During the routine impurity profile of lisinopril bulk drug by HPLC (high-performance liquid chromatography), a potential impurity was detected. Using multidimensional NMR (nuclear magnetic resonance) technique, the trace-level impurity was unambiguously identified to be 2-(-2-oxo-azocan-3-ylamino)-4-phenyl-butyric acid after isolation from lisinopril bulk drug by semi-preparative HPLC. Formation of the impurity was also discussed. To our knowledge, this is a novel impurity and not reported elsewhere.
Butyrates ; analysis ; isolation & purification ; Drug Contamination ; Lisinopril ; analysis ; Magnetic Resonance Spectroscopy ; Models, Molecular

The ability of implanted embryonic neural stem cells (NSCs) to improve survival, migration, and functional recovery following a compression spinal cord injury (SCI) was tested in adult rats. NSCs were isolated from E14-16 rat cerebral cortex and SCI was produced by using an aneurysm clip applicator applied to the 8th thoracic spinal cord according to method of Dolan and Tator. Two weeks after the injury, NSCs (4 microl of 1 x 10(4) cells/microl) were injected into the lesion site. The grafted NSCs were noted to survive and integrate with the host spinal cord 1 month after transplantation, which was demonstrated by the presence of Hoechst 33342 (a nuclear dye) pre-labeled NSCs within and surrounding the lesion site. Some of these cells remained undifferentiated and were stained with nestin, a marker for NSCs. Transplanted NSCs migrated for at least 3 mm from the injury epicenter towards both the rostral and caudal directions. Significant reduction in the lesion area (P<0.05) and improvement in inclined plane (P<0.05) and BBB locomotor rating scale (P<0.05) were found in the cases that received implantation of NSCs, as compared with those that received vehicle injection. More importantly, when glial cell line-derived neurotrophic factor (GDNF; 1.5 microg/microl) was added to the transplants, further reduction in lesion area (P<0.01) and improvement in the function were observed in the combined treatment group as compared with the vehicle infused group. Our results suggest that intraspinal treatment with NSCs and GDNF synergistically reduced lesion size and improved functional outcome after a compressive SCI in adult rats.
Animals ; Embryonic Stem Cells ; transplantation ; Female ; Glial Cell Line-Derived Neurotrophic Factor ; pharmacology ; therapeutic use ; Neural Stem Cells ; transplantation ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Injuries ; therapy ; Spinal Cord Regeneration ; physiology

OBJECTIVETo characterize the structural and the functional feature of a novel gene HSPCSET isolated from human CD34+ hematopoietic stem/progenitor cells (HS/PCs).

METHODSBioinformatic technology was used to identify the structural features of the HSPCSET protein and perform the multiple sequence alignment. Yeast-two-hybrid system was used to identify the proteins interacting with the HSPCSET protein. After sequencing, we selected out the positive clones which had clear functions, and carried out beta-gal experiment and GST pull down assay to confirm the results. The cellular location of the HSPCSET was checked by immunofluorescence assay.

RESULTSThe HSPCSET protein belongs to a SET domain family, which is evolutionarily conserved across species. It implied that HSPCSET may have biologically important function. Using yeast-two-hybrid system, we showed that the protein sequence with SET domain might bind to 13 proteins, which involved in signaling transduction, transcriptional regulation, apoptosis, tumorigenesis, development, etc. And 4 proteins (GADD34, SIVA, DNAJ and PHF1) were confirmed by one-on-one back of the hybrid experiment, beta-gal test and GST pull down assay. When GADD34 and HSPCSET were co-transfected, they co-localized in the nucleus, suggesting a strong interaction.

CONCLUSIONThe novel gene HSPCSET is likely to have biologically important function. This study provides the basis for further studies of its function in hematopoiesis and tumorigenesis.

