BACKGROUND:The extracellular-regulated protein kinase 5(ERK5)signaling protein is essential for the survival of organisms,and resveratrol can promote osteoblast proliferation through various pathways.However,whether resveratrol can regulate osteoblast function through the ERK5 signaling protein needs further verification. OBJECTIVE:To explore the regulatory effect of ERK5 on the proliferation of MC3T3-E1 cells and related secreted proteins,and to further verify whether resveratrol can complete the above process by activating ERK5. METHODS:Mouse MC3T3-E1 preosteoblasts were treated with complete culture medium,XMD8-92(an ERK5 inhibitor),epidermal growth factor(an ERK5 activator),resveratrol alone,XMD8-92+EGF,and resveratrol+XMD8-92,respectively.Western blot assay was used to detect the expression of ERK5 and p-ERK5 proteins,proliferation-related proteins Cyclin D1,CDK4 and PCNA,and osteoblast-secreted proteins osteoprotegerin and receptor activator of nuclear factor-κB ligand in MC3T3-E1 cells of each group.The fluorescence intensity of ERK5,osteoprotegerin and receptor activator of nuclear factor-κB ligand in each group was detected by cell immunofluorescence staining,and cell proliferation was detected by EdU staining,respectively.The appropriate concentration and time of resveratrol intervention in MC3T3-E1 cells were determined by cell morphology observation and cell counting kit-8 assay. RESULTS AND CONCLUSION:The activation of ERK5 signaling protein could effectively promote the proliferation of MC3T3-E1 cells,up-regulate the osteoprotegerin/receptor activator of nuclear factor-κB ligand ratio.The appropriate concentration and time for resveratrol intervention in MC3T3-E1 cells was 5 μmol/L and 24 hours,respectively.Resveratrol could activate ERK5 signaling protein,thereby promoting osteoblast proliferation and up-regulating the osteoprotegerin/RANKL ratio.All these results indicate that resveratrol can promote the proliferation of MC3T3-E1 cells and up-regulate the osteoprotegerin/RANKL ratio by activating the ERK5 signaling protein.

Human exhaled breath is rich in volatile organic compounds （VOCs） with thousands of varieties. In addition to VOCs inhaled from external air， the vast majority of VOCs come from human metabolism and metabolism of the internal microorganisms. Therefore， exhaled VOCs carry abundant information about the human body， which works as "fingerprint" of an individual's exhalation pointing to the underlying metabolic status， making VOCs an ideal tool for health monitoring and disease diagnosis. In recent years， a large number of studies on disease and exhaled VOCs have shown valuable results. Many diseases in the human body are closely related to oxidative stress reaction which also produces plentiful VOCs discharged through the lungs， offering a new window for monitoring diseases. In the future， the use of exhaled VOCs analysis to detect and diagnose infectious diseases， metabolic diseases and tumors may become a new trend. This paper presents a review on VOCs in terms of concept， collection， detection， clinical application， and the relationship between exhaled VOCs and diseases.

ObjectiveTo identify the characteristic exhaled volatile organic compounds （VOCs） associated with postoperative pulmonary complications （PPCs） in patients after abdominal surgery. MethodsThis study prospectively enrolled 76 patients with tracheal intubation who were transferred to intensive care unit （ICU） after abdominal surgery at Peking University People's Hospital between December 10， 2022 and June 30， 2023. The patients' basic information was collected during their perioperative period， and their exhaled VOCs were collected within 24 hours after their admission to the ICU， and then analyzed by gas chromatography and mass spectrometry （GC-MS）. According to whether PPCs occurred 24 hours after surgery， the patients were divided into PPCs group （n=44） and non-PPCs group （n=32）， and the differences of VOCs were compared between the two groups. Lasso regression analysis was used to screen the valuable variables of VOCs， and Logistics regression analysis to determine the characteristic VOCs associated with the occurrence of PPCs. ResultsAmong the 76 patients， 44 had PPCs and 32 had no PPCs. Lasso regression analysis screened 4 PPCs-related compounds from exhaled VOCs of two groups for further analysis and Logistics regression analysis showed that the increase of 1-Hexadecanol content in exhaled breath was significantly correlated with the occurrence of PPCs （OR： 1.000， P=0.002）. ConclusionThis study indicated that the increased content of 1-Hexadecanol in patients' exhaled breath after abdominal surgery may be associated with the occurrence of PPCs.

