Clinical Features, Diagnosis, and Treatment of Congenital and Neonatal Tuberculosis: A Retrospective Study.

INTRODUCTION: Limited studies have explored the clinical features, treatment, and prognosis of neonatal tuberculosis (TB). Here, we attempted to delineate the clinical characteristics of neonatal TB, which may help clinicians further understand this disease. METHODS: A retrospective analysis of neonates diagnosed with congenital and/or neonatal TB disease from January 2010 to December 2020 was performed. Information on the demographic and epidemiological features, clinical symptoms, laboratory and imaging examinations, therapeutic regimens, and outcomes was collected. Kaplan-Meier analysis was used to present the time to disease onset, time to diagnosis, etc. Results: Forty-eight cases of neonatal TB were classified into congenital (n = 33) and postnatal (n = 15). The median time to disease onset in postnatal group was significantly longer than that in congenital group. Positive results for gastric fluid acid-fast bacilli, TB culture, Xpert MTB/RIF, interferon-γ release assay (IGRA), and tuberculin skin test were detected in 26/48 (54.2%), 14/34 (41.2%), 11/18 (61.1%), 19/29 (65.5%), and 8/24 (33.3%) patients, respectively. For lymphadenopathy, computed tomography (CT) scans showed a higher detection rate than did X-ray (80.0% vs. 0). Of the 48 infants, 44/48 (91.7%) received anti-TB therapy, and 33/44 (75%) were clinically improved or cured after 22.1 months (interquartile range: 12.4-27.7) of follow-up. Drug-induced liver injury occurred in 14/44 (31.8%) patients. DISCUSSION/CONCLUSION: IGRA and Xpert MTB/RIF showed good positive rate in neonatal TB infection/disease. In cases where TB is presumed but etiological evidence is lacking, low-dose CT could be considered. Prompt treatment under careful surveillance is important for preventing mortality and avoiding severe adverse effects.

Polyamines inhibit abscisic acid-induced stomatal closure by scavenging hydrogen peroxide.

Stomatal closure is regulated by plant hormones and some small molecules to reduce water loss under stress conditions. Both abscisic acid (ABA) and polyamines alone induce stomatal closure; however, whether the physiological functions of ABA and polyamines are synergistic or antagonistic with respect to inducing stomatal closure is still unknown. Here, stomatal movement in response to ABA and/or polyamines was tested in Vicia faba and Arabidopsis thaliana, and the change in the signaling components under stomatal closure was analyzed. We found that both polyamines and ABA could induce stomatal closure through similar signaling components, including the synthesis of hydrogen peroxide (H2 O2 ) and nitric oxide (NO) and the accumulation of Ca2+ . However, polyamines partially inhibited ABA-induced stomatal closure both in epidermal peels and in planta by activating antioxidant enzymes, including superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), to eliminate the ABA-induced increase in H2 O2 . These results strongly indicate that polyamines inhibit abscisic acid-induced stomatal closure, suggesting that polyamines could be used as potential plant growth regulators to increase photosynthesis under mild drought stress.

Clinical features of Chinese children with COVID-19 and other viral respiratory infections.

OBJECTIVE: Few studies have explored the clinical features in children infected with SARS-CoV-2 and other common respiratory viruses, including respiratory syncytial virus (RSV), Influenza virus (IV), and adenovirus (ADV). Herein, we reported the clinical characteristics and cytokine profiling in children with COVID-19 or other acute respiratory tract infections (ARTI). METHODS: We enrolled 20 hospitalized children confirmed as COVID-19 positive, 58 patients with ARTI, and 20 age and sex-matched healthy children. The clinical information and blood test results were collected. A total of 27 cytokines and chemokines were measured and analyzed. RESULTS: The median age in the COVID-19 positive group was 14.5 years, which was higher than that of the ARTI groups. Around one-third of patients in the COVID-19 group experienced moderate fever, with a peak temperature of 38.27°C. None of the patients displayed wheezing or dyspnea. In addition, patients in the COVID-19 group had lower white blood cells, platelet counts as well as a neutrophil-lymphocyte ratio. Lower serum concentrations of 14 out of 27 cytokines were observed in the COVID-19 group than in healthy individuals. Seven cytokines (IL-1Ra, IL-1ß, IL-9, IL-10, TNF-α, MIP-1α, and VEGF) changed serum concentration in COVID-19 compared with other ARTI groups. CONCLUSION: Patients with COVID-19 were older and showed milder symptoms and a favorable prognosis than ARTI caused by RSV, IV, and ADV. There was a low grade or constrained innate immune reaction in children with mild COVID-19.

