Objective: To explore the clinical characteristics and diagnosis and treatment plans of neurofibromatosis type 1 (NF1), and to provide references for clinical diagnosis and treatment. Methods : The clinical manifestations and treatment of an 8-year-old female patient with NF1 was reported. A literature review was conducted to summarize the clinical characteristics and therapeutic strategies of NF1. Multiple NF1s occurred on the right cheek, orbit, and eyelid, and recurred after surgical resection. The tumor caused ptosis, incomplete closure, and vision loss in the upper eyelid of the right eye. After a multidisciplinary assessment determined that radical resection was not feasible, selumetinib sulfate targeted therapy was adopted (25 mg, Po, bid), 28 days constitute one treatment course, and 14 courses have been completed, combined with symptomatic ocular treatments, such as Befusu. Result: The follow-up showed that the tumor volume did not continue to increase (stable disease), the uncorrected vision of the right eye improved (0.05 vs 0.1), and no drug-related adverse reactions occurred during the treatment period. The literature review summarizes the diverse clinical manifestations of NF1, with café-au-lait macules, multiple neurofibromas, and Lisch nodules being hallmark features. Currently, surgical intervention remains the most commonly employed and primary therapeutic approach for NF1; however, for patients who do not meet the criteria for surgery, alternative treatment strategies should be considered. MEK inhibitors, such as selumetinib, demonstrate significant efficacy in inhibiting the growth of NF1-associated plexiform neurofibromas, with tumor volume reductions of at least 20% observed in 70% of pediatric patients in the SPRINT clinical trial. Furthermore, these inhibitors exhibit favorable long-term safety profiles. Conclusion Café-au-lait macules, multiple neurofibromas, and Lisch nodules are hallmark features of NF1. Selumetinib is safe and effective for NF1 in the head and neck of children, and it is the preferred treatment option for patients who are not suitable for surgery. Long-term follow-up monitoring of tumor changes and drug safety is required.

Objective: To explore the association between serum nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), NIMA-related kinase 7 (NEK7) and pulmonary fibrosis among patients with coal workers' pneumoconiosis, so as to provide a basis for the assessment of the degree of pulmonary fibrosis. Methods: Coal workers with pneumoconiosis hospitalized in the Second Affiliated Hospital of Xuzhou Medical University from July 2022 to July 2023 were selected by simple random sampling. Data such as age, stage of pneumoconiosis, and dust-exposure duration were collected through the hospital's electronic medical record management system. Venous blood was collected to detect the levels of serum NLRP3 and NEK7. High-resolution computed tomography (HRCT) image data of the chest were obtained through the hospital's imaging reporting system. The left and right lungs were divided into 6 pulmonary regions according to the upper, middle, and lower parts. The pulmonary fibrosis score was quantified according to the proportion of the pulmonary area occupied by HRCT manifestations of pulmonary fibrosis, including reticular shadows, pleural and interlobular septal thickening, traction bronchiectasis, and honeycombing. The association between the levels of serum NLRP3, NEK7, and pulmonary fibrosis was analyzed using a multiple linear regression model. Results: A total of 81 patients with coal workers' pneumoconiosis were included, all of whom were male, with a mean age of (71.46±11.69) years. There were 48, 28, and 5 cases in stage Ⅰ, stage Ⅱ, and stage Ⅲ of pneumoconiosis pathological staging, accounting for 59.26%, 34.57%, and 6.17%, respectively. There were 45 cases of tunneling and coal mining, accounting for 55.56%. There were 41 cases with dust exposure years of ≥30 years, accounting for 50.62%. The median serum NLRP3 and NEK7 in patients with coal workers' pneumoconiosis were 2.01 (interquartile range, 2.33) ng/mL and 0.98 (interquartile range, 0.83) ng/mL. The median score of pulmonary fibrosis was 5.00 (interquartile range, 5.50) points. After adjusting for age, stage of pneumoconiosis, type of work and dust-exposure duration, multiple linear regression analysis showed that serum NLRP3 (β'=0.649) and NEK7 (β'=0.346) were positively correlated with the pulmonary fibrosis score. Conclusion The increase in the levels of serum NLRP3 and NEK7 in patients with coal workers' pneumoconiosis is related to the increase in the degree of pulmonary fibrosis.