Amino Acid Sequence ; Animals ; Antigens, Differentiation ; metabolism ; Cell Cycle Proteins ; metabolism ; Computational Biology ; Conserved Sequence ; Hematopoietic Stem Cells ; metabolism ; Humans ; Molecular Sequence Data ; Protein Phosphatase 1 ; Protein Structure, Tertiary ; Proteins ; chemistry ; genetics ; metabolism ; Sequence Homology, Amino Acid ; Two-Hybrid System Techniques

Objective: To investigate the correlation between the consumption of milk tea and takeaway on overweight and obesity of college students, so as to provide a scientific basis for effective prevention and control of overweight and obesity among college students. Methods: A questionnaire survey and physical test were conducted among 14 379 college students from 7 universities in Shanghai, Jiangxi, Hubei and Shanxi provinces from October to November 2023 by the convenient sampling method. The self designed questionnaires on milk tea consumption and takeaway consumption were used to investigate the consumption of milk tea and takeaway among college students. The χ 2 test was used to compare the distribution difference of the detection rate of overweight and obesity among college students in different groups and different consumption frequency of milk tea and takeaway. Multivariate Logistic regression analysis was used to analyze the correlation between the consumption of milk tea takeaway and overweight and obesity. Results: The prevalence of overweight and obesity among college students was 24.29%. The prevalence of overweight and obesity among college students was statistically significant among gender, grade, single child or not and family economic status ( χ 2= 308.72 ,38.83,15.49,16.82, P <0.01). In addition, there were statistically significant differences in the prevalence of overweight and obesity with different takeaway consumption frequency and milk tea consumption frequency among college students ( χ 2=21.32,46.32, P <0.01). Multivariate Logistic regression model showed that different consumption frequency of milk tea (1-3, 4-5, ≤6 times for every week) were positively correlated with overweight and obesity( OR =1.62,1.75,2.39), and eating takeaway every day was also positively correlated with overweight and obesity ( OR =1.32)( P ＜0.01). Interaction analysis showed that frequent joint consumption of milk tea and takeaway was positively correlated with overweight and obesity of college students ( OR =3.00, P ＜0.01). Conclusions The consumptions of milk tea and takeaway are associated with overweight and obesity among college students. Colleges and relevant departments should take effective measures to intervene in overweight and obesity among college students.

OBJECTIVETo investigate the clinical outcome and fusion rate in patients with idiopathic thoracolumbar/lumbar scoliosis treated with anterior correction and interbody fusion with calcium phosphate cement.

METHODSFrom October 2006 to March 2008, 24 cases undergoing anterior correction and interbody fusion with calcium phosphate cement were enrolled. All of them were female, with an age ranged from 12 to 25 years. The mean Cobb angle of main curve was 46° ± 5° (range, 40° - 56°) before surgery. During operation, the most proximal and distal disc spaces were filled with rib autograft, while the remaining levels were filled with calcium phosphate cement. The interbody fusion rate, coronal correction and sagittal profile reconstruction were evaluated respectively by using χ² test and t test.

RESULTSInterbody fusion was performed in 103 levels, including 48 levels with rib autograft and 55 levels with calcium phosphate cement. The mean follow-up period was 23.8 months (range, 12 - 33 months) in this series. At the follow-up of 6 months, fusion rate was found as 54.2% in the levels filled with rib autograft, while 50.9% in those filled with calcium phosphate cement. Solid fusion of the whole instrumented area was achieved in all cases with a minimum one-year follow-up. No instrumentation-related complications occurred. The correction rate of main curve was on an average of 76% ± 11% after surgery. A significant difference was found between preoperative and immediate postoperative value in terms of the main curve magnitude (46° ± 5° vs. 14° ± 5°, t = -26.95, P < 0.05). The correction loss of the main curve was -5.1° - 10.4° at the final follow-up. The coronal balance and lower instrumented vertebra tilting were significantly improved after operation. The thoracolumbar kyphosis was significantly reduced postoperatively (t = 3.11, P < 0.05).

CONCLUSIONSatisfactory bone fusion and correction maintenance can be achieved in idiopathic thoracolumbar/lumbar scoliosis treated by anterior instrumentation combined with interbody fusion using calcium phosphate cement.

Adolescent ; Adult ; Bone Cements ; therapeutic use ; Calcium Phosphates ; therapeutic use ; Child ; Female ; Follow-Up Studies ; Humans ; Lumbar Vertebrae ; surgery ; Scoliosis ; surgery ; Spinal Fusion ; methods ; Thoracic Vertebrae ; surgery ; Treatment Outcome ; Young Adult

Breast cancer is one of the common diseases in women,and its mortality now ranks first among the female malignancies in China.Therefore,early detection,early diagnosis and early treatment have become the focus of the treatment for breast diseases.Neoadjuvant chemotherapy is a standard treatment for locally progressive breast cancer,and magnetic resonance imaging (MRI) is superior to ultrasonography,X-ray and clinical examination in evaluating the efficacy of neoadjuvant chemotherapy for breast cancer.MRI can provide not only structural imaging,but also functional imaging.MRI dynamic contrast enhanced imaging,diffusion weighted imaging,perfusion weighted imaging and magnetic resonance spectroscopy have received extensive attention in the evaluation of therapeutic efficacy for breast cancer.

