Aberrant cortical morphology patterns are associated with cognitive impairment in patients with chronic heart failure.

A mounting body of evidences suggests that patients with chronic heart failure (HF) frequently experience cognitive impairments, but the neuroanatomical mechanism underlying these impairments remains elusive. In this retrospective study, 49 chronic HF patients and 49 healthy controls (HCs) underwent brain structural MRI scans and cognitive assessments. Cortical morphology index (cortical thickness, complexity, sulcal depth and gyrification) were evaluated. Correlations between cortical morphology and cognitive scores and clinical variables were explored. Logistic regression analysis was employed to identify risk factors for predicting 3-year major adverse cardiovascular events. Compared with HCs, patients with chronic HF exhibited decreased cognitive scores (p < .001) and decreased cortical thickness, sulcal depth and gyrification in brain regions involved cognition, sensorimotor, autonomic nervous system (family-wise error correction, all p values <.05). Notably, HF duration and New York Heart Association (NYHA) demonstrated negative correlations with abnormal cortex morphology, particularly HF duration and thickness in left precentral gyrus (r = -.387, p = .006). Cortical morphology characteristics exhibited positive associations with global cognition, particularly cortical thickness in left pars opercularis (r = .476, p < .001). NYHA class is an independent risk factor for adverse outcome (p = .001). The observed correlation between abnormal cortical morphology and global cognition suggested that cortical morphology may serve as a promising imaging biomarker and provide insights into neuroanatomical underpinnings of cognitive impairment in patients with chronic HF.

Circulating extracellular choline acetyltransferase regulates inflammation.

BACKGROUND: Choline acetyltransferase (ChAT) is required for the biosynthesis of acetylcholine, the molecular mediator that inhibits cytokine production in the cholinergic anti-inflammatory pathway of the vagus nerve inflammatory reflex. Abundant work has established the biology of cytoplasmic ChAT in neurons, but much less is known about the potential presence and function of ChAT in the extracellular milieu. OBJECTIVES: We evaluated the hypothesis that extracellular ChAT activity responds to inflammation and serves to inhibit cytokine release and attenuate inflammation. METHODS: After developing novel methods for quantification of ChAT activity in plasma, we determined whether ChAT activity changes in response to inflammatory challenges. RESULTS: Active ChAT circulates within the plasma compartment of mice and responds to immunological perturbations. Following the administration of bacterial endotoxin, plasma ChAT activity increases for 12-48 h, a time period that coincides with declining tumor necrosis factor (TNF) levels. Further, a direct activation of the cholinergic anti-inflammatory pathway by vagus nerve stimulation significantly increases plasma ChAT activity, whereas the administration of bioactive recombinant ChAT (r-ChAT) inhibits endotoxin-stimulated TNF production and anti-ChAT antibodies exacerbate endotoxin-induced TNF levels, results of which suggest that ChAT activity regulates endogenous TNF production. Administration of r-ChAT significantly attenuates pro-inflammatory cytokine production and disease activity in the dextran sodium sulfate preclinical model of inflammatory bowel disease. Finally, plasma ChAT levels are also elevated in humans with sepsis, with the highest levels observed in a patient who succumbed to infection. CONCLUSION: As a group, these results support further investigation of ChAT as a counter-regulator of inflammation and potential therapeutic agent.

Phylogenomics and biogeographical diversification of Collabieae (Orchidaceae) and its implication in the reconstruction of the dynamic history of Asian evergreen broadleaved forests.

The tribe Collabieae (Epidendroideae, Orchidaceae) comprises approximately 500 species. Generic delimitation within Collabieae are confusing and phylogenetic interrelationships within the Collabieae have not been well resolved. Plastid genomes and nuclear internal transcribed spacer (ITS) sequences were used to estimate the phylogenetic relationships, ancestral ranges, and diversification rates of Collabieae. The results showed that Collabieae was subdivided into nine clades with high support. We proposed to combine Ancistrochilus and Pachystoma into Spathoglottis, merge Collabium and Chrysoglossum into Diglyphosa, and separate Pilophyllum and Hancockia as distinctive genera. The diversification of the nine clades of Collabieae might be associated with the uplift of the Himalayas during the Late Oligocene/Early Miocene. The enhanced East Asian summer monsoon in the Late Miocene may have promoted the rapid diversification of Collabieae at a sustained high diversification rate. The increased size of terrestrial pseudobulbs may be one of the drivers of Collabieae diversification. Our results suggest that the establishment and development of evergreen broadleaved forests facilitated the diversification of Collabieae.

