BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome

Objective:To construct a predictive model for mortality in patients with multiple trauma combined with thoracic injuries and evaluate its predictive value.Methods:A retrospective cohort study was conducted to analyze the clinical data of 184 patients with multiple trauma combined with thoracic injuries admitted to the International Zhuang Medicine Hospital Affiliated to Guangxi University of Chinese Medicine from April 2019 to December 2023, including 129 males and 55 females, aged 19-85 years [(46.1±13.7)years]. According to the prognostic outcomes at 3-month follow-up after discharge, the patients were divided into survival group ( n=145) and death group ( n=39). Data were recorded in both groups at admission, including gender, age, and cause of injury, laboratory tests such as systolic blood pressure, oxygen saturation (SaO 2), hemoglobin (Hb), neutrophil-to-lymphocyte ratio (NLR), and lactate, combined injuries such as the number of combined injuries, number of rib fracture, bilateral rib fracture, first-rib fracture, sternum fracture, thoracic vertebral fracture, bilateral pulmonary contusion, bilateral pneumothorax, subarachnoid hemorrhage, subdural hematoma, epidural hematoma, skull fracture, skull base fracture, cervical vertebral fracture, brain herniation, cerebral contusion, lumbar vertebral fracture, pelvic and abdominal cavity hematoma, liver injury, kidney injury, spleen injury, clavicle fracture, scapular fracture, femoral fracture, and pelvic fracture, and injury scores such as shock index (SI), modified shock index (MSI), injury severity score (ISS), revised trauma score (RTS), Glasgow coma score (GCS), and thoracic trauma severity (TTS) score. Univariate binary logistic regression analysis was used to screen for risk factors of death in patients with multiple trauma combined with thoracic injuries. LASSO regression and multivariate logistic regression analysis were employed to identify predictive variables and independent risk factors for mortality in those patients and to construct a regression equation. A nomogram prediction model based on the regression equation was developed using R language. Receiver operating characteristic (ROC) curves were plotted to evaluate the discrimination of the model. The ROC curves were internally validated using the Bootstrap method with 1 000 resamples. The calibration of the model was assessed using the Hosmer-Lemeshow (H-L) goodness-of-fit test. The clinical application value of the model was evaluated using decision curve analysis (DCA) and clinical impact curve (CIC) analysis. Results:There were statistically significant differences between the survival group and the death group in systolic blood pressure, SaO 2, NLR, lactate, number of combined injuries, subarachnoid hemorrhage, subdural hematoma, skull fracture, skull base fracture, brain herniation, liver injury, SI, MSI, ISS, RTS, GCS, and TTS ( P<0.05 or 0.01). The results of the univariate binary logistic regression analysis showed that the above-mentioned related variables except for systolic blood pressure were all significantly associated with death in patients with multiple trauma combined with thoracic injuries ( P<0.05 or 0.01). Five predictive variables, TTS, GCS, brain herniation, ISS, and lactate were obtained in LASSO regression analysis. The results of the multivariate logistic regression analysis showed that GCS ( OR=0.70, 95% CI 0.58, 0.83), brain herniation ( OR=46.18, 95% CI 4.27, 499.26), TTS ( OR=1.71, 95% CI 1.30, 2.24), and lactate ( OR=1.35, 95% CI 1.01, 1.80) were independent risk factors for death in patients with multiple trauma combined with thoracic injuries ( P<0.05 or 0.01). Based on the aforementioned independent risk factors, a regression formula was constructed as follows: P=e x/(1+e x), with the x=-0.36×"GCS"+3.83×"brain herniation"+0.53×"TTS"+0.30×"lactate levels"-11.03. The area under the ROC curve (AUC) of the predictive model for mortality in patients with multiple trauma combined with thoracic injuries based on the equation was 0.97 (95% CI 0.93, 1.00). The AUC was internally validated using the Bootstrap method with 1 000 samples, resulting in an AUC of 0.97 (95% CI 0.91, 1.00). The results of the H-L goodness-of-fit test showed that the bias-corrected calibration curve of the model was in good consistence with the actual curve and both of them were close to the ideal curve. In the evaluation of the clinical application value of the predictive model, the DCA results showed that the predictive model could achieve good clinical net benefit. The CIC results showed that when the threshold probability was greater than 0.7, the model-identified high-risk patients for death highly matched the patients who actually died. Conclusion:The predictive model for mortality in patients with multiple trauma combined with thoracic injuries based on GCS, brain herniation, TTS, and lactate has good predictive performance and clinical application value.

