OBJECTIVE To provide a scientific basis for the quality evaluation and clinical application of Qingwen hufei granules. METHODS Fourteen batches of Qingwen hufei granules were used as samples to establish high-performance liquid chromatography （HPLC） fingerprints using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine （2012 Edition）. The chromatographic peaks were identified and the similarity was evaluated. Cluster analysis （CA）， principal component analysis （PCA）， and orthogonal partial least squares-discriminant analysis （OPLS-DA） were used to conduct chemical pattern recognition analysis on the 14 batches of samples. Meanwhile， the contents of neochlorogenic acid （NGA）， chlorogenic acid （CHA）， cryptochlorogenic acid （CGA）， forsythoside A （FTA）， 3，5-O-dicaffeoylquinic acid （3，5-O- DA）， 4，5-O-dicaffeoylquinic acid （4，5-O-DA）， and angoroside C （AGC） in the samples were determined by HPLC. RESULTS The methodological investigation results of both the fingerprint and the content determination complied with the relevant requirements. Fourteen common peaks were indicated in the HPLC fingerprints of the 14 batches of samples， and 7 of them were identified [NGA （peak 2）， CHA （peak 3）， CGA （peak 5）， FTA （peak 11）， 3，5-O-DA （peak 12）， 4，5-O-DA （peak 13）， and AGC （peak 14）]； the similarity of each sample was greater than 0.94. The results of CA and PCA showed that the samples could be classified into 3 categories； the results of OPLS-DA indicated that peak 4 （unknown）， peak 11 （FTA）， peak 8 （unknown）， peak 9 （unknown）， and peak 1 （unknown） were the differential components. The content ranges of NGA， CHA， CGA， 3，5-O-DA， FTA， 4，5-O-DA and AGC in the 14 batches of samples were 0.210 4-0.458 7， 0.269 1-0.506 3， 0.228 1-0.461 1， 0.443 9-1.044 6， 0.066 7-0.155 7， 0.062 8-0.143 8， and 0.057 4-0.105 7 mg/g， respectively. CONCLUSIONS The HPLC fingerprint and multi-component content determination methods established in this study are efficient and reliable， and can be used for the quality evaluation of Qingwen hufei granules.

Background Prolonged vibration exposure can lead to vascular endothelial cell dysfunction and cellular injury. However, research on the association between vibration and ferroptosis in vascular endothelial cells remains insufficient. Objective To explore whether occupational vibration exposure is associated with alterations in serum markers related to ferroptosis in patients with hand-arm vibration disease (HAVD), and to further investigate, through in vitro cell experiments, whether vibration exposure may induce ferroptosis in vascular endothelial cells. Methods ①A judgmental sampling method was employed to select 50 workers with HAVD (the HAVD group), 50 vibration-exposed workers without HAVD (the vibration exposure group), and 50 non–hand-transmitted vibration-exposed workers (the control group). Serum iron levels, malondialdehyde (MDA) content, and superoxide dismutase (SOD) levels were measured using serum iron assay kits, MDA detection kits, and SOD detection kits, respectively. One-way analysis of variance and binary logistic regression analysis were performed to examine the relationships between these indicators and HAVD. ②Human umbilical vein endothelial cells (HUVEC) were divided into a vibration group and a control group. The vibration group was subjected to vibration at 120 Hz with an acceleration of 6.5 m·s⁻² and further subdivided into four subgroups: 1 d 2 h, 1 d 4 h, 2 d 2 h, and 2 d 4 h. The control group was treated identically except for vibration exposure. Cellular iron (Fe²⁺) content and reduced glutathione (GSH) levels in HUVEC were measured using ferrous iron colorimetric assay kits and GSH colorimetric assay kits, respectively, to assess the effects of different vibration exposure schedules. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to detect the mRNA expression levels of ferroptosis-related genes, including acyl-CoA synthetase long-chain family member 4 (ACSL4), tumor suppressor protein P53 (P53), ferritin heavy chain 1 (FTH1), and glutathione peroxidase 4 (GPX4). Western blot analysis was conducted to determine the protein expression levels of ferroptosis-related markers in HUVEC. Results ①Compared with the control group, the patients in the HAVD group showed increased serum iron and MDA levels, along with decreased SOD levels (P<0.05). The logistic regression analysis indicated that elevated serum iron levels were significantly associated with an increased risk of HAVD (OR=4.034; 95%CI: 2.063, 7.887), and elevated MDA levels were also associated with an increased risk of HAVD (OR=1.523; 95%CI: 1.026, 1.936). ②Compared with the control group, increased intracellular Fe²⁺ content and decreased GSH content were observed in HUVECs in the 1 d 4 h and 2 d 4 h vibration subgroups (P<0.05). The RT-qPCR results showed that, compared with the control group, vibration exposures of 1 d 4 h and 2 d 4 h significantly upregulated the expression of ACSL4 and P53 (P<0.05), whereas the mRNA expression levels of GPX4 and FTH1 were downregulated in all vibration-exposed endothelial cells (P<0.05). The Western blot results revealed that, compared with the control group, the vibration exposure schedules of 1 d 2 h and 1 d 4 h significantly upregulated the protein expression levels of ACSL4 and P53 (P<0.05), while the vibration exposure schedules of 1 d 4 h, 2 d 2 h, and 2 d 4 h significantly downregulated the protein expression levels of FTH1 and GPX4 (P<0.05). Conclusion Occupational vibration exposure is associated with alterations in iron metabolism and oxidative stress status in workers with HAVD. The in vitro experiments further demonstrates that vibration stimulation induces intracellular iron accumulation and reduces antioxidant capacity in vascular endothelial cells, accompanied by dysregulated expression of ferroptosis-related molecules. These findings suggest that ferroptosis may play a role in vibration-induced vascular injury and the pathogenesis of HAVD.