Ionomic and metabolomic analyses reveal the resistance response mechanism to saline-alkali stress in Malus halliana seedlings.

Saline-alkali stress is a major abiotic stress limiting plant growth. The selection of saline-alkali-tolerant rootstock is an effective strategy to reduce salinization-alkalization influence in apple production. M. halliana is a highly saline-alkali-resistant apple rootstock in northwestern China. However, few metabolic response studies have been conducted on this species. In plants under saline-alkali stress, the uptake of K, Mg and Zn in M. halliana leaves were inhibited, whereas the absorption of Fe2+, Cu2+ or Mn2+ were increased. Metabolic analysis revealed 140 differentially expressed metabolites, which were mainly involved in alkaloid biosynthesis, phenylalanine biosynthesis, ATP-binding cassette (ABC) transporters, and mineral absorption. Especially, the expression of sucrose, amino acids, alkaloids, flavonoids and carotenoids were significantly upregulated under saline-alkali stress. qRT-PCR analysis demonstrated that NHX8 and ZTP1 involved in Na+ and Fe2+ transport were upregulated, while AKT1, MRS2-4 and ZTP29 involved in K+, Mg2+ and Zn2+ transport were downregulated, respectively. ANT, ATP2A, CALM and SOS2 are involved in Ca2+ signal transduction, and ABCB1, ABCC10 and NatA are key transporters that maintain ionic homeostasis. M. halliana regulates Na+/K+ homeostasis by mediating Ca2+ signalling and ABC transporters. The accumulation of metabolites contributes to improving the saline-alkali resistance of M. halliana because of the scavenging of ROS. An increase in pheophorbide a content in porphyrin and chlorophyll metabolism leads to leaf senescence in M. halliana leaves, which contributes to a reduction in stress-induced injury. These findings provide important insights into the saline-alkali tolerance mechanism in apple, which also provides an important starting point for future research.

Integrated physiologic, proteomic, and metabolomic analyses of Malus halliana adaptation to saline-alkali stress.

Saline-alkali stress is a severely adverse abiotic stress limiting plant growth. Malus halliana Koehne is an apple rootstock that is tolerant to saline-alkali stress. To understand the molecular mechanisms underlying the tolerance of M. halliana to saline-alkali stress, an integrated metabolomic and proteomic approach was used to analyze the plant pathways involved in the stress response of the plant and its regulatory mechanisms. A total of 179 differentially expressed proteins (DEPs) and 140 differentially expressed metabolites (DEMs) were identified. We found that two metabolite-related enzymes (PPD and PAO) were associated with senescence and involved in porphyrin and chlorophyll metabolism; six photosynthesis proteins (PSAH2, PSAK, PSBO2, PSBP1, and PSBQ2) were significantly upregulated, especially PSBO2, and could act as regulators of photosystem II (PSII) repair. Sucrose, acting as a signaling molecule, directly mediated the accumulation of D-phenylalanine, tryptophan, and alkaloid (vindoline and ecgonine) and the expression of proteins related to aspartate and glutamate (ASP3, ASN1, NIT4, and GLN1-1). These responses play a central role in maintaining osmotic balance and removing reactive oxygen species (ROS). In addition, sucrose signaling induced flavonoid biosynthesis by activating the expression of CYP75B1 to regulate the homeostasis of ROS and promoted auxin signaling by activating the expression of T31B5_170 to enhance the resistance of M. halliana to saline-alkali stress. The decrease in peroxidase superfamily protein (PER) and ALDH2C4 during lignin synthesis further triggered a plant saline-alkali response. Overall, this study provides an important starting point for improving saline-alkali tolerance in M. halliana via genetic engineering.

