Enantioselective Nickel-Catalyzed Reductive Aryl/Alkenyl-Cyano Cyclization Coupling to All-Carbon Quaternary Stereocenters.

An enantioselective nickel-catalyzed intramolecular reductive cross-coupling of C(sp2) electrophiles and cyano groups is reported. Enantioenriched CN-containing all-carbon quaternary stereocenters are assembled by desymmetrizing cyclization of aryl/alkenyl halide-tethered malononitriles. The use of an organic reductant, (EtO)2MeSiH, is crucial to the enantioselectivity and reactivity. Applications of the method are demonstrated through the synthesis of bioactive molecules and their cyanated analogues and the total synthesis of the natural product diomuscinone. This study exhibits the potential of desymmetrizing reductive coupling strategies to access structurally rigid and synthetically versatile molecules from readily available starting materials.

[Action mechanism and active components of Fuzheng Huayu Recipe against liver fibrosis via regulating macrophage with network pharmacology and transcriptomics methods].

We have demonstrated that Fuzheng Huayu Recipe(FZHY) plays an anti-liver fibrosis role by regulating the polarization of intrahepatic macrophages, while the key targets in macrophages and the effective components of FZHY remain unclear. In this study, we obtained the potential anti-liver fibrosis target set of FZHY through network pharmacological analysis, and the differentially expressed gene set of FZHY for the prevention and treatment of mouse liver fibrosis through RNA-Seq of the liver tissue. The potential core targets of FZHY against liver fibrosis were obtained by degree value analysis of the common target proteins between the above two sets. Then, through the retrieval of PubMed database, we identified the potential key targets in macrophages. After that, the effective components in FZHY corresponding to key targets were obtained by reverse pharmacological analysis. Finally, we verified the regulatory effects of these effective components on the expression of key target genes by using the lipopolysaccharide-induced M1 macrophages derived from THP-1 cells. The RNA-Seq data combined with network pharmacological analysis showed that FZHY might alleviate liver fibrosis by regulating the expression of CCL2, TIMP1, and MMP2 genes in macrophages. The results of in vivo experiments showed that FZHY significantly inhibited the expression of CCL2 and TIMP1 genes and promoted the expression of MMP2 genes in liver tissues of liver fibrosis mice. The results of in vitro experiments demonstrated that FZHY and its four effective components(luteolin, ursolic acid, quercetin, and danshensu) significantly inhibited the expression of CCL2 and TIMP1 genes in M1 macrophages derived from THP-1 cells. In addition, the expression of MMP2 gene was up-regulated by luteolin, ursolic acid, and quercetin, not affected by FZHY, and down-regulated by danshensu. FZHY could inhibit the expression of CCL2 and TIMP1 genes in M1 macrophages by the four effective components to achieve the anti-inflammatory and anti-liver fibrosis effects.

Enantioselective Synthesis of α-All-Carbon Quaternary Center-Containing Carbazolones via Amino-palladation/Desymmetrizing Nitrile Addition Cascade.

An enantioselective Pd(II)-catalyzed amino-cyclization and desymmetrizing nitrile addition cascade reaction of alkyne-tethered malononitriles is reported. This reaction forms two rings and one quaternary carbon center in a single step and serves as an efficient strategy for the construction of α-quaternary carbazolones with high enantioselectivities (up to 98:2 er). The utility of this method is demonstrated by product derivatization into a diverse array of heterocycles and a nitrile-containing leucomidine A analog.

Enantioselective Synthesis of Fused Isocoumarins via Palladium-Catalyzed Annulation of Alkyne-Tethered Malononitriles.

An enantioselective palladium-catalyzed annulation of alkyne-tethered malononitriles for the synthesis of 3,4-ring-fused isocoumarins is described. This cascade strategy involves oxypalladation of ortho-alkynylbenzoates and desymmetrizing addition onto one cyano group of the pendant malononitriles, which enables the concurrent construction of two rings and an all-carbon quaternary stereocenter in a single operation.

Enantioselective Assembly of Cycloenones with a Nitrile-Containing All-Carbon Quaternary Center from Malononitriles Enabled by Ni Catalysis.

