection of HTNV or SARS-CoV2 can be found, but also the unexpected manifestations have attracted our attention that presented as more symptoms of HTNV infection including exudative changes in both lungs and an amount of bilateral pleural effusion as well as bilateral kidney enlargement rather than typical viral pneumonia in SARS-CoV2 infection. Fortunately, the conditions of patients gradually return to normal which is beneficial from the antiviral treatment, hemodialysis, and various supportive therapies including anti-inflammation, liver and gastric mucosa protection. Conclusion: Unexpected manifestations of coinfection patients present herein may be associated with multiple factors including virus load, competition or antagonism among antigens, and the susceptibility of target cells to the various pathogens, even though the pathogenesis of HTNV and SARS-CoV2 remains to be elucidated. Given that these two viruses have posed a profound influence on the socioeconomic, healthcare system worldwide, and the threat of coinfection to public health, it is warranted for clinicians, public health authorities, and infectious disease researchers to have a high index of consideration for patients co-infected with HTNV and SARS-CoV2.

Association between vitamin D status and cardiometabolic risk factors in adults with type 2 diabetes in Shenzhen, China.

Background: Evidence of vitamin D status and cardiometabolic health in adults with type 2 diabetes mellitus (T2DM) is still limited. This study aimed to investigate the association between vitamin D status and cardiometabolic risk factors among adults with T2DM in Shenzhen, China. Methods: This cross-sectional study included 164 adults (aged ≥18 years) with T2DM who were hospitalized at Peking University Shenzhen Hospital from March 1, 2023, to May 31, 2023. Serum 25-hydroxyvitamin D [25(OH)D] concentration, the active marker of vitamin D, and three major cardiometabolic risk factors including blood pressure (BP), glucose metabolism-related indicators, and blood lipid profiles were collected. Vitamin D deficiency (VDD) was defined as 25(OH)D < 20 ng/mL. Correlation, Regression, and Logistic analysis were applied to verify the association among serum 25(OH)D concentration, VDD, and 11 cardiometabolic risk factors. Results: Median 25(OH)D concentration was 21.78 [interquartile range (IQR)=17.51-28.05] ng/mL. The prevalence of VDD was 40.24%. Serum 25(OH)D concentration was significantly negatively correlated with diastolic BP (DBP) and glycated hemoglobin A1c (HbA1c) rather than systolic BP, plasma glucose, plasma C-peptide, and blood lipid profiles among adults with T2DM in both correlation and linear regression analysis. Furthermore, the adjusted odd ratio for poor DBP control (≥90 mmHg) of T2DM patients with VDD was 3.164 (95% confidence interval=1.303, 7.683; P=0.011) compared to those without VDD. Conclusion: In China, VDD was highly prevalent among adults with T2DM and associated with greater cardiovascular risk factors, especially with increased chances of uncontrolled DBP. These findings suggest that vitamin D levels should be monitored in T2DM patients, especially those with high DBP.

Wide dynamic range measurement of blood flow in vivo using laser speckle contrast imaging.

Significance: Laser speckle contrast imaging (LSCI) is a real-time wide-field technique that is applied to visualize blood flow in biomedical applications. However, there is currently a lack of relevant research to demonstrate that it can measure velocities over a wide dynamic range (WDR), which is critical for monitoring much higher and more pulsatile blood flow in larger size myocardial vessels, such as the coronary artery bypass graft, and visualizing the spatio-temporal evolution of myocardial blood flow perfusion in cardiac surgery. Aim: We aim to demonstrate that the LSCI technique enables measuring velocities over a WDR from phantom experiments to animal experiments. In addition, LSCI is preliminarily applied to imaging myocardial blood flow distribution in vivo on rabbits. Approach: Phantom and animal experiments are performed to verify that the LSCI method has the ability to measure blood velocities over a wide range. Our method is also validated by transit time flow measurement, which is the gold standard for blood flow measurement in cardiac surgery. Results: Our method is demonstrated to measure the blood flow over a wide range from 0.2 to 635 mm/s. To validate the phantom results, the varying blood flow rate from 0 to 320 mm/s is detected in the rat carotid artery. Additionally, our technique also obtains blood flow maps of different myocardial vessels, such as superficial large/small veins, veins surrounded by fat, and myocardial deeper arteriole. Conclusions: Our study has the potential to visualize the spatio-temporal evolution of myocardial perfusion in coronary artery bypass grafting, which would be of great benefit for future research in the life sciences and clinical medicine.

