Sesquiterpenoids are widely found in nature, while nitrobenzoyl sesquiterpenoids are relatively rare. Twelve natural nitrobenzoyl sesquiterpenoids were all derived from marine Aspergillus fungi, which are typical natural products with marine characteristics. These natural products exhibit good antitumor, antiviral, and inhibition of osteoclast differentiation activity, especially in the treatment of osteoclast-related diseases, showing good medicinal development value. This article reviews the natural product sources, chemical structure, chemical synthesis, biosynthesis, bioactivity, and pharmacological mechanisms of nitrobenzoyl sesquiterpenoids and predicts and discusses their absorption, distribution, metabolism, excretion, toxicity (ADME/T), and drug-likeness, providing a comprehensive understanding of the natural products of nitrobenzoyl sesquiterpenoids from marine sources and their potential for pharmaceutical development.

Objective To explore the influence of intravenous injection of cis-atracurium during anesthesia induction on QT interval(QTc),hemodynamics and oxidative stress level in patients undergoing hysteroscopic surgery.Methods Patients undergoing hysteroscopic surgery were classified into control group and treatment group.The treatment group was given intravenous injection of 2 mg·kg-1 of propofol emulsion injection+3 μg·kg-1 of fentanyl+0.15 mg·kg-1 of cis-atracurium besylate for injection,while the control group was given intravenous injection of 2 mg·kg-1 of propofol emulsion injection+3 μg·kg-1 of fentanyl+the same amount of 0.9％NaCl as treatment group.Laryngeal mask was placed in the two groups after 3 min,and laryngeal mask ventilation was given for general anesthesia.QTc value and hemodynamics[mean arterial pressure(MAP)]were detected before entering the room(T0),after 1 min of propofol+fentanyl intravenous injection(T1),after 1 min of cis-atracurium besylate for injection/0.9％NaCl(T2),immediately after laryngeal mask insertion(T3)and after 3 min of laryngeal mask insertion(T4).The anesthetic effect,postoperative dynamic pain visual analogue scale(VAS)score and sore throat were counted.The levels of serum oxidative stress indicators[superoxide dismutase(SOD),malondialdehyde(MDA)]at T0 and at the end of surgery(T5)were detected,and the safety was assessed.Results Fifty-two cases in treatment group and forty-four cases in control group were included.There was no statistical difference in QTc value between treatment group and control group at T0-T4(all P＞0.05).The MAP values in treatment group and control group at T3 were(84.22±5.96)and(86.78±6.11)mmHg,respectively,with a statistical difference(P＜0.05).The laryngeal mask insertion times in treatment group and control group were(17.02±2.47)and(19.52±2.34)s;the spontaneous breathing recovery times were(8.51±1.84)and(6.18±1.15)min;the eye opening time were(10.49±2.42)and(9.53±2.17)min;the laryngeal mask removal time were(11.16±2.16)and(10.21±2.34)min;the incidence rates of postoperative sore throat were 13.46％and 31.82％,and the differences were statistically significant(all P＜0.05).The levels of SOD in treatment group and control group at T5 were(36.63±4.17)and(33.26±4.86)nU·mL-1;the levels of MDA were(7.42±2.14)and(8.59±2.83)mmol·L-1(all P＜0.05).The adverse drug reactions in treatment group were mainly nausea and vomiting,respiratory depression and hypotension,and the adverse drug reactions in control group were mainly nausea and vomiting and respiratory depression.The incidence rates of adverse reactions in treatment group and control group were 13.46％and 11.36％,respectively(P＞0.05).Conclusion Cis-atracurium intravenous injection during anesthesia induction has no influence on QTc in patients undergoing hysteroscopic surgery,and has advantages in stabilizing intraoperative hemodynamics,reducing postoperative sore throat and improving serum oxidative stress indicators.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

italic>Salvia miltiorrhiza, a commonly used traditional Chinese medicine, has been widely recognized for its blood-activating and stasis-removing properties in the clinical treatment of cardiovascular and cerebrovascular diseases. The synthesis and regulatory mechanism of tanshinones, the key active constituents of Salvia miltiorrhiza, have been a hot topic of research. The paper summarized the research findings on the regulation of tanshinone biosynthesis by transcription factors such as AP2/ERF, bHLH, MYB, bZIP, and WRKY in recent years. The review identifies the existing issues in the transcriptional regulation studies of Salvia miltiorrhiza and discusses the research direction of transcription factors in the regulation of tanshinone biosynthesis, providing a theoretical basis for the further discovery and utilization of functional genes involved in the regulation of tanshinone bioactive constituents.

