Objective:To analyze the current status of red blood cell transfusion in very preterm infants (VPI) (gestational age at birth <32 weeks) from Chinese Neonatal Network (CHNN) in 2022.Methods:This cross-sectional study was based on the CHNN VPI cohort. It included 6 985 VPI admitted to CHNN 89 participating centers within 24 hours after birth in 2022. VPI with major congenital anomalies or those transferred to non-CHNN centers for treatment or discharged against medical advice were excluded. VPI were categorized based on whether they received red blood cell transfusions, their gestational age at birth, the type of respiratory support received during transfusion, and whether the pre-transfusion hemoglobin levels exceeded the thresholds. General characteristics, red blood cell transfusion rates, number of transfusions, timing of the first transfusion, and pre-transfusion hemoglobin levels were compared among different groups. The incidence of adverse outcomes between the group of VPI who received transfusions above the threshold and those who received transfusions below the threshold were compared. Comparison among different groups was conducted using χ2 tests, Kruskal-Wallis H tests, Mann-Whitney U test, and so on. Trends by gestational age at birth were evaluated by Cochran-Armitage tests and Jonckheere-Terpstra tests for trend. Results:Among the 6 985 VPI, 3 865 cases(55.3%) were male, with a gestational age at birth of 30.0 (28.6, 31.0) weeks and a birth weight of (1 302±321) g. Overall, 3 617 cases (51.8%) received red blood cell transfusion, while 3 368 cases (48.2%) did not. The red blood cell transfusion rate was 51.8% (3 617/6 985), with rates of 77.7% (893/1 150) for those born before 28 weeks gestational age and 46.7% (2 724/5 835) for those born between 28 and 31 weeks gestational age. A total of 9 616 times red blood cell transfusions were administered to 3 617 VPI, with 632 times missing pre-transfusion hemoglobin data, and 8 984 times included in the analysis. Of the red blood cell transfusions, 25.6% (2 459/9 616) were administered when invasive respiratory support was required, 51.3% (4 934/9 616) were receiving non-invasive respiratory support, while 23.1% (2 223/9, 616) were given when no respiratory support was needed. Compared to the non-transfusion group, the red blood cell transfusion group had a higher rate of pregnancy-induced hypertension in mothers, lower rates of born via cesarean section and mother′s antenatal steroid administration, smaller gestational age, lower birth weight, a higher proportion of small-for-gestational-age, multiple births, and proportions of Apgar score at the 5 th minute after birth ≤3 (all P<0.05). They were also less likely to be female, born in hospital or undergo delayed cord clamping (all P<0.01). Additionally, higher transport risk index of physiologic stability score at admission were observed in the red blood cell transfusion group ( P<0.001). The number of red blood cell transfusion was 2 (1, 3) times, with the first transfusion occurring at an age of 18 (8, 29) days, and a pre-transfusion hemoglobin level of 97 (86, 109) g/L. For VPI ≤7 days of age, the pre-transfusion hemoglobin levels for invasive respiratory support, non-invasive respiratory support, or no respiratory support, respectively, with no statistically significant differences between groups ( H=5.59, P=0.061). For VPI aged 8 to 21 days and≥22 days, the levels with statistically differences between groups (both P<0.01). Red blood cell transfusions above recommended thresholds were observed in all respiratory support categories at different stages of life, with the highest prevalence in infants aged 8 to 21 days and≥22 days who did not require respiratory support, at 90.1% (264/273) and 91.1%(1 578/1 732), respectively. The rate of necrotizing enterocolitis was higher in the above-threshold group ( χ2=10.59, P=0.001), and the duration of hospital stay was longer in the above-threshold group ( Z=4.67, P<0.001) compared to the below-threshold group. Conclusions:In 2022, the red blood cell transfusion rate was relatively high among VPI from CHNN. Pre-transfusion hemoglobin levels frequently exceeded recommended transfusion thresholds.

