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Although the incidence of rare diseases is extremely low, 6% to 8% of the global population are affected by more than 7000 rare diseases. Rare diseases guidelines are playing an increasingly important role as guiding documents in improving the health outcomes of patients with rare diseases. Therefore, we aim to systematically elaborate on the status quo, challenges and opportunities of rare disease guidelines at home and abroad, and put forward thoughts and suggestions on promoting the development of rare diseases guidelines in the future.

Background: Airway epithelial cells constitute the first line of defense against external noxious stimuli and play crucial roles in the release of epithelial inflammatory cytokines (IL33, IL25 and TSLP), initiating airway allergic inflammatory diseases such as asthma. IL33 plays critical physiological processes in T2-endotype asthma. However, the mechanisms by which allergen exposure triggers IL33 release from airway epithelial cells remain unclear. Methods: Integrated bioinformatic analysis and transcriptional analysis of bulk RNA-seq and single cell RNA-seq (scRNA-seq) data were used to identify core genes and determine the internal gene network associated with IL33. The expression of EGR1 was subsequently analyzed in vitro in the BEAS-2B cell line and in vivo in a house dust mite (HDM)-induced mouse asthma model. The functional experiments of EGR1 were investigated in vitro via siRNA knockdown and over-expressed plasmid. Chromatin immunoprecipitation (ChIP)-PCR and dual-luciferase reporter assay validation were subsequently performed to investigate the mechanisms by which EGR1 regulates IL33 secretion. Results: Bulk RNA-seq and scRNA-seq data identified EGR1 as an epithelial cell-derived gene implicated in IL33 expressions in asthma. The comprehensive analysis of multiple datasets indicated that the high EGR1 expression in epithelial cells may suggest a mechanistic basis of T2-endotype childhood asthma. Moreover, we verified that the expressions of EGR1 in airway epithelial cells were elevated both in vitro and in vivo asthma models. EGR1 regulated the production of IL33. Ultimately, ChIP and luciferase reporter assays confirmed that transcription factor EGR1 directly regulate the transcription of IL33 mRNA. Conclusions: Our integrated bioinformatic analysis elucidated that EGR1 directly regulates the production of IL33 in T2-asthma and provide insights underlying the progression of asthma. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis (PF) is a lethal pathological change of fibrotic interstitial lung diseases (ILDs) with abundant fibroblasts proliferation after severely or continually alveolar epithelial cells (AECs) injury. Barely therapies are helpful for PF. Here we use bleomycin intratracheally injection to model PF with or without human umbilical cord–mesenchymal stem cells (hUC–MSCs) and/or nintedanib intervention. RNA‐Seq followed with real‐time PCR and western blot were used to find out the specific possible mechanisms of the effects of hUC–MSC and nintedanib on PF. Immunostaining, cell counting kit‐8 (CCK‐8), and 5‐bromo‐2′‐deoxyuridine (BrdU) incorporation assay were used to detect the cell proliferation in vivo or in vitro separately. We found that hUC–MSCs alone had prophylactic, but not therapeutic effects on bleomycin induced mouse PF. Nevertheless, the combination therapy of hUC–MSCs and low‐dose nintedanib significantly improved survival and reversed lung fibrosis in PF model mice. The factors secreted by hUC–MSCs have promotional effects on the proliferation both of fibroblasts and AECs. Nintedanib could hamper the facilitation of fibroblasts caused by hUC–MSCs without influence on AECs proliferation, which might be related with the inhibition on FGFR, PDGFR, and VEGFR activities. Our study indicated that the combination therapy of hUC–MSCs and nintedanib should be a promising strategy for PF. [ABSTRACT FROM AUTHOR]

Mycoplasma pneumoniae (MP) is highly resistant to macrolides in China. However, macrolides still exhibit clinical effectiveness in some macrolide-resistant patients. We tend to explore azithromycin effectiveness in Mycoplasma pneumoniae pneumonia (MPP) children with A2063/2064G mutation. Methods: This retrospective observational cohort study was conducted at the Children's Hospital of the Chongqing Medical University. Children with macrolide-resistant mutations (A2063/2064G) diagnosed as MPP were retrospectively enrolled. Receiver operating characteristic (ROC) curves and logistic regression analysis were used to evaluate and identify independent risk factors for treatment failure (progress to refractory Mycoplasma pneumoniae pneumonia [RMPP]) in macrolide-unresponsive Mycoplasma pneumoniae pneumonia (MUMPP) children with the A2063/2064G mutation. Results: One hundred fifty-five children were retrospectively enrolled. More than 20% (36/155, 23.23%) of patients experienced defervescence within 3 days of azithromycin treatment. RMPP was diagnosed in 54 patients (54/155, 34.84%) and the incidence of RMPP during hospitalization was 22.72 per 1000 person-days. Logistic regression analysis showed that lactate dehydrogenase (LDH) ≥ 399 (U/L) was an independent risk factor for RMPP (odds ratio [OR] 4.66, 95% confidence interval [CI] 1.31– 17.10, P=0.017). During the year followed, RMPP patients had a significantly higher incidence of bronchiolitis obliterans and bronchiectasis than non-RMPP patients (16.67% vs 1.98%, P=0.001; 9.26% vs 0.00%, P=0.005, respectively). Conclusion: Azithromycin was effective in children with MPP with the A2063/2064G mutation. For MUMPP children with A2063/2064G mutation, children with LDH ≥ 399 (U/L) had significant higher risk for progression to RMPP, and should consider to be treated with alternative antibiotics (eg tetracyclines, and fluoroquinolones). [ABSTRACT FROM AUTHOR]

Objective: As a large and populous country, China releases a high number of diagnostic criteria. However, the published diagnostic criteria have not yet been systematically analyzed. Therefore, the aim of this study is to investigate the characteristics, development methods, reporting quality, and evidence basis of diagnostic criteria published in China. Methods: We searched five databases for diagnostic criteria from their inception until July 31, 2023. All diagnostic criteria were screened through abstract and full‐text reading, and included if satisfying the prespecified criteria. Two researchers independently extracted data on the characteristics, development methods, reporting quality, and evidence basis of diagnostic criteria. Results: A total of 143 diagnostic criteria were included. In terms of development methods, the proportions of diagnostic criteria that involved a systematic literature search (n = 2; 1.4%; 95% confidence interval (CI), 0.4% to 5.0%), adoption of formal consensus methods (n = 4; 2.8%; 95% CI, 1.1% to 7.0%), and criteria validation (n = 9; 6.3%; 95% CI, 3.3% to 11.5%) were relatively low. Regarding reporting quality, the average compliance with the ACCORD checklist was 5.1%; none of the diagnostic criteria reported on registration, expert inclusion criteria, expert recruitment process, or consensus results. A majority (58.7%; 95% CI, 50.6% to 66.5%) of criteria did not cite any research, and only one (0.7%; 95% CI, 0.1% to 3.9%) criterion was derived from a systematic review. Moreover, only 16.1% (95% CI, 11.0% to 23.0%) of diagnostic criteria used evidence from the Chinese population. Conclusion: The diagnostic criteria developed in China exhibit serious flaws, particularly in evidence retrieval, formation of expert panels, consensus methods, and validation. Additionally, only few diagnostic criteria used a systematic synthesis of the evidence or evidence from the China. There is an urgent need to enhance the methodology for developing diagnostic criteria. [ABSTRACT FROM AUTHOR]