Objective To explore the prevalence of depressive symptoms in postoperative patients with ovarian cancer and to analyze its influencing factors from multiple dimensions, including clinical characteristics, psychological factors, and laboratory indicators. Methods A cross-sectional study was conducted, which enrolled 235 postoperative patients with ovarian cancer. Depressive status was assessed using the patient health questionnaire, and the demographic, pathological, and medical record data of the patients were collected using the generalized anxiety disorder scale, Pittsburgh sleep quality index, European organization for research and treatment of cancer quality of life questionnaire core 30, and ECOG performance status score. Peripheral blood tumor marker (CA125), routine blood test, lymphocyte subsets, and serum cytokine levels were measured. Univariate and multivariate binary logistic regression analysis were used for statistical analysis. Results The prevalence of depression in postoperative patients with ovarian cancer was 39.15% (92/235). Univariate analysis showed that ECOG score ≥ 2 points, pain, anxiety, poor sleep quality, low quality of life, low life satisfaction, tumor recurrence, six or more cycles of chemotherapy, as well as higher levels of CA125, NLR, and NAR, and lower hemoglobin levels were significantly associated with depression (all P<0.05). Multivariate binary Logistic regression analysis showed that anxiety (OR=1.975, 95%CI: 1.231-3.170), sleep efficiency (OR=4.181, 95%CI: 1.211-14.43), sleep latency (OR=34.806, 95%CI: 4.258-284.542), ECOG performance status score, cognitive function (OR=0.918, 95%CI: 0.868-0.97), and life satisfaction were independent risk factors for depression (all P<0.05). Laboratory indicators were not independent influencing factors in the multivariate Logistic regression model. Conclusion Depression in postoperative patients with ovarian cancer is influenced by physiological, psychological, and social factors. Clinical management should focus on patients with anxiety, sleep disorders, poor physical condition, and low life satisfaction, and a comprehensive prevention and treatment strategy centered on psychological intervention and taking into account symptom management and social support should be implemented.

