Inflammatory diseases (IDs) are a general term of diseases characterized by chronic inflammation as the primary pathogenetic mechanism, which seriously affect the quality of patient′s life and cause significant social and medical burden. Current drugs for IDs include nonsteroidal anti-inflammatory drugs, corticosteroids, immunomodulators, biologics, and antioxidants, but these drugs may cause gastrointestinal side effects, induce or worsen infections, and cause non-response or intolerance. Given the outstanding performance of metal polyphenol network (MPN) in the fields of drug delivery, biomedical imaging, and catalytic therapy, its application in the diagnosis and treatment of IDs has attracted much attention and significant progress has been made. In this paper, we first provide an overview of the types of IDs and their generating mechanisms, then sort out and summarize the different forms of MPN in recent years, and finally discuss in detail the characteristics of MPN and their latest research progress in the diagnosis and treatment of IDs. This research may provide useful references for scientific research and clinical practice in the related fields.

The pathogenesis of cardiovascular diseases (CVD) is complex, and dynamic imbalances in protein acylation modification are significantly associated with the development of CVD. In recent years, most studies on exercise-regulated protein acylation modifications to improve cardiovascular function have focused on acetylation and lactylation. Protein acylation modifications are usually affected by exercise intensity. High-intensity exercise directly affects oxidative stress and cellular energy supply, such as changes in ATP and NAD⁺ levels; moderate-intensity exercise is often accompanied by improvements in aerobic metabolism, such as fatty acid β-oxidation and TCA cycle, which modulate mitochondrial biogenesis. The above processes may affect the acylation status of relevant regulatory enzymes and functional proteins, thereby altering their function and activity and triggering signaling cascades to adapt to exercise’s metabolic demands and stresses. Exercise regulates the levels of acylation modifications of H3K9, H3K14, H3K18, and H3K23, which are involved in regulating the transcriptional expression of genes involved in oxidative stress, glycolysis, inflammation, and hypertrophic response by altering chromatin structure and function. Exercise can regulate the acylation modification of non-histone-specific sites in the cardiovascular system involved in mitochondrial function, glycolipid metabolism, fibrosis, protein synthesis, and other biological processes, and participates in the regulation of protein activity and function by altering the stability, localization, and interaction of proteins, and ultimately works together to achieve the improvement of cardiovascular phenotypes and biological functions. Exercise affects acyl donor concentration, acyltransferase, and deacetylase expression and activity by influencing acyl donor concentration, acyltransferase, and deacetylase. Exercise regulates the abundance of acyl donors such as acetyl coenzyme A, propionyl coenzyme A, butyryl coenzyme A, succinyl coenzyme A, and lactoyl coenzyme A by promoting glucose and lipid metabolism and improving intestinal bacterial flora, which in turn affects protein acylation modification, accelerates oxidative decarboxylation of pyruvic acid in the body, and activates the energy-sensing molecule, adenosine monophosphate-activated protein kinase (AMPK), to improve cardiovascular function. Exercise may affect protein acylation modifications in the cardiovascular system by regulating the activity and expression of adenoviral E1A binding protein of 300 kDa (p300)/cyclic adenosine monophosphate response element-binding protein (CBP), general control nonderepressible 5-related N-acetyltransferases (GNAT), and alanyl-transfer t-RNA synthetase (AARS), which in turn improves cardiovascular function. The relationship between exercise and cardiovascular deacetylases has attracted much attention, with SIRT1 and SIRT3 of the silence information regulator (SIRT) family of proteins being the most studied. Exercise may exert transient or long-term stable cardiovascular protective benefits by promoting the enzymatic activity and expression of SIRT1, SIRT3, and HDAC2, inhibiting the enzymatic activity and expression of HDAC4, and mediating the deacylation of metabolic regulation-related enzymes, cytokines, and molecules of signaling pathways. This review introduces the role of protein acylation modification on CVD and the effect of exercise-mediated protein acylation modification on CVD. Based on the existing studies, it analyzes the possible mechanisms of exercise-regulated protein acylation modification to improve CVD from the perspectives of acylation modification donors, acyltransferases, and deacetylases. Deciphering the regulation of cardiovascular protein acylation and modification by exercise and exploring the essential clues to improve cardiovascular disease can enrich the theoretical basis for exercise to promote cardiovascular health. However, it is also significant for developing new cardiovascular disease prevention and treatment targets.