Chiral nitriles are valuable molecules in modern organic synthesis and drug discovery. Selectively differentiating the two nitrile groups of widely available malononitrile derivatives is a straightforward yet underdeveloped route to construct enantioenriched nitriles. Here we report an enantioselective nickel-catalyzed desymmetrization of malononitriles for the generation of nitrile-containing all-carbon quaternary stereocenters. This protocol involves a nickel-catalyzed addition of aryl boronic acids to alkynes, followed by a selective nitrile insertion, providing unprecedented access to enantioenriched 5-7-membered α-cyano-cycloenones with a fully substituted olefin from a broad range of substrates. The synthetic utility of these nitrile products is demonstrated by gram-scale synthesis and conversion to several useful functional groups.

Missed manubriosternal dislocation in patient with thoracolumbar fracture, a case report.

BACKGROUND: Spine fractures combined with sternal injury are most commonly occur in the thoracic region. Lower cervical and thoracolumbar injuries have also been reported, especially for the patients with manubriosternal dislocation. The type of spine injury is easily recognized in initial presentation, but we may miss the sternal fracture and manubriosternal dislocation. CASE PRESENTATION: A 23-year-old male patient complained with chest, right ankle, and lumbar pain after a fall at ground level, with diagnosis of right distal tibial fracture, sternal fracture, calcaneus fracture, and L2 vertebral fracture. However, neurologically he was completely normal. He underwent the operation for his lower extremity and spine, but we missed his manubriosternal dislocation after discharged. After one month, he came to the clinic with complained of chest pain, the imaging exams showed anterior dislocation of manubriosternal joint. We chose conservative treatment for manubriosternal dislocation. He was followed up at monthly intervals and radiographs along with computerized tomography showed satisfactory in fracture healing of lumber and the sternal fracture. However, the manubriosternal dislocation was malunioned. The patient had appearance deformity of the manubriosternal joint. CONCLUSION: This case supports the concept of the existence and clinical relevance of the thoracic cage theory, the thoracolumbar vertebrae should also be included in the thoracic cage theory.

Surgical treatment of compressive spinal hemangioma : A case series of three patients and literature review.

PURPOSE: In this article we describe the treatment of compressive vertebral hemangioma. METHODS: Our case series comprised three patients with aggressive hemangioma. We performed a combination of posterior decompression and vertebroplasty for the two patients with a sacral hemangioma and a thoracic hemangioma, and en bloc resection for the third patient, who also had a thoracic lesion. RESULTS: Surgical intervention is indicated in cases of rapidly progressive tumors or severe myelopathy. All three patients had good clinical results. The follow-up period ranged from 8 to 56 months. The mean blood loss was around 700 ml, and mean surgical time was 2.1 h. Blood loss for the en bloc procedure was around 1,200 ml, and surgical time was 2.3 h. CONCLUSION: A combination of posterior decompression, vertebroplasty, and posterior fixation for aggressive hemangioma can reduce blood loss during surgery. For patients with hemangioma and with incomplete paralysis, total en bloc spondylectomy should be considered. Adjuvant radiotherapy can reduce the recurrence of cavernous vertebral hemangiomas.

Repair of segmental long bone defect in a rabbit radius nonunion model: comparison of cylindrical porous titanium and hydroxyapatite scaffolds.

A segmental long bone defect in a rabbit radius nonunion model was repaired using cylindrical porous titanium (Ti) and hydroxyapatite (HA) scaffolds. Each scaffold was produced using the same method, namely, a slurry foaming method. Repairing ability was characterized using x-radiographic score 12 and 24 weeks postprocedure; failure load of the radius-ulna construct, under three-point bending, 12 weeks postprocedure; and the percentage of newly formed bone within the implant, 12 and 24 weeks after postprocedure. For each of these parameters, the difference in the results when porous Ti scaffold was used compared with when HA scaffolds were used was not significant; both porous scaffolds showed excellent repairing ability. Because the trabecular bone is a porous tissue, the interconnected porous scaffolds have the advantages of natural bone, and vasculature can grow into the porous structure to accelerate the osteoconduction and osteointegration between the implant and bone. The porous Ti scaffold not only enhanced the bone repair process, similar to porous HA scaffolds, but also has superior biomechanical properties. The present results suggest that porous Ti scaffolds may have promise for use in the clinical setting.

Effect of celecoxib on inhibiting tumor repopulation during radiotherapy in human FaDu squamous cell carcinoma.