Circuit-based neuromodulation enhances delayed recall in amnestic mild cognitive impairment.

BACKGROUND: This study aimed to investigate the efficacy of circuits-based paired associative stimulation (PAS) in adults with amnestic mild cognitive impairment (aMCI). METHODS: We conducted a parallel-group, randomised, controlled clinical trial. Initially, a cohort of healthy subjects was recruited to establish the cortical-hippocampal circuits by tracking white matter fibre connections using diffusion tensor imaging. Subsequently, patients diagnosed with aMCI, matched for age and education, were randomly allocated in a 1:1 ratio to undergo a 2-week intervention, either circuit-based PAS or sham PAS. Additionally, we explored the relationship between changes in cognitive performance and the functional connectivity (FC) of cortical-hippocampal circuits. RESULTS: FCs between hippocampus and precuneus and between hippocampus and superior frontal gyrus (orbital part) were most closely associated with the Auditory Verbal Learning Test (AVLT)_N5 score in 42 aMCI patients, thus designated as target circuits. The AVLT_N5 score improved from 2.43 (1.43) to 5.29 (1.98) in the circuit-based PAS group, compared with 2.52 (1.44) to 3.86 (2.39) in the sham PAS group (p=0.003; Cohen's d=0.97). A significant decrease was noted in FC between the left hippocampus and left precuneus in the circuit-based PAS group from baseline to postintervention (p=0.013). Using a generalised linear model, significant group×FC interaction effects for the improvements in AVLT_N5 scores were found within the circuit-based PAS group (B=3.4, p=0.017). CONCLUSIONS: Circuit-based PAS effectively enhances long-term delayed recall in adults diagnosed with aMCI, which includes individuals aged 50-80 years. This enhancement is potentially linked to the decreased functional connectivity between the left hippocampus and left precuneus. TRIAL REGISTRATION NUMBER: ChiCTR2100053315; Chinese Clinical Trial Registry.

Evolutionary history of the angiosperm flora of China.

High species diversity may result from recent rapid speciation in a 'cradle' and/or the gradual accumulation and preservation of species over time in a 'museum'. China harbours nearly 10% of angiosperm species worldwide and has long been considered as both a museum, owing to the presence of many species with hypothesized ancient origins, and a cradle, as many lineages have originated as recent topographic changes and climatic shifts-such as the formation of the Qinghai-Tibetan Plateau and the development of the monsoon-provided new habitats that promoted remarkable radiation. However, no detailed phylogenetic study has addressed when and how the major components of the Chinese angiosperm flora assembled to form the present-day vegetation. Here we investigate the spatio-temporal divergence patterns of the Chinese flora using a dated phylogeny of 92% of the angiosperm genera for the region, a nearly complete species-level tree comprising 26,978 species and detailed spatial distribution data. We found that 66% of the angiosperm genera in China did not originate until early in the Miocene epoch (23 million years ago (Mya)). The flora of eastern China bears a signature of older divergence (mean divergence times of 22.04-25.39 Mya), phylogenetic overdispersion (spatial co-occurrence of distant relatives) and higher phylogenetic diversity. In western China, the flora shows more recent divergence (mean divergence times of 15.29-18.86 Mya), pronounced phylogenetic clustering (co-occurrence of close relatives) and lower phylogenetic diversity. Analyses of species-level phylogenetic diversity using simulated branch lengths yielded results similar to genus-level patterns. Our analyses indicate that eastern China represents a floristic museum, and western China an evolutionary cradle, for herbaceous genera; eastern China has served as both a museum and a cradle for woody genera. These results identify areas of high species richness and phylogenetic diversity, and provide a foundation on which to build conservation efforts in China.

A novel nomogram to predict the recurrence of hepatocellular carcinoma after liver transplantation using extended selection criteria.

BACKGROUND: Liver transplantations (LTs) with extended criteria have produced surgical results comparable to those obtained with traditional standards. However, it is not sufficient to predict hepatocellular carcinoma (HCC) recurrence after LT according to morphological criteria alone. The present study aimed to construct a nomogram for predicting HCC recurrence after LT using extended selection criteria. METHODS: Retrospective data on patients with HCC, including pathology, serological markers and follow-up data, were collected from January 2015 to April 2020 at Huashan Hospital, Fudan University, Shanghai, China. Logistic least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analyses were performed to identify and construct the prognostic nomogram. Receiver operating characteristic (ROC) curves, Kaplan-Meier curves, decision curve analyses (DCAs), calibration diagrams, net reclassification indices (NRIs) and integrated discrimination improvement (IDI) values were used to assess the prognostic capacity of the nomogram. RESULTS: A total of 301 patients with HCC who underwent LT were enrolled in the study. The nomogram was constructed, and the ROC curve showed good performance in predicting survival in both the development set (2/3) and the validation set (1/3) (the area under the curve reached 0.748 and 0.716, respectively). According to the median value of the risk score, the patients were categorized into the high- and low-risk groups, which had significantly different recurrence-free survival (RFS) rates (P < 0.01). Compared with the Milan criteria and University of California San Francisco (UCSF) criteria, DCA revealed that the new nomogram model had the best net benefit in predicting 1-, 3- and 5-year RFS. The nomogram performed well for calibration, NRI and IDI improvement. CONCLUSIONS: The nomogram, based on the Milan criteria and serological markers, showed good accuracy in predicting the recurrence of HCC after LT using extended selection criteria.

