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Introduction: Underimmunization of CHD children is a public health concern in China. This study aimed to analyze the vaccination status of CHD children to provide additional evidence on optimal vaccination strategies and to make suggestions to promote appropriate vaccination services for these children., Methods: This cross-sectional study evaluated 155 CHD children who received at least one vaccine at Peking University First Hospital. Vaccine-specific immunization rates were calculated. A telephone questionnaire survey was conducted that covered the following: the prognosis, reasons for delayed vaccinations and getting vaccination in the hospital. All statistical analyses were performed using the SPSS version 22 software., Results: The left-to-right shunt group involved 138 children, while the other type CHD group involved 17. The vaccination rate was the highest for MPSV-AC (87.1%) and the lowest for DTaP (40.1%). The most frequent reason for vaccination in the hospital was refusal from community health centers (61.5%). No participant reported vaccine-related adverse effects., Conclusions: The age-appropriate vaccine-specific immunization rates in CHD children are low, with the lowest for DTaP. Refusal of community health centers was the primary reason. Our findings support that clinically stable CHD children may be safely vaccinated on a schedule similar to that of ordinary children in China., Impact: From our investigation, we found that the age-appropriate vaccine-specific immunization rates in children with CHD in China are low, with the lowest for diphtheria and tetanus toxoid and acellular pertussis. Refusal of community health centers to vaccinate was the primary reason for the low rates. We believe our study provides additional evidence on optimal vaccination strategies for children with CHD and it can be used to develop strategies to promote appropriate vaccination services for these children., (© 2022. The Author(s).)

Objective: To analyze the disease spectrums underlying orthostatic intolerance (OI) and sitting intolerance (SI) in Chinese children, and to understand the clinical empirical treatment options., Methods: The medical records including history, physical examination, laboratory examination, and imagological examination of children were retrospectively studied in Peking University First Hospital from 2012 to 2021. All the children who met the diagnostic criteria of OI and SI were enrolled in the study. The disease spectrums underlying OI and SI and treatment options during the last 10 years were analyzed., Results: A total of 2 110 cases of OI and SI patients were collected in the last 10 years, including 943 males (44.69%) and 1 167 females (55.31%) aged 4－18 years, with an average of (11.34±2.84) years. The overall case number was in an increasing trend over the year. In the OI spectrum, postural tachycardia syndrome (POTS) accounted for 826 cases (39.15%), followed by vasovagal syncope (VVS) (634 cases, 30.05%). The highest proportion of SI spectrum was sitting tachycardia (STS) (8 cases, 0.38%), followed by sitting hypertension (SHT) (2 cases, 0.09%). The most common comorbidity of OI and SI was POTS coexisting with STS (36 cases, 1.71%). The highest proportion of treatment options was autonomic nerve function exercise (757 cases, 35.88%), followed by oral rehydration salts (ORS) (687 cases, 32.56%), metoprolol (307 cases, 14.55%), midodrine (142 cases, 6.73%), ORS plus metoprolol (138 cases, 6.54%), and ORS plus midodrine (79 cases, 3.74%). The patients with POTS coexisting with VVS were more likely to receive pharmacological intervention than the patients with POTS and the patients with VVS (41.95% vs. 30.51% vs . 28.08%, χ 2 = 20.319, P < 0.01), but there was no significant difference in the proportion of treatment options between the patients with POTS and the patients with VVS., Conclusion: POTS and VVS in children are the main underlying diseases of OI, while SI is a new disease discovered recently. The number of children with OI and SI showed an increasing trend. The main treatment methods are autonomic nerve function exercise and ORS. Children with VVS coexisting with POTS were more likely to take pharmacological treatments than those with VVS or POTS only.

Nerve injury-induced chronic pain has been an urgent problem for both public health and clinical practice. While transition to chronic pain is not an inevitable consequence of nerve injuries, the susceptibility/resilience factors and mechanisms for chronic neuropathic pain after nerve injuries still remain unknown. Current preclinical and clinical studies, with certain notable limitations, have shown that major histocompatibility complex class II-restricted T helper (Th) cells is an important trigger for nerve injury-induced chronic tactile allodynia, one of the most prevalent and intractable clinical symptoms of neuropathic pain. Moreover, the precise pathogenic neuroimmune interfaces for Th cells remain controversial, not to mention the detailed pathogenic mechanisms. In this review, depending on the biology of Th cells in a neuroimmunological perspective, we summarize what is currently known about Th cells as a trigger for chronic tactile allodynia after nerve injuries, with a focus on identifying what inconsistencies are evident. Then, we discuss how an interdisciplinary perspective would improve the understanding of Th cells as a trigger for chronic tactile allodynia after nerve injuries. Finally, we hope that the expected new findings in the near future would translate into new therapeutic strategies via targeting Th cells in the context of precision medicine to either prevent or reverse chronic neuropathic tactile allodynia.