Background Pneumoconiosis is the most serious occupational disease in China, among which silicosis accounts for more than 50%. microRNA (miRNA) plays an important role in the occurrence process of silicosis fibrosis, but the mechanism of it has not been fully clarified yet. Objective To explore the molecular mechanism by which miR-411-3p modulates the ubiquitination degradation of SMAD specific E3 ubiquitin protein ligase (SMURF) 2/Smad7, thereby suppressing epithelial-mesenchymal transition (EMT) in mouse alveolar type II epithelial cells and counteracting silica-induced pulmonary fibrosis. Methods Twenty-four 8-week-old SPF male C57BL/6J mice were randomly divided into four groups: Control group, silica group, silica +miR-411-3p agomir-NC group, and silica +miR-411-3p agomir group, with 6 mice in each group. Silicosis model was prepared by a one-time bronchial infusion of silicon dioxide (SiO₂) (200 mg·mL^-1, 50 μL). In vitro MLE-12 cells were divided into (1) control group and SiO₂ group, (2) SiO₂+negative control siRNA (siRNA-NC) group and SiO₂+Smurf2 gene silencing (si-Smurf2) group, (3) SiO₂+solvent (DMSO) group and SiO₂+protease inhibitor (MG132) group, (4) mutant sequence plasmid (Mut)+miR-411-3p mimic control (miR-NC) group, Mut+miR-411-3p mimic group, wild sequence plasmid (Wt)+miR-NC group, and Wt+miR-411-3p mimic group, (5) SiO₂+miR-NC group and SiO₂+miR-411-3p mimic group. The pathological morphology and collagen deposition of lung tissue were observed after staining. Detection of miR-411-3p and proteins was conducted by real-time fluorescent quantitative PCR and Western blot. The binding of SMURF2 to Smad7 protein and Smad7 to ubiquitin (Ub) were detected by co-immunoprecipitation (Co-IP) method. Dual-luciferase reporter gene assay was adopted to verify the regulatory effect of miR-411-3p on Smurf2. Results In the SiO₂-induced MLE-12 cells, compared to the control group, the SiO₂-treated group showed significantly upregulated expressions of N-cadherin (N-Cad), collagen I (CoL I), SMURF2, transforming growth factor-β1 (TGF-β1), and phosphorylated Smad2/3 (p-Smad2/3). In contrast, the expressions of E-cadherin (E-Cad), Smad7, and miR-411-3p were significantly downregulated (P<0.05). The dual-luciferase reporter gene assay revealed a regulatory effect of miR-411-3p on Smurf2 (P<0.05). Meanwhile, in the MLE-12 cells induced by SiO₂, the miR-411-3p mimic down-regulated the protein expressions of SMURF2, N-Cad, CoL I, TGF-β1, and p-Smad2/3, while up-regulated the protein expressions of E-Cad and Smad7 (P<0.05). The silenced Smurf2 gene inhibited the expressions of N-Cad, CoL I, and p-Smad2/3 proteins, while promoted the expressions of E-Cad and Smad7 proteins in the MLE-12 cells (P<0.05). The Co-IP results showed that the binding of SMURF2 to Smad7 was enhanced, and the ubiquitin binding ability of Smad7 was enhanced in the SiO₂ group. In the lung tissue of mice, the results of pathological observation with hematoxylin-eosin (HE) and sirius red (VG) staining showed that compared with the agomir-NC, the lesion was relieved in the lung tissue of the miR-411-3p agomir group. Meanwhile, the expressions of SMURF2, N-Cad, CoL I, TGF-β1, and p-Smad2/3 were significantly down-regulated, while the expressions of E-Cad and Smad7 were significantly up-regulated (P<0.05). Conclusion MiR-411-3p alleviates the EMT of alveolar type II epithelial cells and antagonizes silicosis fibrosis progression in mice by inhibiting SMURF2-mediated ubiquitination and degradation of Smad7.

BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

Wound cleansing is an essential step in skin wound management. It can prevent local infection and optimize healing micro-environment by removing necrotic tissue and foreign matter, reducing microbial load, breaking bacterial biofilm formation and so on. Many randomized controlled trials and meta-analysis abroad have concluded that there is no significant difference in the incidence of wound infection and healing rate between the wounds irrigated with tap water and with sterile normal saline for skin wound cleansing. Considering the current requirements of medical fee policies in China, we recommend the use of tap water instead of saline or other wound cleansing solutions for cleansing skin wounds.

Skin is an organ with complex structure and function. Extensive skin defects and chronic non-healing wounds cause serious problems for patients and clinicians, while traditional repair methods are still not able to completely reconstruct the structure and function of skin. To achieve complete reconstruction of skin structure and function is a great challenge that needs to be solved in the field of wound repair. Induced pluripotent stem cells, which have the potential to differentiate into any human cells, are widely used in the field of regenerative medicine research. In recent years, skin organoids constructed through in vitro cultivation of stem cells contain epidermis, dermis, and multiple skin appendages, which overcomes the limitations of traditional skin substitute and opens new avenues for wound repair and its basic research. This review outlines the status of the research and application of skin organoids and discusses their current challenges in clinical translation and prospects for development.

