Supernatural Beliefs-Based Intervention to Improve Type-2 Diabetes Self-Management: A Pilot Randomized Controlled Trial from China.

China has over 100 million people living with type 2 diabetes mellitus (T2DM). Interventions framed around pre-existing personal beliefs in the supernatural may improve T2DM self-management, but such interventions are lacking in China. This pilot randomized controlled trial (RCT) assessed the feasibility of a full-scale RCT to evaluate the efficacy of a supernatural beliefs-based intervention on T2DM management self-efficacy in China. In 2019, 62 T2DM patients were enrolled at two hospitals in Suzhou, China. Participants were randomly assigned to view a 30-s control or intervention video at baseline. The control video showed general diabetes self-management information. The intervention video showed identical information, but also indicated that some diabetics with supernatural beliefs (chao ziran xinnian) have lower glycemic levels, because their beliefs enhance their confidence in diabetes self-management. Development of the intervention was guided by the theory of planned behavior and literature on spiritual framing health interventions. Baseline and follow-up measures after two weeks were assessed by interviewer administered surveys in-person and by telephone, respectively. Diabetes management self-efficacy was assessed with the diabetes management self-efficacy scale. Randomization of intervention allocation appeared to be successful. However, follow-up retention was low, especially for the intervention group (3% vs. 31%). A full-size efficacy RCT using the current study design is unlikely to succeed. T2DM patients shown the supernatural beliefs-based intervention had significantly higher loss to follow-up that was insurmountable. T2DM patients in Suzhou, China may not be receptive to brief, non-tailored supernatural beliefs-based interventions delivered to a general population in clinical settings.

Platinum-resistance in epithelial ovarian cancer: an interplay of epithelial-mesenchymal transition interlinked with reprogrammed metabolism.

BACKGROUND: Epithelial ovarian cancer is the most lethal gynaecological cancer worldwide. Chemotherapy resistance represents a significant clinical challenge and is the main reason for poor ovarian cancer prognosis. We identified novel expression of markers related to epithelial mesenchymal transitions (EMT) in a carboplatin resistant ovarian cancer cell line by proteomics. This was validated in the platinum resistant versus sensitive parental cell lines, as well as platinum resistant versus sensitive human ovarian cancer patient samples. The prognostic significance of the different proteomics-identified marker proteins in prognosis prediction on survival as well as their correlative association and influence on immune cell infiltration was determined by public domain data bases. METHODS: We explored the proteomic differences between carboplatin-sensitive OVCAR5 cells (parental) and their carboplatin-resistant counterpart, OVCAR5 CBPR cells. qPCR and western blots were performed to validate differentially expressed proteins at the mRNA and protein levels, respectively. Association of the identified proteins with epithelial-mesenchymal transition (EMT) prompted the investigation of cell motility. Cellular bioenergetics and proliferation were studied to delineate any biological adaptations that facilitate cancer progression. Expression of differentially expressed proteins was assessed in ovarian tumors obtained from platinum-sensitive (n = 15) versus platinum-resistant patients (n = 10), as well as matching tumors from patients at initial diagnosis and following relapse (n = 4). Kaplan-Meier plotter and Tumor Immune Estimation Resource (TIMER) databases were used to determine the prognostic significance and influence of the different proteomics-identified proteins on immune cell infiltration in the tumor microenvironment (TME). RESULTS: Our proteomics study identified 2422 proteins in both cell lines. Of these, 18 proteins were upregulated and 14 were downregulated by ≥ twofold (p < 0.05) in OVCAR5 CBPR cells. Gene ontology enrichment analysis amongst upregulated proteins revealed an overrepresentation of biological processes consistent with EMT in the resistant cell line. Enhanced mRNA and/or protein expression of the identified EMT modulators including ITGA2, TGFBI, AKR1B1, ITGAV, ITGA1, GFPT2, FLNA and G6PD were confirmed in OVCAR5 CBPR cells compared to parental OVCAR5 cell line. Consistent with the altered EMT profile, the OVCAR5 CBPR cells demonstrated enhanced migration and reduced proliferation, glycolysis, and oxidative phosphorylation. The upregulation of G6PD, AKR1B1, ITGAV, and TGFß1 in OVCAR5 CBPR cells was also identified in the tumors of platinum-resistant compared to platinum-sensitive high grade serous ovarian cancer (HGSOC) patients. Matching tumors of relapsed versus newly diagnosed HGSOC patients also showed enhanced expression of AKR1B1, ITGAV, TGFß1 and G6PD protein in relapsed tumors. Among the identified proteins, significant enhanced expression of GFPT2, FLNA, TGFBI (CDGG1), ITGA2 predicted unfavorable prognosis in ovarian cancer patients. Further analysis suggested that the expression of TGFBI to correlate positively with the expression of identified and validated proteins such as GFPT2, FLNA, G6PD, ITGAV, ITGA1 and ITGA2; and with the infiltration of CD8+ T cells, macrophages, neutrophils, and dendritic cells in the TME. CONCLUSIONS: Our research demonstrates proteomic-based discovery of novel EMT-related markers with an altered metabolic profile in platinum-resistant versus sensitive ovarian cancer cell lines. The study also confirms the expression of selected identified markers in the tumors of platinum-resistant versus sensitive, and in matching relapsed versus newly diagnosed HGSOC patients. The study provides insights into the metabolic adaptation of EMT-induced carboplatin resistant cells that confers on them reduced proliferation to provide effective migratory advantage; and the role of some of these identified proteins in ovarian cancer prognosis. These observations warrant further investigation of these novel target proteins in platinum-resistant patients.