INTRODUCTION: Takayasu arteritis is the most common large-vessel vasculitis in childhood, but there is a lack of literature regarding childhood-onset Takayasu arteritis (c-TAK) in Southeast Asia. We aim to describe a c-TAK cohort in Singapore and highlight a unique subset that first presents with Kawasaki-like disease (KD). METHOD: A single-centre cohort study in Singapore of consecutive children diagnosed with c-TAK between 2002 and 2023 was performed. Demographic and clinical features, laboratory and angiographic findings, treatment, and outcomes were summarised. Disease activity was evaluated using the Paediatric Vasculitis Disease Activity Score and inflammatory markers. RESULTS: Twenty-three patients, fulfilling both the EULAR/ PRINTO/PReS and ACR/EULAR 2022 criteria, were recruited. The most common clinical features at diagnosis were fever (15, 65%) and neurological symptoms (11, 48%, half of which presented with stroke), while the most prevalent angiographic pattern by Hata's classification was Type V (21, 91%). Eight children (35%) initially presented with refractory KD, and these patients were significantly younger, more male-predominant, and had higher inflammatory markers at diagnosis; all of them had coronary artery involvement, but none had intracranial vascular findings. Of the entire cohort, 16 (70%) achieved inactive disease on medications with a median duration of 6 months (interquartile range [IQR]: 4-11), and 8 (35%) achieved remission off medications with a median duration of 43 months (IQR 35-60). CONCLUSION Our c-TAK cohort has high proportions of neurological involvement and stroke. This is also the first cohort study to describe a distinct group of patients who first presented with refractory KD.
Humans ; Takayasu Arteritis/complications* ; Singapore/epidemiology* ; Male ; Female ; Child ; Adolescent ; Age of Onset ; Mucocutaneous Lymph Node Syndrome/diagnosis* ; Cohort Studies ; Child, Preschool ; Fever/etiology* ; Stroke/epidemiology* ; Retrospective Studies

This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

The 95% ethanol extract from bulbs of Narcissus tazetta var. chinensis(BNTC) was eluted with 30%, 60%, and pure methanol on D-101 macroporous resin. The elution fractions were isolated and purified by silica gel column chromatography, thin layer chromatography, D-101 macroporous resin, semi-preparative high performance liquid chromatography(HPLC), and HPLC. The purified compounds were identified using one-dimensional and two-dimensional spectroscopy, high-resolution mass spectrometry, and other techniques. A total of 15 compounds were isolated and identified as 5-(4-hydroxy-3-methoxyphenyl)-3-(4-hydroxyphenyl)-N-methyl-3,6-dihydropyridine-2(1H)-one(1), 3,5-di(hydroxyphenyl)-N-methyl-3,6-dihydropyridine-2(1H)-one(2), protocatechualdehyde(3), protocatechuic acid(4), 3,4-dihydroxyacetophenone(5), syringic acid(6), vanillic acid(7), p-hydroxybenzoic acid(8),(2S)-4'-hydroxy-7-methoxyflavan(9), 2,4,6-trimethoxyacetophenone(10), N-trans-ferulic acid p-hydroxyphenylethylamine(11), N-cis-p-coumaroyltyramine(12), N-trans-p-coumaroyltyramine(13), piscidic acid(14), 5-hydroxymethylfurfural(15). Compounds 1 and 2 are new compounds with similar structure that have not been reported yet, named narcissus A and narcissus B. Compounds 8-13 were isolated and identified from the genus Narcissus for the first time, and compounds 14 and 15 were isolated from BNTC for the first time. Compounds 1 and 2 inhibited the release of NO from RAW264.7 cells induced by lipopolysaccharide(LPS)(P<0.001), with compound 1 having an IC_(50) value of(72.76±2.97) μmol·L~(-1) and compound 2 having an IC_(50) value of(63.59±0.96) μmol·L~(-1).
Mice ; Animals ; Narcissus/chemistry* ; Drugs, Chinese Herbal/isolation & purification* ; Plant Roots/chemistry* ; Chromatography, High Pressure Liquid ; Macrophages/immunology* ; RAW 264.7 Cells

Syringa pinnatifolia, belonging to the family Oleaceae, is a species endemic to China. It is predominantly distributed in the Helan Mountains region of Inner Mongolia and Ningxia of China. The peeled roots, stems, and thick branches have been used as a distinctive Mongolian medicinal material known as "Shan-chen-xiang", which has effects such as suppressing "khii", clearing heat, and relieving pain and is employed for the treatment of cardiovascular and pulmonary diseases and joint pain. Over the past five years, significant increase was achieved in research on chemical constituents and pharmacological effects. There were a total of 130 new constituents reported, covering sesquiterpenoids, lignans, and alkaloids. Its effects of anti-myocardial ischemia, anti-cerebral ischemia/reperfusion, sedation, and analgesia were revealed, and the mechanisms of agarwood formation were also investigated. To better understand its medical value and potential of clinical application, this review updates the research progress in recent five years focusing on the chemical constituents and pharmacological effects of S. pinnatifolia, providing reference for subsequent research on active ingredient and support for its innovative application in modern medicine system.
Medicine, Mongolian Traditional ; Humans ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Syringa/chemistry*