Short-term postoperative bacteriobilia or fungibilia in liver transplantation patients with donation after circulatory death allografts associated with a longer hospital stay: A single-center retrospective observational study in China.

BACKGROUND: Normal bile is sterile. Studies have shown that cholangitis after liver transplantation (LT) was associated with a relatively poor prognosis. It remains unclear whether the bacteriobilia or fungibilia impact the patient outcomes in LT recipients, especially with donation after circulatory death (DCD) allografts, which was correlated with a higher risk of allograft failure. METHODS: This retrospective study included 139 LT recipients of DCD grafts from 2019 to 2021. All patients were divided into two groups according to the presence or absence of bacteriobilia or fungibilia. The prevalence and microbial spectrum of postoperative bacteriobilia or fungibilia and its possible association with outcomes, especially hospital stay were analyzed. RESULTS: Totally 135 and 171 organisms were isolated at weeks 1 and 2, respectively. Among all patients included in this analysis, 83 (59.7%) developed bacteriobilia or fungibilia within 2 weeks post-transplantation. The occurrence of bacteriobilia or fungibilia (ß = 7.43, 95% CI: 0.02 to 14.82, P = 0.049), particularly the detection of Pseudomonas (ß = 18.84, 95% CI: 6.51 to 31.07, P = 0.003) within 2 weeks post-transplantation was associated with a longer hospital stay. However, it did not affect the graft and patient survival. CONCLUSIONS: The occurrence of bacteriobilia or fungibilia, particularly Pseudomonas within 2 weeks post-transplantation, could influence the recovery of liver function and was associated with prolonged hospital stay but not the graft and patient survival.

Transient Receptor Potential Ankyrin-1-expressing vagus nerve fibers mediate IL-1ß induced hypothermia and reflex anti-inflammatory responses.

BACKGROUND: Inflammation, the physiological response to infection and injury, is coordinated by the immune and nervous systems. Interleukin-1ß (IL-1ß) and other cytokines produced during inflammatory responses activate sensory neurons (nociceptors) to mediate the onset of pain, sickness behavior, and metabolic responses. Although nociceptors expressing Transient Receptor Potential Ankyrin-1 (TRPA1) can initiate inflammation, comparatively little is known about the role of TRPA1 nociceptors in the physiological responses to specific cytokines. METHODS: To monitor body temperature in conscious and unrestrained mice, telemetry probes were implanted into peritoneal cavity of mice. Using transgenic and tissue specific knockouts and chemogenetic techniques, we recorded temperature responses to the potent pro-inflammatory cytokine IL-1ß. Using calcium imaging, whole cell patch clamping and whole nerve recordings, we investigated the role of TRPA1 during IL-1ß-mediated neuronal activation. Mouse models of acute endotoxemia and sepsis were used to elucidate how specific activation, with optogenetics and chemogenetics, or ablation of TRPA1 neurons can affect the outcomes of inflammatory insults. All statistical tests were performed with GraphPad Prism 9 software and for all analyses, P ≤ 0.05 was considered statistically significant. RESULTS: Here, we describe a previously unrecognized mechanism by which IL-1ß activates afferent vagus nerve fibers to trigger hypothermia, a response which is abolished by selective silencing of neuronal TRPA1. Afferent vagus nerve TRPA1 signaling also inhibits endotoxin-stimulated cytokine storm and significantly reduces the lethality of bacterial sepsis. CONCLUSION: Thus, IL-1ß activates TRPA1 vagus nerve signaling in the afferent arm of a reflex anti-inflammatory response which inhibits cytokine release, induces hypothermia, and reduces the mortality of infection. This discovery establishes that TRPA1, an ion channel known previously as a pro-inflammatory detector of cold, pain, itch, and a wide variety of noxious molecules, also plays a specific anti-inflammatory role via activating reflex anti-inflammatory activity.