Health Effects of Religion, Spirituality, and Supernatural Beliefs in Mainland China: A Systematic Review.

Effects of religion, spirituality and supernatural beliefs (RSS) upon health in mainland China remain poorly understood, despite strong RSS beliefs influencing Chinese society. We conducted a Chinese-English bilingual systematic review to summarize the state of RSS-health research in mainland China. Study quality was assessed using the Critical Appraisal Skills Program tool. We screened 1858 studies, 162 of which were included in the review. From 2000-2004 to 2015-2019, the number of RSS-health studies in China increased from five to 73. However, only 7% of studies were rated as higher quality. Cross-sectional and case-control studies represented the vast majority of study designs (94%) and religious affiliation was the only RSS measure for 58% of studies. Higher, moderate, and lower quality studies indicated that RSS has both beneficial and adverse health implications. RSS-health research in China has accelerated rapidly in the last 20 years, but fundamental gaps in knowledge remain. Longitudinal study designs and nuanced RSS measures are needed to advance understanding of RSS health effects in China.

Overlaps, gaps, and complexities of mouse models of Developmental and Epileptic Encephalopathy.

Mouse models have made innumerable contributions to understanding the genetic basis of neurological disease and pathogenic mechanisms and to therapy development. Here we consider the current state of mouse genetic models of Developmental and Epileptic Encephalopathy (DEE), representing a set of rare but devastating and largely intractable childhood epilepsies. By examining the range of mouse lines available in this rapidly moving field and by detailing both expected and unusual features in representative examples, we highlight lessons learned in an effort to maximize the full potential of this powerful resource for preclinical studies.

Design, synthesis and structure-activity relationship study of aminopyridine derivatives as novel inhibitors of Janus kinase 2.

Janus Kinase 2 (JAK2) is a kind of intracellular non-receptor protein tyrosine kinase and has been certified as an important target for the treatment of myeloproliferative neoplasms and rheumatoid arthritis. However, the low selectivity and potential safety issues restrict the clinical applications of JAK2 inhibitors. Here we found that crizotinib showed good inhibitory activity against JAK2 by enzymatic assays (IC50 = 27 nM). Then we carried out structure-based drug design and synthesized a series of compounds with an aminopyridine scaffold. Finally, compound 12k and 12l were identified as the promising inhibitors of JAK2, which exhibited high inhibitory activity (IC50 = 6 nM and 3 nM, respectively) and selectivity for JAK2 over JAK1 and JAK3, and showed potent antiproliferative activities toward HEL human erythroleukemia cells. Moreover, 12k suppressed symptoms of the collagen-induced arthritis (CIA) model in rats.

Evidence for Internal Desynchrony Caused by Circadian Clock Resetting.

