Evolution and development of potent monobactam sulfonate candidate IMBZ18g as a dual inhibitor against MDR Gram-negative bacteria producing ESBLs

A series of new monobactam sulfonates is continuously synthesized and evaluated for their antimicrobial efficacies against Gram-negative bacteria. Compound 33a (IMBZ18G) is highly effective in vitro and in vivo against clinically intractable multi-drug-resistant (MDR) Gram-negative strains, with a highly druglike nature. The checkerboard assay reveals its significant synergistic effect with β-lactamase inhibitor avibactam, and the MIC values against MDR enterobacteria were reduced up to 4-512 folds. X-ray co-crystal and chemoproteomic assays indicate that the anti-MDR bacteria effect of 33a results from the dual inhibition of the common PBP3 and some class A and C β-lactamases. Accordingly, preclinical studies of 33a alone and 33a‒avibactam combination as potential innovative candidates are actively going on, in the treatment of β-lactamase-producing MDR Gram-negative bacterial infections.

Mechanism of electroacupuncture regulating the ligand pathway of tyrosine kinase receptor in improving vascular dementia / 解剖学报

Objective To observe the potential mechanism of electroacupuncture regulating the erythropoietin-producing hepatocellular receptor B2/erythropoietin-producing hepatocellular receptor-interacting B2/big mitogen-activated protein kinase 1(EphB2/EphrinB2/BMK1) signaling pathway to improve neural damage in vascular dementia rats. Methods Eighty SD male adult rats were randomly divided into a sham surgery group, a model group, a non acupoint electroacupuncture group, a nimodipine group, and an electroacupuncture three needle group. The vascular dementia rat model was made by the modified Pulsinelli four vessel occlusion method. After grouping, the rats in each group were subjected to water maze test, HE staining, Nissl staining, and transmission electron microscopy(TEM) to observe the pathological changes in the hippocampal CA1 area, and the expression of EphB2 and BMK1 in the hippocampal CA1 area was detected by immunohistochemistry; Detection of EphB2 and BMK1 protein expression in rat hippocampal CA1 region was detected by Western blotting. Results Compared with the model group, the escape latency of vascular dementia rats treated with electroacupuncture and nimodipine decreased (P0.05). Compared with the nimodipine group, the expression of EphB2 and BMK1 in the hippocampal CA1 region of rats in the electroacupuncture Zhisanzhen group significantly increased (P<0.05). Conclusion Electroacupuncture may improve the damage of hippocampal neurons in vascular dementia rats by increasing the expression of EphB2 and BMK1 in the CA1 region of the hippocampus, thereby improving the learning and memory of vascular dementia rats.

Neuroprotective effect and mechanism of cPLA2 inhibitor increases autophagic flux on spinal cord injury / 中国骨伤

OBJECTIVE@#To investigate the mechanism of cytosolic phospholipase A2(cPLA2) inhibitor to improve neurological function after spinal cord injury (SCI).@*METHODS@#Thirty-six 3 months old female SD rats, with body mass (280±20) g, were divided into three groups (n=12):sham group, SCI group, and SCI+ arachidonyl trifluoromethyl ketone(AACOCF3) group. Balloon compression SCI model was established in all three groups. In the sham model group, the spinal cord compression model was created after the balloon was placed without pressure treatment, and the remaining two groups were pressurized with the balloon for 48 h. After successful modeling, rats in the SCI+AACOCF3 group were injected intraperitoneally with AACOCF3, a specific inhibitor of cPLA2. The remaining two groups of rats were injected intraperitoneally with saline. The animals were sacrificed in batches on 7 and 14 days after modeling, respectively. And the damaged spinal cord tissues were sampled for pathomorphological observation, to detect the expression of cPLA2 and various autophagic fluxPrelated molecules and test the recovery of motor function.@*RESULTS@#Spinal cord histomorphometry examination showed that the spinal cord tissue in the sham group was structurally intact, with normal numbers and morphology of neurons and glial cells. In the SCI group, spinal cord tissue fractures with large and prominent spinal cord cavities were seen. In the SCI+AACOCF3 group, the spinal cord tissue was more intact than in the SCI group, with more fused spinal cord cavities, more surviving neurons, and less glial cell hyperplasia. Western blot showed that the sham group had the lowest protein expression of LC3-Ⅱ, Beclin 1, p62, and cPLA2 compared with the SCI and SCI+AACOCF3 groups (P<0.05) and the highest protein expression of LC3-Ⅰ (P<0.05). P62 and cPLA2 expression in the SCI group were higher than in the SCI+AACOCF3 group (P<0.05). Behavioral observations showed that the time corresponding to BBB exercise scores was significantly lower in both the SCI and SCI+AACOCF3 groups than in the sham group (P<0.05). Scores at 3, 7, and 14 days after pressurization were higher in the SCI+AACOCF3 group than in the SCI group (P<0.05).@*CONCLUSION@#cPLA2 inhibitors can reduce neuronal damage secondary to SCI, promote neurological recovery and improve motor function by improving lysosomal membrane permeability and regulating autophagic flux.

