Trace elements and vitamins are essential micronutrients for metabolism.Micronutrients deficiency results in adverse effects on human body,and brings huge challenge to clinical nutrition therapy.To normalize micronutrients application in clinical practice,European Society for Clinical Nutrition and Metabolism(ESPEN)published ESPENpractical short micronutrient guideline on January 2024.Based on previous version published in 2022,current guideline shortens the interpretation of biochemical and physical mechanisms,focuses on micronutrients deficiency and inflammation,recommends the methods of micronutrients assessment and supplementation in different statuses during clinical practices.This paper summarizes specific recommendations and comments for domestic peers to communicate,and provides reference for the management of micronutrient therapy in China.

Objective To establish a new program of blood cell processing apparatus(NGL-BBS)for the preparation of washed mixed plateletsand to study the effect on biological activity of platelets compared with tradi-tional manual method.Methods Mixed concentrated platelets were separated and prepared from whole blood by white membrane method.Blood cell processing apparatus with new program set(experimental group)and manual method(control group)was used for thepreparation of washed mixed platelets.The expression rate of CD62P and CD63 in the two groups of washed mixed platelets was compared by flow-cytometry.Thrombus elastography(TEG)was used to measure and compare the MA value between the two groups.Results The expression rate of CD62P and CD63 in the experimental group was lower than that in the control group(t = 4.11,P<0.01;t = 10.78,P<0.01).TheTEG MA valueof the experimental group was higher than that of the control group(t = 6.67,P<0.01).Conclusion The present study demonstrates that the use of NGL-BBS for the preparation of washed mixed plate-lets has a lesser impact on biological activity compared to manual preparation methods.

Objective:To investigate the influence of nutritional therapy on short-term efficacy of gastric cancer patients with malnutrition after radical gastrectomy.Methods:The prospec-tive randomized control study was conducted. The clinicopathological data of patients with malnutri-tion after radical resection of gastric cancer who were admitted to the Zhongshan Hospital of Fudan University from December 2020 to December 2022 were selected. Based on random number table, all patients were allocated into the nutritional therapy group and the control group. Patients in the nutritional therapy group were given dietary guidance and daily oral nutrition supplements for 90 days after discharge, while patients in the control group were only given the same dietary guidance. Observation indicators: (1) grouping situations of the enrolled patients; (2) follow-up; (3) comparison of nutritional indicators at 90 days after discharge; (4) comparison of inflammation and physical function indicators at 90 days after discharge; (5) comparison of clinical outcome indicators at 90 days after discharge. Measurement data with normal distribution were expressed as Mean± SD, and independent sample t test was used for comparison between groups. Measurement data with skewed distribution were expressed as M(IQR), and non-parameter rank sum test was used for comparison between groups. Count data were expressed as absolute numbers or percentages, and chi-square test was used for comparison between groups. Comparison of ordinal data was conducted using the chi-square test. Results:(1) Grouping situations of the enrolled patients. A total of 187 patients were selected for eligibility. There were 131 males and 56 females, aged (65±12)years. Of the 187 patients, there were 95 patients in the nutritional therapy group and 92 patients in the control group, respectively. The gender (male, female), age, cases with cardiovascular complications, cases with respiratory complications, cases with diabetes, surgical methods (partial gastrectomy, total gastrectomy), tumor staging (Ⅰ stage, Ⅱ stage, Ⅲ stage), body mass, body mass index (BMI), skeletal muscle index, albumin (Alb), hemoglobin (Hb), neutrophil-to-lymphocyte ratio (NLR), 6-minutes walking distance, grip strength were 68, 27, (64±12)years, 21, 4, 7, 59, 36, 17, 27, 51, (59±11)kg, (21.5±3.1)kg/m 2, (42±7)cm 2/m 2, (39±5)g/L, (112±25)g/L, 2.3(8.0), (456±97)m, (29±8)kg in patients of the nutritional therapy group, versus 63, 29, (66±13)years, 22, 3, 9, 56, 36, 14, 24, 54, (58±11)kg, (21.1±2.9)kg/m 2, (42±7)cm 2/m 2, (39±4)g/L, (111±26)g/L, 2.2(8.4), (459±98)m, (29±8)kg in patients of the control group, showing no significant difference in the above indicators between the two groups ( χ2=0.21, t=-1.29, χ2=0.09, 0, 0.35, 0.03, 0.51, t=0.80, 0.85, 0.19, 0.14, 0.16, Z=-0.28, t=-0.17, 0.43, P>0.05). (2) Follow-up. All 187 patients were followed up for 90 days after surgery. During the follow-up period, all patients had good compliance and were able to follow the dietary guidance. Five patients in the nutrition therapy group experienced diarrhea and nausea adverse reactions, which were relieved after symptomatic treatment. No adverse reactions were found in the control group. (3) Comparison of nutritional indicators at 90 days after discharge. The body mass, body mass loss, BMI, skeletal muscle index, Alb, Hb were (58±10)kg, 2(6)kg, (21.0±2.9)kg/m 2, (41±7)cm 2/m 2, (41±4)g/L, (125±18)g/L in patients of the nutritional therapy group, versus (56±10)kg, 3(6)kg, (20.4±2.7)kg/m 2, (39±7)cm 2/m 2, (41±4)g/L, (121±21)g/L in patients of the control group. There were significant differences in body mass loss and skeletal muscle index between the two groups ( Z=-4.70, t=2.39, P<0.05), and there was no significant difference in body mass, BMI, Alb, and Hb ( t=1.30, 1.51, 0.80, 1.32, P>0.05). (4) Comparison of inflammation and body function indicators at 90 days after discharge. The NLR, 6-minutes walking distance, grip strength were 2.1(5.1), (478±99)m, and (33±9)kg in patients of the nutritional therapy group, versus 2.2(5.7), (465±96)m, (30±8)kg in patients of the control group. There was a significant difference in grip strength between the two groups ( t=2.08, P<0.05), and there were no significant difference in NLR and 6-minutes walking distance ( Z=-1.28, t=0.91, P>0.05). (5) Comparison of clinical outcome indicators at 90 days after discharge. The quality of life score and readmission rate were (79±14)points, 4.2%(4/95) in patients of the nutritional therapy group, versus (78±16)points, 6.5%(6/92) in patients of the control group, showing no significant difference in the above indicators between the two groups ( t=0.58, χ2=0.14, P>0.05). Conclusion:Nutritional therapy with daily oral nutrition supplements can improve the short-term nutritional status and body function of patients with malnutrition after radical gastrectomy for gastric cancer.