AIM OF THE STUDY: FaDu human squamous cell carcinoma (FaDu-hSCC) demonstrated accelerated tumor repopulation during fractionated irradiation with pathological validation in a xenograft model system. Previous studies showed that the selective cyclooxygenase (COX)-2 inhibitor celecoxib can enhance the tumor response to radiotherapy. So we aimed to explore the effect of celecoxib in inducing apoptosis and inhibiting repopulation of FaDu tumors in nude mice during fractionated radiotherapy. MATERIAL AND METHODS: FaDu-hSCC was transplanted into the right hind leg of BALB/C nude mice. Mice were treated with celecoxib and/or fractionated irradiation. Celecoxib (100 mg/kg/day) was administered by daily gavage. Irradiation was delivered with 12 to 18 fractions of 3.0 Gy daily or every second day based on Petersen's repopulation model. At different time points, tumors were excised for immunohistochemistry staining. RESULTS: Significant tumor repopulation occurred after about 18 days of radiotherapy. On average, Ki-67 and bromodeoxyuridine (BrdUrd) labeling indices (LI) decreased with daily irradiation (both p < 0.05) and increased with every-second-day irradiation (both p > 0.05), suggesting accelerated repopulation. Ki-67 LI decreased in celecoxib concurrent with radiotherapy for 12 fractions in 24 days and 18 fractions in 36 days compared with irradiated alone (p = 0.004 and 0.042, respectively). BrdUrd LI values were lower in the concurrent groups than irradiated alone (p = 0.001 and 0.006, respectively). Epithelial growth factor receptor (EGFR) expression score decreased in the concurrent groups than irradiated alone (p = 0.037 and 0.031, respectively). Caspase-3 expression scores were higher in the concurrent groups than irradiated alone (p = 0.05 and 0.006, respectively). CONCLUSIONS: Celecoxib concurrent radiotherapy could inhibit tumor repopulation and increase tumor apoptosis during the treatment in FaDu squamous cell carcinoma.

Anesthesia/surgery activate MMP9 leading to blood-brain barrier disruption, triggering neuroinflammation and POD-like behavior in aged mice.

Anesthesia and surgery activate matrix metalloproteinase 9 (MMP9), leading to blood-brain barrier (BBB) disruption and postoperative delirium (POD)-like behavior, especially in the elderly. Aged mice received intraperitoneal injections of either the MMP9 inhibitor SB-3CT, melatonin, or solvent, and underwent laparotomy under 3 % sevoflurane anesthesia(anesthesia/surgery). Behavioral tests were performed 24 h pre- and post-operatively. Serum and cortical tissue levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) were measured using ELISA. Levels of PDGFRß, MMP9, tight junction, Mfsd2a, caveolin-1, synaptophysin, and postsynaptic densin (PSD)-95 proteins in the prefrontal cortex were assayed using Western blotting. BBB permeability was assessed by detecting IgG in the prefrontal cortex and serum S100ß levels. Anesthesia/surgery-induced peripheral inflammation activated MMP9, which in turn injured pericytes and tight junctions and increased transcytosis, thereby disrupting the BBB. Impaired BBB allowed the migration of peripheral inflammation into the central nervous system (CNS), thereby inducing neuroinflammation, synaptic dysfunction, and POD-like behaviors. However, MMP9 inhibition reduced pericyte and tight junction injury and transcytosis, thereby preserving BBB function and preventing the migration of peripheral inflammation into the CNS, thus attenuating synaptic dysfunction and POD-like behavior. In addition, to further validate the above findings, we showed that melatonin exerted similar effects through inhibition of MMP9. The present study shows that after anesthesia/surgery, inflammatory cytokines upregulation is involved in regulating BBB permeability in aged mice through activation of MMP9, suggesting that MMP9 may be a potential target for the prevention of POD.

The prognostic value of 11th Japanese classification and 8th AJCC staging systems in Chinese patients with esophageal squamous cell carcinoma.

