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.

Lung cancer remains one of the leading causes of cancer-related morbidity and mortality worldwide, and its treatment continues to face major challenges such as therapeutic resistance and tumor recurrence. Pyroptosis, a newly characterized form of programmed cell death, induces tumor cell death through gasdermin-mediated membrane pore formation and is accompanied by the release of inflammatory mediators, thereby playing complex roles in lung cancer initiation, progression, and modulation of the tumor microenvironment. Active components and herbal formulas derived from traditional Chinese medicine can modulate pyroptosis-related signaling pathways through multi-target mechanisms, showing potential advantages in inducing lung cancer cell death, inhibiting proliferation and migration, and reversing chemoresistance. This review systematically summarizes relevant studies from domestic and international sources, focusing on the molecular mechanisms of pyroptosis, its roles in lung cancer development and tumor microenvironment remodeling, and the current research progress on traditional Chinese medicine-based interventions targeting pyroptosis, with the aim of providing references for the prevention and treatment of lung cancer using traditional Chinese medicine.

BACKGROUND/OBJECTIVES: Unhealthy diets are associated with chronic stress. An allostatic load (AL) is a comprehensive physiological index that measures the chronic stress response of the body. As a healthy dietary pattern, the role of Dietary Approaches to Stop Hypertension (DASH) in the development of an AL during pregnancy remains unclear. This study examined the relationship between the DASH dietary pattern and AL during pregnancy. SUBJECTS/METHODS: This study was a prospective study. From January 2024 to November 2024, 134 pregnant women in the second trimester (23–27 weeks) and third trimester (32–36 weeks) of pregnancy who met the inclusion and exclusion criteria in the obstetrics clinic of a tertiary general hospital in Anhui Province were selected for a questionnaire survey, physical examination, and laboratory examination. The DASH dietary pattern was assessed using the DASH scoring tool, and the total AL score was calculated using nine biomarkers that represent the cardiovascular, metabolic, and immune systems. Logistic regression was used to analyze the relationship between the DASH score and AL. RESULTS: One hundred and thirty-four pregnant women were included in this study. At the second and third trimesters, 41.8% and 37% of pregnant women, respectively, were in the high AL group. The binary logistic regression results showed that the DASH score was negatively correlated with the AL in the unadjusted model (odds ratio [OR], 0.878; 95% confidence interval [CI], 0.807–0.957; P = 0.003) and adjusted model (OR, 0.878; 95% CI, 0.792–0.973; P = 0.013) in the second trimester, the DASH score was negatively correlated with the AL in the unadjusted model (OR, 0.832; 95% CI, 0.758–0.913; P < 0.001) and adjusted model (OR, 0.806; 95% CI, 0.716–0.908; P < 0.001) in the third trimester. CONCLUSION The DASH score was negatively correlated with the AL in pregnant women.A low DASH score may increase the risk of a high AL, which may have adverse effects on physical and mental health.

OBJECTIVE To clarify the current development status of clinical pharmacist training bases and the pharmacist workforce in China， and to provide evidence for standardizing base construction and promoting the high-quality development of hospital pharmacy. METHODS Questionnaires were distributed to all clinical pharmacist training bases for urgently-needed health professionals and clinical pharmacist training bases under the Chinese Hospital Association that had been approved by the end of 2023 to collect data including base profiles and pharmacist staffing conditions. Expert teams carried out field investigations to verify the collected data. Descriptive statistical analyses were conducted on the quantity， type and regional distribution of training bases， and the influencing factors of pharmacist staffing in the bases were analyzed. RESULTS Field surveys were completed covering 297 training bases across 31 provincial-level administrative regions. Among the base hospitals， 87.88% were Grade A tertiary general hospitals， and 65.32% were located in provincial capitals. The eastern region had the largest number of bases （136， accounting for 45.79%）， followed by the western region （79， 26.60%）. Great disparities existed among provinces in terms of base quantity and hospital scale. The median proportion of pharmaceutical technical personnel in base hospitals was 4.05%， and the median number of clinical pharmacists per 100 hospital beds was 0.53. Both indicators reached the highest in the eastern region （0.57， 4.43%） and the lowest in the northeastern region （0.45， 3.01%）. A total of 3 627 full-time clinical pharmacists were employed in all surveyed bases， among whom 83.68% held clinical pharmacist training certificates， 35.43% possessed senior professional titles， and 78.19% had postgraduate or higher educational background. The total annual training capacity of the surveyed bases was 4 291 trainees， with obvious differences in annual training capacity across regions and provinces. Training specialties covered 19 specialized disciplines plus one general discipline， and no province could deliver training for all 20 specialties simultaneously. Multivariate Logistic regression analysis showed that geographic region exerte d a significant impact on the proportion of pharmaceutical technical personnel （≥4%） （ P ＜0.05）， while the approval time of training bases and hospital scale had significant effects on the number of clinical pharmacists per 100 beds （≥0.6） （ P ＜0.05）. CONCLUSIONS China’s clinical pharmacist training system has basically matured and taken initial shape. The distribution of clinical pharmacist training resources is generally consistent with regional population and economic development levels. However， the allocation of pharmaceutical staff and clinical pharmacists has not yet met national standards and clinical service demands.