Aim To compare the pharmacokinetics of pemirolast potassium tablets in healthy subjects in Chi-na under single fasting and postprandial conditions,and to evaluate the bioequivalence of the test prepara-tion(T)and the reference preparation(R).Methods A randomized,open-ended,single-dose,two-cycle,double-cross bioequivalence trial design was adopted,and 26 and 30 subjects were enrolled in the fasting group and the postprandial group,respectively,and 10 mg of the test preparation and the reference preparation were taken in the fasting or postprandial state each cy-cle,and venous blood was collected at the designed time points before and after the administration cycle.The concentration of pemirolast potassium in plasma was determined by LC-MS/MS method,and the phar-macokinetic parameters were calculated with PhoenixTM WinNonlin ?(8.3)software,and the bioequivalence analysis of the two preparations was performed.Re-sults The t1/2 of the test preparation and the reference preparation was(4.44±0.91)h and(4.49±0.93)h,respectively;the median tmax was(1.96±1.29)h and(2.18±1.25)h,respectively;the Cmax was(867.12±205.56)μg·L-1 and(863.35±172.03)μg·L-1,respectively;the AUC0-t was(5 513.23±1463.67)h·μg·L-1 and(5 661.32±1 628.65)h·μg·L-1,respectively;AUC0_∞ was(5 699.81±1477.68)h·μg·L-1 and(5 849.44±1 644.75)h·μg·L-1,respectively.The statistical results of the 90％confidence intervals of the main pharmacokinetic parameters Cmax,AUC0-t,and AUC0-∞ was 92.49％～107.53％,94.71％～100.67％and 95.28％～100.27％,respectively,all of which were within the range of 80.00％～125.00％,and the safety of the tested preparation and the reference preparation was good when taken orally on an empty stomach.The t1/2 of single oral administration after prandial administra-tion of the tested preparation and the reference prepara-tion was(4.46±0.78)and(4.51±0.84)h,respec-tively;the median tmax was(3.08±1.36)h and(3.28±1.28)h,respectively;the Cmax was(683.83±111.87)μg·L-1 and(689.77±110.24)μg·L-1,respectively;the AUC0-t was(5 695.99±1566.05)h·μg·L-1 and(5 773.60±1 551.04)h·μg·L-1,respectively;the AUC0-∞ was(5 914.06±1 551.86)h·μg·L-1 and(5 967.30±1552.89)h·μg·L-1,respectively.The 90％confi-dence interval of Cmax,AUC0-t,and AUC0-∞ was 93.56％～104.69％,96.43％～100.83％,and 97.29％～101.14％,respectively,which was in the range of 80.00％～125.00％,and the safety of the tested preparation and the reference preparation was good after meals.Conclusion In the state of fasting and postprandial single oral administration,the two kinds of pemirolast potassium tablets have good bio-equivalence.

Aim To observe the effect of Astragalus membranaceus and Angelica sinensis on the apoptosis of chondrocytes,and to investigate the effect of Astrag-alus membranaceus and Angelica sinensis on the sur-vival of fresh ostecartilage allograft.Methods Forty-eight 4-month-old New Zealand white rabbits,half male and half female,were randomly divided into sham operation group,model group,positive group and As-tragalus and Angelica 5∶1 group.In addition to the sham operation group,the other groups were both male and female donors and recipients for knee joint osteo-cartilage cross transplantation modeling.After 8 weeks of drug intervention,samples were taken for general observation,HE staining,saffrane-O staining,immu-nohistochemical staining,qPCR and Western blot de-tection.Results Compared with model group,As-tragalus and Angelica 5∶1 group and positive group,the repair site healed better,the morphology of osteo-chondrocytes tended to be normal,and the division and proliferation were obvious.Proteoglycan deposition in-creased and type Ⅱ collagen content was higher,the differences were statistically significant(P＜0.05).qPCR and Western blot results showed that compared with model group,the mRNA and protein expressions of Bax,caspase-3 and caspase-9 in other groups were significantly decreased(P＜0.05).Conclusion As-tragalus and Angelica can promote the survival of fresh osteochondral allograft,and its mechanism may be re-lated to promoting collagen production,promoting chondrocyte proliferation and inhibiting chondrocyte apoptosis.

