ObjectiveTo explore the clinical efficacy and mechanism of Bupi Qingfei prescription （BPQF） in treating stable bronchiectasis in the patients with syndromes of lung-spleen Qi deficiency and phlegm-heat accumulation in the lungs. MethodsA randomized， double-blind， placebo-controlled trial was conducted. Patients were randomized into BPQF and placebo control （PC） groups. On the basis of conventional Western medicine treatment， the BPQF granules and placebo were respectively administered at 10 g each time， twice a day， for a course of 24 weeks. The TCM symptom scores， Quality of Life Questionnaire for Bronchiectasis （QOL-B） scores， lung function indicators， T lymphocyte subsets， level of inflammatory factors in the sputum， level of neutrophil elastase （NE） in the sputum， and occurrence of adverse reactions were observed before and after treatment in the two groups. ResultsA total of 64 patients completed the study， encompassing 32 in the BPQF group and 32 in the PC group. After treatment， the BPQF group showed decreased TCM symptom scores （P<0.01）， increased QOL-B scores （P<0.01）， and declined levels of tumor necrosis factor （TNF）-α and NE （P<0.05， P<0.01）. The PC group showed decreased TCM symptom （except spleen deficiency） scores （P<0.01）， increased the QOL-B health cognition and respiratory symptom domain scores （P<0.05， P<0.01）， and a declined TNF-α level （P<0.01）. Moreover， the BPQF group had lower TCM symptom （except chest tightness） scores （P<0.05， P<0.01）， higher QOL-B （except treatment burden） scores （P<0.05， P<0.01）， and lower levels of interleukin-6 and TNF-α （P<0.05） than the PC group. Neither group showed serious adverse reactions during the treatment process. ConclusionBPQF can ameliorate the clinical symptoms of stable bronchiectasis patients who have lung-spleen Qi deficiency or phlegm-heat accumulation in the lungs by regulating the immune balance and inhibiting airway inflammatory responses.

Retinoblastoma(RB)represents the most common primary intraocular malignant tumor in infants and young children, posing a severe threat to the visual acuity and life of affected patients. Clinically, it is categorized into hereditary and non-hereditary subtypes. Mounting evidence indicates that RB cells most likely originate from cone photoreceptor precursor cells, and the tumorigenesis is closely associated with the inactivation of the RB1 gene. Beyond RB1, a growing list of genes including MYCN, TP53 and PRMT1 have been implicated in the initiation and progression of RB. Concurrently, the dysregulation of multiple signaling pathways such as RB/E2F, WNT, and PI3K/AKT synergistically drives the survival, proliferation, invasion, and metastasis of RB tumor cells. The therapeutic paradigm for RB has undergone a dramatic shift from the conventional enucleation-dominated approach to personalized multimodal therapies that prioritize globe salvage and visual preservation, encompassing local therapies, chemotherapy and radiotherapy. Moreover, novel therapeutic modalities including targeted therapy, immunotherapy and gene therapy are currently under active preclinical and clinical investigation. In recent years, long non-coding RNAs(lncRNAs), as pivotal regulators of genetic expression, have attracted increasing attention for their critical roles in RB oncogenesis and progression. These molecules hold great promise to serve as novel diagnostic biomarkers and offer innovative insights and strategies for RB treatment. This review summarizes the latest research advances in the aforementioned aspects of retinoblastoma.

OBJECTIVE To explore a model for constructing a platform for medical institution formulation and provide insights for promoting their development. METHODS By systematically reviewing the development status and challenges of medical institution preparations in China， and based on the theory of industry-university-research collaborative innovation， the organizational structure， collaborative processes， and safeguard mechanisms of the platform were designed. RESULTS & CONCLUSIONS Medical institution formulations in China mainly faced challenges such as weak research and development （R&D） capacity， uneven quality standards， and blocked transformation pathways. This study established a full-chain， whole- industry collaborative innovation network covering the government， medical institutions， universities/research institutes， pharmaceutical enterprises， and the market， forming a new “government-industry-university-research-application” five-in-one platform model for medical institution formulations. By establishing mechanisms such as multi-entity collaborative cooperation， full- chain intellectual property management， contribution-based benefit distribution， staged risk-sharing， and third-party evaluation， the model clarified the responsibilities and collaborative pathways of all parties. The new model highlights the whole-process transformation of clinical experience-based prescriptions， enabling precise alignment between clinical needs and technological R&D， as well as between preparation achievements and industrial transformation. While breaking down the barriers of traditional platform construction， it effectively achieves optimal resource allocation and complementary advantages， addresses problems emerging in the development of medical institution preparations， and provides reference value for the formulation of relevant systems.

