ObjectiveTo explore the molecular mechanism of Sanhuang Xiexintang （SHXXT） in protecting stress gastric ulcer （SGU） in rats through network pharmacology， molecular docking， and animal experiments. MethodThe active ingredients and corresponding targets in SHXXT were collected and screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Traditional Chinese Medicine Information Database （TCMID）， Bioinformation Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）， and Swiss Target Prediction database. SGU-related targets were screened from the Online Mendelian Inheritance in Man （OMIM）， Therapeutic Target Database （TTD）， GeneCards database， and PharmGKB database. Herbal-ingredient-target （H-C-T） network was constructed by using Cytoscape 3.9.1 software. Protein-protein interaction （PPI） of drug and disease intersection targets was analyzed by using the Protein Interaction Platform （STRING） database. Gene ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis were conducted through the Database for Annotation Visualization and Integrated Discovery （DAVID）. The active ingredients and key targets were validated using AutodockVina 1.2.2 molecular docking software， and the experimental results were further validated through animal experiments. ResultThe 55 active ingredients were screened， and 255 potential target genes for SHXXT treatment of SGU were predicted. The PPI analysis showed that protein kinase B （Akt）， phosphatase and tensin homolog deleted on chromosome ten （PTEN）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and cyclooxygenase-2 （COX-2） are the core targets of SHXXT for protecting SGU. GO and KEGG analyses showed that SHXXT may affect the development of SGU by regulating various biological processes such as the phosphoinositide 3-kinase （PI3K）/Akt signaling pathway and inflammatory processes. The molecular docking results showed that both the active ingredients and key targets had good binding ability. Animal experiments showed that compared with the blank group， the ulcer index （UI） of the model group was significantly increased （P<0.01）， and the serum levels of TNF-α and IL-1β significantly increased （P<0.01）. The phosphorylation level of PTEN in gastric mucosal tissue was significantly down-regulated （P<0.05）. The phosphorylation levels of PI3K， Akt， and nuclear factor kappa-B （NF-κB） were significantly up-regulated （P<0.05）. Compared with the model group， the UI of the treatment group was significantly reduced （P<0.01）， and the serum levels of TNF-α and IL-1β were significantly reduced （P<0.01）. The phosphorylation level of PTEN in gastric mucosal tissue was significantly up-regulated （P<0.01）， and the phosphorylation levels of PI3K， Akt， and NF-κB were significantly downregulated （P<0.01）. ConclusionThe application of network pharmacology prediction， molecular docking simulation， and animal experimental validation confirms that SHXXT regulates the PI3K/Akt/NF-κB signaling pathway to regulate the inflammatory response of rats and thus protects the gastric mucosa of SGU rats.

Objective:To investigate the correlation between serum sclerostin and sarcopenia-related indicators in chronic kidney disease (CKD) patients, and to find biomarkers and potential therapeutic targets that can take into account both osteoporosis and sarcopenia.Methods:It was a single-centre cross-sectional study. The clinical data of CKD stage 5 patients undergoing maintenance hemodialysis regularly and CKD stage 1-5 non-dialysis inpatients in the Hemodialysis Centre of Guangzhou Red Cross Hospital from March 2021 to March 2023 were collected retrospectively. The enzyme-linked immunosorbent assay was used to detect the level of serum sclerostin. The anthropometric data such as height, weight, upper arm circumference, upper arm muscle circumference, skinfold thickness, pinch strength and handgrip strength were measured. Body composition analyzer was used to measure the body composition. The patients were divided into CKD stage 1-3 group, CKD stage 4-5 group, and stage 5 hemodialysis group. One-way ANOVA, Kruskal-Wallis H test, and chi-square test were used to compare the differences of demographics and clinical characteristics in different stages of CKD. Spearman correlation analysis and multiple linear stepwise regression analysis were utilized to analyze the correlation between serum sclerostin and sarcopenia-related indicators in CKD patients. Results:The study included 104 patients with CKD stage 5 hemodialysis and 104 patients with CKD stage 1-5 non-dialysis patients, with age of (61.8±13.7) years old and 114 males (54.8%). There were 89 patients (42.8%) with diabetic nephropathy and 67 patients (32.2%) with sarcopenia. As renal injury progressed, serum sclerostin levels were 0.4 (0.3, 0.9) ng/L, 0.5 (0.3, 1.1) ng/L, and 1.1 (0.6, 2.3) ng/L in patients with CKD stage 1-3, stage 4-5, and stage 5 undergoing hemodialysis ( χ2=8.934, P<0.001), and the prevalence of sarcopenia was 16.4% (10/61), 34.9% (15/43), and 40.4% (42/104) ( χ2=10.312, P=0.006), respectively. Spearman correlation analysis showed that serum sclerostin was negatively correlated with estimated glomerular filtration rate ( r=-0.314, P<0.001), pinch strength ( r=-0.229, P=0.007), skinfold thickness ( r=-0.254, P<0.001), appendicular skeletal muscle index ( r=-0.169, P=0.010), body cell mass ( r=-0.174, P=0.020), and phase angle ( r=-0.264, P<0.001), and positively correlated with serum phosphorus ( r=0.227, P=0.002) and intact parathyroid hormone ( r=0.297, P<0.001). Multiple linear stepwise regression analysis showed that lg[appendicular skeletal muscle index] was negatively correlated with male ( β=0.330, t=5.675, P<0.001) and serum sclerostin ( β=-0.125, t=-2.143, P=0.033), and positively correlated with body mass index ( β=0.474, t=8.090, P<0.001). Conclusion:Serum sclerostin can be used as a good index and a potential therapeutic target for sarcopenia in CKD patients.