Most chemical medicines have polymorphs. The difference of medicine polymorphs in physicochemical properties directly affects the stability, efficacy, and safety of solid medicine products. Polymorphs is incomparably important to pharmaceutical chemistry, manufacturing, and control. Meantime polymorphs is a key factor for the quality of high-end drug and formulations. Polymorph prediction technology can effectively guide screening of trial experiments, and reduce the risk of missing stable crystal form in the traditional experiment. Polymorph prediction technology was firstly based on theoretical calculations such as quantum mechanics and computational chemistry, and then was developed by the key technology of machine learning using the artificial intelligence. Nowadays, the popular trend is to combine the advantages of theoretical calculation and machine learning to jointly predict crystal structure. Recently, predicting medicine polymorphs has still been a challenging problem. It is expected to learn from and integrate existing technologies to predict medicine polymorphs more accurately and efficiently.

AIM To investigate the variation rules of main secondary metabolites in Hedysari Radix before and after rubbing strip.METHODS UPLC-MS/MS was adopted in the content determination of formononetin,ononin,calycosin,calycosin-7-glucoside,medicarpin,genistein,luteolin,liquiritigenin,isoliquiritigenin,vanillic acid,ferulic acid,γ-aminobutyric acid,adenosine and betaine,after which cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were used for chemical pattern recognition to explore differential components.RESULTS After rubbing strip,formononetin,calycosin,liquiritigenin and γ-aminobutynic acid demonstrated increased contents,along with decreased contents of ononin,calycosin-7-glucoside and vanillic acid.The samples with and without rubbing strip were clustered into two types,calycosin-7-glucoside,formononetin,γ-aminobutynic acid,vanillic acid,calycosin-7-glucoside and formononetin were differential components.CONCLUSION This experiment clarifies the differences of chemical constituents in Hedysari Radix before and after rubbing strip,which can provide a reference for the research on rubbing strip mechanism of other medicinal materials.

Objective:To analyze the clinical phenotype and genotypes of two children with Carnitine-acylcarnitine translocase deficiency (CACTD).Methods:Two children diagnosed with CACTD at the Gansu Provincial Maternal and Child Health Care Hospital respectively on January 3 and November 19, 2018 were selected as the study subjects. Trio-whole exome sequencing (trio-WES) was carried out, and candidate variants were validated through Sanger sequencing and pathogenicity analysis.Results:Both children were males and had manifested mainly with hypoglycemia. Trio-WES and Sanger sequencing showed that child 1 had harbored compound heterozygous variants of the SLC25A20 gene, namely c. 49G>C (p.Gly17Arg) and c. 106-2A>G, which were inherited from his father and mother, respectively. Child 2 had harbored homozygous c. 199-10T>G variants of the SLC25A20 gene, which were inherited from both of his parents. Among these, the c. 106-2A>G and c. 49G>C variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 49G>C (p.Gly17Arg), c. 106-2A>G, and c. 199-10T>G variants were classified as likely pathogenic (PM2_supporting+ PP3+ PM3_strong+ PP4), pathogenic (PVS1+ PM2_supporting+ PM5+ PP3), and pathogenic (PVS1+ PM2_supporting+ PP3+ PP5), respectively. Conclusion:Combined with their clinical phenotype and genetic analysis, both children were diagnosed with CACTD. Above finding has provided a basis for their treatment as well as genetic counseling and prenatal diagnosis for their families.