Background: Influenza A virus (IAV) is a negative-sense RNA virus of the Orthomyxoviridae family and is the etiological agent of a highly contagious acute respiratory disease that can lead to acute lung injury. Objective: To elucidate the molecular mechanisms of IAV infection, an integrative research approach combining gene expression profiling, multinetwork analysis, and in vivo experimental validations was employed. Methods: First, a series of network-based analyses were performed, including protein-protein interaction network construction, weighted gene co-expression network analysis, and subsequent gene set enrichment analysis, to identify the major underlying mechanisms of IAV infection. Following gene expression analysis, core targets, both direct and indirect regulators, were screened. An IAV (H1N1) strain A/PR/8/34-induced acute lung injury mouse model was constructed for in vivo validations. Batch one included two groups to evaluate findings from the multi-network analysis: Mock (n = 10; 5 males and 5 females) and IAV (n = 10; 5 males and 5 females). Batch two included three groups to assess the role of toll-like receptor 3 (TLR3) in IAV infection: Mock (n = 6; 3 males and 3 females), IAV (n = 6; 3 males and 3 females), and TLR3 inhibitor (n = 6; 3 males and 3 females). Body weight was measured on days 0, 3, and 5 after infection. On day 5, lung tissues were collected to assess viral load and histopathological changes. Key targets were examined using enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining, both in sera and lung tissues. Results: IAV infection was significantly associated with dysregulation of the immune-inflammation system, such as the LTR, nucle-otide-binding oligomerization domain-(NOD) like receptor, retinoic acid-inducible gene I-like receptor, and nuclear factor kappa-B signaling pathways. Gene set enrichment analysis further indicated that the TLR and necroptosis signaling pathways played crucial roles in the progression of IAV infection (TLR signaling pathway normalized enrichment score = 2.3941, P = 1.00 × 10 ⁻¹⁰; necroptosis normalized enrichment score = 1.9421, P = 6.21 × 10 ⁻⁷). Among the core targets, TLR3 and mixed lineage kinase domain-like protein (MLKL) may regulate gene expression at the transcriptional level (all P < 0.05). In vivo validation using an IAV (PR8) infected acute lung injury mouse model demonstrated increased viral load and lung index, alveolar structural damage, and inflammatory cell infiltration. Immunofluorescence staining exhibited large gaps in Lamin B1 staining and breaches in Emerin signals following IAV-PR8 infection. Expression levels of TLR3, p-receptor-interacting serine/threonine-protein kinase 3 (RIPK3)/RIPK3, and p-mixed lineage kinase domain-like protein (MLKL)/MLKL proteins in lung tissues, as well as proinflammatory factors and mediators in sera, were significantly elevated after IAV infection. Moreover, enhanced neutrophil infiltration (myeloperoxidase) and citrullinated histone H3 (a neutrophil extracellular trap-specific marker), both established indicators of neutrophil extracellular trap formation, were observed. Notably, treatment with a TLR3 inhibitor significantly ameliorated IAV-induced acute lung injury by regulating necroptosis-related targets. Conclusion: Our study provides network-based in vivo evidence that TLR3-receptor-interacting serine/threonine-protein kinase 3-MLKL-mediated necroptosis may underlie IAV-induced acute lung injury and could serve as a potential therapeutic target in severe influenza cases.