Apoptosis of the Tracheal Epithelium Can Increase the Number of Recipient Bone Marrow-Derived Myofibroblasts in Allografts and Exacerbate Obliterative Bronchiolitis After Tracheal Transplantation in Mice.

BACKGROUND: The long-term outcome of lung transplantation is impeded by the development of obliterative bronchiolitis (OB). We sought to investigate the relationship between the apoptosis of tracheal epithelial cells and bone marrow-derived myofibroblasts in the process of OB. METHODS: The mouse orthotopic tracheal transplant model was established. The allografts and syngrafts were harvested at 1, 2, 3, and 4 weeks after tracheal transplant. The percentage of tracheal lumen occlusion was assayed via histology and morphometry. Immunofluorescence staining was used to detect the apoptotic epithelial cells and recipient-derived myofibroblasts. The expression of SDF-1α and TGF-ß and the infiltrations of CD4 and CD8 T cells in the grafts were detected using immunohistochemical staining. RESULTS: We found that there were more apoptotic epithelia in the allograft group than in the syngraft group and that the level of tracheal lumen occlusion was higher at different time points. Moreover, the increase in the apoptosis of the tracheal epithelium occurred earlier than that of occlusion of the tracheal lumen. There were more myofibroblasts derived from the recipient's bone marrow and more CD4 and CD8 T cells in the allografts. The expression of SDF-1α and TGF-ß was higher in the epithelium from allografts than in those of the syngrafts. CONCLUSIONS: Our study indicated that the apoptotic tracheal epithelia in the OB model might increase the amount of myofibroblasts derived from the recipient's bone marrow. Therapeutic methods aimed at preventing apoptosis of the tracheal epithelium may improve the outcome of lung transplantation.

Serum levels of soluble vascular cell adhesion molecules may correlate with the severity of dengue virus-1 infection in adults.

The damage of vascular endothelial cells has been speculated to be involved in the pathogenesis of dengue virus (DENV) infection. However, little is known about the role of soluble vascular cell adhesion molecule-1 (sVCAM-1) in predicting the severity of dengue infection in adults. In this study, 51 adults with DENV-1 infection (21 with severe dengue and 30 with dengue fever (DF) were included, and their serum levels of sVCAM-1 and other parameters were determined. The results indicated that the levels of sVCAM-1 were elevated on days 1-3 to 16.75 (11.55-34.74) ng/mL in the severe dengue patients. These levels increased rapidly to peak values of 43.53 (37.15-47.02) ng/mL on days 10-12 and then declined; however, the values were maintained at a high level (38.07 (26.06-39.63) ng/mL). Other parameters, including reduced platelet (PLT) counts, neutrophil (NEU) counts and increased levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatine kinase (CK), were also observed in the severe dengue group but not in the DF group. The levels of cytokines, such as interleukin (IL)-6, IL-10, interferon γ (IFNγ), and tumor necrosis factor α (TNF-α), were transiently increased in the severe dengue patients. Among the aforementioned parameters, only sVCAM-1 levels were significantly elevated earlier and more persistently in the severe dengue patients than in the DF patients. sVCAM-1 positively correlated with the levels of ALT, AST, LDH, TNF-α, and IL-6 and negatively correlated with the levels of PLT, NEU, and viremia. Notably, the high levels of sVCAM-1 were closely associated with the severe dengue patients. In conclusion, sVCAM-1 may be a superior indicator for monitoring the severity of dengue.

Complete genome sequence of a dengue virus serotype 4 strain isolated in Guangdong, China.

Here we report the first complete genome sequence of a dengue virus serotype 4 genotype II strain, GZ30, isolated in Guangzhou, Guangdong Province, China, in 2010. The sequence information provided herein will help us to understand the molecular epidemiology of dengue virus and predict the risk of severe diseases in mainland China.

