ObjectiveTo investigate the inhibitory effect of Biejia Decoction Pill on the proliferation， migration， and aerobic glycolysis of hepatocellular carcinoma （HCC） using cell experiments， as well as related mechanisms. MethodsHuman liver cancer cell line Huh7 was selected， and Sprague-Dawley rats were randomly divided into blank serum group， inhibitor group， and high-， middle-， and low-dose Biejia Decoction Pill groups. Rat serum containing the drug was prepared for the incubation of Huh7 cells. CCK8 assay and scratch assay were used to explore the effect of Biejia Decoction Pill on the proliferation and migration of HCC cells； glycolytic rate-limiting enzymes and metabolites were measured to explore the effect of Biejia Decoction Pill on aerobic glycolysis of liver cancer cells； RT-qPCR and Western blot were used to explore the effect of Biejia Decoction Pill on the mRNA expression， related proteins， and phosphorylation of the protein kinase B （AKT）/mammalian target of rapamycin （mTOR） signaling pathway. A one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test or the Dunnett’s T3 test were used for further comparison between two groups. ResultsCompared with the blank serum group， the Biejia Decoction Pill groups had significant reductions in OD value， migration rate during different periods of time， glycolytic rate-limiting enzymes （hexokinase， phosphofructokinase， pyruvate kinase）， and glycolytic metabolites （pyruvate， lactic acid， ATP） （all P<0.05）. RT-qPCR results showed that compared with the blank serum group， the high-， middle-， and low-dose Biejia Decoction Pill groups had a significant reduction in the mRNA expression level of mTOR， and the high- and low-dose Biejia Decoction Pill groups had a significant reduction in the mRNA expression level of AKT （all P<0.05）. Western blot results showed that compared with the blank serum group， the high-， middle-， and low-dose Biejia Decoction Pill groups had significant reductions in the expression levels of mTOR-related proteins and phosphorylated proteins， and the high- and middle-dose Biejia Decoction Pill groups had significant reductions in the expression levels of AKT-related proteins and phosphorylated proteins （all P<0.05）. ConclusionThis study preliminarily verifies that the serum containing Bijia Decoction Pill can inhibit the aerobic glycolysis of human hepatoma Huh7 cells， thereby inhibiting their proliferation and migration， possibly by inhibiting the expression of the proteins related to the AKT/mTOR signaling pathway.

ObjectiveThis study aimed to explore the correlation between the quality of life （QOL） and different traditional Chinese medicine （TCM） syndromes in patients with myasthenia gravis （MG）， identifying potential influencing factors to provide new insights for clinical interventions and improving the QOL of patients with MG. MethodsA questionnaire survey was conducted on 93 adults with MG who visited the Department of Neurology at the Affiliated Hospital of Changchun University of Chinese Medicine from March 2023 to January 2024. Statistical analysis was performed on the clinical data collected using SPSS 24.0 software. ResultsAmong the 93 patients with MG， the average score for myasthenia gravis quality of life-15 （MGQOL-15） was 17.65±6.27， and that for the 36-item short form health survey （SF-36） was （106.13±11.83） scores. The QOL was rated as good for 16 patients and moderate for 77 patients. There were no statistically significant differences in the scores of MGQOL-15， SF-36， and their individual scales by gender or education level. Age showed statistically significant differences in MGQOL-15 and the role physical （RP） scale （P<0.05）， and occupational type showed significant differences in the vitality （VT） scale （P<0.01）. The Myasthenia Gravis Foundation of America （MGFA） classification had statistical significance on the total SF-36 score （P<0.01）， VT scale （P<0.01）， role emotional （RE） scale （P<0.05）， social functioning （SF） scale （P<0.05）， and physical functioning （PF） scale （P<0.01）. Among patients with different TCM syndromes， there were significant differences in MGQOL-15 scores （F=4.919， P<0.01）. Moreover， significant differences were observed in SF-36 scores （P<0.01）， VT scale （P<0.01）， RE scale （P<0.05）， mental health （MH） scale （P<0.01）， and SF scale （P<0.05）. ConclusionFactors affecting the QOL of patients with MG include age， occupational type， and clinical classification of MG. Specifically， a greater impact on the QOL of older patients is observed， while physical laborers have a poorer QOL compared to non-physical laborers. Patients classified as MGFA type Ⅱ and higher have a poorer QOL. Additionally， there is a potential correlation between the QOL and TCM syndromes， with patients presenting with spleen and kidney Qi deficiency having a lower QOL than those with spleen and stomach Qi deficiency or Qi and Yin deficiency， which is particularly evident in the VT， RE， MH， and SF scales.