OBJECTIVE: To investigate the predictive value of early lactate/albumin ratio (LAR) combined with quick sequential organ failure assessment (qSOFA) for the 28-day prognosis of patients with sepsis caused by emergency community-acquired pneumonia (CAP). METHODS: The clinical data of patients with sepsis caused by CAP admitted to the department of emergency of Beijing Haidian Hospital from June 2021 to August 2022 were retrospectively analyzed, including gender, age, comorbidities, lactic acid (Lac), serum albumin (Alb), LAR, procalcitonin (PCT) within 1 hour, and 28-day prognosis. Patients were divided into two groups based on 28-day prognosis, and risk factors affecting patients' prognosis were analyzed using univariate and multivariate Cox regression methods. Patients were divided into two groups according to the best cut-off value of LAR, and Kaplan-Meier survival curves were used to analyze the 28-day cumulative survival of patients in each group. Time-dependent receiver operator characteristic curve (ROC curve) were plotted to analyze the predictive value of sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation II (APACHE II), and qSOFA+LAR score on the prognosis of patients with sepsis caused by CAP at 28 days. The area under the curve (AUC) was calculated and compared. RESULTS: A total of 116 patients with sepsis caused by CAP were included, of whom 80 survived at 28 days and 36 died, 28-day mortality of 31.0%. There were no statistically significant differences in age, gender, comorbidities, pH, platelet count, and fibrinogen between the survival and death groups, and there were significantly differences in blood urea nitrogen (BUN), white blood cell count (WBC), hemoglobin, Lac, Alb, PCT, D-dimer, LAR, as well as qSOFA score, SOFA score, and APACHE II score. Univariate Cox regression analyses showed that BUN, WBC, pH, Lac, Alb, PCT, LAR, qSOFA score, SOFA score, and APACHE II score were associated with mortality outcome. Multifactorial Cox regression analysis of the above variables showed that BUN, WBC, PCT, and APACHE II score were independent risk factors for 28-day death in the emergency department in patients with sepsis caused by CAP [hazard ratio (HR) were 1.081, 0.892, 1.034, and 1.135, respectively, all P < 0.05]. The best cut-off value of early LAR for predicting the 28-day prognosis of sepsis patients was 0.088, the Kaplan-Meier survival curve showed that the 28-day cumulative survival rate of sepsis patients in the LAR ≤ 0.088 group was significantly higher than that in the LAR > 0.088 group [82.9% (63/76) vs. 42.5% (17/40), Log-Rank test: χ² = 22.51, P < 0.001]. The qSOFA+LAR score was calculated based on the LAR cut-off value and qSOFA score, and ROC curve analysis showed that the AUCs of SOFA score, APACHE II score, and qSOFA+LAR score for predicting 28-day death of patients with sepsis caued by CAP were 0.741, 0.774, and 0.709, respectively, with the AUC of qSOFA+LAR score slightly lower than those of SOFA score and APACHE II score, but there were no significantly differences. When the best cut-off value of qSOFA+LAR score was 1, the sensitivity was 63.9% and the specificity was 80.0%. CONCLUSION The qSOFA+LAR score has predictive value for the 28-day prognosis of patients with sepsis caused by CAP in the emergency department, its predictive value is comparable to the SOFA score and the APACHE II score, and it is more convenient for early use in the emergency department.
Emergency Service, Hospital/statistics & numerical data* ; Sepsis/etiology* ; Prognosis ; Community-Acquired Pneumonia/mortality* ; Organ Dysfunction Scores ; Predictive Value of Tests ; Lactic Acid/blood* ; Serum Albumin, Human/analysis* ; Biomarkers/blood* ; Retrospective Studies ; Hospital Mortality ; Kaplan-Meier Estimate ; APACHE ; Procalcitonin/blood* ; ROC Curve ; Area Under Curve ; Humans

Objective:To investigate the correlation between insulin resistance surrogate indicators and early-stage kidney injury in type 2 diabetes mellitus(T2DM).Methods:A total of 918 T2DM patients hospitalized in the Endocrinology Department of Xinhua Hospital from January 2018 to December 2020 were selected, including 313 patients with early-stage kidney injury and 605 without. Differences in insulin resistance surrogate indicators, including triglyceride to high-density lipoprotein cholesterol ratio(TG/HDL-C), triglyceride glucose(TyG) index, and triglyceride glucose-body mass index(TyG-BMI), were compared between the two groups. Factors associated with early-stage kidney injury in T2DM were analyzed, and the impact of TG/HDL-C, TyG index, and TyG-BMI on early-stage kidney injury in T2DM were explored.Results:Compared with T2DM patients without early-stage kidney injury, those with early-stage kidney injury exhibited significantly elevated levels of TG/HDL-C, TyG index, and TyG-BMI( P< 0.001). TG/HDL-C, TyG index, TyG-BMI, age, duration of diabetes, systolic blood pressure, fasting insulin, and HbA 1C were identified as independent risk factors for early-stage kidney injury in T2DM. Compared to the Q1 quartile, the risk in the Q4 quartile was 3.168 times(95% CI 1.993-5.036) for TG/HDL-C, 2.714 times(95% CI 1.710-4.306) for TyG index, and 2.893 times(95% CI 1.820-5.598) for TyG-BMI. Conclusion:Insulin resistance surrogate indicators TG/HDL-C, TyG index, and TyG-BMI are significantly elevated in T2DM patients with early-stage kidney injury, serving as independent risk factors for early-stage renal impairment in T2DM.