[Molecular mechanism of acupoint catgut-embedding for experimental colitis in rats].

OBJECTIVE: To explore the effect and its mechanism of acupoint catgut-embedding for experimental colitis in rats. METHODS: Eighteen SD rats were randomly divided into a normal control (NC) group, a model (MO) group and a acupoint catgut-embedding (AC) group, 6 rats in each group. Animals in MO group and AC group were treated by trinitro-benzene-sulfonic acid (TNBS) to establish model with colitis. No other treatment was given to the rats in MO group, but acupoint catgut-embedding was implanted at "Shangjuxu" (ST 37), "Tianshu" (ST 25) and "Dachangshu" (BL 25) in the rats in AC group. The symptoms of diarrhea and bloody stool, and histopathology changes in colon were observed 15 days after the treatment. Expression of IL-17, beta2AR, NFkappaBp65 were observed by immunohistochemistry. Expressions of NF-kappaBp65 and beta2AR in splenic lymphocyte were detected by the Western blot method. RESULTS: Diarrhea and mucus bloody purulent stool were soon controlled, and colon mucosa injures were obviously improved in AC group. The NF-kappaBp65 value in splenic lymphocytes of 249.70 +/- 13.66 in MO) group was higher than 86.22 +/- 8.09 in NC group (P < 0.01), and 219.02 +/- 7.42 in AC group was less than that in MO group (P < 0.01). The expression of beta2AR in splenic lymphocytes of 594.97 +/- 173.22 in MO group was less than 957.45 +/- 171.56 in NC group (P < 0.01), and 1335.93 +/- 244.34 in AC group was higher than that in MO group (P < 0.01). The expression of IL-17 in colon mucosa in MO group was increased, while the expression of IL-17 in colon mucosa in AC group was decreased. CONCLUSION: Acupoint catgut-embedding at Shangjuxu (ST 37), Tianshu (ST 25) and Dachangshu (BL 25) has obviously effect in treating experimental colitis and the mechanism may be related to regulate the expression of IL-17, beta2AR and NF-kappaBp65.

Differentiation character of adult mesenchymal stem cells and transfection of MSCs with lentiviral vectors.

This study examined the differentiation character and pluripotency of mesenchymal stem cells (MSCs) under different conditions. Adult MSCs were initially isolated from the bone marrow of rats, cultured in vitro and identified by flow cytometry. After MSCs were transferred to osteogenic and adipogenic medium respectively, the morphological characterization of induced cells was observed. The expression of marker genes was detected by RT-PCR analysis. Then MSCs were transfected with lentiviral vectors pGC-FU-Sox9-EGFP. Enhanced green fluorescence protein (EGFP) expression and transfection efficiency were determined by fluorescence microscopy. The results demonstrated that EGFP caused no effect on the multilineage potential of adult MSCs. Sox9 gene expression of high level was maintained stable in the transfected MSCs and induced MSCs to differentiate into chondrocytes. Aggracan was positive in chondrogenic lineages and the expression of aggracan and type collagen II was significantly increased during MSCs chondrogenic differentiation. It was concluded that Sox9 gene-modified adult MSCs may be promising candidate cells for further studies on tissue engineering. EGFP facilitates the research on MSCs physiological behavior and application in tissue engineering during differentiation both in vitro and in vivo.

[Selection of basic acupoints for composing "gastric-disorder-formula" for electroacupuncture prevention of acute gastric mucosal lesion in rats].

