The chemical constituents of sesquiterpenes from 95% ethanol extract of Aquilariae Lignum Resinatum were isolated and purified by various column chromatography techniques, including silica gel, Sephadex LH-20, octadecylsilyl(ODS), and semi-preparative high performance liquid chromatography(HPLC). Their planar structures and absolute configurations were elucidated by ultraviolet(UV) spectrometry, infrared(IR) spectroscopy, mass spectrometry(MS), nuclear magnetic resonance(NMR), electronic circular dichroism(ECD), and other techniques. Eight sesquiterpenoids were isolated and identified as(+)-(7R,10R)-selina-4,11-dien-12-dimethoxy-15-al(1),(+)-(7R,10R)-selina-4,11-diene-12,15-dial(2), agalleudesmanol B(3), aquisinenoid C(4), 12,15-dioxo-α-selinen(5), agarospiranic aldehyde B(6), neopetasane(7), and eremophila-7(11),9-dien-8-one(8). Compound 1 was a new compound, and it was the first time to find a dimethoxy substitution on the side chain of eudesmane-type sesquiterpene skeleton.
Sesquiterpenes/isolation & purification* ; Thymelaeaceae/chemistry* ; Molecular Structure ; Drugs, Chinese Herbal/isolation & purification* ; Magnetic Resonance Spectroscopy

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

ObjectiveAt present, the matching reagents of commercially available rapid DNA instruments based on microfluidics chip technology are autosome short tandem repeat (STR) individual identification reagents. The non-recombining part of the human Y chromosome is widely used in forensic DNA analysis, particularly in cases where standard autosomal DNA profile is uninformative. Y-STR loci are useful markers to identify males and male lineages in forensic practice. In order to achieve rapid and fully integrated detection ofY-STR loci, this study constructed the RTyper Y27 microfluidic chip rapid detection system and validated the performance of this system. MethodsThe system was verified and evaluated by sensitivity, success rate, typing accuracy, peak height balance, sizing precision and accuracy, mock case sample tests, mixture detection ability, and inhibition tolerance. ResultsComplete Y-STR profiles can be obtained when the template amount of DNA standard 9948 was ≥8 ng, the number of blood cards was ≥3 pieces, and the number of oral swab scrapings was≥7 times. The success rate of fully integrated detection was 91.52%, and the concordance rates was 99.74% for 165 testing samples. The success rate of 115 blood spots in these samples was 90.43%, with a typing accuracy of 99.65%, the success rate of 50 buccal swabs was 94%, with a typing accuracy of 99.92%. There was no significant difference in typing accuracy between blood spots and buccal swab samples. The peak height ratio between different fluorescence channels was 89.81%. The standard deviation of allelic ladder for 10 runs was within 0.5 bp. The size differences between allele and corresponding allele in allelic ladder was within 0.5 bp. The maximum precision CV values within and between batches were 0.48% and 0.68%, respectively, which were lower than 15%. These data indicate that the system has good accuracy and precision. The system was capable of accurately typing oral swabs, blood cards, saliva cards, cigarette butts, blood swabs and seminal stains. Complete Y-STR profiles can be obtained and distinguish at the 1∶3 ratio of minor and major contributors in artificial male DNA mixtures. Complete Y-STR genotyping can be obtained under the interference of inhibitors, such as different concentrations of humic acid (50-400 mg/L), indigotin (20-100 nmol/L) and hemoglobin (100-500 μmol/L). ConclusionIn this study, the RTyper Y27 microfluidic chip rapid amplification system is combined with the Quick TargSeq 1.0 integrated system, and the Y-STR profile can be obtained in approximately 2 h. Through a series of verification experiments, the results show that the system has good repeatability, accuracy and stability, can meet the on-site Y-STR detection requirements, and can be used in forensic practice.

OBJECTIVE To investigate the embryo-fetal developmental toxicity (EFDT) of careno?prazan hydrochloride (KFP-H008) in rabbits. METHODS Pregnant rabbits were given by gavage KFP-H008 at 5, 15 and 50 mg·kg-1 during the organogenetic period (gestation days 6-18, GD 6-18). Rabbits in positive control group were treated with cyclophosphamide (CP) 10 mg·kg-1 by iv. Maternal body mass and food consumption during gestation were recorded. Pregnant dams were euthanized on GD 29. The numbers of live/dead fetuses, resorptions, implantations, corpora lutea, and gravid uterus mass, placenta mass, fetal gender ratios, body mass, and skeletal development were evaluated. Moreover, the toxicokinetic parameters including AUC and C0-t, and tissue distributions were determined. RESULTS From GD 13, the maternal body mass and the food consumption in KFP-H00815 and 50 mg · kg-1 groups were lower than in the normal control group (P<0.05). Also, the reduced fetal crown rump length and mass, skeletal malformations/variations were observed in KFP-H00815 and 50 mg · kg-1 groups (P<0.05). KFP-H008 was rapidly eliminated, and became undetectable in the maternal plasma after a single administration. Following multiple KFP-H00850 mg · kg-1 treatment, both KFP-H008 and its metabolites were detectable in various tissues of the maternal and fetus, which might be the evidence for carenoprazan-induced developmental toxicity. In KFP-H00815 mg · kg-1 group, KFP-H008 and its metabolites were undetectable in most of maternal and fetal tissues. CONCLUSION The no observed adverse effect level (NOAEL) of KFP-H008 for maternal and fetal rabbits is about 5 mg·kg-1.