BACKGROUND: Two staging systems, the 8th staging system by the American Joint Committee on Cancer (AJCC) and the 11th Japanese classification by Japan Esophageal Society (JES), are currently applied in the clinic for predicting the prognosis of patients with esophageal squamous cell carcinoma (ESCC). The differences between the two staging systems have been widely researched. However, little studies focus on the differences in specific staging between the two systems. Therefore, we aimed to compare the performance of different staging in predicting overall survival (OS) of Chinese patients with ESCC. METHODS: This retrospective study included 268 patients who underwent radical esophagectomy and mediastinal lymph node dissection for ESCC between January 2008 and December 2013. Patients were staged by the 8th AJCC and 11th JES staging systems. OS was estimated using the Kaplan-Meier method and compared between N stages and between stage groupings using the log-rank test. Cox proportional hazards regression analysis was performed to identify factors independently related to outcome. Further, we compared the concordance indexes (C-indexes) of the two staging systems. RESULTS: The mean age was 61.25 ± 7.056 years, median follow-up was 44.82 months, and 5-year OS rate was 47%. The OS was well predicted by the 8th AJCC N staging (P < 0.001) and the 11th JES N staging (P < 0.001), with a c-index of 0.638 (95% CI: 0.592-0.683) for AJCC N staging and 0.627 (95% CI: 0.583-0.670) for JES N staging (P = 0.13). In addition, the OS was also well predicted by stage groupings of the 8th AJCC (P < 0.001) and the 11th JES systems (P < 0.001), with a c-index of 0.658 (95% CI: 0.616-0.699) for 8th AJCC stage grouping and 0.629 (95% CI: 0.589-0.668) for the11th JES stage grouping (P = 0.211). CONCLUSIONS: The prognostic effect of 11th JES staging system is comparable with that of AJCC 8th staging system for patients with ESCC. Therefore, both systems are applicable to clinical practice.

Analgesic Effects of Different Local Infiltration Anesthesia Techniques Combined with Femoral Nerve Block in Patients Undergoing Total Knee Arthroplasty: A Randomized Controlled Clinical Trial.

Objective: Pain after total knee arthroplasty (TKA) remains an unresolved problem. Femoral nerve block (FNB) could relieve pain; however, it alone is insufficient. The local infiltration anesthesia technique (LIA) has been suggested as a supplement to FNB. This study aimed to evaluate the analgesic effects of different LIA combined with FNB in TKA patients. Methods: The femoral nerve was blocked with 0.375% ropivacaine 20mL, and all patients routinely received general anesthesia. The primary indicator was the proportion of patients who did not receive post-operative remedial analgesia. Seventy-eight patients were randomly assigned to PAI (periarticular injection combined with FNB), IAI (intra-articular injection combined with FNB), or control (FNB alone) groups. All patients underwent FNB under general anesthesia. The primary outcome was the proportion of patients who did not receive additional postoperative analgesia within the first 48 h after surgery. Results: Compared with the PAI and control groups, the IAI group had a higher proportion (69.23%) of patients who did not receive remedial analgesia within 48 hours after surgery (P = 0.009; P = 0.009), a lower consumption of diclofenac sodium lidocaine (P = 0.021; P < 0.001), and an earlier time of walking with a walker (P < 0.001; P < 0.001). The time of first need for remedial analgesia postoperatively in IAI group was longer than the PAI group (P = 0.008) and IAI group has a shorter hospital stay than the control group (P = 0.008). The maximum NRS during the first 48 hours postoperatively and NRS 24 hours after surgery in the IAI group were lower than those in the control and PAI groups. The incidences of POD and PONV were similar among the three groups (P = 0.610; P = 0.264). Conclusion: When combined with FNB, intra-articular injection offers a superior analgesic effect and favorable recovery compared to periarticular injection and separate application of FNB.

The Effect of Dezocine on the Median Effective Dose of Sufentanil-Induced Respiratory Depression in Patients Undergoing Spinal Anesthesia Combined with Low-Dose Dexmedetomidine.