OBJECTIVE: To select the best combination of the commonly-used acupoints [Zhongwan (CV 12), Neiguan (PC 6), and Zusanli (ST 36)] for treatment of gastric disorders. METHODS: Forty-eight Wistar rats were randomly divided into 8 groups: model, ST36, CV12, PC6, ST36 + PC6, ST36 + CV12, CV12 + PC6 and ST36 + CV12 + PC6 by factorial design method. Acute gastric mucosal lesion model was established by intragastric perfusion of anhydrous alcohol. EA(1- 3 mA, 30 Hz) was applied to the above-mentioned acupoints for 20 min respectively. And after EA, gastric mucosal lesion index (LI), pathological lesion integral score (PLIS) were calculated and mucosal ultramicrostructural changes observed by optical microscope and transmission electron microscope respectively. RESULTS: Compared with model group, the gastric mucosal LI and PLIS of ST36, CV12, PC6, ST36 + CV12, ST36 + PC6, CV12 + PC6, ST36 + CV12 + PC6 groups all decreased significantly (P < 0.05). Comparison among 7 EA groups showed that both LI and PLIS of ST36 + CV12 + PC6 group were significantly lower than those of ST36, V12, PC6, ST36 + CV12, ST36 + PC6 and CV12 + PC6 groups (P < 0.05). No significant differences were found between every two groups of ST36, CV12, PC6, ST36+ CV12, ST36 + PC6 and CV12 + PC6 groups (P > 0.05) in both LI and PLIS. Ultrastructural results showed that the injury of gastric mucosal parietal cells and delomorphous cells including mitochondrial swelling, crista arrange disorder and breaking, enlargement of the rough endoplasmic reticulum, ribosome exfoliation, etc. in model group was serious, but lightened significantly in EA groups particularly in ST36 + CV12 + PC6 group. CONCLUSION: ST36, PC6 and CV12 combination can effectively reduce anhydrous alcohol-induced gastric mucosal lesion in rats, and may be used as a basic formula

[Effects of electroacupuncture at points "Weibingfang" on EGF and EGFR mRNA expressions in rats with lesion of gastric mucosa].

OBJECTIVE: To probe the mechanism of electroacupuncture at points "Weibingfang" in treatment of acute gastric mucosal lesion. METHODS: Forty Wistar rats of sanitary degree were randomly divided into 4 groups, normal group, model group, sham-model group and Weibingfang group, 10 rats in each group. The acute gastric mucosal lesion model was made by intragastric perfusion of anhydrous alcohol. The Weibingfang group were treated by electroacupuncture at "Neiguan" (PC 6), "Zhongwan" (CV 12) and "Zusanli" (ST 36) with sparse-dense wave, frequency of 10-30 Hz, current intensity of 2 mA, for 20 min. One hour after the treatment, the blood from the abdominal aorta and the gastric mucosa tissue were taken, and serum epidermal growth factor (EGF) level and epidermic growth factor receptor mRNA (EGFR mRNA) expression in the gastric mucosa were detected with enzyme linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR) respectively. RESULTS: There were significant differences in blood EGF level (41.62 +/- 12.58) ng/L and EGFR mRNA expression (0.78 +/- 0.03) in the model group were significantly different from [(60.37 +/- 12.01) ng/L and 0.55 +/- 0.04] in the normal group and [(61.21 +/- 13.46) ng/L and 0.53 +/- 0.05] in the sham-model group (P < 0.05); after electroacupuncture, blood EGF level (70.59 +/- 10.14) ng/L increased and the EGFR mRNA expression (1.18 +/- 0.02) in the gastric mucosa was up-regulated with a significant differences as compared with those in the model group (P < 0.05). CONCLUSION: Point "Weibingfang" can promote proliferation, differentiation and migration of the gastric mucosal epidermic cells to repair the gastric mucosal lesion.

[Survey on the relationship between pathological reactions of acupoints and Zangfu organs/meridians].

In this article, the authors make an analysis on the regularity of correlation between pathological reactions of acupoints and Zangfu organs/meridians, current clinical application and mechanism research, and summarize the relative specificity of the correlation between abnormal reactions of acupoints and states of Zangfu organs/meridians. In addition, the authors also point out some shortcomings in current researches on the above-mentioned aspects, for examples, only observation on the phenomenon without definite conclusion on the regularity of acupoint reactions, being restricted in the objective specificity, etc.. They stress that we should sum up a series of regularities for clinical application (early diagnosis), and conduct profound research on its underlying mechanism in the coming days.