Sesquiterpenes are natural terpenoids with 15 carbon atoms in the basic skeleton, which mainly exist in plant volatile oil and have important physiological and medicinal value. Cytochrome P450 (CYP450) is a kind of monooxygenase encoded by supergene family, which is one of the largest gene families in plants. It is involved in the synthesis and metabolism of terpenoids, alkaloids and other secondary metabolites. In the process of terpene biosynthesis, CYP450 participates in the post-modification stage of terpenes by introducing functional groups such as hydroxyl, carboxyl and carbonyl, which plays an important role in enriching the diversity of terpenes. The CYP450 enzymes involved in sesquiterpene synthesis and their substrate catalytic specificity mechanisms have been partially investigated. In this paper, the biosynthetic pathway of plant sesquiterpenes, the structure and classification of CYP450 enzymes were briefly introduced, and the CYP450 enzymes involved in sesquiterpene biosynthesis were summarized, in order to provide a reference for intensive study of the role of CYP450 enzymes in the synthesis of sesquiterpenoids.

The analysis of ammonia nitrogen in real water samples is challenging due to matrix interferences and difficulties for rapid on-site analysis.On the basis of the standard method,i.e.water quality-determination of ammonia nitrogen-salicylic acid spectrophotometry(HJ 536-2009),a simple device for online detecting ammonia nitrogen was developed using a sequential injection analysis(SIA)system in this work.The ammonia nitrogen transformation system,color reaction system,and detection system were built in compatible with the SIA system,respectively.In particular,the detection system was assembled by employing light-emitting diode as the light source,photodiode as the detector,and polyvinylchloride tube as the cuvette,thus significantly reducing the volume,energy consumption and fabricating cost of the detection system.As a result,the accurate analysis of ammonia nitrogen in complex water samples was achieved.A quantitative detection of ammonia nitrogen in water sample was obtained in 12 min,along with linear range extending to 1000 μmol/L,precisions(Relative standard deviation,RSD)of 4.3%(C=10 μmol/L,n=7)and 4.2%(C=500 μmol/L,n=7),and limit of detection(LOD)of 0.65 μmol/L(S/N=3,n=7).The results of interfering experiments showed that the detection of ammonia nitrogen by the developed device was not interfered by the common coexisting ions and components,therefore the environmental water could be directly analyzed,such as reservoir water,domestic sewage,sea water and leachate of waste landfill.The analytical results were consistent with those obtained by the environmental protection standard method(Water quality determination of ammonia nitrogen-salicylic acid spectrophotometry,HJ 536-2009).In addition,the spiking recoveries were in the range of 92.3%-98.1%,further confirming the accuracy and practicality of the developed device.

Objective·To evaluate the quality of clinical practice guidelines of obstructive sleep apnea(OSA)published worldwide.Methods·The guidelines of OSA were retrieved in PubMed,Embase,China National Knowledge Infrastructure(CNKI),Wanfang Data,SinoMed,MedSci,The Cochrane Library,and the websites such as Medlive,U.S.Preventive Services Task Force(USPSTF),National Institute for Health and Care Excellence(NICE),New Zealand Guidelines Group(NZGG),Scottish Intercollegiate Guidelines Network(SIGN),and Guidelines International Network(GIN)from establishment to December 2022.Two reviewers screened the literature and extracted the main information independently,using the Appraisal of Guidelines for Research and Evaluation Ⅱ(AGREE Ⅱ)and Reporting Items for Practice Guidelines in Healthcare(RIGHT)to evaluate the quality of the included OSA guidelines.Subgroup analysis was performed according to the publication regions of guidelines.The inter-evaluator consistency test was also performed and the results were expressed as the intra-class correlation coefficient(ICC).All the included guidelines were read entirely and the clinical questions they raised were summarized.Results·A total of 35 OSA guidelines were included.The ICC value of 0.975 showed a good inter-evaluator agreement.The results of AGREE Ⅱ showed that the average score of all guidelines was(63.60±16.45)%,with a minimum of 23.40%and a maximum of 91.67%.In the six domains,the scores of"Rigor of development"[(56.07±25.89)%]and"Applicability"[(53.57±15.52)%]were relative low.The average reporting rate of RIGHT of all the included guidelines was(67.84±20.03)%,with a minimum of 14.29%and a maximum of 94.29%,and the three domains with the lowest reporting rates were"Review and quality assurance"[(31.40±45.51)%],"Funding and conflict of interest declaration and management"[(56.43±33.95)%]and"Other aspects"[(56.19±36.85)%].Subgroup analysis showed that guidelines in Asian had a lower score in"Rigor of development"and a lower overall score of AGREE Ⅱ than the guidelines in America and Europe(both P<0.05),and the reporting rates in the domains of"Evidence"and"Other information"of RIGHT of the Asian guidelines were also lower than those in the guidelines in America and Europe(P<0.05).These guidelines focused on 42 clinical questions which were classified to 3 aspects,i.e.screening and diagnosis,treatment and long-term management of OSA.Conclusion·The quality of current global OSA guidelines varies a lot,and they need to be strengthened in terms of rigor of development,applicability,review and quality assurance,funding and conflict of interest declaration and management,especially those in Asia.