Purpose: The application of sedation and analgesia in spinal anesthesia has many benefits, but the risk of respiratory depression (RD) caused by opioids cannot be ignored. We aimed to observe the effect of dezocine, a partial agonist of µ-receptor, on the median effective dose (ED50) of sufentanil-induced RD in patients undergoing spinal anesthesia combined with low-dose dexmedetomidine. Patients and Methods: Sixty-two patients were randomly assigned to dezocine group (DS) and control group (MS). After spinal anesthesia, mask oxygen (5 L/min) and dexmedetomidine (0.1 ug/kg) were given. Five minutes later, patients in the DS group received an Intravenous (IV) bolus of sufentanil and 0.05mg/kg dezocine, while patients in the MS group only received an IV bolus of sufentanil. Results: ED50 of DS group was 0.342 ug/kg, 95% confidence interval (CI) was (0.269, 0.623) ug/kg, and the ED50 of MS group was 0.291 ug/kg, 95% CI was (0.257, 0.346) ug/kg. There was no difference in the type and treatment measures of RD and hemodynamic changes between the two groups, and no serious adverse reactions occurred in either group. Conclusion: Dezocine can improve RD induced by sufentanil in patients with spinal anesthesia combined with low-dose dexmedetomidine, and increase the safety window of sufentanil use.

Preparation of electrospun PLGA-silk fibroin nanofibers-based nerve conduits and evaluation in vivo.

With advances in technical methodology, the grafting of biocompatible conduits may become a viable alternative for the reconstruction of nerve gaps. In this study, electrospinning was used to fabricate nerve conduits (NCs) from poly(L-lactide-coglycolide)-silk fibroin. Conduits or autograft nerves were employed to bridge 10 mm defects in the sciatic nerves of Sprague-Dawley rats. Six weeks after the operation, morphological and functional assessment showed that nerve conduits from PLGA-silk fibroin grafts promoted the regeneration of peripheral nerves. The effects were similar to those obtained using nerve autografts. This method offers a promising alternative to the use of nerve autografts.

[Clinical study of correlation between the expression of ICBP90 and hematopoietic suppression in patients with chronic benzene poisoning].

OBJECTIVE: To observe the change of ICBP90 expression in patients with chronic benzene poisoning and explore the correlation between the expression of ICBP90 and benzene-induced hematotoxicity. METHODS: The bone marrow samples were from 13 chronic benzene poisoning cases with hematopoietic suppression, 11 chronic benzene poisoning cases with hematopoietic regeneration and 10 controls. Western-blot was applied to detect the ICBP90 expression in bone marrow mononuclear cells (BMNCs). The correlation between ICBP90 expression and hematopoietic suppression in patients with chronic benzene poisoning was analyzed. RESULTS: The ICBP90 expression of BMNCs in 13 chronic benzene poisoning cases with hematopoietic suppression was significantly lower than that in controls (P < 0.01). The ICBP90 expression of BMNCs in 11 chronic benzene poisoning cases with hematopoietic regeneration was significantly higher than those in controls and 13 chronic benzene poisoning cases with hematopoietic suppression (P < 0.05 or P < 0.01), respectively. There were good correlations between the expression of ICBP90 and white blood cell and platelet counts in patients with chronic benzene poisoning (r(1) = 0.555,P = 0.006; r(2) = 0.854,P < 0.01). CONCLUSION: The ICBP90 expression of BMNCs in the chronic benzene poisoning cases with hematopoietic suppression decreased significantly, and the ICBP90 expression of BMNCs in the chronic benzene poisoning cases with hematopoietic regeneration increased significantly. There was good correlation between hematopoietic suppression and ICBP90 expression in patients with chronic benzene poisoning.

Posterior temporary fixation of C1-C2 screw-rod system for unstable C1 burst fracture.

Whether an unstable C1 burst fracture should be treated surgically or conservatively is controversial. The purpose of this study is to evaluate the effectiveness and motion-preserving function of temporary fixation of C1-C2 screw-rod system for the reduction and fixation of unstable C1 burst fracture. We retrospectively reviewed 10 patients who were treated with posterior C1-C2 temporary fixation without fusion. We assessed age at surgery, gender, pre- and postoperative visual analog scale (VAS), Neck Disability Index (NDI), atlanto-dens interval (ADI), lateral mass distance (LMD), and rotation function of C1-C2 complex. Six males and 4 females were included in our study. The average follow-up duration was 14.1 ± 1.37 months. The left-to-right ROMs of C1-C2 rotation was 9.6° ± 1.42°. The preoperative cervical VAS was 8.30 ± 0.48; the postoperative cervical VAS of C1-C2 fusion was 2.90 ± 0.57. The preoperative VAS for removal was 2.0 ± 0.00, and the postoperative VAS for removal was 2.3 ± 0.48. The preoperative cervical NDI was 81.40% ± 2.07%, the postoperative cervical NDI of C1-C2 fusion was 18.10% ± 1.52%. The preoperative NDI for removal was 15.9% ± 1.20%. The postoperative NDI for removal was 14.5% ± 1.08%. The preoperative ADI was 4.43 ± 0.34 mm, and postoperative ADI was 1.94 ± 0.72 mm. The preoperative LMD was 6.36 ± 0.58 mm, and postoperative LMD was 1.64 ± 0.31 mm. Posterior temporary C1-C2 fixation can achieve a good fusion and satisfied reduction of C1 fracture, relieve the pain, improve the cervical function outcome, but may reduce the rotational range of motion of C1-C2. Posterior C1-C2 temporary fixation without fusion was not suitable for C1 burst fracture. We recommend permanent C1-C2 fixation and fusion for C1 burst fracture if surgery is necessary.

