Using chemoproteomic techniques, we first identified EIF2AK2, eEF1A1, PRDX3 and VPS4B as direct targets of berberine (BBR) for its synergistically anti-inflammatory effects. Of them, BBR has the strongest affinity with EIF2AK2 via two ionic bonds, and regulates several key inflammatory pathways through EIF2AK2, indicating the dominant role of EIF2AK2. Also, BBR could subtly inhibit the dimerization of EIF2AK2, rather than its enzyme activity, to selectively modulate its downstream pathways including JNK, NF-κB, AKT and NLRP3, with an advantage of good safety profile. In EIF2AK2 gene knockdown mice, the inhibitory IL-1β, IL-6, IL-18 and TNF-α secretion of BBR was obviously attenuated, confirming an EIF2AK2-dependent anti-inflammatory efficacy. The results highlight the BBR's network mechanism on anti-inflammatory effects in which EIF2AK2 is a key target, and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammation-related disorders.

Objective:To report the clinical manifestations and total exon detection results of one case of MYSM1 gene complex heterozygosity mutation of bone marrow failure syndrome 4 and the results of total exon detection of her family to provide a case phenotype for the early diagnosis of bone marrow failure syndrome 4.Methods:A 1-month-old girl with severe anemia was sequenced with trio-WES. Similarly, the family was also sequenced with tribe-WES to confirm the molecular diagnosis. BWA, GATK, and other software were used for annotation analysis of sequencing results. After polymerase chain reaction, Sanger sequencing was performed by ABI3730 sequencer to verify the target sequence. Moreover, the verification results were obtained by the sequence analysis software. The clinical diagnosis of this girl was reported and the relevant pieces of literature were reviewed.Results:The girl presented with pancytopenia, polydactylism, nonspecific white matter changes, and cysts. However, CD3 -CD19 + B decreased. The child was identified with MYSM1 complex heterozygous mutation by whole-exome sequencing, NM_001085487.2:c.1607_c.1611delAAGAG and c.1432C>T, which was respectively inherited from his parents. Genealogy verification confirmed that the c.1432C>T mutation carried by the father was from the grandfather (father's father) , whereas the c.1607_c.1611delAAGAG mutation carried by the mother was from the grandfather (mother's father) , whereas the grandmothers, aunts, and uncle did not carry the mutation. The child was diagnosed with BMFS4 combined with clinical phenotypic and molecular genetic findings. Conclusion:This case provides a case phenotype for the early diagnosis of BMFS4 and extends the pathogenicity variation and phenotype spectrum of the MYSM1 gene. The newly discovered pathogenic variant of MYSM1 c. 1607_c.1611delAAGAG has not been reported at home or abroad.

In medical follow-up studies, longitudinal data and survival data are often accompanied and associated with each other, thus respective analysis of longitudinal and survival data might lead to biased results. Joint model can correct deviations, improve the efficiency of parameter estimation and provide effective inferences by simultaneously processing longitudinal and survival data. It is a popular method in medical research. Joint model has made much progress, whereas the literature about the joint model and its application is limited in China. This paper summarizes the main idea, basic framework, parameter estimation methods of random effect joint model and introduces the analysis on AIDS data set based on the R software package 'JM’ to clarify the advantages of the joint model in processing medical follow-up data and promote the use of the joint model in clinical research.

Objective To investigate the efficacy and influence factors of uterine artery embolization (UAE)in treatment of intractable postpartum hemorrhage (PPH).Methods 126 patients with intractable PPH were treated by UAE in our hospital.We analyzed the influence factors of failed UAE treatments according to the amount of bleeding,the stability of hemodynamics,with disseminated intravascular coagulation(DIC)or not and active extravasation detected in angiography.Results In 126 intractable PPH patients,13 cases (10.3%) failed to stop bleeding after UAE and the other 113 cases (89.7%)successfully got hemostasis.Logistic regression analysis showed that DIC was a significant factor in failed UAE group (P=0.033,OR 0.107,95%CI 0.014-0.835).Conclusion UAE is an effective method of treating intractable PPH.DIC may be the main cause of the failure of UAE in treatment of intractable PPH.