Objective:To evaluate the efficacy and safety of less invasive surfactant administration (LISA) combined with budesonide versus the intubation-surfactant-extubation (INSURE) technique in preterm infants (26–32 weeks’ gestation) with respiratory distress syndrome (RDS).Methods:This randomized controlled trial enrolled 136 premature infants with RDS admitted to our NICU between January 2021 and December 2023. Participants were allocated to either the LISA+budesonide group ( n = 70) or the INSURE group ( n = 66). The LISA+budesonide group received surfactant mixed with budesonide via a laryngoscope-guided catheter during noninvasive continuous positive airway pressure (NCPAP) ventilation, while the INSURE group underwent endotracheal intubation for surfactant delivery followed by extubation to NCPAP. Outcomes included adverse events during administration, blood gas parameters (PaO 2/FiO 2 [P/F ratio] and PaCO 2 at 1 h and 6 h post-administration), respiratory support duration, oxygen dependency, intubation rates within 72 h, apnea episodes, budesonide-related complications, and incidence of bronchopulmonary dysplasia (BPD). Results:The LISA+budesonide group exhibited significantly lower rates of adverse events during administration compared to the INSURE group: regurgitation (10.0% vs. 24.2%; P < 0.05), bradycardia (8.6% vs. 24.2%; P < 0.05), and oxygen desaturation (15.7% vs. 30.3%; P < 0.05). Intubation time did not differ between groups ( P > 0.05).At 1 h and 6 h post-administration, the LISA+budesonide group demonstrated higher P/F ratios ( P < 0.05), with no significant differences in PaCO 2 ( P > 0.05).The LISA+budesonide group required shorter durations of noninvasive respiratory support [(10.4 ± 4.4) d vs. (13.9 ± 5.2) d; P < 0.05] and total oxygen therapy [(15.7 ± 6.2) d vs. (19.2 ± 8.2) d; P < 0.05]. Rates of intubation within 72 h, PS re-administration, apnea episodes, weaning failure, and hospitalization length were comparable ( P > 0.05).BPD incidence was significantly lower in the LISA+budesonide group (10.0% vs. 22.7%; P < 0.05), with no increase in glucocorticoid-related complications ( P > 0.05). Conclusions:In preterm infants (26–32 weeks) with RDS, LISA with budesonide reduces adverse events during surfactant delivery, improves oxygenation, shortens respiratory support duration, and lowers BPD incidence without additional complications compared to INSURE.

To explore the application effectiveness of generative artificial intelligence(GAI) in the standardized training assessment of critical care medicine residents.

CD20 is a surface marker protein of B-cell lymphoma, and its extracellular region is the target of specific antibodies and drugs. To obtain a cheap and easily modified specific preparation targeting CD20, we optimized the gene of CD20 extracellular region according to codon degeneracy to facilitate its expression in Escherichia coli. The optimized gene was cloned into pGEX-4T-1 vector, and the recombinant vector was transformed into E. coli BL21(DE3) for expression. The purified protein was identified by SDS-PAGE and Western blotting. Systematic evolution of ligands by exponential enrichment (SELEX) was employed to screen the ssDNA aptamer that specifically binds to the fusion protein, and the affinity of the aptamer to CD20 was detected by flow cytometry. Then, the cytotoxicity test was carried out to examine the inhibitory effect of the aptamer on B lymphoma cells. In this study, we established the prokaryotic expression method of CD20 and obtained the aptamer specifically binding to the extracellular region of CD20, which laid a foundation for the development of therapeutic drugs targeting CD20.
Humans ; Escherichia coli/metabolism* ; SELEX Aptamer Technique/methods* ; Aptamers, Nucleotide/genetics* ; Antigens, CD20/metabolism* ; Ligands

OBJECTIVE: To retrospectively analyze the clinical data of newly diagnosed acute myeloid leukemia (AML) patients treated with venetoclax combined with azacitidine (Ven/Aza) or standard "3+7" regimen and similar regimens, collect real-world study data, compare the treatment response and adverse events between the two regimens, as well as perform survival analysis. METHODS: To retrospectively analyze the efficacy, survival, and adverse reactions of newly diagnosed AML patients treated with Ven/Aza (24 cases) and "3+7" regimens (117 cases ) in our hospital from September 2009 to March 2023, as well as factors influencing outcomes. A propensity score matching (PSM) was performed on age and Eastern Cooperative Oncology Group performance status (ECOG PS) to obtain a 1:1 matched cohort of 20 pairs, and the efficacy and survival before and after the matching were compared. RESULTS: The median age of patients in the Ven/Aza group was 69 years, while that in the "3+7" group was 56 years (P <0.001). Objective remission rate (ORR) was 62.5% in Ven/Aza group and 74.8% in "3+7" group (P >0.05). The median overall survival (OS) in the Ven/Aza group was 522 days, while that in the "3+7" group was 1 002 days (P >0.05). After controlling the two variables of age and ECOG PS, a PSM cohort of 20 pairs was obtained, in which the ORR was 65% in Ven/Aza group and 60% in "3+7" group (P >0.05). The median OS was 522 days and 629 days, and median progression-free survival (PFS) was 531 days and 198 days between the two groups, respectively. There were no statistically significant differences in OS and PFS between the two groups (both P >0.05). Additionally, the incidence of adverse events in the Ven/Aza group was significantly reduced. CONCLUSION The overall cohort shows that the "3+7" regimen has advantages in efficacy and survival, but Ven/Aza regimen is relatively safer. After performing PSM on age and ECOG PS, the Ven/Aza group showed improved efficacy, and a longer median PFS compared to "3+7" group.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Retrospective Studies ; Sulfonamides/administration & dosage* ; Azacitidine/administration & dosage* ; Bridged Bicyclo Compounds, Heterocyclic/administration & dosage* ; Aged ; Middle Aged ; Male ; Female ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Treatment Outcome

