BACKGROUND:Disseminated intravascular coagulation(DIC)is associated with increased mortality in sepsis patients.In this study,we aimed to assess the clinical ability of sepsis-induced coagulopathy(SIC)and sepsis-associated coagulopathy(SAC)criteria in identifying overt-DIC and pre-DIC status in sepsis patients. METHODS:Data from 419 sepsis patients were retrospectively collected from July 2018 to December 2022.The performances of the SIC and SAC were assessed to identify overt-DIC on days 1,3,7,or 14.The SIC status or SIC score on day 1,the SAC status or SAC score on day 1,and the sum of the SIC or SAC scores on days 1 and 3 were compared in terms of their ability to identify pre-DIC.The SIC or SAC status on day 1 was evaluated as a pre-DIC indicator for anticoagulant initiation. RESULTS:On day 1,the incidences of coagulopathy according to overt-DIC,SIC and SAC criteria were 11.7％,22.0％and 31.5％,respectively.The specificity of SIC for identifying overt-DIC was significantly higher than that of the SAC criteria from day 1 to day 14(P＜0.05).On day 1,the SIC score with a cut-off value＞3 had a significantly higher sensitivity(72.00％)and area under the curve(AUC)(0.69)in identifying pre-DIC than did the SIC or SAC status(sensitivity:SIC status 44.00％,SAC status 52.00％;AUC:SIC status 0.62,SAC status 0.61).The sum of the SIC scores on days 1 and 3 had a higher AUC value for identifying the pre-DIC state than that of SAC(0.79 vs.0.69,P＜0.001).Favorable effects of anticoagulant therapy were observed in SIC(adjusted hazard ratio[HR]=0.216,95％confidence interval[95％CI]:0.060-0.783,P=0.018)and SAC(adjusted HR=0.146,95％CI:0.041-0.513,P=0.003). CONCLUSION:The SIC and SAC seem to be valuable for predicting overt-DIC.The sum of SIC scores on days 1 and 3 has the potential to help identify pre-DIC.

Objective:To explore the clinical efficacy of ultrasound-indicated cervical cerclage in twin pregnancies.Methods:This retrospective cohort study included 96 asymptomatic twin pregnancies with cervix length (CL)≤2.5 cm at 16-27 +6 weeks indicated by transvaginal ultrasound from January 2013 to May 2022 in Fujian Maternity and Child Health Hospital. They received either cervical cerclage (cerclage group, n=45) or conservative treatment (conservative group, n=51). The subgroup analysis was further performed after stratifying the subjects into the CL≤1.0 cm subgroup, the CL>1.0-≤1.5 cm subgroup, and the CL>1.5 cm subgroup. Two independent samples t-test, Mann-Whitney U test, and Chi-square test were used to compare the differences in the pregnancy and perinatal outcomes between different groups. Multivariate logistic regression was used to analyze the impact of cervical cerclage on pregnancy outcomes of women with different CLs. Results:The average gestational age at delivery and the prolonged gestation were significantly greater in the cerclage group than those in the conservative group [35.9 (34.9-37.0) weeks vs 34.9 (29.1-36.1) weeks; 10.7 (9.6-13.1) weeks vs 8.7 (4.8-11.0) weeks, Z=－2.59 and -3.63, both P<0.05]. The incidences of preterm birth before 34 weeks and 28 weeks, chorioamnionitis, and preterm premature rupture of membrane were lower in the cerclage group than those in the conservative group [17.8% (8/45) vs 45.1% (23/51), χ2=8.16; 2.2% (1/45) vs 15.7% (8/51), Fisher' exact test; 8.9% (4/45) vs 25.5% (13/51), χ2=4.52; 15.6% (7/45) vs 33.3% (17/51), χ2=4.03; all P<0.05]. There were no statistically significant differences in the proportion of postpartum hemorrhage and live births between the two groups (both P>0.05). In the women with CL≤1.0 cm, the cerclage group had a greater gestational age at delivery [36.0 (34.8-37.3) weeks vs 34.9 (28.6-35.4) weeks, Z=－2.61, P=0.009], greater prolonged gestation [12.3 (9.7-13.9) weeks vs 7.3 (3.4-9.1) weeks, Z=－3.34, P=0.001], higher birthweight [2 430.0 (2 173.8-2 646.3) g vs 1 900.0 (1 372.5-2 435.0) g, Z=－3.06, P=0.002], lower incidence of adverse neonatal outcomes [16.7% (6/36) vs 36.7% (11/30), χ2=4.22, P=0.048] compared with the conservative group. Multivariate Logistic regression analysis showed that cerclage reduced the risks of preterm birth before 34 and 32 weeks [ aOR (95% CI)=0.083 (0.009-0.790) and 0.092 (0.009-0.939), both P<0.05]. However, cerclage did not reduce the risk of preterm birth in women with CL>1.5 cm or CL>1.0-≤1.5 cm (both P>0.05). Conclusion:Ultrasound- indicated cervical cerclage can reduce the risk of preterm birth before 34 and 32 weeks, prolong pregnancy, and improve perinatal outcomes in asymptomatic twin pregnancies with CL≤1.0 cm.