Implementation and effectiveness of a nurse navigation programme based on noddings' care theory in first-year undergraduate nursing students for professional identity and career planning: A quasi-experimental study.

AIMS: Development and evaluation of the effectiveness of a Nurse Navigation programme based on Noddings' Care theory on two dependent variables which were professional identity and career planning among first-year undergraduate nursing students. BACKGROUND: First-year undergraduate nursing students generally have a low sense of professional identity and career planning, resulting in a loss of nursing power after graduation. Implemention of a Nurse Navigation program based on Noddings' Care theory may be potentially useful in cultivating their professional identity and career planning. DESIGN: A quasi-experimental study. METHODS: A convenience sample of 122 first-year undergraduate nursing students from two medical universities was recruited between September 2021 and June 2022. Students in the experimental group (n = 63) participated in the Nurse Navigation programme based on Noddings' Care theory, which contained four core components, spreading over 50 lessons. Those in the control group (n = 59) underwent a traditional training programme with five components across 44 lessons. The two groups were compared in terms of their level of professional identity by Professional identity questionnaire for nurse students (PIQNS) and career planning by Career planning questionnaire (CPQ) after the training using the t-test. RESULTS: The mean score of professional identity in the experimental group increased significantly from 51.02 ± 8.46 at baseline to 58.02 ± 8.81 after the intervention (p < 0.001), with a large effect size (Cohen's d=0.810). Also, this post-intervention score was statistically significantly higher than that (52.86 ± 9.27) in the control group (p = 0.002), with a medium effect size (Cohen's d=0.571). The mean score of career planning in the experimental group increased significantly from 81.76 ± 9.86 at baseline to 94.52 ± 10.81 after the intervention (p < 0.001), with a large effect size (Cohen's d = 1.233). Also, this post-intervention score was statistically significantly higher than that (88.25 ± 9.30) in the control group (p < 0.001), with a medium effect size (Cohen's d=0.623). CONCLUSIONS: The Nurse Navigation programme based on Noddings' Care theory showed effectiveness in enhancing professional identity and career planning among first-year undergraduate nursing students in China. Further rigorous studies are needed to examine its effectiveness and long-term impacts on these students.

Early tirofiban versus heparin for bridging dual antiplatelet therapy in patients undergoing coronary endarterectomy combined with coronary artery bypass grafting: a multicenter randomized controlled trial protocol (the THACE-CABG trial).

BACKGROUND: For complete revascularization, patients with diffuse coronary artery disease should have a coronary endarterectomy and a coronary artery bypass graft (CE-CABG). Sadly, CE can lead to a lack of endothelium, which raises the risk of thrombotic events. Even though daily dual antiplatelet therapies (DAPT) have been shown to reduce thrombotic events, the risk of perioperative thrombotic events is high during the high-risk period after CE-CABG, and there is no consistent protocol to bridge DAPT. This trial aims to compare safety and efficacy between tirofiban and heparin as DAPT bridging strategies after CE-CABG. METHODS: In phase I, 266 patients undergoing CE-CABG will be randomly assigned to tirofiban and heparin treatment groups to compare the two treatments in terms of the primary safety endpoint, chest tube drainage in the first 24 h. If the phase I trial shows tirofiban non-inferiority, phase II will commence, in which an additional 464 patients will be randomly assigned. All 730 patients will be studied to compare major cardiovascular and cerebrovascular events (MACCEs) between the groups in the first 30 days after surgery. DISCUSSION: Given the possible benefits of tirofiban administration after CE-CABG, this trial has the potential to advance the field of adult coronary heart surgery. TRIAL REGISTRATION: chictr.org.cn, ChiCTR2200055697. Registered 6 January 2022. https://www.chictr.org.cn/com/25/showproj.aspx?proj=149451 . Current version: 20,220,620.

Development and validation of a noninvasive prediction model of autoimmune hepatitis in patients with liver diseases.