The AGH score is a predictor of disease-free survival and targeted therapy efficacy after liver transplantation in patients with hepatocellular carcinoma.

BACKGROUND: Liver transplantation (LT) is the "cure" therapy for patients with hepatocellular carcinoma (HCC). However, some patients encounter HCC recurrence after LT. Unfortunately, there is no effective methods to identify the LT patients who have high risk of HCC recurrence and would benefit from adjuvant targeted therapy. The present study aimed to establish a scoring system to predict HCC recurrence of HCC patients after LT among the Chinese population, and to evaluate whether these patients are suitable for adjuvant targeted therapy. METHODS: Clinical data of HCC patients who underwent LT from March 2015 to June 2019 were retrospectively collected and analyzed. RESULTS: A total of 201 patients were included in the study. The multivariate Cox analysis suggested that preoperative alpha-fetoprotein (AFP) > 200 µg/L (HR = 2.666, 95% CI: 1.515-4.690; P = 0.001), glutamyl transferase (GGT) > 96 U/L (HR = 1.807, 95% CI: 1.012-3.224; P = 0.045), and exceeding the Hangzhou criteria (HR = 2.129, 95% CI: 1.158-3.914; P = 0.015) were independent risk factors for poor disease-free survival (DFS) in patients with HCC who underwent LT. We established an AFP-GGT-Hangzhou (AGH) scoring system based on these factors, and divided cases into high-, moderate-, and low-risk groups. The differences in overall survival (OS) and disease-free survival (DFS) rates among the three groups were significant (P < 0.05). The efficacy of the AGH scoring system to predict DFS was better than that of the Hangzhou criteria, UCSF criteria, Milan criteria, and TNM stage. Only in the high-risk group, we found that lenvatinib significantly improved prognosis compared with that of the control group (P < 0.05). CONCLUSIONS: The AGH scoring system provides a convenient and effective way to predict HCC recurrence after LT in HCC patients in China. Patients with a high-risk AGH score may benefit from lenvatinib adjuvant therapy after LT.

The effect of endoscopic ultrasound on the precise selection of endoscopic treatment for submucosal tumors in the upper gastrointestinal tract.

OBJECTIVE: To summarize and discuss the guiding role of endoscopic ultrasound (EUS) in selecting endoscopic treatments for submucosal tumors (SMTs) in the upper gastrointestinal tract. METHODS: A retrospective investigation was conducted on 156 SMT patients who received endoscopic resection guided by EUS in the endoscopy center of the Second Affiliated Hospital of Guangzhou University of Chinese Medicine from May 2019 to September 2021. Next, the size, pathological type, and distribution of lesions were analyzed; the correlation of the tumor origin with distribution of lesions and selection of treatments was explored; and the consistency of preoperative EUS diagnosis and postoperative pathological diagnosis was summarized and analyzed. RESULTS: The tumor diameters of the included SMT patients ranged from 0.3 to 4 cm, with a mean diameter of 0.95 cm; the lesions were mostly located in the esophagus, gastric fundus or fundic cardia and gastric body. As for the pathological types, liomyoma was the most common tumor in the esophagus, liomyoma and mesenchymoma were mainly located in the fundic cardia and gastric body, and heterotopic pancreas was mostly discovered in the gastric sinus. Among 38 esophageal SMT patients, some with lesions originating from muscularis mucosa and submucosa under EUS mainly underwent endoscopic submucosal dissection (ESD) and endoscope band ligation (EBL); while others with lesions originated from muscularis propria mainly received submucosal tunneling endoscopic resection (STER). Of 115 gastric SMT patients under EUS, some with lesion origins from the muscularis mucosa and submucosa mainly underwent endoscopic submucosal excavation (ESE), while others from muscularis propria mainly underwent ESE, ESD, and endoscopic full-thickness resection (EFTR). Besides, 3 duodenal SMT patients with lesion origins from submucosa and muscularis propria under EUS were given ESD and ESE, respectively. Additionally, 121 cases showed a consistency between the EUS diagnosis and the postoperative pathological nature, and the consistency rate was 84.6%. CONCLUSION: Clarifying the origin layer, size, growth pattern, and pathological nature of the lesion through preoperative EUS can guide the precise selection of endoscopic treatments, thereby ensuring a safe, effective, and complete surgical outcomes and reducing complications.

IVM of human immature oocytes for infertility treatment and fertility preservation.