Objective To analyze the pathogenic characteristics and drug sensitivity of candidaemia,and construct a short-term mortality risk prediction scoring model.Methods The clinical data of patients with candidaemia admitted to the 909 Hospital of Joint Logistics Support Force from January 2011 to December 2020 were retrospectively analyzed,and the composition of pathogen composition,drug sensitivity test results and incidence of hospitalized patients were analyzed.324 cases of candidaemia were randomly divided into modeling group(190 cases)and validation group(134 cases),and the risk factors were screened by binary logistic regression.According to the odds ratio(OR)score,the 30 day mortality risk prediction scoring model was constructed,and the predictive performance of the model was verified both in modeling and validation groups.Results 356 strains of Candida including 126 strains of C.albicans(35.39%),79 strains of C.tropicalis(22.19%),74 strains of C.parapsilosis(20.79%),48 strains of C.glabrata(13.48%),14 strains of C.guilliermondii(3.93%),8 strains of C.krusei(2.25%),and 7 strains of other Candida(1.97%)were detected in 336 patients with candidemia.The incidence of candidaemia among hospitalized patients increased from 0.20 ‰ in 2011 to 0.48 ‰ in 2020.The resistance rate of candida to amphotericin B was significantly lower than that of fluconazole,voriconazole and itraconazole(P＜0.05).Among the 324 cases included in the model,95 patients died in 30 days after diagnosis,and the mortality rate was 29.32%.The proportion of males,fever,and parenteral nutrition in modeling group was significantly higher than that in validation group(P＜0.05),while the proportion of chronic lung disease and surgical history within one month were lower than those in validation group(P＜0.05).Logistic regression analysis showed that chronic renal failure,mechanical ventilation,severe neutropenia,failure to receive anti-fungal treatment within 72 hours,and APACHE Ⅱ≥20 were risk factors for short-term death of candidaemia,the OR values were 3.179,1.970,2.979,2.080,and 2.399,and the risk scores were 6,4,6,4,and 5,respectively.The area under the curve(AUC)of the risk scoring model for modeling group was 0.792(95%CI 0.721-0.862),and the result of Hosmer-Lemeshow(H-L)test was P=0.305;The AUC of validation group was 0.796(95%CI 0.735-0.898),and the H-L test result was P=0.329.A risk score≤8 indicated a low risk group for short-term mortality,a score of 9-15 indicated a medium risk group,and a score≥16 indicated a high risk group.Conclusions The incidence of candidemia in hospitalized patients is increasing and the mortality is high.The risk prediction score model can effectively predict the short-term prognosis and facilitate the early identification of the prognosis.