There are certain limitations in the current clinical evaluation methods and evaluation modes of new Chinese herbal medicines for syndromes， and there is a lack of a clinical evaluation system that meets the characteristics of traditional Chinese medicine （TCM）. Based on the characteristics of TCM "syndrome differentiation and treatment" and "correspondence of formulas and syndromes"， the target design model， hypothesis and its scope of application are proposed on the basis of the combination of diseases and syndromes. On the basis of fully considering the dual factors of diseases and syndromes， we distinguished the "centre of the target"， "middle ring" and "outer ring" through the differences of different signs and symptoms in people with same syndrome， in order to determine the degree of conformity of the syndrome. Then， the population with same syndrome could be analysed according to the "centre of the target"， "middle ring" and "outer ring"， so as to achieve the precise positioning of new Chinese herbal medicines for syndromes， and try to provide research ideas and methods for syndrome differentiation and treatment of TCM and precise intervention.

The covalent binding of drugs and their metabolites to proteins forms drug-protein adducts, which may cause adverse reactions in the body. The development of adductomics technology is helpful for the identification of covalent adducts between drugs and human plasma proteins. For many drugs, such as beta-lactam antibiotics, acyl glucuronides, covalent tyrosine kinases inhibitors, and reactive metabolites, human serum albumin (HSA) is a potential target and biomarker for the formation of drug-protein adducts. In this review, we will describe the relevant technical advances, describe the methods for the identification of covalent adducts of drugs and HSA, define the chemical reactions that form adducts, and preliminarily explore the role of drug-HSA adducts in adverse drug reactions and the potential effect on pharmacokinetics.

The objective of this study was to observe the effect of Astragalus membranaceus on high sugar-induced Caenorhabditis elegans, and to explore its mechanism of action. UPLC-MS method was used to identify the components of Astragalus membranaceus. A high glucose model was established by using Caenorhabditis elegans as a model organism, and the effects of Astragalus membranaceus on body length, body bending, swallowing frequency, and reactive oxygen species (ROS) of the nematode were determined; the effects of Astragalus membranaceus on the expression of mRNA of genes related to the protein skinhead-1 (SKN-1) signaling pathway were examined by using the real-time fluorescence quantitative polymerase chain reaction (PCR). The results showed that compared with the normal group, the nematode body length, body bending, and swallowing frequency expression were significantly reduced and the ROS content in the body was significantly increased in the high glucose state; after the administration of Astragalus membranaceus, the body length, body bending, and swallowing frequency expression were significantly increased, and the ROS content was significantly reduced (P < 0.01). Compared with the normal group, SKN-1, superoxide dismutas-3 (SOD-3), glutathione S-transferase 4 (GST-4), and glutathione S-transferase 7 (GST-7) expression were significantly decreased in Caenorhabditis elegans in the high glucose condition; SKN-1, SOD-3, GST-4, and GST-7 expression were significantly increased after administration of Astragalus membranaceus (P < 0.01). In the present study, we demonstrated that Astragalus membranaceus has an effect on high glucose-induced Caenorhabditis elegans nematodes, and its mechanism of action may be through the modulation of the SKN-1 signaling pathwaym in order to ameliorate the oxidative stress response induced by high glucose.