BACKGROUND: With the increasing number of patients undergoing knee arthroplasty in China, the complications caused by the mismatch of prosthesis with anatomical parameters arouse extensive attentions.OBJECTIVE: To measure the anatomical parameters of the knee joints in healthy Zhuang ethnic group from Guangxi Zhuang Autonomous Region, China, using three-dimensional (3D) reconstruction technology, thus providing reference for the design and placement of the hip prosthesis.METHODS: Sixty-eight individuals, including 30 females and 38 males, were selected from 217 healthy people undergoing CT examination. All data were imported into Mimics 15.0 software used for 3D reconstruction, and then the knee parameters were then measured and analyzed.RESULTS AND CONCLUSION: There was no significant difference in the parameters of the bilateral femur and tibia (P > 0.05). The femoral parameters had significant differences between genders (P < 0.05). The width of tibial platform, sagittal length of lateral tibial platform, distance between medial tibial plateau and fibular head, and posterior slope of tibial plateau showed no significant differences between genders (P > 0.05), while there were significant differences in the width of medial/lateral tibial platform, and sagittal length of medial tibial platform between genders (P < 0.05). The sagittal length of medial femoral condyle was negatively correlated with age, and all femoral parameters were positively correlated with height; while only the width of medial and lateral tibial platform were positively correlated with height. To conclude, 3D reconstruction technology is available for research on the morphology of the knee joint in the Zhuang ethnic group from Guangxi Zhuang Autonomous Region, which provides references for prosthesis design and research appropriate for the Zhuang ethnic group.

BACKGROUND:Previous studies have confirmed that ethanol can promote adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), and up-regulate the expression of PPARγ and aP2 in the tumor necrosis factor α (TNF-α) signaling pathway. As a member of the ZIP protein family, Zrt/Irt-like protein 1 (ZIP1) is closely related to bone metabolism and osteogenic differentiation.OBJECTIVE:To study the effect of BMSCs transfected by ZIP1 on TNF-α signaling pathway in the process of adipogenic differentiation.METHODS:The BMSCs from rabbits were isolated and cultured under different concentrations of alcohol (0.03, 0.09,0.15, 0.21 mol/L), followed by transfection by ZIP1 siRNA and ZIP1 expression vector.RESULTS AND CONCLUSION:After culture in alcohol, the expression levels of aP2 and PPARγ proteins were both significantly increased (P < 0.05), and the level of triglyceride was increased in all alcohol groups except for 0.03 mol/L alcohol group (P < 0.05). After siRNA transfection, the expression levels of aP2 and PPARγ as well as the level of triglyceride were increased significantly in all the alcohol groups (P < 0.05); however, ZIP1 transfection decreased the expression levels of aP2 and PPARγ proteins (P < 0.05). To conclude, ZIP1 siRNA could promote the adipogenic differentiation of BMSCs through the activation of TNF-α signaling pathway.

Objective To establish CT image-based, three-dimensional finite element models of healthy tibiae and plateau-fracture tibiae, and to calculate the displacement and stress distribution of the tibial models .Methods Continuous-time tomographic images of knee joints of a healthy adult and a patient with tibial plateau fractures were obtained using multi-slice spiral CT scan , and inputed to Mimics to establish three-dimensional surface mesh models of tibiae .The models underwent global meshing procedures and material properties assignment to construct finite element models of normal and plateau-fracture tibiae in ANSYS , and the newly established models were analyzed and calculated .Results In case of applied load on the tibial plateau , the peak strains of the load-contact sites in the healthy subject and the patient presented divergent directions , with peak strains on the medial tibia in the healthy subject and lateral tibia in the patient , respectively . Equivalent stress decreased gradually down the tibiae and concentrated in the one -third of the upper and middle regions in both types of tibiae .Moreover, concentration of stress was also present in the locus of the fractured tibia .The deformation displacement gradients were more evident in the healthy tibia than in the fractured tibiae .There was significant difference in overall stress distribution between the two types of tibiae .Conclusion Three-dimensional finite element models of tibiae have been established that can demonstrate the differences in biomechanical properties between healthy and plateau -fracture tibiae, which might provide reference and guidance for orthopedic regimens .

Taking 12-N-p-chlorobenzyl sophoridinol 2 as a lead, a series of novel sophoridinic derivatives with various 3'-substituents at the 11-side chain were synthesized and evaluated for their anticancer activity from sophoridine (1), a natural antitumor medicine. Among them, the sophoridinic ketones 5a-b, alkenes 7a-b and sophoridinic amines 14a-b displayed reasonable antiproliferative activity with IC50 values ranging from 3.8 to 5.4 μmol/L. Especially, compounds 5a and 7b exhibited an equipotency in both adriamycin (AMD)-susceptible and resistant MCF-7 breast carcinoma cells, indicating a different mechanism from AMD. The primary mechanism of action of 5a was to arrest the cell cycle at the G0/G1 phase, consistent with that of parent compound 1. Thus, we consider 12-chlorobenzyl sophoridinic derivatives with a tricyclic scaffold to be a new class of promising antitumor agents with an advantage of inhibiting drug-resistant cancer cells.