Objective To determine the neurotoxic effects of amyloid beta 42(Aβ42)oligomers and investigate the mechanism of their induction of Alzheimer's disease(AD)-like pathogenesis in neuronal cells.Methods Western blotting and transmission electron microscopy were used to identify the synthesized Aβ42 oligomers.In order to assess the impact of the oligomers,MTT assay was employed to measure cell viability in neuroblastoma cell line SH-SY5Y treated with 10μmol/L Aβ42 oligomers for 12 or 24 h,glutamatergic neurons derived from human embryonic stem cells(hESC)exposed to Aβ42 oligomers for 24,48,or 96 h,and corresponding control cells.TUNEL assay was utilized to assess the apoptosis of glutamatergic neurons.Additionally,immu-nofluorescence assay was applied to detect the changes in Aβ plaques and p-tau pathology.Results Western blotting displayed monomers and small-molecule aggregation(＜30 000)in our synthe-sized Aβ42 oligomers,and transmission electron microscopy showed that the synthesized oligomers were mainly in a shape of spherical particles.Treatment of 10 μmol/L Aβ42 oligomers for 12 and 24 h in SH-SY5Y cells significantly decreased cell viability when compared with the control cells[(70.89±2.54)％vs(100.00±2.02)％,(52.63±3.37)％vs(100.00±2.80)％,P＜0.05].The 10μmol/L oligomers treatment for 24,48 and 96 h also decreased cell viability in glutamatergic neu-rons(P＜0.05).The apoptotic rates was significantly higher in glutamatergic neurons after treat-ment for 48 and 96 h when compared to the control cells[(1.44±0.31)％vs(1.00±0.38)％,(1.75±0.64)％vs(1.00±0.31)％,P＜0.05].Furthermore,circular granular Aβ-positive plaque signals were observed in the glutamatergic neurons after treated with the oligomers for 24,48,and 96 h,but no such plaque signals were seen in the control cells.Additionally,glutamatergic neurons incu-bation with 10 μmol/L oligomers for 24 h resulted in tau hyperphosphorylation at the Thr231 site,with the average fluorescence intensity significantly higher than that in control cells(P＜0.05).Conclusion Aβ42 oligomers show toxic effects to both SH-SY5Y cells and glutamatergic neurons,and they can also induce glutamatergic neurons to produce AD pathology.

Antimony is a toxic metalloid and exhibits different geochemical properties in different valence states,leading to distinct migration,transformation,and behavioral patterns in the environment.To further study the transfer and source-sink relationship of antimony and its compounds in the earth's surface ecological environment,it is very important to accurately determine the isotopic composition of antimony with different speciations.In this study,a pretreatment method for chromatographic separation and determination of different speciation's antimony isotopes in water samples was established by using multi-collector inductively coupled plasma mass spectrometry(MC-ICP-MS)to measure the isotopic composition of different speciation's antimony.This method was successfully applied to detection of natural rainwater and groundwater samples from the Qilong mining area.During the pretreatment,5 mmol/L ethylenediaminetetraacetic acid dipotassium salt(EDTA)and 2 mmol/L potassium hydrogen phthalate(KHP)(pH 4.5)were used as mobile phase,successfully separating trivalent antimony(Sb(Ⅲ))and pentavalent antimony(Sb(Ⅴ))from water samples using a Hamilton PRP-X100 anion exchange chromatographic column.A series of single-factor experiments identified the optimal separation and determination conditions as a column temperature of 40 ℃ and a high-performance liquid pump flow rate of 1.5 mL/min.The recoveries of Sb(Ⅲ)and Sb(Ⅴ)from the standard solutions of Sb(Ⅲ)and Sb(Ⅴ),and the mixed oxidation states solutions were 99％±1％,103％±1％,106％±1％,and 101％±1％,respectively.Moreover,the isotopic compositions of different speciation's antimony remained consistent before and after the chromatographic column treatment,and the reliability of the method was verified by detecting different oxidation state antimony in the natural rainwater samples.This research might provide important technical support for further studies on the geochemical cycling of antimony and its compounds in the ecological environment of the Earth's surface.