BTG2 is an LXXLL-dependent co-repressor for androgen receptor transcriptional activity.

The tumor suppressor gene, BTG2 has been down-regulated in prostate cancer and the ectopic expression of this gene has been shown to inhibit prostate cancer cell growth. Sequence analysis revealed that the BTG2 protein contains two leucine-rich motifs ((20)LxxLL(24) and (92)LxxLL(96)), which are usually found in nuclear receptor co-factors. Based on this, we postulated that there will be an association between BTG2 and AR. In this study, we discovered that BTG2 directly bound to the androgen receptor (AR) in the absence of 5α-dihydrotestosterone (DHT), and in the presence of the androgen, this interaction was increased. BTG2 bearing the mutant (20)LxxLL(24) motif bound to AR equally efficient as the wild-type BTG2, while BTG2 bearing the mutant (92)LxxLL(96) motif failed to interact with AR. Functional studies indicated that ectopic expression of BTG2 caused a significant inhibition of AR-mediated transcriptional activity and a decreased growth of prostate cancer cells. Androgen-induced promoter activation and expression of prostate-specific antigen (PSA) are significantly attenuated by BTG2. The intact (92)LxxLL(96) motif is required for these activities. These findings, for the first time, demonstrate that BTG2 complexes with AR via an LxxLL-dependent mechanism and may play a role in prostate cancer via modulating the AR signaling pathway.

Contralateral radiculopathy after unilateral transforaminal lumbar interbody fusion: causes and prevention.

BACKGROUND: Unilateral transforminal lumbar interbody fusion (TLIF) with a single cage can provide circumferential fusion and biomechanical stability. However, the causes and prevention of contralateral radiculopathy following unilateral TLIF remain unclear. METHODS: In total, 190 patients who underwent unilateral TLIF from January 2017 to January 2019 were retrospectively reviewed. Radiological parameters including lumbar lordosis, segmental angle, anterior disc height, posterior disc height (PDH), foraminal height (FH), foraminal width, and foraminal area (FA) were measured preoperatively and postoperatively. Preoperative and postoperative visual analog scale scores were also recorded. RESULTS: The incidence of contralateral radiculopathy after unilateral TLIF was 5.3% (10/190). The most common cause was contralateral foraminal stenosis. Unilateral TLIF could increase the lumbar lordosis, segmental angle, and anterior disc height but decrease the PDH, FA, and FH in patients with symptomatic contralateral radiculopathy. The intervertebral cage should be placed to cover the epiphyseal ring and cortical compact bone of the midline, and the disc height can be increased to enlarge the contralateral foramen. CONCLUSION: The most common cause of contralateral radiculopathy is contralateral foraminal stenosis. Careful preoperative planning is necessary to achieve satisfactory outcomes. Improper unilateral TLIF will decrease the PDH, FA, and FH, resulting in contralateral radiculopathy.

Apigenin Inhibits the Growth of Hepatocellular Carcinoma Cells by Affecting the Expression of microRNA Transcriptome.