Circadian disruption has been linked to markers for poor health outcomes in humans and animal models. What is it about circadian disruption that is problematic? One hypothesis is that phase resetting of the circadian system, which occurs in response to changes in environmental timing cues, leads to internal desynchrony within the organism. Internal desynchrony is understood as acute changes in phase relationships between biological rhythms from different cell groups, tissues, or organs within the body. Do we have strong evidence for internal desynchrony associated with or caused by circadian clock resetting? Here we review the literature, highlighting several key studies from measures of gene expression in laboratory rodents. We conclude that current evidence offers strong support for the premise that some protocols for light-induced resetting are associated with internal desynchrony. It is important to continue research to test whether internal desynchrony is necessary and/or sufficient for negative health impact of circadian disruption.

The Evolution of Antibody-Drug Conjugates: Toward Accurate DAR and Multi-specificity.

Antibody-drug conjugates (ADCs) consist of antibodies, linkers and payloads. They offer targeted delivery of potent cytotoxic drugs to tumor cells, minimizing off-target effects. However, the therapeutic efficacy of ADCs is compromised by heterogeneity in the drug-to-antibody ratio (DAR), which impacts both cytotoxicity and pharmacokinetics (PK). Additionally, the emergence of drug resistance poses significant challenges to the clinical advancement of ADCs. To overcome these limitations, a variety of strategies have been developed, including the design of multi-specific drugs with accurate DAR. This review critically summarizes the current challenges faced by ADCs, categorizing key issues and evaluating various innovative solutions. We provide an in-depth analysis of the latest methodologies for achieving homogeneous DAR and explore design strategies for multi-specific drugs aimed at combating drug resistance. Our discussion offers a current perspective on the advancements made in refining ADC technologies, with an emphasis on enhancing therapeutic outcomes.

Expression of GCaMP6s in the dentate gyrus induces tonic-clonic seizures.

GCaMP is a genetically encoded calcium indicator (GECI) widely used in neuroscience research. It measures intracellular Ca2+ level by fluorescence changes as it directly binds to Ca2+. In this process, the effect of this calcium buffer on the intracellular calcium signaling and cell physiology is often not taken into consideration. However, growing evidence from calcium imaging studies shows GCaMP expression under certain conditions can generate aberrant activity, such as seizures. In this study, we examined the effect of GCaMP6 expression in the dentate gyrus (DG) on epileptogenesis. We found that viral expression of GCaMP6s but not GCaMP6f in the DG induces tonic-clonic seizures several weeks after viral injection. Cell-type specific expression of GCaMP6s revealed the granule cells (GCs) as the key player in GCaMP6s-induced epilepsy. Finally, by using slice electrophysiology, we demonstrated that GCaMP6s expression increases neuronal excitability in the GCs. Together, this study highlights the ability of GCaMP6s in DG-associated epileptogenesis.

Investigating the effects of Laggera pterodonta on H3N2-Induced inflammatory and immune responses through network pharmacology, molecular docking, and experimental validation in a mice model.

For centuries, Laggera pterodonta (LP), a Chinese herbal medicine, has been widely employed for treating respiratory infectious diseases; however, the mechanism underlying LP's effectiveness against the influenza A/Aichi/2/1968 virus (H3N2) remains elusive. This study aims to shed light on the mechanism by which LP combats influenza in H3N2-infected mice. First, we conducted quasi-targeted metabolomics analysis using liquid chromatography-mass spectrometry to identify LP components. Subsequently, network pharmacology, molecular docking, and simulation were conducted to screen candidate targets associated with AKT and NF-κB. In addition, we conducted a series of experiments including qPCR, hematoxylin-eosin staining, flow cytometry, immunohistochemistry, and enzyme-linked immunosorbent assay to provide evidence that LP treatment in H3N2-infected mice can reduce pro-inflammatory cytokine levels (TNF-α, IL-6, IL-1ß, and MCP-1) while increasing T cells (CD3+, CD4+, and CD8+) and syndecan-1 and secretory IgA expression. This, in turn, aids in the prevention of excessive inflammation and the fortification of immunity, both of which are compromised by H3N2. Finally, we utilized a Western blot assay to confirm that LP indeed inhibits the AKT/NF-κB signaling cascade. Thus, the efficacy of LP serves as a cornerstone in establishing a theoretical foundation for influenza treatment.

