Identification of the central role of RNA polymerase mitochondrial for angiogenesis.

Mitochondria are central to endothelial cell activation and angiogenesis, with the RNA polymerase mitochondrial (POLRMT) serving as a key protein in regulating mitochondrial transcription and oxidative phosphorylation. In our study, we examined the impact of POLRMT on angiogenesis and found that its silencing or knockout (KO) in human umbilical vein endothelial cells (HUVECs) and other endothelial cells resulted in robust anti-angiogenic effects, impeding cell proliferation, migration, and capillary tube formation. Depletion of POLRMT led to impaired mitochondrial function, characterized by mitochondrial depolarization, oxidative stress, lipid oxidation, DNA damage, and reduced ATP production, along with significant apoptosis activation. Conversely, overexpressing POLRMT promoted angiogenic activity in the endothelial cells. In vivo experiments demonstrated that endothelial knockdown of POLRMT, by intravitreous injection of endothelial specific POLRMT shRNA adeno-associated virus, inhibited retinal angiogenesis. In addition, inhibiting POLRMT with a first-in-class inhibitor IMT1 exerted significant anti-angiogenic impact in vitro and in vivo. Significantly elevated expression of POLRMT was observed in the retinal tissues of streptozotocin-induced diabetic retinopathy (DR) mice. POLRMT endothelial knockdown inhibited pathological retinal angiogenesis and mitigated retinal ganglion cell (RGC) degeneration in DR mice. At last, POLRMT expression exhibited a substantial increase in the retinal proliferative membrane tissues of human DR patients. These findings collectively establish the indispensable role of POLRMT in angiogenesis, both in vitro and in vivo.

The Effect of Continuous Theta Burst Stimulation over the Right Dorsolateral Prefrontal Cortex on Cognitive Function and Emotional Regulation in Patients with Cerebral Small Vessel Disease.

OBJECTIVES: Cognitive impairment in cerebral small vessel disease (CSVD) is a common cause of vascular dementia and is often accompanied by mental disorders. The purpose of this study was to investigate the effect of continuous theta burst stimulation (cTBS) over the right dorsolateral prefrontal cortex (DLPFC) on the cognitive function and Hamilton depression (HAMD) scores in patients with CSVD. METHODS: A total of 30 CSVD patients who met the inclusion criteria were randomly assigned to either the sham or cTBS group. The patients in both groups received routine cognitive function training. All the patients were under treatment for 14 sessions, with one session per day (each cTBS conditioning session consisted of three-pulse bursts at 50 Hz repeated at 5 Hz, 80% MT, and 600 pulses). Before and after the treatment, the patients in both groups were evaluated using the Montreal Cognitive Assessment (MoCA), Stroop Color-Word Test (SCWT), Trail Marking Test (TMT), Digital Span Test (DST), and HAMD test. The time to complete the SCWT and TMT were recorded. The scores of the MoCA, DST and HAMD test were recorded. RESULTS: The HAMD scores in the cTBS group decreased significantly compared to the control (p < 0.05). There were no significant differences in the MoCA (including the MoCA subitems) or DST scores or in the SCWT or TMT completion times between the two groups (p > 0.05). For the HAMD scores and the MoCA subitem visuospatial/executive scores, the SCWT-B and SCWT-C completion times in the two groups both improved significantly before and after treatment (p < 0.05). For the MoCA scores, the DST-backward scores and the TMT-B completion times in the cTBS group improved significantly before and after treatment (p < 0.05). There was no significant difference in the SCWT-A, TMT-A completion times and MoCA subitems naming, attention, language, abstraction, delayed recall, and orientation scores either before or after treatment in the two groups or between the two groups (p > 0.05). CONCLUSIONS: In this study, cTBS over the right DLPFC decreased the HAMD scores significantly in patients with CSVD but had no significant improvement or impairment effects on cognitive function. cTBS over the right DLPFC could be used to treat CSVD patients with depression symptoms.

Consensus for criteria of running a pediatric inflammatory bowel disease center using a modified Delphi approach.

BACKGROUND: Good quality of care for inflammatory bowel disease (IBD) depends on high-standard management and facility in the IBD center. Yet, there are no clear measures or criteria for evaluating pediatric IBD (PIBD) center in China. The aim of this study was to develop a comprehensive set of quality indicators (QIs) for evaluating PIBD center in China. METHODS: A modified Delphi consensus-based approach was used to identify a set of QIs of structure, process, and outcomes for defining the criteria. The process included an exhaustive search using complementary approaches to identify potential QIs, and two web-based voting rounds to select the QIs defining the criteria for PIBD center. RESULTS: A total of 101 QIs (35 structures, 48 processes and 18 outcomes) were included in this consensus. Structure QIs focused on the composition of multidisciplinary team, facilities and services that PIBD center should provide. Process QIs highlight core requirements in diagnosing, evaluating, treating PIBD, and disease follow-up. Outcome QIs mainly included criteria evaluating effectiveness of various interventions in PIBD centers. CONCLUSION: The present Delphi consensus developed a set of main QIs that may be useful for managing a PIBD center. Video Abstract.