Background: Thousands of healthy babies are born from in vitro maturation (IVM) procedures, but the rate of efficiency differs with the source of immature oocytes obtained. Recently, there are different IVM protocols proposed for infertility treatment and fertility preservation. Methods: Based on the literature, the clinical application for IVM of immature oocytes was summarized. Main findings Results: Immature oocytes may be retrieved from women after priming with or without the use of follicular stimulation hormone (FSH), human chorionic gonadotrophin (hCG) or a combination of both FSH and hCG. Successful pregnancy rates with IVM technology seem to be correlated with the number of immature oocytes obtained. With the source and culture course of immature oocytes, there are various IVM protocols. IVM of immature oocytes is profoundly affected by the culture conditions, but no breakthrough has been made by improving the IVM medium itself. Thus, the clinical application of IVM technology continues to evolve. Conclusion: IVM technology is a useful technique for infertile women and fertility preservation. Mild stimulation IVF combined with IVM of immature oocytes is a viable alternative to the conventional stimulation IVF cycle treatment as it may prove to be an optimal first-line treatment approach.

Influence of diabetes mellitus on the diagnostic performance of machine learning-based coronary CT angiography-derived fractional flow reserve: a multicenter study.

OBJECTIVES: To examine the diagnostic accuracy of machine learning-based coronary CT angiography-derived fractional flow reserve (FFRCT) in diabetes mellitus (DM) patients. METHODS: In total, 484 patients with suspected or known coronary artery disease from 11 Chinese medical centers were retrospectively analyzed. All patients underwent CCTA, FFRCT, and invasive FFR. The patients were further grouped into mild (25~49 %), moderate (50~69 %), and severe (≥ 70 %) according to CCTA stenosis degree and Agatston score < 400 and Agatston score ≥ 400 groups according to coronary artery calcium severity. Propensity score matching (PSM) was used to match DM (n  = 112) and non-DM (n  = 214) groups. Sensitivity, specificity, accuracy, and area under the curve (AUC) with 95 % confidence interval (CI) were calculated and compared. RESULTS: Sensitivity, specificity, accuracy, and AUC of FFRCT were 0.79, 0.96, 0.87, and 0.91 in DM patients and 0.82, 0.93, 0.89, and 0.89 in non-DM patients without significant difference (all p > 0.05) on a per-patient level. The accuracies of FFRCT had no significant difference among different coronary stenosis subgroups and between two coronary calcium subgroups (all p > 0.05) in the DM and non-DM groups. After PSM grouping, the accuracies of FFRCT were 0.88 in the DM group and 0.87 in the non-DM group without a statistical difference (p > 0.05). CONCLUSIONS: DM has no negative impact on the diagnostic accuracy of machine learning-based FFRCT. KEY POINTS: • ML-based FFRCT has a high discriminative accuracy of hemodynamic ischemia, which is not affected by DM. • FFRCT was superior to the CCTA alone for the detection of ischemia relevance of coronary artery stenosis in both DM and non-DM patients. • Coronary calcification had no significant effect on the diagnostic accuracy of FFRCT to detect ischemia in DM patients.

Transcriptomic analysis reveals process of autolysis of Kluyveromyces marxianus in vacuum negative pressure and the higher temperature.

Kluyveromyces marxianus is expected to be used in the production of yeast extracts due to its good fermentation ability and nutritional properties. Yeast autolysis is a key process to produce yeast extract and vacuum negative pressure stress can be used as an effective way to assist autolysis. However, the molecular mechanism of initiating Kluyveromyces marxianus autolysis induced by vacuum negative pressure and the higher temperature is still unclear. In this study, RNA-seq technology was performed mainly to analyze autolytic processes in Kluyveromyces marxianus strains. Considerable differentially expressed genes (DEGs) of downregulation were significantly enriched in 7 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to synthesis and transport of RNA and ribosome, which indicated that abnormal protein translations had already occurred in autolytic process. Interestingly, due to obvious change of related DEGs, endoplasmic reticulum-associated degradation (ERAD) and autophagy were activated and cell wall integrity pathway was hindered. Under the continuous influence of the external stress environment, the long-term changes of the above pathways triggered a vicious circle of gradual damage to yeast cells, which is the main cause of yeast autolysis. These results may provide important clues for the in-depth interpretation of the yeast autolytic mechanism.

Functional CAD-RADS using FFRCT on therapeutic management and prognosis in patients with coronary artery disease.