Objective:To evaluate the effects and underlying mechanisms of metabolites derived from the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction on the proliferation of multiple myeloma (MM) KM3 cells.Methods:MM KM3 cells in the logarithmic growth phase were treated with 3%, 6%, 9%, or 12% metabolites of kidney-reinforcing, blood circulation-activating, and collateral dredging decoction. Cell viability was assessed using the CCK-8 assay. Apoptosis and necrosis were evaluated using flow cytometry and TUNEL staining. Mitochondrial and cellular ultrastructural changes were examined using transmission electron microscopy. mRNA and protein expression levels of dynamin-related protein 1 (Drp1), mitochondrial fission protein 1 (Fis1), mitochondrial fission factor (MFF), PTEN-induced kinase 1 (Pink1), and E3 ubiquitin ligase (Parkin) were determined through quantitative real-time PCR and western blotting. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) combined with network pharmacology, was utilized for reverse verification of the pharmacodynamic mechanisms and therapeutic targets underlying the anti-MM activity of this decoction.Results:The metabolites of the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction inhibited KM3 cell proliferation and induced apoptosis in a dose-dependent manner. Transmission electron microscopy revealed increased mitochondrial fission and autophagic structures, with effects intensifying at higher metabolite concentrations. mRNA and protein expression of Drp1, Fis1, MFF, Pink1, and Parkin were significantly upregulated in treatment groups compared to controls ( P<0.05), with the most pronounced effects observed in the 12% metabolite group ( P<0.01). HPLC-MS/MS identified 121 bioactive compounds in BHTF, which shared 474 overlapping targets with MM. Enrichment analysis suggested that BHTF exerts antitumor effects primarily through apigenin, palmatine, and other key components by modulating TNF, NF-κB, and mitophagy pathways. Conclusion:The kidney-reinforcing and blood circulation-activating and collateral dredging decoction suppresses the proliferation of MM KM3 cells, potentially through mechanisms involving the regulation of mitochondrial dynamics and induction of autophagy.

Objective:To explore the value of paediatric age-adjusted shock index（SIPA）in early identification of septic shock in children，and to evaluate the relationship between SIPA and disease severity and prognosis.Methods:The infected children admitted to the department of critical care medicine of the Children's Hospital Affiliated to Capital Institute of Pediatrics from May 2023 to July 2024 were collected. Dynamic assessment was performed 0 to 6 hours after admission. Patients diagnosed with sepsis without septic shock were classified as the sepsis group and those diagnosed with sepsis with septic shock were classified as the septic shock group. According to whether the blood pressure of the children decreased，they were divided into two groups：compensated septic shock group and decompensated septic shock group. The difference of SIPA among the three groups was analyzed，and the predictive value of SIPA on case fatality rate，lactate level，pediatric critical illness score，ventilator utilization rate and length of hospital stay were analyzed.Results:Among 203 children with sepsis，112 were males and 91 were females. There were 146 cases in the sepsis group，37 cases in the compensated septic shock group and 20 cases in the decompensated septic shock group. There was no significant difference between the three groups in gender（ P>0.05），but there was a statistically significant difference in age（ χ 2=32.905， P<0.001）. There was no significant difference in age between the sepsis group and the compensated septic shock group（ P>0.05）. The age of sepsis group and decompensated septic shock group，compensated septic shock group and decompensated septic shock group were statistically significant（ χ 2=29.431， P<0.001； χ 2=19.764， P=0.001）. The proportion of increased SIPA was statistically different among the three groups，with both the compensated septic shock group and the decompensated septic shock group being higher than the sepsis group（ χ2=20.383， P<0.001； χ2=33.600， P<0.001）. The decompensated septic shock group was higher than the compensated septic shock group（ χ2=6.555， P=0.01）. SIPA was correlated with case fatality rate，lactate level，pediatric critical illness score，ventilator use rate and length of stay of the children，with statistically significant differences（ P<0.05）. Conclusion:The increase of SIPA can be used for the early identification of septic shock in children，and it has a certain early warning value for the prognosis assessment of sepsis and septic shock.

Due to the difficulty of overcoming the abnormal epidermal barriers and addressing S. aureus infections without disrupting indigenous skin microbiota, effective treatment of bacterial infection atopic dermatitis (AD) remains a significant clinical challenge. Skin microbiota-derived extracellular vesicles (EVs) shows protentional for skin disease treatment, but the lack of antimicrobial activity and limited skin penetration hamper their application in bacterial infection AD treatment. Here, we developed novel nanoantibiotics by loading Lev into S. epidermidis-derived EVs (Lev@SE-EVs), with supreme antimicrobial activity, regulating epidermal immune responses and enhanced epidermal barrier functionality. The nanoantibiotics were further integrated into hyaluronic acid-based microneedle (MN) for efficient transdermal delivery of therapeutic agents and effectively treating bacterial infection in AD. Upon insertion into the skin, the rapidly released Lev@SE-EVs from MN are uptake by S. aureus in a selective manner, fibroblasts, and surrounding immune cells to exert therapeutic effects in the infected dermal layer, resulting in mitigated skin inflammation, reduced S. aureus burden and increased dermis repair. Notably, Lev@SE-EVs induce IL-17A⁺ CD8⁺ T-cell accumulation in the skin in an unrelated inflammation manner, which may represent heterologous protection. This EVs-integrated MN assisted Lev@SE-EVs to alleviate skin inflammation, repair skin, and provide an effective and safe therapeutic approach for bacterial infection AD treatment.