BACKGROUND: Apigenin, as a natural flavonoid, has low intrinsic toxicity and has potential pharmacological effects against hepatocellular carcinoma (HCC). However, the molecular mechanisms involving microRNAs (miRNAs) and their target genes regulated by apigenin in the treatment of HCC have not been addressed. OBJECTIVE: In this study, the molecular mechanisms of apigenin involved in the prevention and treatment of HCC were explored in vivo and in vitro using miRNA transcriptomic sequencing to determine the basis for the clinical applications of apigenin in the treatment of HCC. METHODS: The effects of apigenin on the proliferation, cell cycle progression, apoptosis, and invasion of human hepatoma cell line Huh7 and Hep3B were studied in vitro, and the effects on the tumorigenicity of Huh7 cells were assessed in vivo. Then, a differential expression analysis of miRNAs regulated by apigenin in Huh7 cells was performed using next-generation RNA sequencing and further validated by qRT-PCR. The potential genes targeted by the differentially expressed miRNAs were identified using a curated miRTarBase miRNA database and their molecular functions were predicted using Gene Ontology and KEGG signaling pathway analysis. RESULTS: Compared with the control treatment group, apigenin significantly inhibited Huh7 cell proliferation, cell cycle, colony formation, and cell invasion in a concentration-dependent manner. Moreover, apigenin reduced tumor growth, promoted tumor cell necrosis, reduced the expression of Ki67, and increased the expression of Bax and Bcl-2 in the xenograft tumors of Huh7 cells. Bioinformatics analysis of the miRNA transcriptome showed that hsa-miR-24, hsa-miR-6769b-3p, hsa-miR-6836-3p, hsa-miR-199a-3p, hsa-miR-663a, hsa-miR-4739, hsa-miR-6892-3p, hsa-miR-7107-5p, hsa-miR-1273g-3p, hsa-miR-1343, and hsa-miR-6089 were the most significantly up-regulated miRNAs, and their key gene targets were MAPK1, PIK3CD, HRAS, CCND1, CDKN1A, E2F2, etc. The core regulatory pathways of the up-regulated miRNAs were associated with the hepatocellular carcinoma pathway. The down-regulated miRNAs were hsa-miR-181a-5p and hsa-miR-148a-3p, and the key target genes were MAPK1, HRAS, STAT3, FOS, BCL2, SMAD2, PPP3CA, IFNG, MET, and VAV2, with the core regulatory pathways identified as proteoglycans in cancer pathway. CONCLUSION: Apigenin can inhibit the growth of HCC cells, which may be mediated by up-regulation or down-regulation of miRNA molecules and their related target genes.

[Treatment strategy and curative effect analysis of os odontoideum complicated with atlantoaxial joint dislocation].

OBJECTIVE: To explore the treatment strategy and clinical efficacy for os odontoideum complicated with atlantoaxial dislocation. METHODS: The clinical data of 17 patients with os odontoideum complicated with atlantoaxial dislocation surgically treated from January 2006 to January 2015 were retrospectively analyzed, including 7 males and 10 females, aged 17 to 53 (43.1±11.3) years old;course of disease was 3 to 27(10.2±6.9) months. All patients received cranial traction before operation, 12 of 14 patients with reducible dislocation were treated by posterior atlantoaxial fixation and fusion, and 2 patients with atlantooccipital deformity were treated by posterior occipitocervical fixation and fusion;3 patients with irreducible alantoaxial dislocation were treated by transoral approach decompression combined with posterior atlantoaxial fixation and fusion. The operation time, intraoperative blood loss and perioperative complications were recorded. Visual analogue scale (VAS) and Japanese Orthopaedic Association (JOA) score were used to evaluate the change of neck pain and neurological function. Atlantoaxial joint fusion rate was evaluated by CT scan. RESULTS: The operation time of posterior fixation and fusion ranged from 86 to 170 (92.2±27.5) min, and the intraoperative blood loss was 200-350 (250.7±65.2) ml. No vertebral artery injury and spinal cord injury were recorded. Among the patients underwent atlantoaxial fixation and fusion, 1 patient with reducible dislocation fixed by C2 laminar screw lost reduction after primary operation, and received anterior release again and finally occipitocervical fusion. All patients were followed up for 15 to 58 (32.0±12.2) months. VAS score was decreased from preoperative 4.2±0.9 to 1.3±0.7 at final follow up and the JOA score was improved from preoperative 11.2±1.2 to 16.9±0.8 at final follow-up. CT scan confirmed that the atlantoaxial or occipitocervical fusion wasgood, and the fusion time was 5 to 9 (6.7±0.6) months. CONCLUSION: Surgical treatment of os odontoideum complicated with atlantoaxial dislocation can achieve satisfactory results, improve the patient's neurological function and improve the quality of life, however the surgical options needs to be individualized.