Spontaneous nystagmus with an upbeat component: Central or peripheral vestibular disorders?

Objective: To determine the topical diagnosis and etiologies of spontaneous nystagmus (SN) with an upbeat component. Methods: We retrospectively recruited 43 patients with SN with an upbeat component at a university hospital in China from 2020 to 2022. SN with an upbeat component was divided into pure upbeat nystagmus (UBN), SN with a predominant upbeat component, and SN with a non-predominant upbeat component. We analyzed their clinical and neurotologic findings and the final diagnosis. Results: Fourteen (32.6%) of them showed pure UBN, while 29 (67.4%) exhibited SN mixed with an upbeat component, mixed upbeat-horizontal in 15, mixed upbeat-horizontal-torsional in 13, and upbeat-torsional in the remaining one. Pure UBN and SN with a predominant upbeat component were more common in central than in peripheral vestibular disorders [16 (80.0%) vs. 0 (0%), Chi-Square test, p < 0.001]. Central vestibular disorders were diagnosed in 20 (46.5%) patients, peripheral in 14 (32.6%), and undetermined in nine (20.9%) patients. The underlying causes mainly included acute unilateral peripheral vestibulopathy (n = 11), posterior circulation infarction (n = 9), benign recurrent vertigo (n = 4), vestibular migraine (VM, n = 3), and VM of childhood (n = 2). Conclusion: SN with an upbeat component can be seen in both central and peripheral vestibular disorders. Pure UBN was a characteristic sign of central vestibular dysfunction. Central vestibular disorders should be highly suspected when patients show pure UBN or SN with a predominant upbeat component.

The relationship between severe extracranial artery stenosis or occlusion and cerebral small vessel disease in patients with large artery atherosclerotic cerebral infarction.

Background and purpose: Extracranial artery stenosis (ECAS) is associated with the presence of individual markers of cerebral small vessel disease (CSVD). Here, we investigated the relationship between severe extracranial artery stenosis or occlusion and CSVD in patients with large artery atherosclerotic (LAA) cerebral infarction. Methods: A total of 128 patients with LAA cerebral infarction who met our specific inclusion criteria were selected, including 92 males and 36 females. These patients were divided into three groups based on whether they had severe symptomatic extracranial arterial stenosis or occlusion, severe asymptomatic extracranial artery stenosis or occlusion, or severe extracranial artery stenosis or occlusion (both symptomatic and asymptomatic). Intra-group comparisons were then performed to examine whether there were any differences in the total CSVD scores and Fazekas scores. Results: Patients with severe extracranial arterial stenosis or occlusion and those with severe asymptomatic extracranial arterial stenosis or occlusion had a significantly higher total CSVD score (P < 0.05), but there were no significant differences between the groups in terms of Fazekas scores. Furthermore, there were no significant difference in the total CSVD scores and Fazekas scores when compared between patients with or without severe symptomatic extracranial arterial stenosis or occlusion. Conclusion: Severe stenosis or occlusion of the contralateral extracranial artery may increase the incidence of CSVD in patients with LAA cerebral infarction. Active and effective clinical intervention following comprehensive evaluation should be undertaken for unilateral cerebral infarction patients with severe stenosis or occlusion of the contralateral extracranial arterial.

Single-tube Multiplex Nested PCR System for Efficient Detection of Pathogenic Microorganisms in SPF Rodents.

PCR testing is increasingly important for microbial control in SPF facilities. However, most current PCR methods are timeconsuming and require compromise between high sensitivity and high multiplexing. We developed a one-tube multiplex nested PCR strategy (MN-PCR) for simultaneous direct (that is, without culturing) detection of multiple pathogens. We first aligned sequences for the 16S rDNA genes of selected target bacteria and a panel of closely related organisms. From these data, we designed a pair of universal primers and multiple sets of species-specific PCR primers to amplify the target sequences; the universal primers were modified to include various degenerate bases and locked nucleic acids. In a single tube, 16S rDNA sequences were amplified by using the nested PCR primers under high temperature (that is, above 65°C) during the first stage of the MN-PCR procedure, when the target-species-specific PCR primers do not support amplification due to their short length. In addition, the concentration of the nested PCR primers during the first stage was adjusted to ensure that they were consumed and did not yield visible bands themselves. During the second stage, the enriched 16S rDNA sequences then served as templates for amplification of the species-specific fragments by using the multiple PCR primers at low annealing temperatures (that is, below 60°C). The results showed that our MN-PCR method detected as little as 1 fg of target bacterial DNA in a 20-µL reaction volume, whereas conventional multiplex PCR detected a minimum of 1 pg only. Compared with traditional multiplex PCR assays, our MN-PCR system is an effective and efficient culture-free process.

Relationship Between Serum Concentration of Adrenomedullin and Myocardial Ischemic T Wave Changes in Patients With Lung Cancer.