Prunellae Spica is the dried spica of Prunella vulgaris belonging to Labiatae and it is widely used in pharmaceutical and general health fields. As a traditional Chinese medicine cultivated on a large scale, it produces a large amount of non-medicinal parts, which are discarded because they are not effectively used. To analyze the chemical constituents in the different samples from spica, seed, stem, and leaf of P. vulgaris, and explore the application value and development prospect of these parts, this study used ultrahigh performance liquid chromatography-tandem quadrupoles time of flight mass spectrometry(UPLC-Q-TOF-MS/MS) to detect chemical constituents in different parts of P. vulgaris. As a result, 117 compounds were detected. Among them, 87 compounds were identified, including 32 phenolic acids, 8 flavonoids, and 45 triterpenoid saponins. Some new triterpenoid saponins containing the sugar chain with 4-6 sugar units were found. Further, multivariate statistical analysis was conducted on BPI chromatographic peaks of multiple batches of different parts, and the results showed that spica had the most abundant chemical constituents, including salviaflaside and linolenic acid highly contained in the seed and phenolic acids, flavonoids, and triterpenoid saponins in the stem and leaf. In general, the constituents in the spica were composed of those in the seed, stem, and leaf. UPLC was used to determine the content of 6 phenolic acids(danshensu, protocatechuic acid, protocatechuic aldehyde, caffeic acid, salviaflaside, and rosmarinic acid) in different parts. The content of other phenolic acids in the seed was generally lower than that in the spica except that of salviaflaside. The content of salviaflaside in the spica was higher than that in the stem and leaf, but the content of other phenolic acids in the spica was not significantly different from that in the stem. The content of protocatechuic aldehyde and caffeic acid in the spica was lower than that in the leaf. DPPH free radical scavenging method was used to detect the antioxidant activity of four parts, and there was no significant difference in the antioxidant activity between the spica and the stem and leaf, but that was significantly higher than the seed. Moreover, the antioxidant activity of these parts was correlated with the content of total phenolic acids. Based on the above findings, the stem and leaf of P. vulgaris have potential application value. Considering the traditional medication rule, it is feasible to use the whole plant as a medicine. Alternatively, salviaflaside, occurring in the seed, can be used as a marker compound for the quality evaluation of Prunellae Spica, if only using spica as the medicinal part of P. vulgaris, as described in the Chinese Pharmacopoeia(2020 edition).
Antioxidants/chemistry* ; Tandem Mass Spectrometry/methods* ; Prunella/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Caffeic Acids ; Flavonoids/analysis* ; Triterpenes/analysis* ; Saponins ; Sugars

OBJECTIVE: To evaluate the prospective association between cumulative resting heart rate (cumRHR) and rapid renal function decline (RRFD) in a cohort of individuals aged 60 and older. METHODS: In the Tianjin Chronic Kidney Disease Cohort Study, the individuals who underwent three consecutive physical examinations between 2014 and 2017, with estimated glomerular filtration rate (eGFR) greater than 60 mL/min per 1.73 m² and aged 60 years or older were enrolled. A total of 27,564 patients were prospectively followed up from January 1, 2017 to December 31, 2020. The 3-year cumRHR was calculated. The primary outcome was RRFD, defined as an annualized decline in eGFR of 5 mL/min per 1.73 m² or greater. Logistic and restricted spline regression models and subgroup analysis were used to investigate the association of cumRHR with RRFD after adjusting for all confounders. RESULTS: During a median follow-up of 3.2 years, a total of 4,347 (15.77%) subjects developed RRFD. In fully-adjusted models, compared with the lowest quartile of cumRHR, the odds ratio (OR) for the highest was 1.44 (1.28-1.61), P < 0.001. Furthermore, each 1-standard deviation (27.97 beats/min per year) increment in cumRHR was associated with a 17% (P < 0.001) increased risk of RRFD, with a linear positive correlation (P for non-linear = 0.803). Participants with a 3-year cumRHR ≥ 207 (beats/min) * year (equivalent to ≥ 69 beats/min per year in 3 years) were found to be at a higher risk of RRFD. CONCLUSIONS The cumRHR is significantly associated with a higher risk of RRFD among older adults. These results might provide an effective goal for managing and delaying the decline of renal function in the older adults.