Triterpenoids widely exist in nature,displaying a variety of pharmacological activities.Determining triterpenoids in different matrices,especially in biological samples holds great significance.High-performance liquid chromatography(HPLC)has become the predominant method for triterpenoids analysis due to its exceptional analytical performance.However,due to the structural similarities among botanical samples,achieving effective separation of each triterpenoid proves challenging,necessitating significant improvements in analytical methods.Additionally,triterpenoids are characterized by a lack of ultraviolet(UV)absorption groups and chromophores,along with low ionization efficiency in mass spectrometry.Consequently,routine HPLC analysis suffers from poor sensitivity.Chemical derivatization emerges as an indispensable technique in HPLC analysis to enhance its performance.Considering the structural characteristics of triterpenoids,various derivatization reagents such as acid chlorides,rho-damines,isocyanates,sulfonic esters,and amines have been employed for the derivatization analysis of triterpenoids.This review comprehensively summarized the research progress made in derivatization strategies for HPLC detection of triterpenoids.Moreover,the limitations and challenges encountered in previous studies are discussed,and future research directions are proposed to develop more effective derivatization methods.

Objective To explore the effect of CircCSNK1G1 on the proliferation,apoptosis and migration of gastric cancer(GC)cells by regulating the miR-381-3p/S kinase-related protein 2(Skp2)axis.Methods HGC-27 cells were divided into non transfected group,si-NC group,si-CircCSNK1G1 group,si-CircCSNK1 G1+anti-miR-NC group,and si-CircCSNK1G1+anti-miR-381-3p group.The expressions of CircCSNK1G1,miR-381-3p and Skp2 mRNA in GC tumor tissues and GC cell lines were detected by qRT-PCR respectively;cell proliferation was detected by MTT assay;the number of cell clones was detected by clonogenic assay;apoptosis was detected by flow cytometry;cell migration and invasion ability were determined by transwell;the expression of E-cadherin and Vimentin was detected by Western Blot;and the targeting relationship among CircCSNK1G1,miR-381-3p and Skp2 was verified by double luciferase experiment.Results Compared with GES-1 in normal tissues adjacent to cancer and normal human gastric mucosal epithelial cells,the expression of CircCSNK1 G1 and Skp2 mRNA in GC tumor tissues and GC cell lines is high,and the expression of miR-381-3p is low(P＜0.05),and the expression level of miR-381-3p in HGC-27 cells is the lowest,and the expression level of CircCSNK1G1 and Skp2 mRNA is the highest,therefore,HGC-27 cells were selected and CircCSNK1G1 was knocked down for the experiment.Compared with untransfected group and si-CircCSNK1G1-NC group,transfection of si-CircCSNK1G1 could reduce the expression of CircCSNK1G1,Skp2 mRNA,cell proliferation activity,cell migration number,and the expression of Vimentin protein in HGC-27 cells(P＜0.05),the expression of miR-381-3p,apoptosis rate,and the expression of E-cadherin protein were increased(P＜0.05).The double luciferase experiment verified that CircCSNK1G1 and Skp2 had a targeting relationship with miR-381-3p,moreover,CircCSNK1G1 could be used as sponge RNA of miR-381-3p to further regulate the expression and activity of Skp2.Conclusion Knockdown of CircCSNK1G1 can target up-regulate the expression of miR-381-3p,and inhibit the expression of Skp2,thus promoting the apoptosis of GC cells,and inhibiting their proliferation and migration.