Objective:To investigate the efficacy and safety of Venetoclax combined with CACAG regimen in treatment of patients with refractory/relapse acute myeloid leukemia(R/R AML).Methods:The study was a singlecenter prospective clinical trial.The enrolled patients met the criteria for R/R AML.Treatment included Azacidine(75mg/m2,d1-7),Ara-C(75-100 mg/m2,q12h,d1-5),Aclacinomycin(20 mg d1,d3,d5),Chidamide(30 mg d1,d4),Venetoclax(100 mg d1,200 mg d2,400 mg d3-d14,in combination with Triazole Drug,reduced to 100 mg/d),and granulocyte colony-stimulating factor(300 μg/d until neutrophil recovery).The primary endpoint of observation was overall response rate after 1 course of treatment.Results:A total of 19 patients were enrolled from January 2022 to April 2023.After 1 course of treatmen,the overall response rate was 81.3％(13/16),the CR rate was 68.8％(11/16),and the PR was 12.5％(2/16).Among the 11 patients who got CR/CRi,8 cases achieved CRm(minimal residual disease negative CR)and 3 cases did not.As of March 27,2023,the median follow-up time was 111(19-406)days.The six-month overall survival and progression-free survival rates were both 55.7％,the 1-year overall survival and progression-free survival rates were 46.4％and 47.7％,respectively.In addition,compared with the non-CRm group,CRm patients had a better PFS(377 days vsi11 days,P=0.046).Treatment-related adverse events were mainly 3-4 degrees of bone marrow suppression,complicated by various degrees of infection(n=12),hypokalemia(n=12)and hypocalcemia(n=10)and elevated liver enzymes(n=8),of which 3/4 degrees accounted for 47.4％(9/19).Conclusion:The Venetoclax combined with CACAG regimen is an effective salvage therapy for patients with R/R AML,with high remission rate and safety profile.

Objective:To study the molecular mechanism of functional defect of protein C (PC) caused by point mutations of human protein C gene (PROC) N355S,G392E and T314A. Methods:The wild-type and mutant plasmids (PCWT,PCN355S,PCG392E,PCT314A) of PROC gene were constructed and transiently transfected into HEK293 cells. The expression of mutant proteins in vitro were tested. The mRNA level changes of wild-type and mutant PC after 24 h of transfection were detected by real-time PCR. Western blot and ELISA were used to detect the changes of intracellular and extracellular protein levels of wild-type and mutant PC. The supernatant of cells transfected for 24-48 h was concentrated by ultrafiltration. The protein in the concentrated solution was quantified,and PC activation and enzyme kinetics tests were performed. Clustal Omega multiple sequence alignment was used to analyze the conservation of amino acid mutation sites. The effect of mutation on PC protein structure was analyzed by PyMOL software. Results:The relative expression abundances of PROC mRNA in PCN355S,PCG392E and PCT314A groups were 1.14±0.46,0.96±0.08 and 1.08±0.17,respectively,and there were no significant differences compared with 1.02±0.24 in PCWT group (P>0.05). Western blot analysis of the lysates of transfected cells showed that the content of PCT314A recombinant protein slightly decreased and the band became relatively lighter. The ELISA results of the concentrated cell culture supernatants showed that the PC:Ag levels of PCN355S and PCG392E were 98.8％±2.4％ and 101.4％±3.1％,respectively,with no significant differences compared with PCWT,while PCT314A decreased compared with PCWT (PC:Ag:88.6％±3.2％) (P<0.05). The results of enzyme kinetics test showed that APCN355S (Km=338.3±43.2,Vmax=2.015±0.12),APCG392E (Km=292.2±28.4,Vmax=1.893±0.07) and APCT314A (Km=299.5±24.6,Vmax=1.775±0.06) showed an increase in Km and a decrease in Vmax compared with APCWT (Km=238.2±4.58,Vmax=3.205±0.06). Multiple sequence alignment suggested that the three mutations be highly conservative in different species. The structural model suggested that the amino acid substitutions of N355S,G392E and T314A mutations collide with the surrounding amino acid groups,causing distortion of the surrounding structure,which may have adverse effects on the folding and biological function of PC. Conclusion:The N355S,G392E and T314A mutations in the PROC gene cause functional defects in PC by weakening the binding between PC and substrate. These three mutations have caused serious spatial collisions in the protein structure,affecting the folding of PC and the reactivity of active sites.