As the research of traditional Chinese medicine （TCM） on knee osteoarthritis （KOA） is progressing， researchers have discovered that a variety of Chinese medicines can delay the progress of KOA by regulating signaling pathways at the molecular level. The Chinese medicines and their active ingredients mentioned in this article are associated with the signaling pathways in KOA. They can regulate the levels of targeted molecules via different signaling pathways to inhibit cartilage inflammatory cytokine， apoptosis， and cartilage matrix degradation and promote chondrocyte autophagy， so as to reduce the synovial inflammatory edema and delay cartilage degeneration. This paper systematically reviews the studies about the TCM intervention of KOA. Baicalein can reduce the inflammatory cytokines and apoptosis and promote the autophagy of chondrocytes by blocking the phosphatidylinositol-3 kinase/protein kinase （PI3K/Akt） signaling pathway. Cornuside I can decrease the phosphorylation activity of Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3） pathway to reduce synovial inflammation and delay cartilage matrix degeneration. Salvianolic acid A can reduce inflammation and cartilage matrix degradation by inhibiting the phosphorylation of the nuclear factor-κB （NF-κB） pathway. Emodin can reduce the activity of Wnt/β-catenin pathway to inhibit the decomposition of collagen and proteoglycan. Myristicoside can inhibit apoptosis by blocking the p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway. Akebia saponin D can enhance the activity of nuclear factor E₂-related factor 2/heme oxygenase 1（Nrf2/HO-1） pathway to inhibit oxidative stress in chondrocytes. The saponins in Achyranthis Bidentatae Radix reduce cartilage matrix degradation by enhancing the transforming growth factor-β （TGF-β）/Smad signaling pathway. Crocin inhibits the cartilage inflammation and apoptosis factor increase by stimulating the activity of hippo-Yes-associated protein （Hippo-YAP）. Ligustrazine blocks the Notch pathway to improve the morphology and abnormality of chondrocytes. Oleanolic acid reduces the destruction and degeneration of cartilage matrix via the estrogen signaling pathway. The above summary aims to provide references for future clinical and experimental research on KOA.

Aldolase B (ALDOB), a glycolytic enzyme, is uniformly depleted in clear cell renal cell carcinoma (ccRCC) tissues. We previously showed that ALDOB inhibited proliferation through a mechanism independent of its enzymatic activity in ccRCC, but the mechanism was not unequivocally identified. We showed that the corepressor C-terminal-binding protein 2 (CtBP2) is a novel ALDOB-interacting protein in ccRCC. The CtBP2-to-ALDOB expression ratio in clinical samples was correlated with the expression of CtBP2 target genes and was associated with shorter survival. ALDOB inhibited CtBP2-mediated repression of multiple cell cycle inhibitor, proapoptotic, and epithelial marker genes. Furthermore, ALDOB overexpression decreased the proliferation and migration of ccRCC cells in an ALDOB-CtBP2 interaction-dependent manner. Mechanistically, our findings showed that ALDOB recruited acireductone dioxygenase 1, which catalyzes the synthesis of an endogenous inhibitor of CtBP2, 4-methylthio 2-oxobutyric acid. ALDOB functions as a scaffold to bring acireductone dioxygenase and CtBP2 in close proximity to potentiate acireductone dioxygenase-mediated inhibition of CtBP2, and this scaffolding effect was independent of ALDOB enzymatic activity. Moreover, increased ALDOB expression inhibited tumor growth in a xenograft model and decreased lung metastasis in vivo. Our findings reveal that ALDOB is a negative regulator of CtBP2 and inhibits tumor growth and metastasis in ccRCC.
Humans ; Carcinoma, Renal Cell/genetics* ; Fructose-Bisphosphate Aldolase/metabolism* ; Co-Repressor Proteins/metabolism* ; Transcription Factors/genetics* ; Kidney Neoplasms/genetics* ; Cell Line, Tumor ; Cell Proliferation/genetics* ; Gene Expression Regulation, Neoplastic