OBJECTIVES: To propose a novel functional Coronary Artery Disease-Reporting and Data System (CAD-RADS) category system integrated with coronary CT angiography (CCTA)-derived fractional flow reserve (FFRCT) and to validate its effect on therapeutic decision and prognosis in patients with coronary artery disease (CAD). METHODS: Firstly, we proposed a novel functional CAD-RADS and evaluated the performance of functional CAD-RADS for guiding treatment strategies with actual clinical treatment as a reference standard in a retrospective multicenter cohort with CCTA and invasive FFR performed in all patients (n = 466). Net reclassification improvement (NRI) of functional CAD-RADS over anatomical CAD-RADS was calculated. Secondly, the prognostic value of functional CAD-RADS in a prospective two-arm cohort (566 [FFRCT arm] vs. 567 [CCTA arm]) was calculated, after a 1-year follow-up, functional CAD-RADS in FFRCT arm (n = 513) and anatomical CAD-RADS in CCTA arm (n = 511) to determine patients at risk of adverse outcomes were compared with a Cox hazard proportional model. RESULTS: Functional CAD-RADS demonstrated superior value over anatomical CAD-RADS (AUC: 0.828 vs. 0.681, p < 0.001) and comparable performance to FFR (AUC: 0.828 vs. 0.848, p = 0.253) in guiding therapeutic decisions. Functional CAD-RADS resulted in the revision of management plan as determined by anatomical CAD-RADS in 30.0% of patients (n = 140) (NRI = 0.369, p < 0.001). Functional CAD-RADS was an independent predictor for 1-year outcomes with indexes of concordance of 0.795 and the corresponding value was 0.751 in anatomical CAD-RADS. CONCLUSION: The novel functional CAD-RADS gained incremental value in guiding therapeutic decision-making compared with anatomical CAD-RADS and comparable power in 1-year prognosis with anatomical CAD-RADS in a real-world scenario. KEY POINTS: • The novel functional CAD-RADS category system with FFRCT integrated into the anatomical CAD-RADS categories was originally proposed. • The novel functional CAD-RADS category system was validated superior value over anatomical CAD-RADS (AUC: 0.828 vs. 0.681, p < 0.001) in guiding therapeutic decisions and revised management plan in 30.0% of patients as determined by anatomical CAD-RADS (net reclassification improvement index = 0.369, p < 0.001). • Functional CAD-RADS was an independent predictor with an index of concordance of 0.795 and 0.751 in anatomical CAD-RADS for 1-year prognosis of adverse outcomes.

Meta-analysis of clinical trials focusing on hypertonic dextrose prolotherapy (HDP) for knee osteoarthritis.

Hypertonic dextrose prolotherapy (HDP) is an injection of a concentrated dextrose solution for the purpose of local treatment of musculoskeletal pain and possible enhancement of repair mechanisms. This systematic review and meta-analysis examines the clinical utility of HDP injection for treatment of knee osteoarthritis (OA). Randomized controlled trials (RCTs) utilizing HDP to treat knee OA were retrieved from MEDLINE, EMBASE, and Cochrane Library (CENTRAL). Identification and inclusion of RCTs utilizing intra-articular and extra-articular administration of HDP vs administration of other injectate or physical therapy as control for knee OA were included. Primary clinical outcomes were changes in knee WOMAC, pain and function score. Secondary outcomes were adverse events related to HDP. For continuous outcomes with same or different measurements, we calculated, respectively the weighted mean difference (WMD) or the standardized mean difference (SMD), respectively. Results were pooled using DerSimonian and Laird random effect models across the included studies and heterogeneity between studies was estimated using the I2 index. Five studies comprising a total of 319 treated patients met inclusion criteria and were included in the final analysis. At a mean of 22.8 weeks follow-up, HDP treatment significantly improved total WOMAC score (WMD = 13.77, 95% CI: 6.75-20.78; p < 0.001; I2 = 90%), pain (SMD = 1.33, 95% CI: 0.49-2.17; p < 0.001; I2 = 91%) and knee function (SMD = 1.30, 95% CI: 0.45-2.14; p < 0.001; I2 = 91%) compared with control group. There were no severe adverse events related to dextrose injection reported in all the included studies. HDP is a promising treatment for knee OA with a reasonable safety profile. Further research in mechanism of HDP activity and long-term follow-up study will be needed for exploring this novel therapy modality.

Systemic administration of choline acetyltransferase decreases blood pressure in murine hypertension.