Glioblastoma (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis. Conventional chemo-radiotherapy demonstrates limited therapeutic efficacy and is often accompanied by significant side effects, largely due to factors such as drug resistance, radiation resistance, the presence of the blood-brain barrier (BBB), and the activation of DNA damage repair mechanisms. There is a pressing need to enhance treatment efficacy, with BRD4 identified as a promising target for increasing GBM sensitivity to therapy. Lacking small molecule inhibitors, BRD4 can be degraded using PROteolysis Targeting Chimera (PROTAC), thereby inhibiting DNA damage repair. To deliver PROTAC, SIAIS171142 (SIS) effectively, we designed a responsive nanocapsule, MPL_(SS)P@SIS, featuring GBM-targeting and GSH-responsive drug release. Modified with 1-methyl-l-tryptophan (MLT), nanocapsules facilitate targeted delivery of SIS, downregulating BRD4 and sensitizing GBM cells to radiotherapy and chemotherapy. After intravenous administration, MPL_(SS)P@SIS selectively accumulates in tumor tissue, enhancing the effects of radiotherapy and temozolomide (TMZ) by increasing DNA damage and oxidative stress. GSH activates the nanocapsules, triggering BRD4 degradation and hindering DNA repair. In mouse models, the nanosensitizer, combined with TMZ and X-ray irradiation, efficiently inhibited the growth of GBM. These findings demonstrate a novel PROTAC-based sensitization strategy targeting BRD4, offering a promising approach for effective GBM therapy.

The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson's disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K⁺ channels, or Ca²⁺-activated K⁺ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.
Animals ; Histamine/metabolism* ; Male ; Oxidopamine/toxicity* ; Rats ; Ventral Thalamic Nuclei/physiopathology* ; Rats, Sprague-Dawley ; Disease Models, Animal ; Parkinson Disease/metabolism* ; Neurons/physiology* ; Humans ; Optogenetics

Chronic cerebral hypoperfusion leads to white matter injury (WMI), which plays a significant role in contributing to vascular cognitive impairment. While 13-docosenamide is a type of fatty acid amide, it remains unclear whether it has therapeutic effects on chronic cerebral hypoperfusion. In this study, we conducted bilateral common carotid artery stenosis (BCAS) surgery to simulate chronic cerebral hypoperfusion-induced WMI and cognitive impairment. Our findings showed that 13-docosenamide alleviates WMI and cognitive impairment in BCAS mice. Mechanistically, 13-docosenamide specifically binds to cannabinoid receptor 1 (CNR1) in oligodendrocyte precursor cells (OPCs). This interaction results in an upregulation of ubiquitin-specific peptidase 33 (USP33)-mediated CNR1 deubiquitination, subsequently increasing CNR1 protein expression, activating the phosphorylation of the AKT/mTOR pathway, and promoting the differentiation of OPCs. In conclusion, our study suggests that 13-docosenamide can ameliorate chronic cerebral hypoperfusion-induced WMI and cognitive impairment by enhancing OPC differentiation and could serve as a potential therapeutic drug.
Animals ; Oligodendrocyte Precursor Cells/metabolism* ; Mice ; Cell Differentiation/drug effects* ; Male ; Receptor, Cannabinoid, CB1/metabolism* ; Mice, Inbred C57BL ; Ubiquitin Thiolesterase/metabolism* ; Ubiquitination/drug effects* ; Carotid Stenosis/complications* ; Cognitive Dysfunction/drug therapy*