BACKGROUND AND AIMS: There is no golden standard for the diagnosis of autoimmune hepatitis which still dependent on liver biopsy currently. So, we developed a noninvasive prediction model to help optimize the diagnosis of autoimmune hepatitis. METHODS: From January 2017 to December 2019, 1739 patients who had undergone liver biopsy were seen in the second hospital of Nanjing, of which 128 were here for consultation. Clinical, laboratory, and histologic data were obtained retrospectively. Multivariable logistic regression analysis was employed to create a nomogram model that predicting the risk of autoimmune hepatitis. Internal and external validation was both performed to evaluate the model. RESULTS: A total of 1288 patients with liver biopsy were enrolled (1184 from the second hospital of Nanjing, the remaining 104 from other centers). After the univariate and multivariate logistic regression analysis, nine variables including ALT, IgG, ALP/AST, ALB, ANA, AMA, HBsAg, age, and gender were selected to establish the noninvasive prediction model. The nomogram model exhibits good prediction in diagnosing autoimmune hepatitis with AUROC of 0.967 (95% CI: 0.776-0.891) in internal validation and 0.835 (95% CI: 0.752-0.919) in external validation. CONCLUSIONS: ALT, IgG, ALP/AST, ALB, ANA, AMA, HBsAg, age, and gender are predictive factors for the diagnosis of autoimmune hepatitis in patients with unexplained liver diseases. The predictive nomogram model built by the nine predictors achieved good prediction for diagnosing autoimmune hepatitis.

Study and application of coupling relationship between water-salt-resistivity-soil structure in saline soils in arid and semi-arid areas of northwest China.

Widespread saline soils in Northwest China pose a serious threat to the region's ability to use infrastructure safely because they are prone to soil structure damage when subjected to external environmental fluctuations, which in turn affects the stability of the foundations for buildings. The non-destructive approach of measuring resistivity can be used to swiftly reflect the subsoil body's state and make assumptions about its safety. However, the electrical resistivity of the underground soil body can be used to quickly identify unstable areas because the resistivity is influenced by the water content, salt content, and structural characteristics of the soil body. To do this, it is necessary to understand the coupling relationship between various factors. In this study, we first constructed samples with various water, salt, and soil structure characteristics, and then used indoor tests, such as soil resistivity measurement and thermogravimetric analysis, to analyze the multiple factors affecting the resistivity characteristics of the soil. The relationship between soil resistivity and actual saline soil diseases in Northwest China was then further discussed in conjunction with the results of the indoor tests and analyses. subsequently, the resistivity and soil properties have been measured in the field at specific locations in Northwest China where railway roadbeds are diseased. The study's findings can theoretically support a deeper comprehension of the law and mechanism of soil resistivity change, as well as provide assistance for building infrastructure in Northwest China.

Clinical characteristics and prognosis of non-APAP drug-induced acute liver failure: a large multicenter cohort study.

BACKGROUND: There is growing recognition of natural history, complications, and outcomes of patients who develop non-acetaminophen (APAP) drug-induced acute liver failure (ALF). To clarify high-risk factors and develop a nomogram model to predict transplant-free survival (TFS) in patients with non-APAP drug-induced ALF. METHODS: Patients with non-APAP drug-induced ALF from 5 participating centers were retrospectively analyzed. The primary endpoint was 21-day TFS. Total sample size was 482 patients. RESULTS: Regarding causative agents, the most common implicated drugs were herbal and dietary supplements (HDS) (57.0%). The hepatocellular type (R ≥ 5) was the main liver injury pattern (69.0%). International normalized ratio, hepatic encephalopathy grades, the use of vasopressor, N-acetylcysteine, or artificial liver support system were associated with TFS and incorporated to construct a nomogram model (drug-induced acute liver failure-5, DIALF-5). The AUROC of DIALF-5 for 7-day, 21-day, 60-day, and 90-day TFS in the internal cohort were 0.886, 0.915, 0.920, and 0.912, respectively. Moreover, the AUROC of DIALF-5 for 21-day TFS had the highest AUROC, which was significantly higher than 0.725 of MELD and 0.519 of KCC (p < 0.05), numerically higher than 0.905 of ALFSG-PI but without statistical difference (p > 0.05). These results were successfully validated in the external cohort (147 patients). CONCLUSIONS: Based on easily identifiable clinical data, the novel DIALF-5 model was developed to predict transplant-free survival in non-APAP drug-induced ALF, which was superior to KCC, MELD and had a similar prediction performance to ALFSG-PI but is more convenient, which can directly calculate TFS at multiple time points.

Safety evaluation of human umbilical cord-mesenchymal stem cells in type 2 diabetes mellitus treatment: A phase 2 clinical trial.