Human mass balance study is a pivotal research in the field of clinical pharmacology, aiming at elucidating the metabolic and excretion pathways of drugs in humans. Currently, human mass balance studies predominantly employ radiolabeling techniques. Recently, both the U.S. Food and Drug Administration (FDA) and the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) issued related research drafts and guidelines to encourage and guide the pharmaceutical industry to conduct research in compliance with established standards. The selection of radiolabeling sites is crucial for obtaining critical information on drug metabolism. However, in vivo biotransformation may lead to partial disintegration of the molecular structure, thereby resulting in the loss of metabolic product information of the unlabeled moiety. Administering drugs with different radiolabeling sites separately or in combination, or labeling multiple radioactive isotopes within one molecule, can effectively solve this problem. This article reviews relevant technological progress, analyzes radiolabeling strategies, and discusses the application of drugs with multiple radiolabeling sites in human mass balance studies.

BACKGROUND:Pulsed electromagnetic fields,as an important physical therapy,are exactly effective in the treatment of osteoarthritis,but the mechanism has not been fully clarified. OBJECTIVE:To observe the effect of pulsed electromagnetic field on the degeneration of knee joint cartilage in aged rats. METHODS:Eight 6-month-old Sprague-Dawley rats were selected as the young group and were subjected to normal diet with no treatment.Sixteen 22-month-old Sprague-Dawley rats were randomly divided into old group(n=8)and pulsed electromagnetic field group(n=8).The rats in the pulsed electromagnetic field group were subjected to a pulsed electromagnetic field intervention,once a day,5 days per week for continuous 8 weeks.The rats in the old group were given no treatment.All rats were anesthetized and executed after 8 weeks for the detection of relevant indexes. RESULTS AND CONCLUSION:Compared with the young group,serum type Ⅱ collagen C-terminal peptide level was increased in the old group(P<0.05);compared with the old group,serum type Ⅱ collagen C-terminal peptide level was decreased in the pulsed electromagnetic field group(P<0.05).Micro-CT showed that the bone volume fraction,bone mineral density,and number of bone trabeculae decreased(P<0.05)and the trabecular separation increased(P<0.05)in the tibia of rats in the aged group compared with the young group;and the bone volume fraction,bone density,and number of trabeculae increased(P<0.05)and the trabecular separation decreased(P<0.05)in the tibia of rats in the pulsed electromagnetic field group compared with the aged group.The tibial plateau Safranin O-fast green staining showed that the articular cartilage structure of rats in the aged group was disorganized,and the number of chondrocytes was obviously reduced,and the tidal line could not be distinguished.The above results were improved in the pulsed electromagnetic field group.RT-qPCR and western blot assay showed that the mRNA and protein expression levels of matrix metalloproteinase 1,matrix metalloproteinase 13,P53 and P21 in the articular cartilage and subchondral bone of rats were elevated in the aged group compared with the young group(P<0.05)and decreased in the pulsed electromagnetic field group compared with the old group(P<0.05).To conclude,pulsed electromagnetic fields may improve osteoarthritis in aged rats by inhibiting chondrocyte senescence,alleviating articular cartilage degradation and inhibiting subchondral bone osteoporosis through suppressing the expression of P53/P21.

Lipid and glucose metabolism play crucial roles in maintaining energy homeostasis, and their dysregulation can lead to the development of metabolic disorders, such as obesity and diabetes. Studies indicate that the skeleton, involved in lipid and glucose metabolism, functions as an endocrine organ, regulating systemic metabolism through bone-derived molecules. Sclerostin is a protein mainly produced by osteocytes, possessing the ability to inhibit bone formation, and its antibodies have become therapeutic targets for treating osteoporosis. Recent evidence suggests that sclerostin also plays a role in lipid and glucose metabolism disorders. Therefore, through summarizing in vitro and in vivo researches, this article reviews the role of sclerostin in lipid and glucose metabolism, its relationship with obesity and diabetes, and potential role in the treatment of metabolic diseases in the future.

Objective:To investigate the application value of ultrasound-guided multimodal examinations in the diagnosis of lymph node mycobacterial infection.Methods:The clinical data of 42 patients with suspected lymph node mycobacterial infection who were initially diagnosed at the Affiliated Hospital of Shaoxing University from January 2019 to December 2020 were retrospectively analyzed. All patients underwent an ultrasound-guided lymph node-negative pressure puncture. Acid-fast staining, bacterial culture, pathological examination or their combination were used to screen lymph nodes for mycobacterial infection. The results were compared with those of acid-fast staining and bacterial culture of sputum and bronchoalveolar lavage fluid smears.Results:The combined application of acid fast staining, bacterial culture, and pathological examination for the puncture fluid smear showed a positive rate of 71.4% (30/42), which was significantly higher than the positive rate [26.2% (11/42)] for acid fast staining of the puncture fluid smear, the positive rate [42.9% (18/42)] for bacterial culture of the puncture fluid, and the positive rate [50.0% (21/42)] of pathological examination ( χ2 = 17.20, 7.00, 4.04, P < 0.001, P < 0.01, P = 0.040). The positive rate for sputum smear and bacterial culture was 21.4% (9/33). The positive rate for acid fast staining and bacterial culture of the bronchoalveolar lavage fluid was 28.6% (12/30). The differences were statistically significant ( χ2 = 21.11, 15.43, both P < 0.001). Conclusion:Ultrasound-guided negative pressure aspiration and puncture biopsy of lymph nodes combined with acid fast staining, bacterial culture, and pathological examinations can markedly increase the detection rate and diagnostic rate of mycobacterial infection.

