Proanthocyanidin B_2(PAC-B_2), a polyphenolic dimeric compound comprising two epicatechin molecules linked by a C-C bond, is extensively found in traditional Chinese medicines, with anti-tumor and anti-oxidant activities. Given the limited bioavailability, a thorough investigation and comprehensive understanding of PAC-B_2 metabolism in vivo are essential for elucidating therapeutic forms and mechanisms. In the present study, ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) in the negative ion mode was employed to acquire the MS/MS information of PAC-B_2 and metabolites in urine and feces samples of the rats administrated with PAC-B_2. Online energy-resolved MS(ER-MS) was applied as supplementary to obtain the full collision energy ramp-MS~2 spectra(FCER-MS~2) of isomers-of-interest, which implied comprehensive MS~2 information of targeted compounds. Finally, the possible metabolic pathways of PAC-B_2 in rats were proposed. The primary fragmentation behaviors of PAC-B_2 in the negative ion mode included quinone methide fission between C_4-C_8 bond, retro Diels-Alder cracking of F-ring, heterocyclic ring fission of C-ring, and neutral loss of small molecules such as H_2O. A total of 25 metabolites were tentatively elucidated in urine and feces samples of rats administrated with PAC-B_2 by fragmentation pattern and reported literature. Two groups of isomers, M3/M4/M5 and M9/M11, were confirmatively differentiated based on the relationships between optimal collision energy provided by FCER-MS~2 and bond properties, including bond length and bond dissociation energy. In addition to the ring-opening and methylation, PAC-B_2 could also be metabolized into epicatechin and low molecular weight phenolic acids, which were subsequently subjected to dehydroxylation, ring-opening, methylation, sulfation, and glucuronidation. The structural information provided by online ER-MS and FCER-MS~2 enabled the differentiation of isomers and improved the identification confidence. More importantly, the present study deeply analyzes the in vivo metabolic pathways of PAC-B_2, providing a basis for the research on the pharmacological mechanism of this compound.
Animals ; Proanthocyanidins/urine* ; Rats ; Male ; Drugs, Chinese Herbal/chemistry* ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry ; Chromatography, High Pressure Liquid ; Feces/chemistry* ; Molecular Structure

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

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Acute pancreatitis(AP)is a common digestive disorder associated with moderate to high nutritional risks,necessitating timely nutritional support.Over the past five decades,medical nutrition therapy for AP has undergone a paradigm shift,transitioning from traditional fasting based on the"pancreatic rest theory"to the current emphasis on early enteral feeding to"awaken the gut."Currently,nutritional treatment has become a cornerstone of comprehensive AP management.The European Society for Clinical Nutrition and Metabolism(ESPEN),founded in 1980,is a leading professional organization dedicated to advancing research,clinical practice,and education in clinical nutrition and metabolism.To date,ESPEN has published five evidence-based guidelines on nutritional management in pancreatic diseases.This article reviews the evolution of AP nutritional therapy as outlined in these ESPEN guidelines,highlighting key recommendations and their clinical implications.