Cost-effectiveness analysis of Chaiyin Granules in treatment of influenza / 中国中药杂志

This study aimed to evaluate the cost-effectiveness of Chaiyin Granules compared with Oseltamivir Phosphate Capsules in the treatment of influenza(exogenous wind-heat syndrome). Based on a randomized, double-blind, positive drug parallel control clinical trial, this study evaluated the pharmacoeconomics of Chaiyin Granules with cost-effectiveness analysis method. A total of 116 patients with influenza from eight hospitals(grade Ⅱ level A above) in 6 cities were selected in this study, including 78 cases in the experimental group with Chaiyin Granules and Oseltamivir Phosphate Capsules placebo, and 38 cases in the control group with Oseltamivir Phosphate Capsules and Chaiyin Granules placebo. The total cost of this study included direct medical cost, direct non-medical cost, and indirect cost. The remission time of clinical symptoms, cure time/cure rate, antipyretic onset time/complete antipyretic time, viral nucleic acid negative rate, and traditional Chinese medicine(TCM) syndrome curative effect were selected as the effect indicators for cost-effectiveness analysis. Four-quadrant diagram was used to estimate the incremental cost-effectiveness ratio. The results showed that Chaiyin Granules were not inferior to Oseltamivir Phosphate Capsules in the remission time of clinical symptoms of influenza(3.1 d vs 2.9 d, P=0.360, non-inferiority margin was 0.5 d). Compared with Oseltamivir Phosphate Capsules, Chaiyin Granules would delay the remission time of clinic symptoms of influenza for 1 d, but could save 213.9 yuan. 1 d delay in cure time could save 149.3 yuan; 1% reduction in the cure rate could save 8.2 yuan; 1 d delay in antipyretic onset time could save 295.4 yuan; 1 d delay in complete antipyretic time could save 114.3 yuan; 1% reduction in the 5-day cure rate of TCM syndrome could save 19.2 yuan. Different from other indicators, there was no statistically significant difference between two groups in the effect of negative conversion rate of viral nucleic acid, but the cost was lower and the effect was superior, and the pharmacoeconomics was not different from that of Oseltamivir Phosphate Capsules in the field of influenza treatment.

Effects of Apheresis Platelet Transfusion on PLT, MPV, PDW and PCT / 中国实验血液学杂志

OBJECTIVE@#To investigate the changes of platelet count (PLT), plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width (PDW) before and after apheresis platelet transfusion, the correlation between the parameters and their clinical significance.@*METHODS@#A total of 38 patients who received apheresis platelet transfusion were selected, their results of blood routine test closest to the time point of apheresis platelet transfusion were consulted from hospital information system and the changes of PLT, PCT, MPV and PDW were compared before and after transfusion. The correlation between above parameters was analyzed. The correlation of body mass index (BMI) with the increased multiple and increased value after platelet infusion was also analyzed.@*RESULTS@#Compared with pre-infusion, PLT and PCT significantly increased (both P <0.001) while MPV and PDW showed no significant difference after apheresis platelet transfusion (P >0.05). The difference of PLT and PCT before and after apheresis platelet transfusion had no correlation with PLT and PCT before transfusion (r =0.002, r =0.001), while the difference of MPV and PDW was negatively correlated with MPV and PDW before transfusion (r =-0.462, r =-0.610). The PLT growth rate was positively correlated with PCT growth rate before and after apheresis platelet transfusion (r =0.819). BMI was positively correlated with the increased multiple of PLT after infusion (r =0.721), but not with the increased value of PLT after infusion (r =0.374).@*CONCLUSION@#Apheresis platelet transfusion can cause platelet parameters change and shows different characteristics. Characteristic changes of platelet parameters and their correlation can be used as reference indices to evaluate the efficacy of apheresis platelet transfusion.