BACKGROUND: The proximal femur anti-rotation intramedullary nail is an ideal internal fixation method for the treatment of intertrochanteric fractures, but there is still a 6% to 21% failure rate of internal fixation. Tip-apex distance is considered as an important cause of postoperative proximal femur anti-rotation intramedullary nail failure. Tip-apex distance is the sum of the distance from the tip of lag screw to the vertex of femoral head measured on anteroposterior and lateral X-ray films. Most scholars now believe that the tip-apex distance of head pulp nail ≤ 25 mm has a good prognosis, but there is still a lot of controversy. OBJECTIVE: To investigate the biomechanical differences of the treatment of intertrochanteric femoral fractures by proximal femoral anti-rotation intramedullary nail with different tip-apex distances and provide a new idea and experimental basis for the clinical treatment of intertrochanteric fractures. METHODS: CT data of one volunteer were imported into Mimics 19.0 and Geomagic studio 2017 software to extract and optimize the three-dimensional model of the right femur. SolidWorks 2017 software was used to draw the internal fixation model and assemble it with the AO2.1 type fracture femur model in different tip-apex distance according to the standard operation technology. Totally four models with tip-apex distance of 15, 20, 25, and 30 mm were obtained and imported into HyperMesh 14.0 software to mesh. The four models were imported into Abaqus 2016 software in inp format to set up with material property parameters, boundary conditions and applied loads. Finally, operation results were viewed in the visualization module. RESULTS AND CONCLUSION: (1) When tip-apex distance was too large (30 mm) or too small (15 mm), the stress at the proximal femur was reduced, but the displacement of the femur head and neck fragment and the lesser trochanter fragment was larger and the inversion was more serious. When tip-apex distance was in the middle (20, 25 mm), the displacement and varus of femoral head and neck fragment were small, and the lesser trochanteric fragment was basically unshifted. (2) In the treatment of intertrochanteric femur fractures, tip-apex distance should be adjusted to 20-25 mm to reduce displacement and obtain a better biomechanical effect.

Purpose: The purpose of this study was to compare the survival and toxicities in cervical esophageal squamous cell carcinoma (CESCC) treated by concurrent chemoradiothrapy with either three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) techniques. Materials and Methods: A total of 112 consecutive CESCC patients were retrospectively reviewed. 3D-CRT and IMRT groups had been analyzed by propensity score matching method, with sex, age, Karnofsky performance status, induction chemotherapy, and tumor stage well matched. The Kaplan-Meier method and Cox proportional hazards model were used for overall survival (OS) and progression-free survival (PFS). Toxicities were compared between two groups by Fisher exact test. Results: With a median follow-up time of 34.9 months, the 3-year OS (p=0.927) and PFS (p=0.859) rate was 49.6% and 45.8% in 3D-CRT group, compared with 54.4% and 42.8% in IMRT group. The rates of grade ≥ 3 esophagitis, grade ≥ 2 pneumonitis, esophageal stricture, and hemorrhage were comparable between two groups, while the rate of tracheostomy dependence was much higher in IMRT group than 3D-CRT group (14.3% vs.1.8%, p=0.032). Radiotherapy technique (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.01 to 0.79) and pretreatment hoarseness (HR, 0.12; 95% CI 0.02 to 0.70) were independently prognostic of tracheostomy dependence. Conclusion No survival benefits had been observed while comparing IMRT versus 3D-CRT in CESCC patients. IMRT with fraction dose escalation and pretreatment hoarseness were considered to be associated with a higher risk for tracheostomy dependence. Radiation dose escalation beyond 60 Gy should be taken into account carefully when using IMRT with hypofractionated regimen.

Treatment of large bone defects caused by trauma, osteomyelitis, and tumors has been a major challenge in clinical. In the past, there have been many ways to repair and reconstruct the large bone defects. However, there is a long period of treatment, high technical requirement and complications such as ununion. After Masquelet reported the induced membrane technology in 2000, the technique was widely used in treatment of trauma, osteomyelitis, and large bone defects caused by tumors. It has been obtained good results. It has the advantages of short course, high healing rate, easy operation and easy to master. The induced membrane has unique structural characteristics and biological characteristics. There are many kinds of osteogenic factors that are included in the membrane, such as vascular endothelial growth factor, and morphogenetic protein-2, transforming growth factor-β1, etc. These osteogenic factors contribute to accelerate bone healing. With the development of induced membrane technology. The technology of Reamer Irrigator Aspirator technology, engineering tissue technology and internal fixation is used in clinic.It can provide bone source, promote bone defect reconstruction, improve long-term limb function and reduce complications.This paper retrospectively summarizes the experimental research and clinical progress of Masquelet technique in the treatment of large bone defects.