Objective:To investigate the efficacy and safety of sintilimab combined with the SOX regimen for adjuvant treatment of stage Ⅲgastric cancer after D2 radical resection and to provide a reference for individualized clinical treatment.Methods:The clinical data of 245 pa-tients with stage III gastric cancer who underwent D2 radical resection at the 940th Hospital of the Joint Support Force of the People's Liber-ation Army from June 2019 to May 2022 were retrospectively analyzed.The 180 patients who received only the SOX regimen were desig-nated the control group,and the 65 patients who received sintilimab combined with the SOX regimen were designated the experimental group.The 3-year disease-free survival(DFS)rate,overall survival(OS)rate,and adverse reactions among the two groups and different sub-groups(HER-2 positive,dMMR,CPS≥5)were compared.Results:The 3-year DFS(81.5%vs.59.4%)and OS(84.6%vs.70.6%)rates in the experimental group were significantly higher than those in the control group(both P<0.05).Group analysis showed that in patients with CPS≥5,the 3-year DFS(91.5%vs.67.0%)and OS(95.7%vs.71.6%)rates within the experimental group were significantly better than those in the control group(both P<0.05).Intra-group analysis within the experimental group showed that the 3-year DFS rate(91.5%vs.55.6%)and OS rate(95.7%vs.55.6%)of patients with CPS≥5 were significantly better than those of patients with CPS<5(both P<0.05).The overall and grade≥3 incidences of liver and kidney function damage,thyroid dysfunction,colitis,pneumonia,and rash in the experimental group were higher than those in the control group(all P<0.05),while the differences in other adverse reactions,including leukopenia were not statistic-ally significant(all P>0.05).Conclusions:Sintilimab combined with the SOX regimen can significantly improve 3-year DFS and OS rates in pa-tients with stage Ⅲ gastric cancer after surgery,especially in the CPS≥5 subgroup,with significant benefits and controllable safety.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective:To explore the short-term clinical effects of deep cervical lymph node-venous anastomosis in the treatment of Alzheimer’s disease (AD).Methods:A prospective exploratory study was conducted on the treatment of AD patients using the cervical deep lymph node-venous anastomosis technique in Scar and Wound Treatment Department, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, from September to October 2024. The patients underwent high-frequency ultrasound to locate deep cervical lymph nodes and the external jugular vein. Under general anesthesia, bilateral deep cervical lymph node-venous anastomoses were performed. Indocyanine green (ICG) lymphography was conducted via subcutaneous injection behind the ear to visualize lymph nodes in levels Ⅱ and Ⅲ. After making a skin incision along the posterior margin of the sternocleidomastoid muscle, the external jugular vein, internal jugular veins, and associated lymph nodes were exposed. Adjacent veins were selected for anastomosis of lymph node. Using microsurgical techniques, end-to-side or end-to-end anastomosis was completed for lymph nodes in levels Ⅱ and Ⅲ. Preoperative assessments included the mini-mental state examination (MMSE, a higher score indicates better cognitive function), Alzheimer’s disease assessment scale-cognitive subscale (ADAS-Cog, a higher score indicates greater impairment of cognitive function), Alzheimer’s disease cooperative study scale for activities of daily living (ADCS-ADL, a higher score indicates better ability to perform daily activity), and neuropsychiatric inventory (NPI, a higher score indicates more severe behavioral and emotional symptom). Postoperative follow-up included the same scales to observe changes in cognitive function, activities of daily living, and emotional communication.Results:Four patients (1 male, 3 females, aged 58-79 years) with AD were included. All were diagnosed based on cerebrospinal fluid biomarkers. All patients successfully underwent bilateral deep cervical lymph node-venous anastomoses. On average, 4.3 (2-7 per person) anastomoses were performed per patient. Surgical procedures lasted an average of 6.5 h (5.5-8.5 h) with minimal blood loss (less than 50 ml). Patients resumed normal activity within 6 hours postoperatively and were discharged after an average of 4.1 d (3.5-5.0 d). Postoperative complications included one case each of aspiration pneumonia, lower limb venous thrombosis, and transient delirium, all of whom resolved without long-term effects. Clinical symptoms, including memory decline, mood swings, and anxiety, showed varying degrees of improvement. Patients reported enhanced quality of life, emotional stability, and social engagement, confirming the procedure’s safety and potential cognitive benefits. At one month postoperatively, the MMSE scores of the four patients increased by an average of 0.8 points compared to preoperative levels. Additionally, the two patients who completed the ADAS-Cog assessments showed a decrease in their scores (reduced by 1.0 points and 11.3 points, respectively, compared to preoperative scores), indicating a certain degree of improvement in cognitive function during this period. The ADCS-ADL and NPI scores of four patients varied significantly, without showing any clear pattern.Conclusion:Lymphovenous anastomosis of the deep cervical lymph node-venous anastomosis may provide a new surgical intervention approach for AD, but further large-scale studies and long-term follow-up are needed to validate its safety and effectiveness.

Fear of disease progression(FoP)is a common psychological state among patients with coronary heart dis-ease(CHD),which exists throughout the course of disease and seriously affects the prognosis.High level of FoP not only harms the mental health of patients but also do not benefit their rehabilitation after discharge.This concept was first proposed by foreign researchers studying the psychological state of cancer patients.In recent years,there have been numerous studies on the influencing factors and qualitative aspects of FoP in CHD patients,while related inter-vention studies remain few.This paper reviews the concept,scales and related influencing factors of FoP,providing ideas for medical staff to provide targeted interventions for CHD patients.

Objective:To investigate the clinical characteristics of patients with multiple myeloma(MM)complicated by bone lesions and the risk factors associated with bone lesions.Methods:The clinical data of 294 newly diagnosed MM patients in Gansu Provincial Hospital from January 2017 to June 2021 were retrospectively analyzed.The patients were divided into the bone lesion group(154 cases)and the non-bone lesions group(140 cases)based on the presence of absence of bone lesions at diagnosis.The general data and laboratory parameters were compared between the two groups.The risk factors for bone lesions in MM patients were analyzed by logistic regression analysis,and the characteristic(ROC)curves were plotted to assess the predictive value of each risk factor for the occurrence of bone lesions in MM patients.Results:Compared to the non-bone lesion group,the bone lesion group had significantly higher serum calcium levels and significantly greater proportions of patients with Durie-Salmon(DS)stage Ⅲ,and bone pain(all P＜0.05).Logistic regression analysis showed that elevated serum calcium(OR=5.135,95％CI:1.931-13.653,P=0.001),DS stage Ⅲ(OR=1.841,95％CI:1.019-3.328,P=0.043),and bone pain(OR=8.208,95％CI:4.761-14.151,P＜0.001)were independent risk factors for bone lesions in MM patients.ROC curve analysis showed that serum calcium(AUC=0.619,95％CI:0.555-0.683,P＜0.001)and bone pain(AUC=0.743,95％CI:0.692-0.793,P＜0.001)had predictive value for bone lesions in MM patients.Conclusion:MM patients have a high incidence of bone lesions,and active monitoring and management of risk factors may improve treatment outcomes and prognosis.