Background and aim:Hepatic ischemia-reperfusion injury(IRI)is a significant challenge in liver trans-plantation,trauma,hypovolemic shock,and hepatectomy,with limited effective interventions available.This study aimed to investigate the role of leukocyte cell-derived chemotaxin 2(LECT2)in hepatic IRI and assess the therapeutic potential of Lect2-short hairpin RNA(shRNA)delivered through adeno-associated virus(AAV)vectors. Materials and methods:This study analyzed human liver and serum samples from five patients under-going the Pringle maneuver.Lect2-knockout and C57BL/6J mice were used.Hepatic IRI was induced by clamping the hepatic pedicle.Treatments included recombinant human LECT2(rLECT2)and AAV-Lect2-shRNA.LECT2 expression levels and serum biomarkers including alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatinine,and blood urea nitrogen(BUN)were measured.Histological analysis of liver necrosis and quantitative reverse-transcription polymerase chain reaction were performed. Results:Serum and liver LECT2 levels were elevated during hepatic IRI.Serum LECT2 protein and mRNA levels increased post reperfusion.Lect2-knockout mice had reduced weight loss;hepatic necrosis;and serum ALT,AST,creatinine,and BUN levels.rLECT2 treatment exacerbated weight loss,hepatic necrosis,and serum biomarkers(ALT,AST,creatinine,and BUN).AAV-Lect2-shRNA treatment significantly reduced weight loss,hepatic necrosis,and serum biomarkers(ALT,AST,creatinine,and BUN),indicating thera-peutic potential. Conclusions:Elevated LECT2 levels during hepatic IRI increased liver damage.Genetic knockout or shRNA-mediated knockdown of Lect2 reduced liver damage,indicating its therapeutic potential.AAV-mediated Lect2-shRNA delivery mitigated hepatic IRI,offering a potential new treatment strategy to enhance clinical outcomes for patients undergoing liver-related surgeries or trauma.

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.

Objective To investigate the mechanism by which mycobacterial antigen 85B (Ag85B) inhibits autophagy and promotes apoptosis in Hodgkin lymphoma (HL) cells. Methods The clinical data and pathological tissue slides were retrospectively collected from 80 HL children and 30 children with reactive lymphadenopathy (control group) treated at the First Affiliated Hospital of Xinjiang Medical University. Immunohistochemical analysis was performed to assess the expression of microtubule-associated protein 1 light chain 3 (LC3),sequestosome 1 (P62/SQSTM1),and Beclin-1 in the pathological tissues of HL and control groups. Human Hodgkin lymphoma cells (HDLM-2) were divided into the HDLM-2 group and the HDLM-2+Ag85B groups (with Ag85B concentrations of 0.5,1,2,and 4 μg/mL). The CCK8 method was used to measure HDLM-2 cell proliferation;qRT-PCR was employed to detect the expression of LC3,P62,Beclin-1,Akt,and mTOR mRNA in cells. An apoptosis kit was used to detect cell apoptosis. Results The positive expression of LC3 and Beclin-1 in the HL group were higher than those in the control group (P<0.05),while the positive expression of P62 was lower than that in the control group (P<0.05). In stages Ⅲ-Ⅳ compared to stages Ⅰ-Ⅱ,the positive expression of LC3 and Beclin-1 increased,while the positive expression of P62 decreased (P<0.05). Cell experiment results showed that the HDLM-2+Ag85B group had suppressed cell proliferation compared to the HDLM-2 group,with decreased mRNA expression of LC3 and Beclin-1,and increased mRNA expression of P62,PI3K,Akt,and mTOR,leading to increased cell apoptosis. Notably,when Ag85B was at a concentration of 2 μg/mL,it had the strongest effect on HDLM-2 cells after 24 hours (P<0.05). Conclusions Autophagy is enhanced in children with HL and increases with disease stage. Ag85B can inhibit the proliferation and autophagy of HL tumor cells and promote apoptosis,possibly related to the activation of the PI3K/Akt/mTOR pathway.

Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.