Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

The correlation between hearing loss (HL) and physical performance in patients receiving maintenance hemodialysis (MHD) remains poorly investigated. This study explored the association between HL and physical performance in patients on MHD. Methods: This multicenter cross-sectional study was conducted between July 2020 and April 2021 in seven hemodialysis centers in Shanghai and Suzhou, China. The hearing assessment was performed using pure-tone average (PTA). Physical performance was assessed using the Timed Up and Go Test (TUGT), handgrip strength, and gait speed. Results: Finally, 838 adult patients (male, 516 [61.6%]; 61.2 ± 2.6 years) were enrolled. Among them, 423 (50.5%) had mild to profound HL (male, 48.6% and female, 53.4%). Patients with HL had poorer physical performance than patients without HL (p < 0.001). TUGT was positively correlated with PTA (r = 0.265, p < 0.001), while handgrip strength and gait speed were negatively correlated with PTA (r = –0.356, p < 0.001 and r = –0.342, p < 0.001, respectively). Physical performance in patients aged <60 years showed significant dose-response relationships with HL. After adjusting for confounders, the odds ratios (95% confidence intervals) for HL across the TUGT quartiles (lowest to highest) were 1.00 (reference), 1.15 (0.73–1.81), 1.69 (1.07–2.70), and 2.87 (1.69–4.88) (p for trend = 0.005). Conclusion: Lower prevalence of HL was associated with a faster TUGT and a stronger handgrip strength in patients on MHD.

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.

Aim To research the effect of PDG on bone metabolism in young rats. Methods The experimental rats were randomly divided into contro group, PDG-25 group and PDG-50 group. PDG-25 group and PDG-50 group were given PDG at the dose of 25 mg·kg

The concept of total mesorectal resection provides a quality control standard that can be followed for radical resection of rectal cancer, but some anatomical problems are still controversial. Compared with traditional open surgery, laparoscopic radical rectal surgery has better surgical vision, better neurological protection, better operating space. However, if the surgeon has insufficient understanding of the anatomy, collateral damage may occur, such as uncontrollable bleeding during the operation, postoperative urination and defecation dysfunction and so on. Based on the interpretation of the researches at home and abroad, combined with the clinical experience, we elucidate some associated issues, including anatomic variation of inferior mesenteric vessels, the controversy of inferior mesenteric artery ligation plane, the controversy of lymph node dissection in No. 253, the anatomical variation of middle rectal artery, and the anatomical controversy of lateral lymph node dissection in rectal cancer, in order to provide better cognitive process for the clinical front-line surgeons.
Humans ; Laparoscopy ; Lymph Node Excision ; Lymph Nodes ; Mesenteric Artery, Inferior ; Rectal Neoplasms/surgery* ; Rectum

To a certain extent, put forward the concept of " component of traditional Chinese medicine (TCM)" simplifies the complexity of multi-component and multi-target of TCM, which provides a possibility for the clarification of the material basis of the efficacy of TCM, and also provides a new direction for promoting the modernization and industrialization of TCM, promots the high quality development of TCM. The correlation between prescription and disease syndrome has made rapid progress, both basic research and clinical application are fruitful. However, the correlation between components and disease syndrome still needs to be further studied. The syndrome of blood stasis is a common syndrome of TCM science, and it is more common in various diseases, especially cardiovascular and cerebrovascular diseases, kidney disease, diabetes and hyperlipoidemia. A large number of studies have shown that some specific components contained in TCM or TCM compound can improve the related indexes of patients or experimental animal model with blood stasis syndrome. It is manifested in reducing blood viscosity, inhibiting platelet activation and adhesion aggregation, changing erythrocyte deformability index, inhibiting thrombosis and so on. Blood stasis is not only the pathogenic factor of many diseases, but also the pathological product of many kinds of diseases, which involves a wide range of diseases. Therefore, this study will study the progress of different components of TCM in the prevention and treatment of blood stasis syndrome, focusing on saponins, flavonoids, organic acids, polysaccharides, alkaloids and other active components in improving hemorheological abnormalities, hypercoagulability, platelet activation and adhesion aggregation, thrombosis. Based on the thought of component-disease syndrome, this paper searches the relevant literature in recent 20 years, classifies and summarizes the achievements of different components in the prevention and treatment of blood stasis syndrome, and hopes to provide some ideas for the further study of the pharmacological action of TCM components, the study of compatibility of TCM components and the research of TCM components.