OBJECTIVEThis study aimed to evaluate the morphometric changes in the alveolar bone of the maxillary and mandibular anterior regions after retraction in adolescents.

METHODSThe sample size comprised 30 adolescent patients with class 1 bimaxillary protrusion (12 males and 18 females, age: 12-18 years old) and were treated by extracting four first pre-molars. Cone beam computed tomography (CBCT) was performed 1 month before and 1 month after the retraction. For each maxillary and mandibular anterior tooth, the labial and palatal alveolar plates at cervical 1/3, middle 1/3, and apical 1/3 levels for bone thickness changes during the retraction of the maxillary and mandibular anterior regions were checked. The movements of cervical 1/3, middle 1/3, and apical 1/3 levels of the maxillary central incisor were measured. Statistical analyses were performed with SPSS 16.0.

RESULTSFor the adolescents, alveolar bone thickness increased on the labial side and decreased on the palatal side. The alveolar bone thicknesses of cervical 1/3 and middle 1/3 of maxillary central incisor, cervical 1/3 and apical 1/3 of maxillary lateral incisor, middle 1/3 of mandibular central incisor, apical 1/3 of mandibular lateral incisor, and middle 1/3 and apical 1/3 of mandibular canine all increased after retraction. By contrast, the alveolar bone thickness of the apical 1/3 of maxillary canine and the cervical 1/3 of mandibular canine decreased after retraction. No statistically significant difference was observed in other region.

CONCLUSIONDuring retraction, a controlled tipping movement occur in adolescents. After retraction, the alveolar bone thickness of the labial side increase, whereas that of the palatal side decrease. Moreover, the thicknesses of major areas in the alveolar bone significantly increase.

Adolescent ; Child ; Cone-Beam Computed Tomography ; Cuspid ; Female ; Humans ; Incisor ; Male ; Maxilla ; Molar ; Palate ; Tooth Movement Techniques

BACKGROUND:It is difficult to perform superselective catheterization of the internal carotid artery in dogs because of the large bending and spiral shape of the interal carotid artery before entering into the skul. At present, the dog models of cerebral infarction established by injecting autologous blood clots and gelatin spongevia the internal carotid artery are far from the perspective of pathological mechanism of human patients with cerebral infarction. Aortography can visualize the structure of cerebral vessels and is likely to provide a new condition for the establishment of dog models of acute cerebral infarction. OBJECTIVE:To explore the feasibility of establishing cerebral infarction models in beagle dogs by superselective catheterizationvia the vertebral basilar artery. METHODS: Five beagle dogs were divided into thrombus group (n=3) and control group (n=2). The beagle dogs in the thrombus group were subjected to digital subtraction angiography of the aortic arch, bilateral common carotid arteries and vertebral arteries in addition to femoral arterial catheterization. The 2.7F micro-catheter was inserted into the convergence zone of the left posterior communicating artery and the internal carotid artery through the vertebrobasilar artery. An autologous blood clot was injected into the convergence zone. The dogs in the control group were injected with appropriate amount of contrast medium. RESULTS AND CONCLUSIONS:Through angiography of the left and right common carotid artery of five dogs, thick external carotid arteries (10/10) and their branches were clearly displayed, however, only five (5/10) internal carotid arteries were dimly present. A spiral vascular loop formed in the internal carotid artery with a smal-sized diameter. Through antiography of the left and right vertebral arteries (10/10) angiography, vertebral basilar artery, the circle of “Wilis”, bilateral posterior cerebral arteries, bilateral middle cerebral arteries and bilateral anterior cerebral arteries were clearly displayed, al these contribute to insertion of microcatheter into the convergence zone of the left posterior communicating artery and the internal carotid artery through the vertebrobasilar artery. High signal intensity of the left temporal lobe was shown on 3-hour and 6-hour diffusion weighted images.The results demonstrate that the beagle dog models of acute cerebral infarction can be successfuly established by injecting autologous blood clots into the left middle cerebral artery through a microcathter insertedvia the vertebrobasilar artery, which provides a new method of precisely occluding the middle cerebral artery of beagle dogs by catheterization.