Objective:To evaluate the efficacy and safety of daratumumab in treating patients with monoclonal immunoglobulin deposition disease (MIDD) with renal injury.Methods:A case-series analysis study was conducted in MIDD patients with renal injury who received daratumumab treatment at the Department of Nephrology, Ruijin Hospital, affiliated to Shanghai Jiao Tong University School of Medicine, from December 2021 to October 2023. The clinical data of patients at the time of diagnosis and during the follow-up period were collected. Hematological and renal responses were assessed and adverse reaction events were recorded.Results:Seven patients diagnosed with MIDD were included in this study, with a male-to-female ratio of 5∶2 and age of 46 (43, 52) years. One patient was light-heavy chain deposition disease, and the remaining 6 patients were light chain deposition disease. Among them, 5 patients had received prior treatment (1-2 lines of treatment with the regimen of cyclophosphamide, bortezomib and dexamethasone), while 2 patients were newly treated, one of whom had already started hemodialysis at diagnosis. Prior to receiving monoclonal antibody treatment, difference of serum free light chain (dFLC) among the 7 patients was 52 (7, 295) mg/L. Excluding 1 patient on dialysis, the remaining 6 patients had 24-hour urinary protein of 1.1 (0.2, 4.7) g, serum creatinine of 178.5 (157.8, 279.8) μmol/L and estimated glomerular filtration rate of 33.9 (24.2, 41.1) ml·min -1·（1.73 m 2） -1. The daratumumab treatment was 17 (10, 20) infusions, with treatment duration of 17 (9, 23) months and follow-up time of 24 (13, 32) months. After treatment, among 5 previously treated patients, hematological response evaluation showed that 1 patient with baseline dFLC <20 mg/L and minimal residual disease negativity upon re-examination, while the remaining 4 patients achieved hematological responses of complete response or better. Renal response evaluation revealed that, except for 1 patient with partial response, the other 4 patients achieved very good partial response (VGPR) or better. Among 2 newly diagnosed patients, both achieved hematological efficacy at least VGPR, with one achieving renal complete response, while the other one remaining dialysis- dependent. Overall, dFLC of 7 patients was 4.9 (2.1, 11.5) mg/L. Among 6 non-dialysis patients, 24-hour urinary protein was 0.19 (0.06, 0.42) g, serum creatinine was 153.0 (120.8, 188.0) μmol/L and estimated glomerular filtration rate was 40.4 (35.2, 57.3) ml·min -1·(1.73 m 2) -1. No severe adverse reactions were observed during daratumumab treatment. Conclusion:The application of daratumumab in the treatment of MIDD with renal injury is effective and well tolerated, achieving high-quality hematological responses, with high renal responses reaching or exceeding VGPR and improvement of renal function.

Objective:To explore the treatment methods and prognosis of pregnancy-related uterine arteriovenous malformation (UAVM).Methods:A retrospective analysis was conducted on clinical data from 81 patients with UAVM treated at Peking Union Medical College Hospital between March 2019 and March 2024. Clinical manifestations, diagnostic approaches, treatment strategies and prognosis were evaluated.Results:(1) General Information: the age of patients with UAVM was (32.7±4.6) years, with median gravidity and parity of 1 (quartile range: 1, 2) and 0 (0, 1), respectively. Pregnancy termination methods included surgical abortion or curettage in 46 cases (57%, 46/81), medical induction in 17 cases (21%, 17/81), spontaneous abortion in 16 cases (20%, 16/81), vaginal delivery in 1 case (1%, 1/81), and laparoscopic pregnancy tissue removal in 1 case (1%, 1/81). (2) Clinical manifestations: clinical presentations comprised vaginal bleeding in 59 cases [73%, 59/81; median blood loss: 740 ml (440, 1 360 ml)], massive hemorrhage in 9 cases (11%, 9/81, and bleeding combined with lower abdominal pain in 8 cases (10%, 8/81). Ultrasonography revealed intrauterine masses in 65 cases [80%, 65/81; median size: 2.5 cm (1.8, 4.2 cm)]. Elevated serum human chorionic gonadotrophin-β subunit (β-hCG) levels were observed in in 55 cases [85%, 55/65; median: 62.6 U/L (14.9, 300.1 U/L)]. The median time to UAVM diagnosis via ultrasound was 30.0 days (16.0, 52.0 days) after pregnancy termination, with median peak systolic velocity (PSV) and resistance index of 59.8 cm/s (45.0, 79.6 cm/s) and 0.39 (0.36, 0.43), respectively. (3) Treatment and prognosis: treatment modalities included expectant management in 49 cases (36%, 29/81), medication in 13 cases (16%, 13/81), lesion resection in 31 cases (38%, 31/81), and uterine artery angiography in 8 cases (10%, 8/81; 5 confirmed as arteriovenous fistula). The median time of PSV returning to normal after treatment was 53.8 days (36.0, 93.4 days). The average time for β-hCG returning to normal was (60.4±20.4) days. The median return time of menses was 59.0 days (43.0, 75.4 days).Conclusions:Pregnancy-related UAVM carries a high risk of life-threatening hemorrhage, necessitating management in centers equipped for emergency uterine artery embolization. Informed consent must emphasize disease progression risks and prognosis. Treatment stratification should integrate clinical parameters and imaging features.