Background: Vasovagal syncope (VVS) is common in children and greatly affect both physical and mental health. But the mechanisms have not been completely explained. This study was designed to analyze the gut microbiota in children with VVS and explore its clinical significance., Methods: Fecal samples from 20 VVS children and 20 matched controls were collected, and the microbiota were analyzed by 16S rRNA gene sequencing. The diversity and microbiota compositions of the VVS cases and controls were compared with the independent sample t test or Mann-Whitney U test. The correlation between the predominant bacteria and clinical symptoms was analyzed using Pearson or Spearman correlation test., Results: No significant differences in diversity were evident between VVS and controls (P > 0.05). At the family level, the relative abundance of Ruminococcaceae was significantly higher in VVS children than in controls (median [Q1, Q3]: 22.10% [16.89%, 27.36%] vs. 13.92% [10.31%, 20.18%], Z = -2.40, P < 0.05), and LEfSe analysis revealed Ruminococcaceae as a discriminative feature (linear discriminant analysis [LDA] score > 4, P < 0.05). The relative abundance of Ruminococcaceae in VVS patients was positively correlated with the frequency of syncope (r = 0.616, P < 0.01). In terms of its correlation with hemodynamics, we showed that relative abundance of Ruminococcaceae was negatively correlated with the systolic and diastolic pressure reduction at the positive response in head-up tilt test (HUTT; r = -0.489 and -0.448, all P < 0.05), but was positively correlated with the mean pressure drop and decline rate (r = 0.489 and 0.467, all P < 0.05) as well as diastolic pressure drop and decline rate at the HUTT positive response (r = 0.579 and 0.589, all P < 0.01) in VVS patients., Conclusion: Ruminococcaceae was the predominant gut bacteria and was associated with the clinical symptoms and hemodynamics of VVS, suggesting that gut microbiota might be involved in the development of VVS.

Background: Antigen-specific and MHCII-restricted CD4+ αβ T cells have been shown or suggested to play an important role in the transition from acute to chronic mechanical allodynia after peripheral nerve injuries. However, it is still largely unknown where these T cells infiltrate along the somatosensory pathways transmitting mechanical allodynia to initiate the development of chronic mechanical allodynia after nerve injuries. Therefore, the purpose of this study was to ascertain the definite neuroimmune interface for these T cells to initiate the development of chronic mechanical allodynia after peripheral nerve injuries., Methods: First, we utilized both chromogenic and fluorescent immunohistochemistry (IHC) to map αβ T cells along the somatosensory pathways for the transmission of mechanical allodynia after modified spared nerve injuries (mSNIs), i.e., tibial nerve injuries, in adult male Sprague-Dawley rats. We further characterized the molecular identity of these αβ T cells selectively infiltrating into the leptomeninges of L4 dorsal roots (DRs). Second, we identified the specific origins in lumbar lymph nodes (LLNs) for CD4+ αβ T cells selectively present in the leptomeninges of L4 DRs by two experiments: (1) chromogenic IHC in these lymph nodes for CD4+ αβ T cell responses after mSNIs and (2) fluorescent IHC for temporal dynamics of CD4+ αβ T cell infiltration into the L4 DR leptomeninges after mSNIs in prior lymphadenectomized or sham-operated animals to LLNs. Finally, following mSNIs, we evaluated the effects of region-specific targeting of these T cells through prior lymphadenectomy to LLNs and chronic intrathecal application of the suppressive anti-αβTCR antibodies on the development of mechanical allodynia by von Frey hair test and spinal glial or neuronal activation by fluorescent IHC., Results: Our results showed that during the sub-acute phase after mSNIs, αβ T cells selectively infiltrate into the leptomeninges of the lumbar DRs along the somatosensory pathways responsible for transmitting mechanical allodynia. Almost all these αβ T cells are CD4 positive. Moreover, the temporal dynamics of CD4+ αβ T cell infiltration into the lumbar DR leptomeninges are specifically determined by LLNs after mSNIs. Prior lymphadenectomy to LLNs specifically reduces the development of mSNI-induced chronic mechanical allodynia. More importantly, intrathecal application of the suppressive anti-αβTCR antibodies reduces the development of mSNI-induced chronic mechanical allodynia. In addition, prior lymphadenectomy to LLNs attenuates mSNI-induced spinal activation of glial cells and PKCγ + excitatory interneurons., Conclusions: The noteworthy results here provide the first evidence that CD4+ αβ T cells selectively infiltrate into the DR leptomeninges of the somatosensory pathways transmitting mechanical allodynia and contribute to the transition from acute to chronic mechanical allodynia after peripheral nerve injuries.