Acetylcholine (ACh) decreases blood pressure by stimulating endothelium nitric oxide-dependent vasodilation in resistance arterioles. Normal plasma contains choline acetyltransferase (ChAT) and its biosynthetic product ACh at appreciable concentrations to potentially act upon the endothelium to affect blood pressure. Recently we discovered a T-cell subset expressing ChAT (TChAT), whereby genetic ablation of ChAT in these cells produces hypertension, indicating that production of ACh by TChAT regulates blood pressure. Accordingly, we reasoned that increasing systemic ChAT concentrations might induce vasodilation and reduce blood pressure. To evaluate this possibility, recombinant ChAT was administered intraperitoneally to mice having angiotensin II-induced hypertension. This intervention significantly and dose-dependently decreased mean arterial pressure. ChAT-mediated attenuation of blood pressure was reversed by administration of the nitric oxide synthesis blocker L-nitro arginine methyl ester, indicating ChAT administration decreases blood pressure by stimulating nitic oxide dependent vasodilation, consistent with an effect of ACh on the endothelium. To prolong the half life of circulating ChAT, the molecule was modified by covalently attaching repeating units of polyethylene glycol (PEG), resulting in enzymatically active PEG-ChAT. Administration of PEG-ChAT to hypertensive mice decreased mean arterial pressure with a longer response duration when compared to ChAT. Together these findings suggest further studies are warranted on the role of ChAT in hypertension.

The effect of coronary calcification on diagnostic performance of machine learning-based CT-FFR: a Chinese multicenter study.

OBJECTIVE: To investigate the effect of coronary calcification morphology and severity on the diagnostic performance of machine learning (ML)-based coronary CT angiography (CCTA)-derived fractional flow reserve (CT-FFR) with FFR as a reference standard. METHODS: A total of 442 patients (61.2 ± 9.1 years, 70% men) with 544 vessels who underwent CCTA, ML-based CT-FFR, and invasive FFR from China multicenter CT-FFR study were enrolled. The effect of calcification arc, calcification remodeling index (CRI), and Agatston score (AS) on the diagnostic performance of CT-FFR was investigated. CT-FFR ≤ 0.80 and lumen reduction ≥ 50% determined by CCTA were identified as vessel-specific ischemia with invasive FFR as a reference standard. RESULTS: Compared with invasive FFR, ML-based CT-FFR yielded an overall sensitivity of 0.84, specificity of 0.94, and accuracy of 0.90 in a total of 344 calcification lesions. There was no statistical difference in diagnostic accuracy, sensitivity, or specificity of CT-FFR across different calcification arc, CRI, or AS levels. CT-FFR exhibited improved discrimination of ischemia compared with CCTA alone in lesions with mild-to-moderate calcification (AUC, 0.89 vs. 0.69, p < 0.001) and lesions with CRI ≥ 1 (AUC, 0.89 vs. 0.71, p < 0.001). The diagnostic accuracy and specificity of CT-FFR were higher than CCTA alone in patients and vessels with mid (100 to 299) or high (≥ 300) AS. CONCLUSION: Coronary calcification morphology and severity did not influence diagnostic performance of CT-FFR in ischemia detection, and CT-FFR showed marked improved discrimination of ischemia compared with CCTA alone in the setting of calcification. KEY POINTS: • CT-FFR provides superior diagnostic performance than CCTA alone regardless of coronary calcification. • No significant differences in the diagnostic performance of CT-FFR were observed in coronary arteries with different coronary calcification arcs and calcified remodeling indexes. • No significant differences in the diagnostic accuracy of CT-FFR were observed in coronary arteries with different coronary calcification score levels.

Impact of obstructive sleep apnea complicated with type 2 diabetes on long-term cardiovascular risks and all-cause mortality in elderly patients.