China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.

Objective:To investigate the role of serotonin reuptake transporter(SERT)and P2X3 receptor of dorsal root ganglion(DRG)in regulating visceral hypersensitivity of rats with irritable bowel syndrome(IBS)by electroacupuncture(EA). Methods:Male Sprague-Dawley and SERT-/-rats were subjected to preparing IBS visceral hypersensitivity models with 2,4,6-trinitrobenzene sulfonic acid(TNBS)enema.Three weeks post-modeling,interventions including EA,intrathecal injection,and EA plus intrathecal injection were applied,respectively.Hematoxylin-eosin staining and abdominal withdrawal reflex(AWR)score were used to confirm the successful establishment of the IBS model.AWR score,whole-cell patch clamp technique,and Western blotting assay were used to evaluate the changes in visceral pain sensitivity,electrophysiological properties of DRG neurons,and the expression of DRG P2X3 receptor and SERT in IBS rats. Results:Compared to the model group,the AWR score in the EA group decreased significantly(P<0.05),the resting membrane potential(P<0.05)and the number of action potentials(P<0.05)of DRG neurons reduced,and the baseline intensity increased(P<0.05);additionally,the expression of P2X3 receptor in DRG decreased(P<0.01),and the SERT expression increased(P<0.05).Compared to the P2X3 receptor agonist group,the SERT protein expression in DRG was higher in the EA group.In SERT-/-rats,the P2X3 receptor expression in DRG increased in the EA group compared to the model group(P<0.01). Conclusion:EA modulates the electrophysiological characteristics of intestinal primary sensory neurons by regulating the expression of SERT and P2X3 receptor in DRG of IBS rats.This modulation may contribute to the mechanism by which EA alleviates peripheral sensitization of visceral pain in IBS rats.