OBJECTIVE To clarify the current development status of clinical pharmacist training bases and the pharmacist workforce in China， and to provide evidence for standardizing base construction and promoting the high-quality development of hospital pharmacy. METHODS Questionnaires were distributed to all clinical pharmacist training bases for urgently-needed health professionals and clinical pharmacist training bases under the Chinese Hospital Association that had been approved by the end of 2023 to collect data including base profiles and pharmacist staffing conditions. Expert teams carried out field investigations to verify the collected data. Descriptive statistical analyses were conducted on the quantity， type and regional distribution of training bases， and the influencing factors of pharmacist staffing in the bases were analyzed. RESULTS Field surveys were completed covering 297 training bases across 31 provincial-level administrative regions. Among the base hospitals， 87.88% were Grade A tertiary general hospitals， and 65.32% were located in provincial capitals. The eastern region had the largest number of bases （136， accounting for 45.79%）， followed by the western region （79， 26.60%）. Great disparities existed among provinces in terms of base quantity and hospital scale. The median proportion of pharmaceutical technical personnel in base hospitals was 4.05%， and the median number of clinical pharmacists per 100 hospital beds was 0.53. Both indicators reached the highest in the eastern region （0.57， 4.43%） and the lowest in the northeastern region （0.45， 3.01%）. A total of 3 627 full-time clinical pharmacists were employed in all surveyed bases， among whom 83.68% held clinical pharmacist training certificates， 35.43% possessed senior professional titles， and 78.19% had postgraduate or higher educational background. The total annual training capacity of the surveyed bases was 4 291 trainees， with obvious differences in annual training capacity across regions and provinces. Training specialties covered 19 specialized disciplines plus one general discipline， and no province could deliver training for all 20 specialties simultaneously. Multivariate Logistic regression analysis showed that geographic region exerte d a significant impact on the proportion of pharmaceutical technical personnel （≥4%） （ P ＜0.05）， while the approval time of training bases and hospital scale had significant effects on the number of clinical pharmacists per 100 beds （≥0.6） （ P ＜0.05）. CONCLUSIONS China’s clinical pharmacist training system has basically matured and taken initial shape. The distribution of clinical pharmacist training resources is generally consistent with regional population and economic development levels. However， the allocation of pharmaceutical staff and clinical pharmacists has not yet met national standards and clinical service demands.

OBJECTIVE To investigate the current status of quality management in clinical pharmacist training bases in China， and to provide references for the standardized development and improvement of these bases. METHODS A combined approach of questionnaire survey and on-site investigation was adopted， targeting the healthcare highly sought-after talent （clinical pharmacist） training bases in 31 provinces of China as well as the clinical pharmacist training bases affiliated with the Chinese Hospital Association. A training quality management evaluation index system consisting of 25 tertiary indicators was established. Investigations were conducted from two dimensions： structural quality of training and quality management of training processes. Data were statistically analyzed using descriptive statistical methods. RESULTS On-site investigations were completed for 297 clinical pharmacist training bases across the 31 provinces， among which 284 were affiliated with the Chinese Hospital Association and 271 were healthcare highly sought-after talent （clinical pharmacist） training bases. In terms of structural quality， the core indicator compliance rate for hospital-level training systems exceeded 80%， the rate of special fund utilization for designated purposes reached 80.13%， and the overall compliance rate for software and hardware facilities surpassed 88%. A total of 1 348 preceptors were employed across the training bases， among whom those with senior professional titles and full-time specialist clinical pharmacists as lead preceptors accounted for 62.91% and 94.36%， respectively. Regarding process quality， the compliance rate for “establishment of clinical practice teaching groups in accordance with regulations during clinical department rotations” was 85.19%， and 79.80% and 76.09% of the bases were found to implement strict confidentiality in theoretical examinations and meet the required scale of assessment cases， respectively. However， formal documents of corresponding training management regulations were formulated in only 57.91% of the bases， and the completeness and standardization rate of training manual completion was merely 47.47%. In addition， considerable disparities in quality management levels were observed among provinces， with issues in training process quality being particularly prominent. CONCLUSIONS The management system， hardware facilities， and preceptor staffing of clinical pharmacist training bases in China are relatively well-established， yet notable variations in quality management exist among training bases across different provinces.