ObjectiveTo investigate the induction of ferroptosis by polyphyllin Ⅱ （PPⅡ） in hepatocellular carcinoma HepG2 cells and its underlying mechanism. MethodThe effect of PPⅡ （0， 1.5， 3.0， 4.5， 6.0， 9.0， 18.0 mg·L^-1） on the in vitro proliferation of HepG2 cells was assessed using the methyl thiazolyl tetrazolium （MTT） assay. Colony formation ability of HepG2 cells was evaluated through a colony formation assay. Cell migration ability was assessed via a scratch assay. Lactate dehydrogenase （LDH） content in HepG2 cells was measured using a kit. Reactive oxygen species （ROS） levels in HepG2 cells were observed using a fluorescence inverted microscope. Malondialdehyde （MDA）， glutathione （GSH）， and free Fe²⁺ content in HepG2 cells were detected using respective kits. The mitochondrial ultrastructure in HepG2 cells was observed by transmission electron microscopy. The expression of ferroptosis-related proteins p53， solute carrier family 7 member 11 （SLC7A11）， glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4）， and transferrin receptor 1 （TFR1） in HepG2 cells was detected using Western blot. ResultCompared with the control group， the PPⅡ treatment groups showed significantly decreased survival rate of HepG2 cells in a dose-dependent manner （P<0.01）， significantly reduced number of cell colonies （P<0.01）， significantly shortened scratch healing distance， inverse correlation of the migration distance with drug concentration （P<0.01）， significantly increased LDH leakage in cells （P<0.01）， significantly enhanced relative fluorescence intensity of intracellular ROS， and significantly increased accumulation of lipid peroxide MDA （P<0.01）， decreased intracellular GSH content with increasing drug concentration （P<0.01）， and significantly enhanced fluorescence intensity of FeRhoNox-1 in cells （P<0.01）. Moreover， cells exhibited vacuolation， and mitochondria showed significant shrinkage with reduced or even disappeared cristae. Compared with the results in the control group， the expression of p53， ACSL4， and TFR1 proteins significantly increased， while the expression of SLC7A11 and GPX4 proteins significantly decreased in the PPⅡ treatment groups （P<0.05）. ConclusionIn summary， PPⅡ induces ferroptosis in HepG2 cells by regulating the p53/SLC7A11/GPX4 signaling axis， promoting ACSL4 expression and Fe³⁺ uptake， leading to an imbalance in the antioxidant system.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective To discuss the evaluation basis of the clinical rational use of Dahuang Zhechong Capsule and to establish its rationality evaluation criterion to promote the sensible use of Dahuang Zhechong Capsule.Methods The rationality evaluation criterion for Dahuang Zhechong Capsule was formulated by referring to the package insert,treatment guidelines,and other literature.According to the criterion,270 outpatient prescriptions using Dahuang Zhechong Capsule in Xiyuan Hospital,China Academy of Chinese Medical Sciences were reviewed from January to June 2020.The indication,usage and dosage,drug combination,and repeated administration were analyzed.The pharmaceutical intervention was performed to address the problems found in the prescription reviews,and 328 outpatient prescriptions using Dahuang Zhechong Capsule in October 2020 were reevaluated.Results The irrational use rate of Dahuang Zhechong Capsule from January to June 2020 was 42.22％(114 cases),including 108(40％)cases of inappropriate indications,five(1.85％)cases of improper usage and dosage,and one(0.37％)case of inappropriate administration route.However,the pharmaceutical intervention in October 2020 remarkably reduced the irrational use rate of Dahuang Zhechong Capsule(4.27％,14 cases),all of which were inappropriate indications.Conclusion Dahuang Zhechong Capsule is being used irrationally;therefore,establishing an evaluation criterion is required.The specific situation of irrational drug use can be identified by prescription review according to its rationality evaluation criterion to manage its clinical use better and promote its rational use.

Grooming,as an evolutionarily conserved repetitive behavior,is common in various animals,including humans,and serves essential functions including,but not limited to,hygiene maintenance,thermoregulation,de-arousal,stress reduction,and social behaviors.In rodents,grooming involves a patterned and sequenced structure,known as the syntactic chain with four phases that comprise repeated stereotyped movements happening in a cephalocaudal progression style,beginning from the nose to the face,to the head,and finally ending with body licking.The context-dependent occurrence of grooming behavior indicates its adaptive significance.This review briefly summarizes the neural substrates responsible for rodent grooming behavior and explores its relevance in rodent models of neuropsychiatric disorders and neurodegenerative diseases with aberrant grooming phenotypes.We further emphasize the utility of rodent grooming as a reliable measure of repetitive behavior in neuropsychiatric models,holding promise for translational psychiatry.Herein,we mainly focus on rodent self-grooming.Allogrooming(grooming being applied on one animal by its conspecifics via licking or carefully nibbling)and heterogrooming(a form of grooming behavior directing towards another animal,which occurs in other contexts,such as maternal,sexual,aggressive,or social behaviors)are not covered due to space constraints.