Objective:To identify factors associated with depressive symptoms in maintenance hemodialysis patients and to examine the relationship between these symptoms and mortality.Methods:Between January and December 2019, patients who received maintenance hemodialysis in the Blood Purification Center of the Second Affiliated Hospital of Nanjing Medical University were enrolled in a prospective cohort study. Depressive symptoms were assessed using the internationally validated patient health questionnaire-8 (PHQ-8). Sleep quality and anxiety were measured with the Pittsburgh sleep quality index (PSQI) and the generalized anxiety disorder-7 (GAD-7) scale, respectively. Follow-up continued until December 31, 2022, with all-cause mortality as the primary outcome. Ordinal logistic regression was used to identify independent predictors of depression severity. Cox proportional hazards models evaluated the association between depressive symptoms and mortality.Results:A total of 532 maintenance hemodialysis (MHD) patients completed the study. Among them, 177 (33.3%) exhibited depressive symptoms. Compared with patients without depression, those with mild or moderate-to-severe depression were older [median age: 58 (50, 66) vs. 60 (55, 65) vs. 55 (46, 64)], more likely to smoke [35.9% (51/142) vs. 40.0% (14/35) vs.26.2% (93/355)], had poorer sleep quality [PSQI: 9 (6, 13) vs. 12 (9, 17) vs. 5 (3, 9)], and higher anxiety levels [GAD-7: 1 (0, 3) vs. 3 (1, 6) vs. 0 (0, 1)], the differences among the three groups were statistically significant (all P<0.05). Ordinal logistic regression identified smoking status, history of diabetes or cardiovascular disease, hemoglobin level, PSQI score, and GAD-7 score as independent predictors of depression severity ( OR=1.60, 1.80, 1.81, 0.98, 3.67, 8.67; all P<0.05). After a median follow-up of 40 (35, 44) months, 109 patients died, including 66 (60.6%) from cardio-cerebrovascular causes and 24 (22.0%) from infections. Kaplan-Meier analysis revealed significantly lower cumulative survival in the depression group compared to the non-depression group ( P<0.001). Cox regression analysis demonstrated that depressive symptoms remained independently associated with all-cause mortality after adjusting for confounders ( HR=1.06, 95% CI 1.00-1.13, P=0.048), with an even stronger association observed for patients with PHQ-8 scores≥2.9 ( HR=1.10, 95% CI 1.03-1.16, P=0.005). However, the associations between depression and cardio-cerebrovascular mortality ( P=0.111) or infection-related mortality ( P=0.509) were not statistically significant. Conclusions:Depressive symptoms are prevalent among maintenance hemodialysis patients and are independently associated with increased all-cause mortality. Smoking, comorbid diabetes or cardiovascular disease, low hemoglobin level, poor sleep quality, and anxiety are risk factors contributing to depression. Maintenance hemodialysis patients with PHQ-8 scores≥3 should be considered at heightened risk for mortality.

The incidence of cutaneous squamous cell carcinoma (CSCC) is increasing rapidly. This study discussed the effects of artesunate (ART) on CSCC cell proliferation and migration via the solute carrier family 7 member 11 (SLC7A11)-glutathione peroxidase 4 (GPX4) pathway. MTT assessed cell viability and analyzed the IC50 value (69.26 μM). Accordingly, human CSCC cells (A431) were cultured in vitro, and treated with 70 μM ART, Ferrostatin-1, oe-SLC7A11, and C646, with cell biological behavior assessed.The potential targets of ART were predicted. p53 acetylation and protein stability and ART-p300 binding were examined. Thymusless nude mice were subcutaneously inoculated with A431 cells, and treated with ART and C646. ART-treated A431 cells showed weakened proliferation, migration, lactate dehydrogenase levels, oxidized glutathione/glutathione ratio, reactive oxygen species, malondialdehyde, and active Fe2+ levels, which could be reversed by suppressing ferroptosis. ART promoted p53 acetylation and protein stability and curbed the SLC7A11-GPX4 pathway by targeting p300. ART stimulated ferroptosis via the SLC7A11-GPX4 pathway, thereby repressing CSCC cell proliferation and migration, which were counteracted by p300 inhibition. ART regulated the SLC7A11-GPX4 pathway by up-regulating the p300-p53 axis, thereby hindering tumor growth in vivo. Collectively, ART inhibits CSCC proliferation and migration by modulating the SLC7A11-GPX4 pathway through the p300-p53 axis.