Integrated analysis of intestinal microbiota and transcriptome reveals that a coordinated interaction of the endocrine, immune system and gut microbiota response to heat stress in Litopenaeus vannamei.

Due to the ongoing global warming, the risk of heatwaves in the oceans is continuously increasing while our understanding of the physiological response of Litopenaeus vannamei under extreme temperature conditions remains limited. Therefore, this study aimed to evaluate the physiological responses of L. vannamei under heat stress. Our results indicated that as temperature rose, the structure of intestinal and hepatopancreatic tissues was damaged sequentially. Activity of immune-related enzymes (acid phosphatase/alkaline phosphatase) initially increased before decreased, while antioxidant enzymes (superoxide dismutase and glutathione-S transferase) activity and malondialdehyde content increased with rising temperature. In addition, the total antioxidant capacity decreased with rising temperature. With the rising temperature, there was a significant increase in the expression of caspase-3, heat shock protein 70, lipopolysaccharide-induced tumor necrosis factor-α, transcriptional enhanced associate domain and yorkie in intestinal and hepatopancreatic tissues. Following heat stress, the number of potentially beneficial bacteria (Rhodobacteraceae and Gemmonbacter) increased which maintain balance and promote vitamin synthesis. Intestinal transcriptome analysis revealed 852 differentially expressed genes in the heat stress group compared with the control group. KEGG functional annotation results showed that the endocrine system was the most abundant in Organismal systems followed by the immune system. These results indicated that heat stress leads to tissue damage in shrimp, however the shrimp may respond to stress through a coordinated interaction strategy of the endocrine system, immune system and gut microbiota. This study revealed the response mechanism of L. vannamei to acute heat stress and potentially provided a theoretical foundation for future research on shrimp environmental adaptations.

An engineered multidomain fungicidal peptide against plant fungal pathogens.

Fungal pathogens represent major problems for human health and agriculture. As eukaryotic organisms, fungi share some important features with mammalian cells. Therefore, current anti-fungal antibiotics often can not distinguish between fungi and mammalian cells, resulting in serious side effects in mammalian cells. Accordingly, there is strong impetus to develop antifungal alternatives that are both safe and effective. The E1 family of colicin are channel-forming bacteriocins produced by Escherichia coli, which are bactericidal only to E. coli and related species. To target the channel-forming domain of colicin to fungal cell membrane, we engineered a sexual mating pheromone of Candida albicans, α-factor pheromone to colicin Ia. A peptide was constructed consisting of an α mating pheromone of C. albicans fused to the channel-forming domain of colicin Ia to create a new fusion protein, pheromonicin-CA (PMC-CA). Indirect immunolabeling showed that the PMC-CA bound to fungal cells and inhibited growth in the laboratory and field. In the field, the protective activity of pheromonicin against rice blast disease was significantly greater, on a molar basis, than that of triazoles, tricyclazole or isoprothiolane. These results suggest that fusion peptides may be of value as fungicidal agents under agricultural conditions.

Thyroid hormone resistance resulting from a novel mutation in the THRB gene in a Chinese child: A case report.

INTRODUCTION: Thyroid hormone resistance (RTH) (mim # 188570) is a rare autosomal dominant genetic disorder characterized by reduced thyroid hormone response in target tissues. The clinical manifestations of RTH vary from no symptoms to symptoms of thyroid hormone deficiency to symptoms of thyroid hormone excess. PATIENT CONCERN AND CLINICAL FINDINGS: A 24-month-old girl presented with growth retardation, tachycardia, and persistently elevated thyroid hormones despite antithyroid treatment. DIAGNOSIS/INTERVENTION/OUTCOMES: The patient was diagnosed with RTH, after whole exon gene sequencing, found a de novo missense mutation (c.1375T > G,p.Phe459Val) in a novel locus of the thyroid hormone receptor beta gene. She had only mild growth retardation, so the decision was made to monitor her development without intervention. At her last follow-up at 5 years and 8 months of age, she continued to show growth retardation (-2 standard deviation below age-appropriate levels), in addition to delayed language development. Her comprehension ability and heart rate have remained normal. CONCLUSIONS: We report a mild case of RTH caused by a novel thyroid hormone receptor beta gene mutation. RTH should be considered in the differential diagnosis of abnormal serum thyroxine levels during neonatal screening.