Objective:To analyze the clinical features of patients with pyogenic liver abscess (PLA) and the application of mNGS in PLA, thus to provide reference for clinical diagnosis and treatment.Methods:The demographic and clinical data of 549 patients with liver abscess admitted to Zhongshan Hospital Affiliated to Fudan University from December 2015 to June 2020 were analyzed retrospectively. According to the detection of Klebsiella pneumoniae in 246 patients with positive etiological test results, the patients were divided into two groups: KPLA group and nKPLA group, and clinical characteristics of the two groups were compared. At the same time, the application value of mNGS in PLA was analyzed.Results:Among the 549 patients, the main clinical symptom of PLA was fever ( n= 503, 91.6%) and other clinical symptoms included chills and abdominal pain. Most patients had a single abscess ( n= 464, 84.5%) located in the right lobe ( n = 368, 67.0%), with a size between 5 and 10 cm ( n= 341, 62.1%). A total of 246 patients had positive etiological test results, including 202 KPLA patients which was the main pathogen of liver abscess. The prevalence of diabetes and fatty liver was higher in KPLA patients ( P < 0.05), but there were more culture of liver positive factors in nKPLA patients ( P < 0.001). Among the 109 patients with traditional microbiological results, 92 patients were suspected to KPLA (Klebsiella pneumoniae), of which 14 patients (15.2%) were multidrug resistant (MDR) infection; 17 patients were suspected to nKPLA, of which 10 patients (58.8%) were MDR infection; the incidence of MDR infection in patients with nKPLA was significantly higher than that in patients with KPLA ( P < 0.05). The positive rate of mNGS in plasma was 85.2%, the positive rate of traditional microbial culture in plasma was 14.8%, the positive rate of mNGS in pus was 96.2% and traditional microbial culture in pus was 65.4%. The positive rate of traditional culture was significantly lower than that of mNGS ( P < 0.05). Conclusions:PLA is usually manifested as fever, single and at the right lobe of the liver. Klebsiella pneumoniae is the most common pathogenic bacteria of PLA, which is more common in patients with diabetes and fatty liver, while non-Klebsiella pneumoniae is relatively more common in patients with culture of liver positive factors. The positive detection rate of mNGS is high, which has a unique advantage in pathogen detection.

For a long time, the cultivation of medical students’ scientific research and innovation abilitymainly depends on scattered extracurricular scientific research activities. With limited students, unsystematic teaching and inadequate administrative guarantee, it often results in obvious weakness andinefficiency. Since 2002, the Biochemistry and Molecular Biology teaching team in Shantou UniversityMedical College has been working on a “3+X” model to nurture the scientific research and innovationability of medical students. Guided by the concepts of complementary development of science andeducation, student-centeredness, and Problem-based Learning, a model is established based on the‘HEART” professionalism courses and the academy culture specific to Shantou University. We also takefull advantage of the first-tier disciplines of biology, basic medicine and clinical medicine in ShantouUniversity and collaborate with other professional teaching teams. It is conceptualized in a framework thatembraces the comprehensive connotation of scientific research and innovation ability and adopts a corecurriculum system that runs through the 5-year medical undergraduate education. In this model, " 3" means " whole-person training", " whole-process training" and " omni-directional training" for medicalstudents; " X" refers to several confirmatory dimensions of the operational effectiveness of the " 3+X" model, including organizing medical students to participate in various forms of national college students’ innovative experimental research competitions, international college students’ academic seminars, writingand publishing academic papers by medical undergraduates as the first author, etc. The model proves tobe effective in cultivating the scientific research and innovation ability of medical students, hence settinga good example to solve the current problems in the cultivation of medical students’ scientific researchand innovation ability.

