The rapid screening of bioactive constituents within traditional Chinese medicine (TCM) presents a significant challenge to researchers. Prevailing strategies for the screening of active components in TCM often overlook trace components owing to their concealment by more abundant constituents. To address this limitation, a fishing strategy based on offline two-dimensional liquid chromatography (2D-LC) combined with surface plasmon resonance (SPR) was utilized to screen bioactive trace components targeting peroxiredoxin 3 (PRDX3), using Uncaria alkaloids (UAs) as a case study. Initially, an orthogonal preparative offline 2D-LC system combining a positively charged C₁₈ column and a conventional C₁₈ column under disparate mobile phase conditions was constructed. To fully reveal the trace alkaloids, 13 2D fractions of UAs were prepared, and their components were characterized using mass spectrometry (MS). Subsequently, employing PRDX3 as the targeting protein, a SPR-based screening approach was established and rigorously validated with geissoschizine methyl ether (GSM) serving as a positive control for binding. Employing this refined strategy, 29 candidate binding alkaloids were fished from the 13 2D fractions. Notably, combining offline 2D-LC with SPR increased the yield of candidate binding components from 10 to 29 when compared to SPR-based screening alone. Subsequent binding affinity assays confirmed that PRDX3 was a direct binding target for the 12 fished alkaloids, with isovallesiachotamine (IV), corynoxeine N-oxide (CO-N), and cadambine (CAD) demonstrating the highest affinity for PRDX3. Their interactions were further validated through molecular docking analysis. Subsequent intracellular H₂O₂ measurement assays and transfection experiments confirmed that these three trace alkaloids enhanced PRDX3-mediated H₂O₂ clearance. In conclusion, this study introduced an innovative strategy for the identification of active trace components in TCM. This approach holds promise for accelerating research on medicinal components within this field.

OBJECTIVE To investigate the improvement effects and mechanism of Xiangsha yiwei tang on gastric mucosal injury in rats with chronic atrophic gastritis （CAG）. METHODS Rats were randomly assigned into normal control group， model group， Xiangsha yiwei tang low-， medium- and high-dose groups （6， 12， 18 g/kg， calculated by crude drug）， and high-dose group of Xiangsha yiwei tang+740 Y-P [Xiangsha yiwei tang 18 g/kg+transforming growth factor β1/phosphatidyl inositol 3 kinase/ protein kinase B（TGF-β1/PI3K/Akt） pathway activator group 740 Y-P 10 mg/kg]， with 18 rats in each group. Rats in each group were administered the corresponding drugs via oral gavage or injection， once daily， for 4 consecutive weeks. Gastric mucosal blood flow， the levels of serum gastrointestinal hormones [including motilin （MTL）， gastrin （GAS）， and pepsinogen （PP）]， as well as inflammatory cytokines [including tumor necrosis factor- α （TNF- α）， interleukin-1β （IL-1β）， IL-6] in rats were measured. Pathological damage to gastric mucosal tissue was observed in rats； the apoptotic rate of gastric mucosal cells was detected. The expressions of TGF-β1/PI3K/Akt signaling pathway-related proteins and apoptosis-related proteins [including B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax）] in the gastric mucosal tissues of rats were assessed. RESULTS Compared with normal control group， model group had abnormal gastric mucosal tissue structure， with shedding of gastric mucosal epithelial cells， and prominent infiltration of inflammatory cells. Gastric mucosal blood flow， the serum levels of MTL， GAS， PP， and Bcl-2 protein expression were lowered significantly， while serum levels of TNF-α， IL-1β and IL-6， apoptosis rate， protein expressions of Bax and TGF-β1， the phosphorylations of PI3K and Akt were increased significantly （P＜0.05）. Compared with model group， Xiangsha yiwei decoction groups exhibited attenuated histopathological injuries in gastric mucosal tissues， reduced inflammatory cell infiltration， and significant improvements in the aforementioned quantitative parameters （P＜0.05）. Compared with high-dose group of Xiangsha yiwei tang， high-dose group of Xiangsha yiwei decoction combined with 740 Y-P exhibited significantly aggravated histopathological injuries in gastric mucosal tissues， and the aforementioned quantitative parameters were markedly reversed （P＜0.05）. CONCLUSIONS Xiangsha yiwei tang can alleviate gastric mucosal damage in CAG rats， and its mechanism of action is related to the inhibition of TGF-β1/PI3K/Akt signaling pathway.

Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

Sepsis refers to a life-threatening organ dysfunction caused by a dysregulated host response to infection,with persistently high morbidity and mortality,posing a significant healthcare burden.As integral components of innate and adaptive immunity,macrophages exhibit high plasticity and can differentiate into distinct phenotypes(M1 pro-inflammatory and M2 anti-inflammatory)in response to various environmental stimuli,playing crucial roles in both the hyperinflammatory phase and late immunosuppressive phase of sepsis.The metabolic profile of M2 macrophages has gradually become a research focus,and it is regulated by a variety of enzymes and signaling pathways,including adenosine 5'-monophosphate-activated protein kinase,peroxisome proliferator-activated receptor and protein kinase RNA-like ER kinase pathways.These pivotal signaling pathways and enzymes can promote the polarization of M2 macrophages and enhance their anti-inflammatory functions by modulating the metabolism of glucose,lipid,and amino acid,thereby conferring protective effects against sepsis and providing new ideas for the targeted treatment.

Objective:To analyze the relationship between neck pain severity and duration and cervical sagittal parameters in non-specific neck pain (NNP) patients from a real world data, and to initially explore the relationship between NNP and cervical sagittal position sequence.Methods:The clinical data of 126 patients with main complaint of neck pain in the outpatient department of Beijing Friendship Hospital, Capital Medical University from January to September 2023 were retrospectively analyzed. This cohort included 84 female and 42 male patients with a mean age of (42.21±14.88) years (aged from 15 to 76 years). According to the duration of neck pain was more than 3 month or not, patients were divided into acute neck pain group ( n=57) and chronic neck pain group ( n=69). Patients were divided into mild neck pain group ( n=72) and moderate and severe neck pain group ( n=54) according to the severity of neck pain. The duration and visual analogue scale (VAS) of neck pain for each patient was recorded. Cervical sagittal related parameters, including cervical lordosis (C 2-C 7 Cobb′ angle, CL), C 2-C 7 sagittal vertical axis (cSVA), T 1 slope (TS) were measured by cervical lateral X-ray, and the value of T 1 slope minus cervical lordosis (TS-CL) was calculated. At the same time, cervical lateral X-ray was used to record whether the patient had cervical kyphosis and whether the patient was associated with ossification of the nuchal ligament (ONL). The VAS score of neck pain was expressed as the median (interquartile) [ M( Q1, Q3)]. Measurement data with normal distribution were represented as mean±standard deviation( ± s), and the comparison between groups was conducted using the t-test; the comparison of count data were represented as cases and percentage, and was conducted by Chi-square test. Spearman correlation analysis was used to investigate the correlation of VAS score and duration of neck pain with age, gender, imaging parameters (CL, cSVA, TS, TS-CL), cervical kyphosis and ONL. Results:The median VAS score of all patients with neck pain was 4(3, 5). For all patients, VAS score of neck pain was significantly correlated with cSVA ( P=0.029) and TS-CL ( P=0.028). There was no correlation between VAS score and CL ( P=0.235), TS ( P=0.355), with cervical kyphosis or not ( P=0.988), or with ONL or not ( P=0.181). The TS-CL values of acute neck pain group and chronic neck pain group were (11.80±8.38)° and (8.77±7.61)°, respectively, with a significant difference ( P=0.035). There was no significant difference in the incidence of cSVA, CL, TS, ONL and cervical kyphosis between the two groups ( P>0.05). The cSVA of mild neck pain group and moderate and severe neck pain group were (1.16±0.94) cm and (1.80±1.04) cm, respectively. CL was (12.25±10.76)° and (8.27±9.08)°, respectively. The TS-CL values were (8.11±7.54)° and (12.84±8.04)°, respectively, and the differences between the two groups were statistically significant ( P<0.05). The incidence of ONL in moderate and severe neck pain group was significantly higher (35.2% vs 19.4%), and the difference was statistically significant ( P<0.05). Conclusions:The severity of NNP was significantly correlated with cSVA, the more severe the neck pain, the more the mismatch between TS and CL was presented. Compared with chronic neck pain, patients with acute neck pain tended to appear TS and CL mismatch. There was a large value of cSVA and TS-CL in moderate and severe neck pain patients. The incidence of ONL was significantly increased in patients with moderate and severe neck pain.