A case of Sandhoff disease caused by a novel ß-hexosaminidase B (HEXB) mutation c.118delG (p.A40fs*24): A case report from China.

BACKGROUND: Sandhoff disease (SD, Online Mendelian Inheritance in Man: 268800) is an autosomal recessive lysosomal storage disorder caused by variants of the ß-hexosaminidase B (HEXB) gene (Online Mendelian Inheritance in Man: 606873). The HEXB gene has been mapped to chromosome 5q13 and contains 14 exons. The symptoms of SD include progressive weakness, intellectual disability, visual and hearing impairment, exaggerated startle response, and seizures; the patients usually die before the age of 3 years.[1]. CASE SUMMARY: We present a case of SD caused by a homozygous frameshift mutation in the HEXB gene, c.118delG (p.A40fs*24). The male child, aged 2 years 7 months, showed movement retrogression with orbital hypertelorism at age 2 years, accompanied by seizures. Magnetic resonance imaging of the head showed cerebral atrophy and delayed myelination of the white matter of the brain. CONCLUSION: A novel homozygous frameshift c.118delG (p.A40fs*24) variant of HEXB has caused SD in the child. The major symptoms are intellectual disability, visual and hearing impairment, and seizures. Investigation will be continued in the future to comprehensively describe the genotype/phenotype and gain information on other associated features to understand the variable expressivity of this condition.

A nonsense mutation in the CUL3 gene in a Chinese patient with autism spectrum disorder and epilepsy: A case report.

RATIONALE: CUL3 (OMIM: 603136) encodes cullin-3, a core component of ubiquitin E3 ligase. Existing medical research suggests that CUL3 mutations are closely related to neurodevelopmental disorder with or without autism or seizures (neurodevelopmental disorder with autism and seizures, OMIM: 619239). However, the number of published case reports of autism spectrum disorder due to CUL3 gene mutations is limited. PATIENT CONCERN: A four-year-old Chinese girl presented with generalized epilepsy, and then exhibited developmental regression, including loss of her speaking ability, eye contact aversion, and stereotyped behavior. DIAGNOSES: Whole-exome sequencing identified a nonsense mutation in the CUL3 gene, being c.2065A > T (p.Lys689*); no previous similar case was reported. The final diagnosis was autism, epilepsy, and motor growth retardation. INTERVENTION: In order to improve quality of life of the patient, she was provided with exercise rehabilitation training and autism behavioral guidance therapy for 3 months. OUTCOMES: The patient's exercise capacity had improved, and improvements in autism symptoms were not obvious. LESSONS: For clinicians, patients with developmental regression accompanied with concurrent epilepsy and autism spectrum disorder should be advised that relevant genetic tests are necessary to clarify the diagnosis.

A case of West syndrome and global developmental delay in a child with a heterozygous mutation in the TBL1XR1 gene: A case report.

BACKGROUND: TBL1XR1, also known as IRA1 or TBLR1, encodes a protein that is localized in the nucleus and is expressed in most tissues. TBL1XR1 binds to histones H2B and H4 in vitro and functions in nuclear receptor-mediated transcription. TBL1XR1 is also involved in the regulation of the Wnt-ß-catenin signaling pathway. Mutations in the TBL1XR1 gene impair the Wnt-ß-catenin signaling pathway's ability to recruit Wnt-responsive element chromatin, affecting brain development. Mutations in this gene cause various clinical phenotypes, including Pierpont syndrome, autism spectrum disorder, speech and motor delays, mental retardation, facial dysmorphism, hypotonia, microcephaly, and hearing impairment. CASE SUMMARY: A 5-month-old female child was admitted with "episodic limb tremors for more than 1 month." At the time of admission, the child had recurrent episodes of limb tremors with motor retardation and a partially atypical and hypsarrhythmic video electroencephalogram. It was determined that a heterozygous mutation in the TBL1XR1 gene caused West syndrome and global developmental delay. Recurrent episodes persisted for 6 months following oral treatment with topiramate; the addition of oral treatment with vigabatrin did not show any significant improvement, and the disease continued to recur. The child continued to have recurrent episodes of limb tremors at follow-up until 1 year and 3 months of age. Additionally, she developed poor eye contact and a poor response to name-calling. CONCLUSION: We report the case of a child with West syndrome and a global developmental delay caused by a heterozygous mutation in the TBL1XR1 gene. This study adds to our understanding of the clinical phenotype of TBL1XR1 mutations and provides a realistic and reliable basis for clinicians.