Objective To explore the effects of flavonoids of Rhizoma Drynariae on the formation of blood vessels in the induced membrane by Masquelet technique. Methods Seventy-two SD rats were randomly divided into 4 groups,namely model group,and high-,middle-and low-dose drug groups,18 rats in each group. Rat model of critical- sized femoral defect was built,and then polymethyl methacrylate (PMMA)bone cement spacer was inserted into the bone defect to induce the formation of membrane. From the first day after surgery , the rats in high-,middle-and low-dose drug groups were given gastric gavage of 0.44,0.22,0.11 g·kg-1·d-1 of Rhizoma Drynariae flavonoids, respectively, and the rats in the model group were given the same volume of normal saline. After 6-week medication,the pathologic features of bone cement- induced membrane were observed by Haematoxilin-Eosin(HE)staining,the contents of transforming growth factor(TGF)-β1 and vascular endothelial growth factor(VEGF)proteins in the induced membrane were tested by enzyme-linked immunosorbent assay (ELISA),and the mRNA levels of TGF-β1 and VEGF in the induced membrane were determined by real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results More blood vessels in the induced membrane of the high-dose group were found than those of the other groups under the light microscope. The protein and mRNA expression levels of TGF-β1 and VEGF in the induced membrane of the 3 drug groups were much higher than those of the model group(P < 0.05). Except for the VEGF mRNA expression level, the changes of other indexes were dose-dependent. Conclusion Flavonoids of Rhizoma Drynariae are effective on enhancing the protein and mRNA expression levels of TGF-β1 and VEGF in the induced membrane, and can accelerate the vascularization,which promotes the reconstruction of bone defect.

BACKGROUNDChromosomal abnormalities have been shown to play an important prognostic role in multiple myeloma (MM). Interphase fluorescence in situ hybridization (i-FISH) has been much more effective to identify cytogenetic aberrations in MM than conventional cytogenetic technique (CC). To clearly determine the cytogenetic features of Chinese MM patients and identify their prognostic implications, we designed a multicenter study based on i-FISH including 672 patients from 52 hospitals in China.

METHODSAll 672 patients were systematically screened for the following genomic aberrations: del(13q), IgH rearrangement, del(p53) and 1q21 amplifications.

RESULTSThe analysis showed that the chromosomal changes were detected in 22.1% patients by CC and in 82.3% patients by i-FISH. The most common abnormalities by CC were chromosome 1 aberrations (48.4%), -13/13q- (37.6%), hyperdiploidy (36.6%), hypodiploidy (30.1%) and IgH rearrangements (23.7%). The most frequent abnormalities by FISH was del(13q), which was found in 60.4% patients, whereas IgH rearrangement, 1q21 amplification and p53 deletions were detected in 57.6%, 49.0% and 34.7% cases, respectively. By statistical analysis, -13/13q- by CC was associated with low level of platelet (P = 0.015), hyperdiploidy was associated with low level of serum albumin (P = 0.028), and IgH rearrangement by FISH was associated with high level of β2 microglobulin (P = 0.019). Moreover, 1q21 amplification and del(p53) by FISH conferred a high incidence of progressive disease (PD) after initial therapy. Metaphase detection of IgH rearrangements and chromosome 1 aberrations concurrently was associated with a short progression free survival (PFS) (P = 0.036). No significant prognostic implications of other cytogenetic abnormalities were found associated with overall survival and PFS.

CONCLUSIONSChinese MM patients had similar cytogenetic abnormalities compared with the previous reported studies. However, the prognostic significance of FISH aberrations were not clearly determined and further study is required.

Adult ; China ; Chromosome Aberrations ; Chromosomes, Human, Pair 1 ; genetics ; Cytogenetic Analysis ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Male ; Middle Aged ; Multiple Myeloma ; genetics ; pathology

Objective To observe the effect of combination of traditional Chinese medicine and western medicine on the treatment of post-operation endometriosis.Methods 60 cases with post-operation endometriosis were randomly divided into two groups.Patients in control group(n=30)were treated only by routine therapy (gestrinone twice a week).Patients in treatment group(n=30)were treated by combination of traditional Chinese medicinc(a decoction promoting blood flow)and western medicine.The effects were observed before and after treat- merit in both groups for 3 months.Results The accumulative total recurrence rate in treatment group(13.33 %) was lower than that in control group(30.00%,P