OBJECTIVETo study the biological function of fusion gene HRX-EEN and its role in leukemogenesis, and to provide an ideal animal model for anti-leukemia drug screening.

METHODSHRX-EEN fusion gene was constructed by use of three different DNA fragments, and it was inserted into hCG transgenic vector. G(0) transgenic mice were obtained by microinjection of the recombined DNA into the pronucleus of zygotes, followed by implantation of the injected zygotes into pseudopregnant mice. The integration of the transgene was tested by PCR and its expression by reverse transcription-polymerase chain reaction (RT-PCR).

RESULTSThe sequence of recombined HRX-EEN gene was confirmed by sequencing. PCR testing revealed a total of 7 G(0) transgenic mice, these mice were then mated with C57 wild type mice. Except mouse No. 35 that died, the others all had their F1 offsprings. From these 6 lines of transgenic mice, HRX-EEN gene was found to be stably expressed in 3 lines by RT-PCR. Up to now, all transgenic mice expressing the fusion gene have no obvious abnormal phenotypes.

CONCLUSIONA transgenic mice model in which the HRX-EEN fusion gene can be stably expressed has been established.

Animals ; DNA-Binding Proteins ; genetics ; Histone-Lysine N-Methyltransferase ; Intracellular Signaling Peptides and Proteins ; Mice ; Mice, Transgenic ; Myeloid-Lymphoid Leukemia Protein ; Polymerase Chain Reaction ; Proteins ; genetics ; Proto-Oncogenes ; Recombinant Fusion Proteins ; genetics ; Transcription Factors

Objective To investigate the influences of loading time and loading angle on the stress, displacement of human periodontal ligament in dynamic jaw. Methods The three-dimensional assembly model of the mandible front teeth, periodontal ligament and alveolar bone was reconstructed by using the reverse engineering technology. The thickness of periodontal membranes was 0.2 mm. The stress, displacement at different positions of the periodontal ligaments during different jaw cycles were analyzed under dynamic load in the direction from bucca to tongue side with 0°, 15°, 30°, 45°, 60°, 75°, 90° angle to the long axis of the tooth. Results During one jaw cycle, the ratio of the maximum to minimum value of the maximum residual stress due to different loading angles was 5.5, and the ratio of the maximum to minimum value of the maximum displacement was 8.1. The ratio of the maximum to minimum value of the maximum displacement which was caused by five jaw cycles was increased in the range from 1.02 to 1.35 with the increase of loading angles. The ratio of the maximum to minimum value of the maximum residual stress which was caused by different loading angles was increased in the range from 1.86 to 3.00 with the increase of jaw cycles. The location of the maximum stress was at the tongue side of the cervical margin at different loading angles, and the location of the maximum residual stress was distributed at different positions of the cervical margin. Most stress was accumulated at the root of the periodontal ligament under the 0° dynamic load. Conclusions The situation of the accumulated residual stresses and the uncertainties in the distribution of the maximum residual stresses should be observed in the clinical choice of mandible incisors fixed by bridge abutments; large angle force applied to the tooth was harmful to the periodontal ligament and rapid succession of chewing hard food should be avoided as much as possible during the clinical treatment.

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.

The secondary metabolites of endophytic fungus Cerrena sp.A593 from Pogostemon cablin and their cytotoxic activities were investigated. Eight sesquiterpenoids were isolated from the fermentation broth of the strain A593 by silica gel, reverse phase silica gel, Sephadex LH-20, HPLC and so on. Their structures were identified as chloriolin B(1), chloriolin C(2), pleurocybellone A(3), dihydrohypnophilin(4), cucumin F(5), antrodin A(6), 10α-hydroxyamorphan-4-en-3-one(7), and connatusin A(8). Compounds 1- 8 were firstly found from the genus Cerrena. All isolated sesquiterpenoids were evaluated for in vitro cytotoxic activities against HepG-2, SF-268, MCF-7 and NCI-H460 tumor cell lines. Compounds 1-3 showed inhibitory activities against the four tumor cell lines with IC₅₀ values ranging from 20.33 to 63.13 μmol•L⁻¹.