Peptidyl-prolyl cis-trans isomerase Pin1 is over-expressed in prostate cancer cells and the level of expression correlates with the malignancy grade and prognosis in patients. In this work, twenty-one 2-(1H-benzimidazol-2-ylthio) acetic acid derivatives were designed and prepared with the aid of the crystal structure of Pin1 and our previous work. The chemical structures of the target compounds were confirmed by ¹H NMR, ¹³C NMR, ESI-MS and IR. The inhibitory activity of compounds 6a-6i and 13a-13i against Pin1 were determined using a protease-coupled assay. The results indicated that twenty compounds were significantly superior to the positive control drug Juglone, and 6g, 6h and 13i exhibited the most potent Pin1 inhibitory activity, with IC₅₀ values at the sub-micromolar level. The in vitro anti-proliferative activities of these analogs were evaluated by the MTT assay and several showed a moderate effect in human prostate cancer PC-3 cells. Molecular docking studies demonstrated that both the benzimidazole skeleton and the thioacetic acid fragment were indispensable for the compounds to interact with key residues in the catalytic domain of Pin1.

Gastrectomy ; Humans ; Lymph Node Excision ; Lymph Nodes ; Lymphatic Metastasis ; Retrospective Studies ; Stomach Neoplasms/surgery*

Objective: To observe short-term and long-term efficacies of Danlu Tongdu tablets on lumbar disc herniation (LDH) with kidney deficiency and stasis syndrome, and its effect on nucleus pulposus reabsorption and immunoinflammatory factors. Method: One hundred and sixty patients were randomly divided into control group (80 cases) and observation group by random number table. Patients in control group (80 cases) got acupoint massage and acupuncture, 1 time/day. In addition to the therapy of control group, patients in observation group were also given Danlu Tongdu tablets, 4 tablets/time, 3 times/days. A course of treatment was 12 weeks, and a 9-month follow-up was recorded. Lumbago and leg pain were recorded by visual simulation (VAS) before treatment and at the first, second, third month after treatment. Before and after treatment, Japanese orthopaedic association (JOA), symptoms and signs were scored. During the 9-month follow-up, relapse rate and relapse time were recorded, and VAS and JOA were scored. Absorption of nucleus pulposus was assessed, and levels of interleukin-1 (IL-1), IL-17, tumor necrosis factor-α (TNF-α), matrix metalloproteinases-3 (MMP-3) were detected. Result: By rank sum test, the clinical efficacy in observation group was better than that in control group (Z=2.125, P<0.05), and scores of JOA was better than that in control group (Z=1.924, P<0.05). At the first, second and third months after treatment, VAS scores of low back pain, leg pain were lower than those in control group (P<0.01), while the decline range were more than that in control group (P<0.01). And scores of symptoms and signs were lower than that in control group (P<0.01), whereas scores by dimensions of JOA scale and the total score of JOA were all higher than those in control group (P<0.01). Complete absorptivity of nucleus pulposus in observation group was 61.11%, which was higher than 42.03%in observation group (χ²=5.138, P<0.05). Levels of IL-1, IL-17, TNF-α and MMP-3 were lower than that in control group (P<0.01). Relapse rate in observation group was 23.61%, which was lower than 40.58%in control group (χ²=4.668, P<0.05). Average recurrence time was longer than that in control group (P<0.05), score of VAS was lower than that in control group (P<0.05), and the total score of JOA was higher than that in control group (P<0.05). Conclusion: In addition to acupuncture and massage therapy, Danlu Tongdu tablets can also be used to relieve pain and ameliorate function, improve clinical efficacy, reduce relapse rate, promote nucleus pulposus reabsorption, and relieve inflammation of nerve root.