Fluorescent immunolabeling and imaging in free-floating thick (50-60 μm) tissue sections is relatively simple in practice and enables design-based non-biased stereology, or 3-D reconstruction and analysis. This method is widely used for 3-D in situ quantitative biology in many areas of biological research. However, the labeling quality and efficiency of standard protocols for fluorescent immunolabeling of these tissue sections are not always satisfactory. Here, we systematically evaluate the effects of raising the conventional antibody incubation temperatures (4°C or 21°C) to mammalian body temperature (37°C) in these protocols. Our modification significantly enhances the quality (labeling sensitivity, specificity, and homogeneity) and efficiency (antibody concentration and antibody incubation duration) of fluorescent immunolabeling of free-floating thick tissue sections.

A single nucleotide polymorphism of MYC rs9642880 (G>T) at the 8q24.1 locus is thought to be associated with bladder cancer risk based on the results of genome-wide association studies, but the results remain inconclusive. To assess the association between rs9642880[T] allele and bladder cancer risk, we performed this meta-analysis including 18 case-control studies and involving 23,084 cases and 97,164 controls. Electronic searches for publications were conducted to determine the association between this variant and prostate cancer in several databases. The last search update was August 4, 2014. We used odds ratios and 95%CIs to evaluate the strength of the associations. The overall results suggested that the rs9642880[T] allele was associated with bladder cancer susceptibility (T vs G, odds ratio = 1.18, 95%CI = 1.14-1.22). In subgroup analysis by ethnicity and source of controls, the risk remained significant. The present meta-analysis suggests that the MYC rs9642880[T] allele is significantly associated with bladder cancer risk.

Genome-wide studies have reported an association between the HNF1B rs4430796 (A>G) polymorphism and prostate cancer risk, but results have been inconsistent and recent meta-analyses have been inadequate. This study aimed to integrate previous results and explore the validity of this association. Electronic searches for all relevant publications through May 18, 2014, were conducted across several databases. Additional studies were identified manually, and only the most recent or complete were used in this meta-analysis. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. Seven eligible case-control studies were identified, incorporating a total of 14,049 patients and 12,674 controls. Overall, we found that the rs4430796 (A>G) polymorphism had a decreased risk of prostate cancer (GG vs AA: OR = 0.661, 95%CI = 0.615-0.710, P = 0.304; AG vs AA: OR = 0.782, 95%CI = 0.739-0.828, P = 0.435; dominant model: OR = 0.743, 95%CI = 0.704-0.784, P = 0.912; recessive model: OR = 0.764, 95%CI = 0.718-0.813, P = 0.01). Furthermore, in the stratified analysis, there were significantly decreased risks among studies with population- and hospital-based controls. In the subgroup analysis by ethnicity, significantly decreased risks were also found among Caucasians, Americans, and Asians. Our results suggested that the HNF1B rs4430796 (A>G) polymorphism decreased the risk of prostate cancer. In the future, additional and larger studies on patients from across of the world might be required to validate our findings.