Development and validation of the thyroid cancer self-perceived discrimination scale to identify patients at high risk for psychological problems.

Objective: To develop a Thyroid Cancer Self-Perceived Discrimination Scale (TCSPDS) to identify patients at high risk for psychological problems and to test its reliability, validity and acceptability. Methods: Using classical test theory, a total of 176 thyroid cancer patients from November 2021 to October 2022 were recruited to develop the TCSPDS. Item analysis was used to improve the preliminary TCSPDS. Exploratory factor analysis (EFA), confirmatory factor analysis (CFA) and structural equation model (SEM) were used to test the construct validity of the final TCSPDS. Pearson correlation coefficient was used to analyze the validity coefficient between TCSPDS and EORTC QLQ-C30 to test the criterion-related validity (CRV) of the final TCSPDS. The internal consistency coefficient (Cronbach's alpha coefficient), split half reliability (Spearman-Brown coefficient) and test-retest reliability were used to verify the reliability of the final TCSPDS. The questionnaire completion time and effective response rate were used to validate the acceptability of the final TCSPDS. Results: The TCSPDS consisted of 20 items and was divided into 3 subscales: 8 items for stigma, 6 items for self-deprecation, and 6 items for social avoidance. The TCSPDS had good validity (χ2/df=1.971, RMSEA=0.074, GFI=0.921, CFI= 0.930, IFI=0.932, TLI=0.901, Validity coefficient=0.767), reliability (Cronbach's alpha=0.867, Spearman-Brown coefficient=0.828, test-retest reliability coefficient=0.981) and acceptability [average completion time (15.01 ± 1.348 minutes) and an effective response rate of 95.14%]. Patients with higher TCSPDS scores reported a lower quality of life (P<0.05). Conclusion: The TCSPDS could be used for early identification and assessment of the level of self-perceived discrimination in patients with thyroid cancer, which may provide a scientific basis for health education, social support and psychosocial oncology services in the future, especially in Southwest China.

Retinitis pigmentosa with or without skeletal abnormalities due to homozygous mutations in the CWC27 gene: A case report.

RATIONALE: Retinitis pigmentosa with or without skeletal abnormalities (RPSKA) is an autosomal recessive disorder caused by mutations in the CWC27 gene. Skeletal dysplasia and non-syndromic retinitis pigmentosa are typical manifestations, and most patients present with retinopathy such as retinitis pigmentosa and limited visual field. Its clinical manifestations are complex and diverse, often involving multiple systems. Examples include short finger deformities, peculiar facial features, short stature, and neurodevelopmental abnormalities, and it is easy to misdiagnose clinically, and early diagnosis is crucial for prognosis. PATIENT CONCERNS: A 2-year and 2-month-old female child was admitted to the hospital due to "unsteady walking alone and slow reaction for more than half a year." After admission, the child was found to have delayed motor development, accompanied by special face, abnormal physical examination of the nervous system, cranial MRI Dandy-Walker malformation, considering developmental delay. DIAGNOSES: Whole exome sequencing of the family line revealed the presence of a c.617(exon7)C>A pure mutation in the CWC27 gene in the affected child (this locus has been reported in the clinical literature); the final diagnosis is RPSKA. INTERVENTIONS: Unfortunately, there is no specific drug for the disease; we give children rehabilitation training treatment. OUTCOMES: During follow-up process we found that children's condition is better than before. LESSONS SUBSECTIONS AS PER STYLE: We reported a case of RPSKA caused by mutations in the CWC27 gene. This study adds to our understanding of the clinical phenotype of TBL1XR1 mutations and provides a realistic and reliable basis for clinicians.

Deciphering in vivo metabolic profile and pharmacological mechanisms of Jitongning Tablet for the treatment of Ankylosing spondylitis.