BACKGROUND: Progressive pancreatic ß cell dysfunction is a fundamental aspect of the pathology underlying type 2 diabetes mellitus (T2DM). Recently, mesenchymal stem cell (MSC) transplantation has emerged as a new therapeutic method due to its ability to promote the regeneration of pancreatic ß cells. However, current studies have focused on its efficacy, and there are few clinical studies on its safety. AIM: To evaluate the safety of human umbilical cord (hUC)-MSC infusion in T2DM treatment. METHODS: An open-label and randomized phase 2 clinical trial was designed to evaluate the safety of hUC-MSC transplantation in T2DM in a Class A hospital. Ten patients in the placebo group received acellular saline intravenously once per week for 3 wk. Twenty-four patients in the hUC-MSC group received hUC-MSCs (1 × 106 cells/kg) intravenously once per week for 3 wk. Diabetic clinical symptoms and signs, laboratory findings, and imaging findings were evaluated weekly for the 1st mo and then at weeks 12 and 24 post-treatment. RESULTS: No serious adverse events were observed during the 24-wk follow-up. Four patients (16.7%) in the hUC-MSC group experienced transient fever, which occurred within 24 h after the second or third infusion; this did not occur in any patients in the placebo group. One patient from the hUC-MSC group experienced hypoglycemic attacks within 1 mo after transplantation. Significantly lower lymphocyte levels (weeks 2 and 3) and thrombin coagulation time (week 2) were observed in the hUC-MSC group compared to those in the placebo group (all P < 0.05). Significantly higher platelet levels (week 3), immunoglobulin levels (weeks 1, 2, 3, and 4), fibrinogen levels (weeks 2 and 3), D-dimer levels (weeks 1, 2, 3, 4, 12, and 24), and neutrophil-to-lymphocyte ratios (weeks 2 and 3) were observed in the hUC-MSC group compared to those in the placebo group (all P < 0.05). There were no significant differences between the two groups for tumor markers (alpha-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen 199) or blood fat. No liver damage or other side effects were observed on chest X-ray. CONCLUSION: Our study suggested that hUC-MSC transplantation has good tolerance and high safety in the treatment of T2DM. It can improve human immunity and inhibit lymphocytes. Coagulation function should be monitored vigilantly for abnormalities.

Development of a novel prediction model based on protein structure for identifying RPE65-associated inherited retinal disease (IRDs) of missense variants.

Purpose: This study aimed to develop a prediction model to classify RPE65-mediated inherited retinal disease (IRDs) based on protein secondary structure and to analyze phenotype-protein structure correlations of RPE65 missense variants in a Chinese cohort. Methods: Pathogenic or likely pathogenic missense variants of RPE65 were obtained from UniProt, ClinVar, and HGMD databases. The three-dimensional structure of RPE65 was retrieved from the Protein Data Bank (PDB) and modified with Pymol software. A novel prediction model was developed using LASSO regression and multivariate logistic regression to identify RPE65-associated IRDs. A total of 21 Chinese probands with RPE65 variants were collected to analyze phenotype-protein structure correlations of RPE65 missense variants. Results: The study found that both pathogenic and population missense variants were associated with structural features of RPE65. Pathogenic variants were linked to sheet, ß-sheet, strands, ß-hairpins, Fe2+ (iron center), and active site cavity, while population variants were related to helix, loop, helices, and helix-helix interactions. The novel prediction model showed accuracy and confidence in predicting the disease type of RPE65 variants (AUC = 0.7531). The study identified 25 missense variants in Chinese patients, accounting for 72.4% of total mutations. A significant correlation was observed between clinical characteristics of RPE65-associated IRDs and changes in amino acid type, specifically for missense variants of F8 (H68Y, P419S). Conclusion: The study developed a novel prediction model based on the protein structure of RPE65 and investigated phenotype-protein structure correlations of RPE65 missense variants in a Chinese cohort. The findings provide insights into the precise diagnosis of RPE65-mutated IRDs.

Potential clinical biomarkers in monitoring the severity of Hantaan virus infection.

Hantavirus, which causes hemorrhagic fever with renal syndrome (HFRS) is almost prevalent worldwide. While Hantaan virus (HTNV) causes the most severe form of HFRS with typical clinical manifestations of thrombocytopenia, increased vascular permeability, and acute kidney injury. Although the knowledge of the pathogenesis of HFRS is still limited, immune dysfunction and pathological damage caused by disorders of immune regulation are proposed to play a vital role in the development of the disorder, and the endothelium is considered to be the primary target of hantaviruses. Here, we reviewed the production and function of multiple molecules, mainly focusing on their role in immune response, endothelium, vascular permeability regulation, and platelet and coagulation activation which are closely related to the pathogenesis of HTNV infection. meanwhile, the relationship between these molecules and characteristics of HTNV infection including the hospital duration, immune dysfunction, thrombocytopenia, leukocytosis, and acute kidney injury are also presented, to provide a novel insight into the potential role of these molecules as monitoring markers for HTNV infection.