Background Aims: The neuroprotective effects of olfactory ensheathing cells (OECs) after transplantation have largely been known in the injured nervous system. However, the underlying mechanisms still must be further elucidated. We explored the effects of OEC transplantation on the recovery of neurophysiologic function and the related anti-apoptosis mechanism in acute traumatic brain injury., Methods: The OECs from neonatal Sprague-Dawley rats were isolated, identified and labeled and then were immediately transplanted into the regions surrounding the injured brain site that is resulted from free-weight drop injury., Results: Nerve growth factor and it's recepor, p75 was expressed in cultured OECs. Transplanted OECs survived, migrated around the injury site and significantly improved the neurological severe scores compared with the control group (P < 0.05). OEC transplantation significantly increased the number of GAP-43-immunopositive fibers and synaptophysin-positive vesicles (P < 0.05) but significantly decreased the number of apoptotic cells (P < 0.05). On the molecular level, the expression of Bad in the OEC transplantation group was significantly downregulated (P < 0.05)., Conclusions: OEC transplantation could effectively improve neurological deficits in TBI rats; the underlying mechanism may be related with their effects on neuroprotection and regeneration induction, which is associated with the downregulation of the apoptotic molecule Bad., (Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Transplantation of neural stem cells (NSCs) into lesioned spinal cord demonstrated a beneficial effect for neural repair, the underlying mechanism, however, remains to be elusive. Here, we showed that NSCs, possessing the capacity to differentiate toward into neurons and astrocytes, exhibit a neuroprotective effect by anti-apoptosis mechanism in spinal cord hemi-transected rats despite it did not improve behavior. Intravenous NSCs injection substantially upregulated the level of BDNF mRNA but not its receptor TrkB in hemisected spinal cord, while caspase-7, a downstream apoptosis gene of caspase-3, has been largely down-regulated. TUNEL staining showed that the number of apoptosis cells in injured spinal cord decreased significantly, compared with seen in rats with no NSCs administration. The present finding therefore provided crucial evidence to explain neuroprotective effect of NSCs grafts in hemisected spinal cord, which is associated with BDNF upregulation and caspase-7 downregulation.

Background: Hypertension is a common disease of the cardiovascular system. So far, the pathogenesis of primary hypertension remains unclear. The elaboration of its pathogenesis is an important topic in the field which calls for urgent resolution. The aim of this study was to probe into the metabolic imbalance of homocysteine (Hcy) and hydrogen sulfide (H(2)S) in children with essential hypertension, and its significance in the pathogenesis of essential hypertension., Methods: Twenty-five children with essential hypertension and 30 healthy children with normal blood pressure were enrolled in the study. The medical history was investigated and a physical examination was conducted on the subjects. Plasma Hcy content was examined by fluorescence polarization immunoassay (FPIA). The plasma H(2)S level was detected by a modified method with a sulfide electrode. Data were presented as mean +/- standard deviation. The t test was applied to the mean values of both groups. Pearson linear correlation analysis was applied to the plasma Hcy and H(2)S as well as to the systolic pressure against the plasma H(2)S/Hcy ratio., Results: Plasma Hcy, an intermittent metabolite of the endogenous methionine pathway, was markedly increased but plasma H(2)S, a final product of this pathway was significantly decreased in hypertensive cases when compared with normal subjects ((Hcy: (12.68 +/- 9.69) micromol/L vs (6.62 +/- 4.79) micromol/L (t = 2.996, P < 0.01); H(2)S: (51.93 +/- 6.01) micromol/L vs (65.70 +/- 5.50) micromol/L) (t = -8.670, P < 0.01)). The ratio of plasma H(2)S/Hcy in children with hypertension was 5.83 +/- 2.91, while that of the control group was 11.60 +/- 3.30, and the difference is significant with a t = -6.610 and P < 0.01. A negative correlation existed between plasma Hcy and H(2)S concentrations, r = -0.379, P < 0.05. And a negative correlation was found between systolic blood pressure and the plasma H(2)S/Hcy ratio, r = -0.687, P < 0.05., Conclusion: There was a metabolic imbalance of homocysteine and hydrogen sulfide in essential hypertensive children.

This study investigated the effect of L-arginine (L-Arg) on the apoptosis of pulmonary artery smooth muscle cells (PASMC) in rats with hypoxic pulmonary vascular structural remodeling, and its mechanisms. Seventeen Wistar rats were randomly divided into a control group (n=5), a hypoxia group (n=7), and a hypoxia+L-Arg group (n=5). The morphologic changes of lung tissues were observed under optical microscope. Using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay, the apoptosis of PASMC was examined. Fas expression in PASMC was examined using immunohistochemistry. The results showed that the percentage of muscularized artery in small pulmonary vessels, and the relative medial thickness and relative medial area of the small and median pulmonary muscularized arteries in the hypoxic group were all significantly increased. Pulmonary vascular structural remodeling developed after hypoxia. Apoptotic smooth muscle cells of the small and median pulmonary arteries in the hypoxia group were significantly less than those in the control group. After 14 d of hypoxia, Fas expression by smooth muscle cells of median and small pulmonary arteries was significantly inhibited. L-Arg significantly inhibited hypoxic pulmonary vascular structural remodeling in association with an augmentation of apoptosis of smooth muscle cells as well as Fas expression in PASMC. These results showed that L-Arg could play an important role in attenuating hypoxic pulmonary vascular structural remodeling by upregulating Fas expression in PASMC, thus promoting the apoptosis of PASMC.