Objective To observe the cage subsidence after oblique lateral interbody fusion(OLIF)for lumbar spondylo-sis,summarize the characteristics of the cage subsidence,analyze causes,and propose preventive measures.Methods The data of 144 patients of lumbar spine lesions admitted to our hospital from October 2015 to December 2018 were retrospectively ana-lyzed.There were 43 males and 101 females,and the age ranged from 20 to 81 years old,with an average of(60.90±10.06)years old.Disease types:17 patients of lumbar intervertebral disc degenerative disease,12 patients of giant lumbar disc hernia-tion,5 patients of discogenic low back pain,33 patients of lumbar spinal stenosis,26 patients of lumbar degenerative spondy-lolisthesis,28 patients of lumbar spondylolisthesis with spondylolisthesis,11 patients of adjacent vertebral disease after lumbar internal fixation,7 patients of primary spondylitis in the inflammatory outcome stage,and 5 patients of lumbar degenerative scoliosis.Preoperative dual-energy X-ray bone mineral density examination showed 57 patients of osteopenia or osteoporosis,and 87 patients of normal bone density.The number of fusion segments:124 patients of single-segment,11 patients of two-seg-ment,8 patients of three-segment,four-segment 1 patient.There were 40 patients treated by stand-alone OLIF,and 104 patients by OLIF combined with posterior pedicle screw.Observed the occurrence of fusion cage settlement after operation,conducted monofactor analysis on possible risk factors,and observed the influence of fusion cage settlement on clinical results.Results All operations were successfully completed,the median operation time was 99 min,and the median intraoperative blood loss was 106 ml.Intraoperative endplate injury occurred in 30 patients and vertebral fracture occurred in 5 patients.The mean follow-up was(14.57±7.14)months from 6 to 30 months.During the follow-up,except for the patients of primary lumbar interstitial in-flammation and some patients of lumbar spondylolisthesis with spondylolisthesis,the others all had different degrees of cage subsidence.Cage subsidence classification:119 patients were normal subsidence,and 25 patients were abnormal subsidence(23 patients were grade Ⅰ,and 2 patients were grade Ⅱ).There was no loosening or rupture of the pedicle screw system.The height of the intervertebral space recovered from the preoperative average(9.48±1.84)mm to the postoperative average(12.65±2.03)mm,and the average(10.51±1.81)mm at the last follow-up.There were statistical differences between postop-erative and preoperative,and between the last follow-up and postoperative.The interbody fusion rate was 94.4％.The low back pain VAS decreased from the preoperative average(6.55±2.2 9)to the last follow-up(1.40±0.82),and there was statistically significant different.The leg pain VAS decreased from the preoperative average(4.72±1.49)to the final follow-up(0.60± 0.03),and the difference was statistically significant(t=9.13,P＜0.000 1).The ODI index recovered from the preoperative av-erage(38.50±6.98)％to the latest follow-up(11.30±3.27)％,and there was statistically significant different.The complication rate was 31.3％(45/144),and the reoperation rate was 9.72％(14/144).Among them,8 patients were reoperated due to fusion cage subsidence or displacement,accounting for 57.14％(8/14)of reoperation.The fusion cage subsidence in this group had obvious characteristics.The monofactor analysis showed that the number of abnormal subsidence patients in the osteopenia or osteoporosis group,Stand-alone OLIF group,2 or more segments fusion group,and endplate injury group was higher than that in the normal bone mass group,OLIF combined with pedicle screw fixation group,single segment fusion group,and no endplate injury group,and the comparison had statistical differences.Conclusion Cage subsidence is a common phenomenon after 0-LIF surgery.Preoperative osteopenia or osteoporosis,Stand-alone OLIF,2 or more segments of fusion and intraoperative end-plate injury may be important factors for postoperative fusion cage subsidence.Although there is no significant correlation be-tween the degree of cage subsidence and clinical symptoms,there is a risk of cage migration,and prevention needs to be strengthened to reduce serious complications caused by fusion of cage subsidence,including reoperation.