Pinelliae Rhizoma (PR), known as Banxia in Chinese, Hange in Japanese, and Banha in Korean, is a renowned herbal medicine in East Asia derived from the dry tuber of Pinellia ternata (Thunb.) Breit. (PT). It is extensively utilized in dispensing granules, classical prescriptions, and herbal formulas to treat various conditions, including cough, infection, phlegm, nausea, asthma, and inflammation. Despite numerous studies on PR and its classical prescriptions over recent decades, a comprehensive synthesis of available evidence regarding its multifunctional roles and therapeutic potential is lacking. This review aims to address this gap by examining emerging evidence from metabonomics, preclinical studies, and clinical trials, while exploring potential trends and prospects for future research. A systematic literature search was conducted across six electronic databases, including PubMed, Web of Science, Scopus, ScienceDirect, Wanfang, and China National Knowledge Infrastructure, to identify relevant articles on PR published until March 2023. PR contains 107 compounds with diverse pharmacological activities, including anti-inflammatory, immune regulatory, anti-viral, anti-cancer, anti-asthma, antitussive and expectorant, antioxidant, anti-obesity, anti-atherosclerosis, anti-microbial, emetic and anti-emetic, anti-convulsant and anti-epileptic, sedative and hypnotic, learning and memory enhancement, and anti-depressant effects. Metabonomic studies suggest that raw PR may exhibit cardiotoxicity and pregnancy toxicity while showing no apparent hepatorenal toxicity. However, limited pharmacokinetic investigations on PR constrain its clinical translation. Furthermore, clinical safety data on PR is scarce, with only four clinical trials assessing its positive effects in pediatric epilepsy, nausea and vomiting, soft tissue injury, and chronic sinus tract. This review aims to enhance understanding of PR and provide valuable information and recommendations for further research and development of herbal medicine.
Humans ; Pinellia/chemistry* ; Animals ; Ethnopharmacology ; Drugs, Chinese Herbal/chemistry* ; Phytochemicals/chemistry* ; Rhizome/chemistry*

Objective : To explore the correlation between the clinical, pathological, genetic features, prognosis, and tumor lymph node metastasis in patients with stage ⅠA-Ⅲ B lung invasive non-mucinous adenocarcinoma(INMA). Methods: A retrospective analysis was conducted on 67 eligible patients with INMA. Clinical data, histopathological assessments, and genetic testing were collected. Disease progression-free survival(PFS) was the primary endpoint through follow-up. The chi-square test or Fisher's exact test was used to analyse the correlation between tumour lymph node metastasis and clinicopathological and genetic characteristics. The Cox proportional hazards regression model and Kaplan-Meier method were used to analyse the impact of tumour lymph node metastasis on prognosis. Results: A total of 67 patients were included, aged 46-77 years, with a median age of 61 years. Age, gender, and smoking history were not significantly associated with tumor lymph node metastasis. Larger tumor diameter, tumor progression, and receiving postoperative adjuvant treatment were associated with tumour lymph node metastasis(P<0.05). Poorer differentiated tumors according to International Association for the Study of Lung Cancer(IASLC) grading system was more likely to have lymph node metastasis(P=0.043). There was no significant difference in the types of driver gene mutations and lymph node metastasis. However,EGFRmutations were more common in patients without lymph node metastasis, while co-mutations were more common in patients with lymph node metastasis. Lymph node metastasis was significantly associated with PFS. Patients without lymph node metastasis had a significantly better PFS compared to those with lymph node metastasis(P=0.002). Under different treatment conditions, patients without lymph node metastasis exhibited a significant advantage in PFS when untreated. While treatment showed a trend toward improved PFS, the difference did not reach statistical significance. Additionally, no significant differences in PFS were observed between patients with or without lymph node metastasis following chemotherapy or targeted therapy. Conclusion Lymph node metastasis in INMA patients is related to tumor size, progression status, and gene co-mutations, and is a key prognostic indicator affecting PFS.