Cardiovascular diseases (CVDs) and metabolic disorders are major components of noncommunicable diseases, causing an enormous health and economic burden worldwide. There are common risk factors and developmental mechanisms among them, indicating the far-reaching significance in exploring the corresponding therapeutic targets. MST1/2 kinases are well-established proapoptotic effectors that also bidirectionally regulate autophagic activity. Recent studies have demonstrated that MST1/2 influence the outcome of cardiovascular and metabolic diseases by regulating immune inflammation. In addition, drug development against them is in full swing. In this review, we mainly describe the roles and mechanisms of MST1/2 in apoptosis and autophagy in cardiovascular and metabolic events as well as emphasis on the existing evidence for their involvement in immune inflammation. Moreover, we summarize the latest progress of pharmacotherapy targeting MST1/2 and propose a new mode of drug combination therapy, which may be beneficial to seek more effective strategies to prevent and treat CVDs and metabolic disorders.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

【Objective】 To investigate the prevalence of QTc prolongation and the risk factors in hospitalized breast cancer patients. 【Methods】 A total of 296 patients with pathologically diagnosed breast cancer admitted to The First Affiliated Hospital of Xi’an Jiaotong University in 2018 were retrospectively enrolled. The patients’ baseline data， 12-lead ECG， the prevalence of QTc （QTc max） prolongation and its risk factors were analyzed by the multivariate logistic regression. 【Results】 The prevalence of QTc prolongation in the hospitalized breast cancer patients was 13%； multivariate logistic regression analysis showed that increased heart rate （OR=1.04， P<0.05）， combined hypertension （OR=6.48， P<0.05）， and anthracycline administration （OR=3.96， P<0.05） were the risk factors of the prolongation of QTc interval in the breast cancer patients （P<0.05）. 【Conclusion】 The prevalence of prolonged QTc interval in the hospitalized breast cancer patients is increased， which may be due to the increased heart rate， hypertension， and the administration of anthracycline drugs in these patients.

Malnutrition is closely related to clinical outcomes and accurate evaluation of nutritional status is the cornerstone of nutritional therapy. However, consistent diagnostic criteria for malnutrition have been absent for quite a long period. The Global Leadership Initiative on Malnutrition (GLIM) criteria were introduced in September 2018 and served as a consensus-based evaluation tool. As per GLIM criteria, evaluation of malnutrition should follow a two-step approach with nutritional screening as the first step and then malnutrition diagnosis assessment and severity grading based on etiologic as well as phenotypic metrics. Since debut, GLIM criteria have been applied in different countries, healthcare settings and populations, showing good accuracy and prognostic value for outcomes such as complications and survival. However, most of the studies are retrospective in nature and high-quality prospective studies are needed to better validate GLIM criteria. The way to steer nutritional interventions based on GLIM criteria is also worth future investigation.

Objective To analyze the chemical compounds of Shenqi Dihuang decoction by the ultraperformance liquid chromatography coupled with linear quadrupole ion trap-orbitrap mass spectrometry (UPLC-LTQ-Orbitrap-MS). Methods Warters ACQUITY UPLC HSS T3 (2.1 mm ×100 mm, 1.8 μm) was used as chromatographic column with mobile phase: 0.1% formic acid water (A)-0.1% formic acid acetonitrile (B) with gradient elution, and flow rate was 0.3 ml/min. Electrospray ion source (ESI) and an electrostatic field orbital ion trap mass analyzer were adopted, which was used to collect mass spectrometry fragment information with positive and negative ion modes, by comparing with the relative retention time of the reference substance. In addition, the fragment information of the mass spectrum was used to identify the compounds. The accurate identification of the chemical components in Shenqi Dihuang decoction was confirmed with literature. Results The study found that UPLC-LTQ-Orbitrap-MS technology could be used to identify 62 chemical components, including 13 aromatic acids, 9 flavonoids, 8 saponins, and 5 aromatic amines, 3 keto acids, 2 phenols, 1 aromatic quinone and other ingredients in Shenqi Dihuang decoction. Conclusion The identification analysis method in this study was efficient and accurate, which could be applied to the identification and analysis of chemical components in Shenqi Dihuang decoction and provided the important experimental data for the research on the material basis and mechanism.