Objective:To investigate the efficacy of different doses of bortezomib combined with chemotherapy for multiple myeloma (MM).Methods:A prospective case series study was performed. A total of 81 MM patients at Leshan People's Hospital from February 2022 to May 2023 were collected as study subjects. According to the random number table method, patients were divided into high-dose bortezomib group (39 cases treated with 1.6 mg/m 2 bortezomib combined with dexamethasone and thalidomide) and low-dose bortezomib group (42 cases treated with 1.3 mg/m 2 bortezomib combined with dexamethasone and thalidomide). The clinical efficacy after 4 courses of treatment, adverse reactions, C-reactive protein (CRP), β 2 microglobulin (β 2-MG) and serum creatinine levels before and after treatment, survival and prognosis of patients in both groups were compared. Results:There were 29 males and 10 females in the high-dose bortezomib group and the age was (59±5) years; there were 31 males and 11 females in the low-dose bortezomib group and the age was (59±6) years. The differences in the general data of both groups were statistically significant (all P > 0.05). The overall effectiveness rate was 87.2% (34/39) and 80.9% (34/42), respectively in the high-dose bortezomib group and the low-dose bortezomib group, and the difference was not statistically significant of both groups ( χ2 = 0.58, P = 0.446). The incidence rate of adverse reactions was 30.8% (12/39), 19.0% (8/39), respectively in the high-dose bortezomib group and the low-dose bortezomib group, and the difference was not statistically significant of both groups ( χ2 = 1.49, P = 0.222). Before treatment, there were no statistically significant differences in the levels of CRP, β 2-MG and serum creatinine between the 2 groups (all P > 0.05); after treatment, there were statistically significant differences in the levels of CRP [(23.6±2.2) g/L vs. (31.5±3.6) g/L)], β 2-MG [(2 317±63) μg/L vs. (4 212±114) μg/L] and serum creatinine [(70±5) μmol/L vs. (79±7) μmol/L] in the high-dose bortezomib group and the low-dose bortezomib group ( t value was 4.28, 18.29, 4.00, all P<0.05); and the levels of above 3 indicators after treatment were lower than those before treatment of both groups (all P < 0.05). The mortality rate was 10.3% (4/39) and 14.3% (6/42), respectively in the high-dose bortezomib group and the low-dose bortezomib group 1-year follow-up after treatment, and the difference was not statistically significant ( χ2 = 0.30, P = 0.582). Conclusions:The efficacy and safety of high-dose bortezomib combined with chemotherapy are comparable to those of low-dose bortezomib combined with chemotherapy in treatment of MM, while the former could improve renal function and inflammatory status of MM patients.

Objective To evaluate the effect of delayed cleaning on the cleaning and disinfection quality of gastro-scopes after pre-treatment with different solutions.Methods According to the factorial design table,combination of the pre-treatment cleaning solutions(factor A)(including multi-enzyme cleaning solution[A1],clean water[A2])and delayed cleaning durations(factor B)(including 0 minutes after pre-treatment[B1],30 minutes after pre-treat-ment[B2],1 hour after pre-treatment[B3],and 3 hours after pre-treatment[B4])yielded eight groups(A1B1,A1B2,A1B3,A1B4,A2B1,A2B2,A2B3,A2B4).According to the usage order of gastroscopes,96 gastroscopes used in the digestive endoscopy center of a tertiary first-class hospital from May to September,2023 were randomly assigned to each group by random number table method,with 12 gastroscopes in each group.Specimens were taken at four time points:after pre-treatment,before cleaning,after cleaning,and after disinfection.Due to instant clea-ning,no specimen before cleaning were taken from A1B1 and A2B1 groups,thus only 3 specimens were taken from these two groups each.Four specimens were taken from gastroscopes in the rest groups,resulting in 360 specimens in total.The internal condition of the biopsy cavity was observed through a cavity detector during each delayed cleaning period after pre-treatment,and specimens were taken at the subsequent reprocessing processes of the gas-troscopes.The microbial conditions of the gastroscopes after pre-treatment,before cleaning,after cleaning,and af-ter disinfection were compared.Results After pre-treatment with multi-enzyme cleaning solution and clean water,there was no statistically significant difference in microbiological detection result(P＞0.05).The biopsy cavity re-mained moist during the delayed cleaning period.There was no statistically significant difference in the microbial de-tection results of factors A and B before and after delayed cleaning as well as after disinfection(all P＞0.05).There was no interaction effect between factor A and B.The distribution of bacterial colonies and disinfection qualified rate of gastroscopes after pre-treatment with two cleaning solutions were also not statistically different(both P＞0.05).Conclusion Delayed cleaning for 30 minutes,1 hour,and 3 hours after pre-treatment does not affect the cleaning and disinfection quality of gastroscopes.When clinical demand is urgent,immediate cleaning should be carried out.However,a certain buffering time(no longer than 3 hours)before cleaning is acceptable,when cleaning and disin-fection workload is heavy and timely cleaning cannot be carried out.