Objective To understand the current situation and dynamic changing trends of healthcare-associated infection(HAI)in a tertiary first-class hospital in the northwest of Hunan Province from 2015 to 2024,and provide scientific basis for optimizing infection control strategies.Methods A single-day cross-sectional survey method was employed to investigate the HAI prevalence rates of hospitalized patients on the given survey day each year from 2015 to 2024.The standardized survey protocol on prevalence rate issued by the National Medical Institution Infec-tion Surveillance Network was strictly adhered,lanqingting real-time HAI monitoring management platform was adopted to retrieve cases from the hospital information system,and R4.2.2 was applied for statistical analysis.Results From 2015 to 2024,the prevalence rate of HAI decreased from 3.03％in 2015 to 1.76％in 2024(Z=-3.37,P＜0.001),and the HAI case prevalence rate decreased from 3.55％in 2015 to 2.20％in 2024(Z=-2.81,P=0.005).Department of critical care medicine continuously had the highest HAI case prevalence rate,which presented a downward trend over time(Z=-2.84,P=0.004).The main site of HAI was lower respiratory tract,accounting for 39.36％to 48.15％,bloodstream infection increased from 3.57％in 2015-2016 to 10.60％in 2023-2024(Z=2.41,P=0.016).A total of 302 strains of HAI pathogens were detected,including 212 strains(70.20％)of Gram-negative bacteria,mainly Pseudomonas aeruginosa(n=55,18.21％),Escherichia coli(n=45,14.90％),Acinetobacter baumannii(n=33,10.93％),and Klebsiella pneumoniae(n=31i,10.26％).65 strains(21.52％)of Gram-positive bacteria were identified,with Enterococcus faecium(n=19,6.29％)and Staphylococcus aureus(n=18,5.96％)accounting for the highest proportions.25 fungal strains(8.28％)were detected,mainly Candi-da albicans(n=11,3.64％).The use rate of antimicrobial agents showed a downward trend over the past decade(Z=-4.01,P＜0.001).Therapeutic antimicrobial use accounting for 82.42％,and its proportion increased over time(Z=6.02,P＜0.001).Prophylactic antimicrobial use accounted for 16.42％,showing a decreasing trend(Z=-2.75,P＜0.001).The pathogen detection rate presented an upward trend over the past decade(Z=13.01,P＜0.001).Conclusion The prevalence rate and case prevalence rate of HAI present a downward trend in this hospi-tal.In the future,it is necessary to establish a monitoring data-based dynamic analysis mechanism,achieve timely feedback and intervention in data monitoring,pay attention to high-risk links in department of critical care medicine,implement precise prevention and control mearsures,perform targeted prevention and control for lower respiratory tract,urinary tract,and bloodstream infection,optimize diagnosis and treatment processes,use antimicrobial agents rationally,and pay attention to the prevalence trend of Gram-negative bacteria.

ObjectiveTo explore the potential mechanisms of Leigongteng （Tripterygium wilfordii Hook. f.） in treating rheumatoid arthritis （RA） using bioinformatics analysis and experimental validation. MethodsBioinformatics approaches， including the Gene Expression Omnibus （GEO）， the traditional Chinese medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Gene Ontology （GO） enrichment analysis， Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment， protein-protein interaction （PPI） network analysis， molecular docking， receiver operating characteristic （ROC） analysis， and immune infiltration analysis， were used to predict the key active components of Leigongteng and its target genes for RA treatment. Experimental validation was conducted using human rheumatoid arthritis fibroblast-like synoviocytes （HFLS-RA） in vitro， with methotrexate as the positive control. A scratch assay was performed to assess cell migration after 24 hours of culture. Western blotting was used to detect protein expression levels， qPCR was used to measure target gene mRNA levels， and ELISA was conducted to evaluate inflammatory cytokine levels， including interleukin-1β （IL-1β）， interleukin-6 （IL-6）， interleukin-10 （IL-10）， and tumor necrosis factor-α （TNF-α）. ResultsA total of 117 target genes of Leigongteng were identified and intersected with RA-related genes， yielding 55 key genes. Further screening identified three core genes： PTGS2， CXCR4， and TIMP1. Based on the correspondence between potential drug targets and key components， triptolide and nobiletin were identified as the primary active compounds. Molecular docking results showed that both triptolide and nobiletin had binding energies lower than -5 kcal/mol with their respective target proteins， indicating strong interactions. In vitro experiments demonstrated that， compared with the blank control group， the triptolide， nobiletin， and positive control groups exhibited reduced cell migration rates after 24 hours of culture （P＜0.01）. The expression levels of PTGS2 and CXCR4 （both mRNA and protein） were significantly downregulated， while TIMP1 expression was upregulated. Levels of IL-1β， IL-6， and TNF-α decreased， whereas IL-10 levels increased （P＜0.01）. Compared with the positive control group， the triptolide and nobiletin groups showed increased cell migration rates， upregulated PTGS2 and CXCR4 expression （mRNA and protein）， downregulated TIMP1 expression （mRNA and protein）， increased IL-1β， IL-6， and TNF-α levels， and decreased IL-10 levels （P＜0.05 or P＜0.01）. ConclusionThe key active components of Leigongteng， triptolide and nobiletin， may alleviate RA by inhibiting PTGS2 and CXCR4 while promoting TIMP1 expression， thereby suppressing inflammatory responses.

Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), as certain forms of non-melanoma skin cancer (NMSC) or keratinocyte carcinoma, are the most common forms of malignant neoplasms worldwide (Sharp et al., 2024). BCC and cSCC have been identified as two major components of NMSC, comprising one-third of all malignancies (Burton et al., 2016). Generally speaking, patients with NMSC tend to have relatively favorable survival outcomes, while different histopathological subtypes of NMSC exhibit distinct biological behaviors (Stătescu et al., 2023). Keratinocyte carcinoma, although not considered as deadly as melanoma, tends to metastasize if left untreated (Civantos et al., 2023; Nanz et al., 2024). cSCC can evolve locally, then aggressively metastasize, invade, and even lead to fatal consequences in a subset of patients (Winge et al., 2023). A solid, pigmented, smooth plaque or a hyperkeratotic papule with or without central ulceration and hemorrhage appears to be characteristic of cSCC (Thompson et al., 2016; Zhou et al., 2023). Of note, a rare type of intraepidermal cSCC in situ often appears as a velvety, demarcated, slightly raised erythematous plaque on the genitalia of men (Yamaguchi et al., 2016). Accounting for approximately 16.0% of scalp tumors and with a rising incidence, cSCC is now the second most common NMSC in humans (Verdaguer-Faja et al., 2024). According to the latest statistics, up to 2%‒5% of cSCCs in situ may gradually progress into invasive cSCCs in the final step (Rentroia-Pacheco et al., 2023). Several risk factors for the carcinogenesis and development of cSCC have been identified, including age, accumulative exposure to ultraviolet light radiation A and B, human papillomavirus infection, arsenic ingestion, chronic scarring, xeroderma pigmentosa, a relevant history of ionizing radiation, androgenetic alopecia in males, and immunosuppression therapy (Martinez and Otley, 2001; Welsch et al., 2012; Mortaja and Demehri, 2023).
Humans ; Aminolevulinic Acid/therapeutic use* ; Skin Neoplasms/pathology* ; Photochemotherapy/methods* ; Female ; Carcinoma, Squamous Cell/pathology* ; Middle Aged ; Photosensitizing Agents/therapeutic use* ; Carcinoma, Basal Cell/drug therapy*

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Objective:To investigate the effect of intradialytic cerebral blood flow (CBF) fluctuation on cognitive decline in middle-aged and elderly maintenance hemodialysis (MHD) patients.Methods:It was a prospective cohort study. MHD patients aged ≥50 years from Beijing Shijitan Hospital were enrolled from January 2023 to June 2023. Middle cerebral artery mean flow velocity (MFV) was serially monitored via transcranial Doppler (TCD) during dialysis sessions. Cognitive function was assessed at baseline and after 12-month follow-up using standardized neuropsychological tests: montreal cognitive assessment (MoCA), auditory verbal learning test (AVLT 5), complex figure test (CFT), trail making test-B (TMT-B), Stroop color and word test (SCWT), and symbol digit modalities test (SDMT). ΔMFV was calculated as pre-to-post dialysis MFV difference. Multivariable linear regression was used to analyze the association of ΔMFV and cognition.Results:A total of 121 MHD patients were recruited with an age of (63.63±8.44) years. There were 97 males (80.2%), and the dialysis vintage was (55.08±54.73) months. Significant intradialytic MFV reductions were observed ( P<0.05). At 12 months, cognitive decline manifested in global cognition (MoCA), memory (CFT-memory), executive function (TMT-B, SCWT-C, SCWT-T), attention (SDMT), visuospatial ability (CFT-copy)(all P<0.05). Multivariable linear regression analysis revealed ΔMFV independently predicted declines in: MoCA ( B=0.066, 95% CI 0.018-0.113, P=0.007), AVLT5 ( B=0.050, 95% CI 0.004-0.097, P=0.035), TMT-B ( B=-1.955, 95% CI -3.453--0.457, P=0.011), SCWT-C ( B=0.298, 95% CI 0.112-0.484, P=0.002), SCWT-T ( B=-1.371, 95% CI -2.303--0.439, P=0.004). Conclusions:Hemodialysis induces acute CBF reductions detectable by TCD. Cumulative intradialytic CBF fluctuations may accelerate cognitive deterioration in middle-aged and elderly MHD populations, particularly affecting memory and executive domains.