Objective:Evaluation of combined inflammatory and coagulation markers for early identification of DIC in septic patients.Methods:This study was a single-center, retrospective, observational study involving 356 patients with sepsis. Sepsis was defined by the diagnostic criteria of Sepsis version 3.0. Definition of DIC was from the International Society on Thrombosis and Hemostasis (ISTH) DIC Score. Inflammatory biomarkers, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β,2R,6,8,10, etc. and biomarkers of coagulation, like platelet (PLT), international normalized ratio (INR), D-dimer, fibrinogen (Fib), etc. were included in this study.Results:Among 356 patients with sepsis, 301 patients did not develop DIC (non-DIC) during hospitalization, 32 patients had DIC on the day of admission (overt-DIC), and 23 patients developed DIC within 1 week of admission (pre-DIC). Compared to non-DIC patients, pre-DIC patients had lower platelet counts and fibrinogen ( P < 0.05), higher levels of INR and D-dimer ( P < 0.05), higher levels of cytokines (TNF-α、IL-1β、IL-2R、IL-8、IL-10) and procalcitonin ( P < 0.05), higher APACHEⅡ and SOFA scores ( P < 0.05). Using receiver operating characteristics (ROC) analysis, we found that some biomarkers of coagulation and inflammation could discriminate pre-DIC from non-DIC patients. The area under the curve (AUC) of INR in the ROC analysis was 0.773 (95% CI: 0.696-0.851), the AUC of IL-2R was 0.700 (95% CI: 0.599-0.798) which is highest among inflammation markers, the highest AUC was obtained from the combination of platelets, INR, Fib, D-dimer and IL-2R (AUC = 0.843; 95% CI: 0.758-0.928). Kaplan-Meier survival curve suggested that high level of IL-2R (> 1064.5 U/mL) was a valuable predictor of 28-day mortality in septic patients. Conclusion:Inflammatory marker, IL-2R, is related to the occurrence of DIC in septic patients and has predictive value for pre-DIC. Combination of coagulation (platelets, INR, Fib, D-dimer) and inflammatory markers (IL-2R) can help to identify pre-DIC state in septic patients.

OBJECTIVE: To elucidate the active compounds and the molecular mechanism of Cyathula Officinalis as a drug treatment for rheumatoid arthritis (RA). METHODS: The target genes of active ingredients from Cyathula Officinalis were obtained from bioinformatics analysis tool for the molecular mechanism of traditional Chinese medicine. The protein-protein interaction between the target genes were analyzed using STRING and Genemania. The transcriptome of RA patients compared to healthy people (GSE121894) were analyzed using R program package Limma. The relative expression of the target genes was obtained from the RNA-seq datasets. The molecular docking analyses were processed based on the molecular model of estrogen receptor 1 (ESR1) binding with estradiol (PDB ID:1A52). The binding details were analyzed by SYBYL. RESULTS: Inokosterone, ecdysterone, and cyaterone were the 3 active ingredients from Cyathula Officinalis that bind to target genes. Of all the significantly changed genes from RA patients, ESR1, ADORA1, and ANXA1 were significantly increased in mRNA samples of RA patients. CONCLUSION ESR1, the transcription factor that binds inokosterone in the molecular binding analysis, is the target protein of Cyathula Officinalis.
Arthritis, Rheumatoid/genetics* ; Cholestenes ; Estrogen Receptor alpha ; Humans ; Molecular Docking Simulation ; Pharmaceutical Preparations

Blakeslea trispora is a natural source of carotenoids, including β-carotene and lycopene, which have industrial applications. Therefore, classical selective breeding techniques have been applied to generate strains with increased productivity, and microencapsulated β-carotene preparation has been used in food industry (Li et al., 2019). In B. trispora, lycopene is synthesized via the mevalonate pathway (Venkateshwaran et al., 2015). Lycopene cyclase, which is one of the key enzymes in this pathway, is a bifunctional enzyme that can catalyze the cyclization of lycopene to produce β-carotene and exhibit phytoene synthase activity (He et al., 2017).
Citric Acid Cycle ; Fermentation ; Gas Chromatography-Mass Spectrometry/methods* ; Lycopene/metabolism* ; Mucorales/metabolism* ; Nicotine/pharmacology* ; beta Carotene/biosynthesis*

OBJECTIVE: To summarize and critically assess the inhibitory effects of Chinese herbal medicine (CHM) on tumor volume and tumor weight for the treatment of osteosarcoma (OS) in mouse models. METHODS: PubMed, Embase, Web of Science, China Knowledge Resource Integrated Database (CNKI), Wanfang Database, VIP Database, and Chinese BioMedical (CBM) were searched since their inception dates to March 10, 2016. Two reviewers independently selected the controlled studies estimating effects of CHM on mouse OS by administration in vivo. A pair-wise meta-analysis was performed. Twenty-five studies with adequate randomization were included in the systematic review. RESULTS: CHM may significantly inhibit OS growth in mice, as assessed using the tumor weight [20 studies, n=443; 290 for CHM and 153 for the control: pooled mean difference (MD)=-2.90; 95% confidence interval (Cl): -3.50 to -2.31: P<0.01], tumor volume (16 studies, n=382; 257 for CHM and 125 for the control; pooled MD =-2.57; 95% Cl: -3.33 to -1.80; P<0.01) and tumor growth inhibition rate. CONCLUSION CHM could significantly inhibit the growth of OS in mouse models, which might be supportive for the design of preclinical and clinical trials in future.
Animals ; Drugs, Chinese Herbal ; therapeutic use ; Mice ; Osteosarcoma ; drug therapy ; Publication Bias ; Risk Factors ; Tumor Burden ; drug effects ; Xenograft Model Antitumor Assays