OBJECTIVE To evaluate the efficacy and safety of cadonilimab plus chemotherapy in patients with advanced gastric adenocarcinoma or adenocarcinoma of gastroesophageal junction （AEG） with intermediate， low， or no human epidermal growth factor receptor 2 （HER2） expression. METHODS Patients with advanced gastric adenocarcinoma or AEG with intermediate， low， or no HER2 expression who were treated at Liaoning Cancer Hospital between October 1， 2024 and June 30， 2025 were retrospectively included. According to the treatment regimen received， the patients were divided into group A [cadonilimab plus oxaliplatin and capecitabine （XELOX）， n ＝54 ] ， group B （sintilimab plus XELOX， n ＝68）， and group C （tislelizumab plus XELOX， n ＝49）. Short-term efficacy after 4 cycles of treatment， survival outcomes， and adverse events were compared among the three groups. Cox regression and Logistic regression analyses were further performed to evaluate the effects of the treatment regimen and baseline data on survival outcomes and the risk of grade 3-4 treatment related adverse events （TRAEs）. RESULTS No statistically significant differences in objective response rate or disease control rate were observed among the three groups （ P ＞0.05）. The median progression-free survival was 7.56 （5.62， 8.11） months in group A， 7.23 （5.33， 8.23） months in group B， and 7.33 （5.42， 8.19） months in group C， with no statistically significant difference among the three groups （ P ＞0.05）. The median overall survival （mOS） was 11.67 （8.82， 13.88） months in group A， 9.78 （6.82， 12.73） months in group B， and 9.69 （6.78， 12.66） months in group C. The mOS was significantly longer in group A than in group B and group C （ P ＜0.05）， whereas no statistically significant difference was observed between group B and group C （ P ＞0.05）. The correlation analysis indicated that treatment regimen， Eastern Cooperative Oncology Group performance status （ECOG PS）， number of metastatic organs， and peritoneal metastasis may be associated with overall survival （OS）. No significant association was observed between treatment regimen and the risk of grade 3-4 TRAEs. The incidences of grade 1-2 or grade 3-4 TRAEs did not differ significantly among the three groups （ P ＞0.05）. CONCLUSIONS In patients with advanced gastric adenocarcinoma or AEG with intermediate， low， or no HER2 expression， cadonilimab plus XELOX may provide a more significant OS benefit with a safety profile comparable to that of sintilimab or tislelizumab plus XELOX. Further studies with larger sample sizes are required to validate these findings.

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

Recent studies have shown that an imbalance in iron metabolism can affect the composition and microstructural changes of bone, disrupting bone homeostasis and leading to osteoporosis(OP). The imbalance in iron metabolism, along with its induced local abnormal microenvironment and cellular iron death, has become a new focal point in OP research, drawing increasing attention from the academic community regarding the regulation of iron metabolism to prevent and manage OP. From the perspective of traditional Chinese medicine(TCM), iron metabolism imbalance has potential connections to TCM theories regarding internal organs, as well as treatments aimed at tonifying the kidney, strengthening the spleen, and activating blood circulation. Evidence is continually emerging that TCMs and effective components that tonify the kidney, strengthen the spleen, and activate blood circulation can prevent and manage OP by regulating iron metabolism. This article analyzes the relationship between iron and bone, as well as the effects of TCM formulations on improving iron metabolism and influencing bone metabolism, from the perspectives of iron metabolism mechanisms and TCM interventions, aiming to broaden existing clinical strategies for prevention and treatment and inject new momentum into the field of OP as it moves into a new era.
Osteoporosis/drug therapy* ; Humans ; Iron/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Medicine, Chinese Traditional ; Bone and Bones/drug effects*