BACKGROUND: The prognostic significance of obstructive sleep apnea (OSA) in elderly patients with type 2 diabetes is unclear. The aim of this study was to determine the risk of cardiovascular disease (CVD) and mortality in elderly patients with OSA complicated with type 2 diabetes compared to patients with OSA without type 2 diabetes. METHODS: From January 2015 to October 2017, 1113 eligible elderly patients with OSA, no history of cardiovascular, ≥60 years of age, and complete follow-up records were enrolled in this consecutive multicentre prospective cohort study. All patients had completed polysomnography (PSG) examinations. An apnoea-hypopnoea index of ≥5 events per hour recorded by polysomnography was defined as the diagnostic criterion for OSA. We collected baseline demographics, clinical characteristics, sleep parameters and follow-up outcomes. The primary aim of this study was to identify the risk of incident major adverse cardiovascular events (MACE). Secondary outcomes were all-cause mortality, components of MACE and a composite of all events. Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate whether type 2 diabetes was associated with incident events. RESULTS: A total of 266 (23.9%) patients had OSA complicated with type 2 diabetes. MACE occurred in 97 patients during the median 42-month follow-up. Kaplan-Meier survival curves indicated a significant relationship between type 2 diabetes and MACE (log-rank P = 0.003). Multivariable Cox regression analysis showed that type 2 diabetes increased the risk of MACE (HR = 1.64, 95% CI:1.08-2.47, P = 0.019), hospitalisation for unstable angina (HR = 2.11, 95% CI:1.23-3.64, P = 0.007) and a composite of all events in elderly patients with OSA (HR = 1.70, 95% CI:1.17-2.49, P = 0.007). However, there were no significant differences in the incidence of cardiovascular death, all-cause mortality, MI and hospitalisation for heart failure between patients with and without diabetes (P > 0.05). The subgroup analysis demonstrated that females (AHR = 2.46, 95% CI:1.17-5.19, P = 0.018), ≥ 70 years (AHR = 1.95, 95% CI:1.08-3.52, P = 0.027), overweight and obese (AHR = 2.04, 95% CI:1.29-3.33, P = 0.002) with mild OSA (AHR = 2.42, 95% CI: 1.03-5.71, P = 0.044) were at a higher risk for MACE by diabetes. CONCLUSION: OSA and type 2 diabetes are interrelated and synergistic with MACE, hospitalisation for unstable angina and a composite of all events development. Overweight and obese females, ≥ 70 years with mild OSA combined with type 2 diabetes presented a significantly high MACE risk.

Diabetes mellitus is a risk factor of acute kidney injury in liver transplantation patients.

BACKGROUND: Diabetes mellitus has become an increasing global health burden with rapid growing prevalence. Patients with diabetes have higher susceptibility to acute kidney injury (AKI). Liver transplantation (LT) predisposes the kidney to injury. However, the association between diabetes and AKI in LT patients remains unclear. METHODS: We conducted a retrospective cohort study examining risk factors for AKI in patients undergone orthotopic LT. Potential risk factors including baseline estimated glomerular filtration rate (eGFR), the model for end-stage liver disease (MELD) score, diabetes, hypertension and intraoperative blood loss were screened. The primary endpoint was AKI occurrence. Multivariate logistic regression was used to analyze the association between potential risk factors and AKI. RESULTS: A total of 291 patients undergone orthotopic LT were included in the present study. Among them, 102 patients (35.05%) developed AKI within 5 days after LT. Diabetes was identified as an independent risk factor for AKI. Patients who developed AKI had worse graft function recovery and higher mortality within 14 days after LT compared to those who did not develop AKI. AKI patients with diabetes had a significant decline of eGFR within the first postoperative year, compared with patients who did not develop AKI and who developed AKI but without diabetes. CONCLUSIONS: Diabetes is an independent risk factor for AKI after orthotopic LT. AKI is associated with delayed graft function recovery and higher mortality in short-term postoperative period. Diabetic patients who developed AKI after LT experience a faster decline of eGFR within the first year after surgery.

The application of virtual segmentectomy based on three-dimensional computed tomography and angiography in thoracoscopic segmentectomy for children and infants.

OBJECTIVES: The purpose of this retrospective study was to evaluate the efficacy of anatomic thoracoscopic pulmonary segmentectomy performed based on three-dimensional computed tomography bronchography and angiography (3D-CTBA) in children and infants. METHODS: Totally, 22 patients received thoracoscopic segmentectomy from October 2019 to February 2020. The procedures were performed virtual segmentectomy based on 3D-CTBA. The preoperative planning depended on the 3D-CTBA result. RESULTS: All of the 22 cases ( 1 left S1, 1 right S3, 1 left S1 + 2, 1 left S1 + 2 + 3, 1 left S4 + 5, 1 right S6, 1 right S10, 1 left S10, 2 right S9 + 10, 3 left S9 + 10, 1 right S7 + 8 + 9 + 10, 8 left S7 + 8 + 9 + 10) were received thoracoscopic segmentectomy successfully. The mean procedure length was 76.6 ± 17.2 min, and the intraoperative blood loss was 16.5 ± 2.8 ml. The mean duration of chest tube insertion was 3.2 ± 0.7 days, and the mean hospital stay was 8.2 ± 2.8 days. Postoperative complications included infection (n = 1), atelectasis (n = 1), hydropneumothorax (n = 1) and pneumothorax (n = 1). No recurrence or mortality was observed during the short-term follow-up period of 3 months. CONCLUSIONS: Based on the 3D-CTBA technique, the specific pulmonary segments invaded by the lesions and the relationship between the corresponding pulmonary vessels and bronchi can be acknowledged before the operation, which is of positive significance for the resection of complex pulmonary segments and good preoperative surgical planning. It's worth popularizing in the pediatric population.