Transfusion-dependent thalassemia (TDT) is a severe genetic chronic hemolytic disease, and growth retardation is a common clinical feature in patients with TDT. Due to the need for regular blood transfusions, these patients often experience iron overload, which leads to various endocrine dysfunctions, including abnormalities in the growth hormone/insulin-like growth factor axis, hypothyroidism, hypoparathyroidism, hypogonadism, adrenal insufficiency, and decreased bone density. This paper reviews the clinical monitoring and intervention measures for growth disorders and related endocrine functions in patients with TDT, providing references for clinicians.
Humans ; Thalassemia/physiopathology* ; Child ; Growth Disorders/diagnosis* ; Blood Transfusion ; Endocrine System Diseases/therapy*

OBJECTIVE: To investigate the clinical efficacy of moxibustion (Mox) combined with low-dose tadalafil (TAD) in the treatment of diabetes mellitus-induced erectile dysfunction (DMED) with the syndrome of Qi deficiency and blood stasis. METHODS: According to the inclusion and exclusion criteria, we selected 90 patients with DMED for this trial and equally randomized them into a Mox, a TAD, and a Mox combined with TAD (Mox+TAD) group to be treated by mild Mox applied to the acupoints Zusanli, Sanyinjiao and Yinlingquan qd alt, oral medication with low-dose TAD at 5 mg per dose qd, and combination of the above two therapies, respectively, all for 4 weeks. We obtained from the patients their IIEF-5 scores, traditional Chinese medicine (TCM) symptoms scores, Erectile Hardness Scale (EHS) scores, corpus cavernosal hemodynamic indexes, and the peak systolic velocity (PSV), end diastolic velocity (EDV) and resistance index (RI) of the corpus cavernosal arteries before and after treatment, and compared them among the three groups. RESULTS: The total effectiveness rate was significantly higher in the Mox+TAD (90.0%) than in the Mox (46.7%) and TAD groups (60.0%) (P< 0.05). Compared with the baseline, the IIEF-5 and EHS scores were increased, while the TCM symptoms scores decreased in all the three groups after treatment, more significantly in the Mox+TAD group than in the other two (P< 0.05). And the PSV and RI were remarkably increased, while the EDV decreased (P< 0.05) in all the three groups (P< 0.05) after treatment, with PSV even higher in the Mox+TAD than in the Mox and TAD groups (P< 0.05). CONCLUSION Moxibustion combined with tadalafil has a definite efficacy and safety for the treatment of DMED, which can effectively improve the erectile function of the patients by increasing penile blood supply, benefiting qi and activating blood circulation.
Humans ; Male ; Tadalafil ; Erectile Dysfunction/etiology* ; Moxibustion ; Middle Aged ; Prospective Studies ; Adult ; Carbolines/administration & dosage* ; Diabetes Complications/therapy* ; Aged ; Treatment Outcome ; Combined Modality Therapy

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

The PA-PB1 interface of the influenza polymerase is an attractive site for antiviral drug design. In this study, we designed and synthesized a mini-library of indazole-containing compounds based on rational structure-based design to target the PB1-binding interface on PA. Biological evaluation of these compounds through a viral yield reduction assay revealed that compounds 27 and 31 both had a low micromolar range of the half maximal effective concentration (EC₅₀) values against A/WSN/33 (H1N1) (8.03 μmol/L for 27; 14.6 μmol/L for 31), while the most potent candidate 24 had an EC₅₀ value of 690 nM. Compound 24 was effective against different influenza strains including a pandemic H1N1 strain and an influenza B strain. Mechanistic studies confirmed that compound 24 bound PA with a K _d which equals to 1.88 μmol/L and disrupted the binding of PB1 to PA. The compound also decreased the lung viral titre in mice. In summary, we have identified a potent anti-influenza candidate with potency comparable to existing drugs and is effective against different viral strains. The therapeutic options for influenza infection have been limited by the occurrence of antiviral resistance, owing to the high mutation rate of viral proteins targeted by available drugs. To alleviate the public health burden of this issue, novel anti-influenza drugs are desired. In this study, we present our discovery of a novel class of indazole-containing compounds which exhibited favourable potency against both influenza A and B viruses. The EC₅₀ of the most potent compounds were within low micromolar to nanomolar concentrations. Furthermore, we show that the mouse lung viral titre decreased due to treatment with compound 24. Thus our findings identify promising candidates for further development of anti-influenza drugs suitable for clinical use.