Jitongning tablet (JTNT) is a Traditional Chinese Medicine (TCM) prescription used for the treatment of Ankylosing spondylitis (AS). Currently, it is in phase II clinical trial (NCT03932019) for patients with active axial Spondyloarthritis (axSpA), showing great promise for the treatment of AS. However, the potential material basis and the underlying mechanisms for JTNT to treat AS remain elusive. Here, we performed UPLC-Q-TOF-MS to determine the in vivo metabolic profile of JTNT in rats and conducted in vivo studies including acetic acid-induced writhing, hot plate models, and collagen-induced arthritis (CIA) in rats to evaluate and validate the analgesic and anti-inflammatory effects of JTNT, two main symptoms for AS. Additionally, network pharmacology combined with molecular docking was performed to investigate the potential underlying mechanisms. As a result, a total of 116 xenobiotics were identified from the plasma, urine, and brain tissues of rats after oral administration of JTN extracts. Pharmacological evaluation revealed that fractions JTN-3 and JTN-4 exerted significant analgesic activities by reducing the number of writhes in an acetic acid-induced writhing mice model. JTN extract also exerted excellent therapeutic effects in the CIA model by ameliorating paw edema and decreasing systemic manifestation of inflammation and the level of circulating immune complex (CIC) and interferon γ (IFN-γ). Fractions of JTN extract, especially JTN-2 and JTN-4, on the other hand, ameliorated the secondary lesions caused by chicken type II collagen (CII) to a certain extent. Further, network pharmacology combined with molecular docking suggested crucial roles of inflammation and immune-related genes such as MAPK1, MAPK14, NOS3, and RELA in the treatment of AS by JTNT. In conclusion, our studies suggest that the isoquinoline and diterpenoid alkaloids from Corydalis Rhizoma and Aconiti Radix Cocta, along with coumarins from Angelicae Pubescentis Radix, may be the main bioactive components, and the AS treatment mechanism may mainly involve immune regulation of JTNT. These results help clarify the potential material basis and underlying mechanisms of JTNT for the treatment of AS, facilitating the broad application of this TCM in clinical practice.

Children with infectious pneumonia caused by Ralstonia insidiosa: A case report.

BACKGROUND: Ralstonia is a Gram-negative non-fermentative bacterium widespread in nature, and includes four species, Ralstonia pickettii, Ralstonia solanacearum, Ralstonia mannitolilytica, and Ralstonia insidiosa, which were proposed in 2003. Ralstonia is mainly found in the external water environment, including municipal and medical water purification systems. This bacterium has low toxicity and is a conditional pathogen. It has been reported in recent years that infections due to Ralstonia are increasing. Previous studies have shown that most cases of infection are caused by Ralstonia pickettii, a few by Ralstonia mannitolilytica, and infections caused by Ralstonia insidiosa are rare. CASE SUMMARY: A 2-year-old Chinese child suffered from intermittent fever and cough for 20 d and was admitted to hospital with bronchial pneumonia. Bronchoscopy and alveolar lavage fluid culture confirmed Ralstonia insidiosa pneumonia. The infection was well controlled after treatment with meropenem and azithromycin. CONCLUSION: Ralstonia infections are increasing, and we report a rare case of Ralstonia insidiosa infection in a child. Clinicians should be vigilant about Ralstonia infections.

Clinical manifestations and gene analysis of Hutchinson-Gilford progeria syndrome: A case report.

BACKGROUND: This case report describes a child with Hutchinson-Gilford progeria syndrome (HGPS, OMIM: 176670) caused by LMNA (OMIM: 150330) gene mutation, and we have previously analyzed the clinical manifestations and imaging characteristics of this case. After 1-year treatment and follow-up, we focus on analyzing the changes in the clinical manifestations and genetic diagnosis of the patient. CASE SUMMARY: In April 2020, a 2-year-old boy with HGPS was found to have an abnormal appearance, and growth and development lagged behind those of children of the same age. The child's weight did not increase normally, the veins of the head were clearly visible, and he had shallow skin color and sparse yellow hair. Peripheral blood DNA samples obtained from the patient and his parents were sequenced using high-throughput whole-exosome sequencing, which was verified by Sanger sequencing. The results showed that there was a synonymous heterozygous mutation of C.1824 C>T (P. G608G) in the LMNA gene. CONCLUSION: Mutation of the LMNA gene provides a molecular basis for diagnosis of HGPS and genetic counseling of the family.