Objective:To evaluate the perioperative application effect of enhanced recovery after surgery (ERAS) clinical pathway in percutaneous vertebro plasty (PVP).Methods:The clinical data of 274 patients who underwent PVP treatment for osteoporotic vertebral compression fracture (OVCF) in Beijing Friendship Hospital, Capital Medical University from May 2023 to August 2024 were retrospectively analyzed. The patients were divided into two groups according to the different numbers of surgical segments: the single-segment group ( n=211) and the multisegment group ( n=63). Patients in the single-segment group underwent single-segment surgery, while patients in the multisegment group underwent surgery on ≥2 segments. The core points of the ERAS clinical pathway adopted in this study include perioperative education, pain management, early mobilization, application of "outfast", and joint guidance from the departments of nutrition and rehabilitation. Comparison was made between the two groups of patients in terms of visual analog scale (VAS) scores for low back pain at preoperative, 2 h, 6 h, 24 h postoperatively, and on the day of discharge; Oswestry disability index (ODI) scores preoperatively and on the day of discharge; time to first ambulation postoperatively, total length of hospital stay, postoperative length of stay, perioperative complications, and perioperative application of Opioid consumption. Measurement data were expressed as mean±standard deviation ( ± s), and the independent sample t-test was used for comparison between groups; count data were expressed as cases and percentage, and the Chi-square test was used for comparison between groups. The VAS pain scores at each stage of the perioperative period were evaluated using repeated measures analysis of variance or generalized estimating equations. Results:Compared with that before the operation [(6.17±0.93) points, (6.29±0.83) points], the VAS scores of low back pain of patients in the single-segment group and the multisegment group at 2 hours after surgery [(3.09±0.82) points, (3.27±0.65) points], 6 hours after surgery [(2.60±0.79) points, (2.62±0.55) points], and 24 hours after surgery [(1.89±0.77) points, (1.97±0.72) points] and on the day of discharge [(1.72±0.71) points, (1.81±0.64) points] were significantly decreased, and the differences were statistically significant ( P<0.05). At the same stage, the VAS scores of low back pain in both groups were not statistically significant ( P>0.05). The ODI scores of patients in the single-segment group and the multisegment group on the day of discharge [(24.21±2.35) points, (24.63±3.31) points] were significantly lower than those before the operation [(64.50±4.81) points, (65.52±4.08) points], and the differences were statistically significant ( P<0.05). There were no statistically significant differences in perioperative complications and the proportion of Opioid drug application between the two groups of patients ( P>0.05). Conclusion:For patients with single-segment or multisegment OVCF, PVP surgical treatment under ERAS clinical pathway management can achieve immediate pain relief, early ambulation exercise, and satisfactory perioperative efficacy.