Background: Patients with lung cancer are at increased risk for the development of cardiovascular diseases. Molecular markers for early diagnosis of cardiac ischemia are of great significance for the early prevention of cardiovascular events in patients with lung cancer. By evaluating the relationship between adrenomedullin (ADM) and myocardial ischemic T wave changes, the clinical value of circulating ADM as a predictor of myocardial ischemia in patients with lung cancer is confirmed. Methods: We enrolled patients with lung cancer and healthy people from 2019 to 2021 and extracted a detailed ECG parameter. After adjustment for potential confounders, logistic regression was used to assess the association of clinical data. We performed analyses on differences in T wave between patients with lung cancer and healthy people, and the relationship between T wave and ADM among patients with lung cancer. Receiver operator characteristic (ROC) curves were drawn to confirm the diagnostic value of biomarkers. Results: After adjusting for potential confounders, the incidence of T wave inversion or flattening in patients with lung cancer was higher than in healthy people (OR: 3.3228, P = 0.02). Also, further analysis of the data of lung cancer patients revealed that the ADM in lung cancer patients with T wave inversion or flat was higher than those with normal T wave (189.8 ± 51.9 vs. 131.9 ± 38.4, p < 0.001). The area under the ROC curve was 0.8137. Conclusion: Among the patients with lung cancer, serum ADM concentration is associated with the incidence of the abnormal T wave. ADM might be a potentially valuable predictor for heart ischemia in patients with lung cancer.

Efficacy on gait and posture control after botulinum toxin A injection for lower-limb spasticity treatment after stroke: A randomized controlled trial.

Objectives: To observe the efficacy of botulinum toxin type A (BoNT-A) for the spasticity of the lower-limb post-stroke on gait and posture control. Methods: A total of 46 patients with hemiplegia gait were randomly divided into the experimental group (23 patients) and the control group (23 patients). In patients in the experimental group received injections of BoNT-A by electrical stimulation-guided. At the same time, patients of the two groups received routine physical therapy. Gait analysis, plantar pressure analysis, lower-limb Fugl-Meyer assessment (L-FMA), 10 meter walking test (10MWT), timed "Up and Go" test (TUGT), and modified Ashworth Scale assess (MAS) of the lower limbs were performed at 0, 1, 4, and 12 weeks after treatment. Results: At 1, 4, and 12 weeks after treatment, the L-FMA, stride length, speed, and TUGT significantly improved than 0 week in both groups. The L-FMA and peak of forefoot pressure, and MAS results in the experimental group were better than those in the control group at 4 and 12 weeks. The TUGT, speed, and stride length in experimental group was significantly shortened than that in control group at 1, 4, and 12 weeks. Conclusion: Botulinum toxin type A injection can improve motor functions of the lower limb, gait, spasticity, forefoot pressure, and posture control of patients after stroke.

Whole-Exome Sequencing Identified a Novel Homozygous Frameshift Mutation of HPS3 in a Consanguineous Family with Hermansky-Pudlak Syndrome.

Hermansky-Pudlak syndrome (HPS) is a rare genetic disorder with an autosomal recessive inherited pattern. It is mainly characterized by deficiencies in lysosome-related organelles, such as melanosomes and platelet-dense granules, and leads to albinism, visual impairment, nystagmus, and bleeding diathesis. A small number of patients will present with granulomatous colitis or fatal pulmonary fibrosis. At present, mutations in ten known genetic loci (HPS1-11) have been identified to be the genetic cause of HPS. In this study, we enrolled a consanguineous family who presented with typical HPS phenotypes, such as albinism, visual impairment, nystagmus, and bleeding diathesis. Whole-exome sequencing and Sanger sequencing were applied to explore the genetic lesions of the patient. A novel homozygous frameshift mutation (NM_032383.5, c.1231dupG/p.Aps411GlyfsTer32) of HPS3 was identified and cosegregated in the family members. Furthermore, real-time PCR confirmed that the mutation decreased the expression of HPS3, which has been identified as the disease-causing gene of HPS type 3. According to ACMG guidelines, the novel mutation, resulting in a premature stop codon at amino acid 442, is a pathogenic variant. In summary, we identified a novel mutation (NM_032383.5, c.1231dupG/p.Aps411GlyfsTer32) of HPS3 in a family with HPS. Our study expanded the variant spectrum of the HPS3 gene and contributed to genetic counseling and prenatal genetic diagnosis of the family.

Effect of Cognitive Function on Balance and Posture Control after Stroke.

Hemiplegic gait is the most common sequela of stroke. Patients with hemiplegic gait are at a risk of falling because of poor balance. The theory of cognitive-motor networks paved the way for a new field of research. However, the mechanism of the relationship of cognition with gait or posture control networks is unclear because of the dynamic characteristics of walking and changing postures. To explore differences in the balance function and fall risk between patients with and without cognitive impairment after stroke, we utilized the Berg balance scale, Timed "Up and Go" test, and 10 m walking test. Patients were divided into two groups: the observation group (16 patients, female 6 and male 10), comprising patients with cognitive impairment after stroke, and the control group (16 patients, female 7 and male 9), comprising patients without cognitive impairment after stroke. We found that patients with cognitive impairment had worse balance function and a higher risk of falls. They needed a longer time to turn around or sit down. Our findings indicated that posture control in turning around and sitting down required more cognitive resources in daily life.