Objective To observe the therapeutic effect and mechanism of Baoyuan Decoction for chronic heart failure model rat.Methods SD rats were randomly divided into blank group,model group,Baoyuan Decoction group,Captopril group,Baoyuan Decoction+CCT020312[protein kinase R-like endoplasmic reticulum kinase(PERK)activator]group,15 rats in each group.Except for the blank group,the rats in the other groups were induced by Adriamycin to construct a chronic heart failure model.After corresponding drug intervention,cardiac function indexes[left ventricular end-diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),brain natriuretic peptide(BNP),cardiac troponin I(cTnI)],inflammation-related factors[tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β)],oxidative stress factors[malondialdehyde(MDA),superoxide dismutase(SOD)]were detected in each group.Changes in apoptosis-related indicators[B-cell lymphoma 2(Bcl-2),B-cell lymphoma 2-associated X protein(Bax),Caspase-3]and PERK/transcription activator 4(ATF4)signaling pathway-related proteins glucose-regulated protein 78(GRP78),PERK,ATF4,C/EBP homologous protein(CHOP)levels.Results Compared with the blank group,LVEDD,BNP,cTnI,TNF-α,IL-1β,MDA levels,protein expression levels of Bax,Caspase-3,GRP78,PERK,ATF4,CHOP in the model group were significantly increased,LVEF,LVFS,SOD levels and Bcl-2 protein expression level were significantly decreased(all P＜0.05).Compared with the model group and Baoyuan Decoction+CCT020312 group,LVEDD,BNP,cTnI,TNF-α,IL-1β,MDA levels,protein expression levels of Bax,Caspase-3,GRP78,PERK,ATF4,CHOP in Baoyuan Decoction group and Captopril group were significantly decreased,LVEF,LVFS,SOD levels and Bcl-2 protein expression level were significantly increased(all P＜0.05).Compared with the Captopril group,there was no significant change in the above indexes(except CHOP protein expression level)in the Baoyuan Decoction group(P＞0.05).Conclusion Baoyuan Decoction can delay the progression of chronic heart failure rats,and its mechanism may be related to inhibiting the PERK/ATF4 signaling pathway to alleviate cardiomyocyte apoptosis,further reducing the degree of inflammatory response and oxidative stress,thereby promoting the repair of cardiac function and myocardial injury.

Chronic atrophic gastritis(CAG)is a common intractable gastric disease in clinic,which belongs to the gastric precancerous lesions.Professor LIU Feng-Bin and his team have performed the exploration and practice in the field of CAG for more than 30 years,and they proposed that the evolution of the traditional Chinse medicine(TCM)pathogenesis of inflammation-to-tumor transition(ITT)in CAG was characterized by spleen deficiency being the root cause,qi stagnation,blood stasis and dampness retention being the branch cause,and stasis and toxin being the aggravating factors.Deificiency of the spleen and stomach is the initial factor of CAG,which influences the whole process of the disease.Qi stagnation,blood stasis and dampness retention are the triggering and aggravating factors for the ITT in CAG.The formation of blood stasis and toxin is the key to the progression and transition of CAG.Treatment of ITT in CAG should be based on the results of syndrome differentiation and gastroscopic findings by staging therapy.Before treatment,disease dianosis and syndrome differentiation should be made,and macro and micro syndrome differentiation should be carried out for assistance.Therapy of strengthening the spleen and supporting healthy qi should be implemented throughout the whole process of the disease.The early stage of CAG has the features of gastric mucosa with mild to moderate atrophy and with or without mild intestinal epithelial hyperplasia,the pathogenesis of early CAG is characterized by weakness of the spleen and stomach and is accompanied with the pathological factors of qi stagnation,damp-retention and blood stasis,and the basic treatment should adopt the therapies of strengthening the spleen and clearing heat,regulating qi and activating blood stasis.The advanced stage of CAG has the features of severe atrophic gastric mucosa with or without moderate to severe intestinal epithelial and/or mild to moderate intraepithelial neoplasia,the pathogenesis is characterized by weakness of the spleen and stomach,phlegm blended with blood stasis,and stasis-toxin in the gastric collaterals,and the basic treatment should adopt the therapies of supporting healthy qi and dissipating masses,and unblocking the collaterals and removing toxin,so as to construct an intact line to blocking the ITT in CAG with traditional Chinese medicine.