Objective:To analyze the causes of out-of-hospital cardiac arrest (OHCA) and the differences in outcomes of pre-hospital first-aid measures and cardiopulmonary resuscitation for different etiologies, improved the success rate of rescue.Methods:A retrospective study was conducted on OHCA patients admitted to Beijing Emergency Medical Centre from January to December 2021. The pre-hospital emergency medical records and rescue results within medical institutions were collected. Compared the basic situation between patients with cardiogenic and non-cardiogenic cardiac arrest, the differences of rescue measures and CPR outcomes between the groups were compared by non-parametric test and χ 2 test. Results:A total of 7 517 patients were included in this study. Cardiogenic arrest patients were older, more underlying diseases (84.2%), and cardiac arrest mainly occurred at home. The cause of non-cardiogenic arrest included disease (85.1%), trauma (2.9%), suicide (5.0%), traffic accidents (1.7%), poisoning (1.1%), and so on. In terms of first-aid measures, after the emergency doctor arrived at the scene, the proportion of first-aid measures used for cardiogenic patients was high (22.3%), and the first aid measures include cardiopulmonary resuscitation, tracheal intubation, defibrillation, oxygen inhalation, injection of adrenaline and use of other drugs. All the proportions of first-aid measures for cardiogenic patients were significantly higher than non-cardiogenic patients (all P<0.001). In terms of clinical outcomes, there were no statistical differences in return of spontaneous circulation ( P=0.072) and 24-hour survival ( P=0.093) between cardiogenic and non-cardiogenic patients. Conclusions:Cardiogenic cardiac arrest was the main cause of OHCA. Cardiogenic arrest patients were more underlying diseases, and older in age, the main clinical feature was onset at home. The comprehensive treatment measures for pre-hospital first-aid cardiac arrest should continue to be strengthened to improve the success rate of rescue for OHCA.

OBJECTIVE To investigate the therapeutic effect of Huashi Baidu Granules on respiratory syncytial virus(RSV)pneumonia model mice and its effect on lung lipid metabolism.METHODS BALB/c mice were randomly divided into control group,model group,Ribavirin group,Dexamethasone group,low dose group of Huashi Baidu Granules and high dose group of Huashi Baidu Granules.Lung tissue samples of mice in each group were collected to observe pathological changes and detect mRNA expression levels of RSV-F,RSV-G,IL-1β,IL-6 and TNF-α genes.The lipid components of lung tissue were extracted and analyzed by ultra-high performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry(UPLC-Q Exactive Orbitrap MS)to find the changes in lipid metabolism.RESULTS The model group exhibited pulmonary interstitial thickening and in-flammatory infiltration compared to the control group,the mRNA levels of viral load and inflammatory factors in lung tissue such as IL-1β and TNF-α were significantly increased(P<0.001).Moreover,the model group exhibited significant abnormalities in lipid metabo-lism,including disorders in phosphatidylserine(PS),phosphatidylglycerol(PG),sphingomyelin(SM),ceramide(Cer),triglyceride(TG),diglyceride(DG),fatty acid(FA),ether phosphatidylcholine(PC O),ether lysophosphatidylcholine(LPC O).However,af-ter the treatment of Huashi Baidu Granules(25.12 g·kg-1·d-1),the above indexes showed a significant improvement.CONCLU-SION Huashi Baidu Granules can treat RSV pneumonia by regulating lipid metabolism,reducing viral load and alleviating inflamma-tory response in lung tissue.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Background/Aims: Gastric intestinal metaplasia (GIM), a common precancerous lesion of gastric cancer, can be caused by bile acid reflux. GATA binding protein 4 (GATA4) is an intestinal transcription factor involved in the progression of gastric cancer. However, the expression and regulation of GATA4 in GIM has not been clarified. Methods: The expression of GATA4 in bile acid-induced cell models and human specimens was examined. The transcriptional regulation of GATA4 was investigated by chromatin immunoprecipitation and luciferase reporter gene analysis. An animal model of duodenogastric reflux was used to confirm the regulation of GATA4 and its target genes by bile acids. Results: GATA4 expression was elevated in bile acid-induced GIM and human specimens.GATA4 bound to the promoter of mucin 2 (MUC2) and stimulate its transcription. GATA4 and MUC2 expression was positively correlated in GIM tissues. Nuclear transcription factor-κB activation was required for the upregulation of GATA4 and MUC2 in bile acid-induced GIM cell models. GATA4 and caudal-related homeobox 2 (CDX2) reciprocally transactivated each other to drive the transcription of MUC2. In chenodeoxycholic acid-treated mice, MUC2, CDX2, GATA4, p50, and p65 expression levels were increased in the gastric mucosa. Conclusions GATA4 is upregulated and can form a positive feedback loop with CDX2 to transactivate MUC2 in GIM. NF-κB signaling is involved in the upregulation of GATA4 by chenodeoxycholic acid.