Clinical efficacy and safety of unilateral biportal endoscopy versus microendoscopic discectomy in treatment of lumbar spinal stenosis: a Meta-analysis / 中华创伤骨科杂志

Objective:To compare the efficacy and safety of unilateral biportal endoscopy (UBE) and microendoscopic discectomy (MED) in the treatment of lumbar spinal stenosis by Meta-analysis.Methods:PubMed, Web of Science, CNKI and Wanfang Data were searched from their establishment to January 2021 for all the studies on UBE and MED in the treatment of lumbar spinal stenosis. The data extracted were authors, year of publication, study design, subject characteristics, sample size, surgical protocol, age, sex ratio, duration of surgery, length of hospital stay, complications, visual analogue scale (VAS), and Oswestry Disability Index (ODI). The Meta-analysis was conducted with software Revman 5.3 to analyze the operation time, hospital stay, complication rate, waist and lower extremity VAS scores and ODI scores at preoperation, early postoperation and the last follow-up. The quality of the case-control studies included was evaluated using the Newcastle Ottawa Scale (NOS) while the methodological quality and risk of bias of the randomized controlled studies (RCT) included were evaluated using the Cochrane Bias Risk Assessment Tool.Results:Finally, 7 studies were included, 6 in English and one in Chinese. There were 2 RCTs and 5 case-control studies. There were 251 patients in the UBE group and 224 patients in the MED group. Compared with the MED group, the UBE group had a significantly shorter hospital stay ( MD=-2.28, 95% CI: -3.42 to -1.14, P<0.001), and a significantly lower VAS score for early postoperative low back pain ( MD=-0.80, 95% CI:-1.44 to -0.16, P=0.01). There were no significant differences between the 2 groups in operation time, complication rate, waist VAS scores at preoperation or the last follow-up, lower extremity VAS or ODI scores at preoperation, early postoperation or the last follow-up, or dural dilatation area ( P>0.05). Conclusions:In the treatment of lumbar spinal stenosis, compared with MED, UBE is superior in early relief of low back pain and hospital stay after operation, but shows no significant difference in long-term efficacy or safety.

Electroacupuncture Attenuates Immune-Inflammatory Response in Hippocampus of Rats with Vascular Dementia by Inhibiting TLR4/MyD88 Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate whether electroacupuncture (EA) alleviates cognitive impairment by suppressing the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling pathway, which triggers immune-inflammatory responses in the hippocampus of rats with vascular dementia (VaD).@*METHODS@#The experiments were conducted in 3 parts and in total the Sprague-Dawley rats were randomly divided into 8 groups by a random number table, including sham, four-vessel occlusion (4-VO), 4-VO+EA, 4-VO+non-EA, sham+EA, 4-VO+lipopolysaccharide (LPS), 4-VO+LPS+EA, and 4-VO+TAK-242 groups. The VaD model was established by the 4-VO method. Seven days later, rats were treated with EA at 5 acupoints of Baihui (DV 20), Danzhong (RN 17), Geshu (BL 17), Qihai (RN 6) and Sanyinjiao (SP 6), once per day for 3 consecutive weeks. Lymphocyte subsets, lymphocyte transformation rates, and inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor α(TNF-α) were measured to assess immune function and inflammation in VaD rats. Transmission electron microscopy was used to observe the ultrastructure of nerve cells in the hippocampus. The levels of TLR4, MyD88, IL-6, and TNF-α were detected after EA treatment. TLR4/MyD88 signaling and cognitive function were also assessed after intracerebroventricular injection of TLR4 antagonist TAK-242 or TLR4 agonist LPS with or without EA.@*RESULTS@#Compared with the 4-VO group, EA notably improved immune function of rats in the 4-VO+EA group, inhibited the protein and mRNA expressions of TLR4 and MyD88 in the hippocampus of rats, reduced the expressions of serum IL-6 and TNF-α (all P0.05).@*CONCLUSIONS@#EA attenuated cognitive impairment associated with immune inflammation by inhibition of the TLR4/MyD88 signaling pathway. Thus, EA may be a promising alternative therapy for the treatment of VaD.

Acupoint catgut embedding inhibiting neuroinflammation in vascular dementia rats / 解剖学报

Objective To observe the effect of acupoint catgut embedding on the expression of inflammatory factor mRNA in cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) signal pathway of vascular dementia (VD) rats, and to explore the protective mechanism of acupoint catgut embedding on the brain inflammatory response of VD rats. Methods VD model was established by the modified Pulsinelli ' s four vessel blocking method. Totally 148 male rats were randomly divided into VD model group, non acupoint catgut embedding group and acupoint catgut embedding group. On the 7th day after operation, catgut embedding at acupoints and catgut embedding at non acupoints were performed in the two treatment groups respectively, and materials were taken out 15 days later. Western blotting was used to detect the expression of COX-2 and PGE2, and real-time PCR was used to detect the mRNA expression of tumor necrosis factor α (TNF-α), intercellular cell adhesion molecule 1 (ICAM-1), interieukin(IL)-6, macrophage inflammatory protein 2 (MIP-2), IL-lβ, and monocyte chemotactic protein 1 ( MCP-1 ) in rat hippocampus. Results Compared with the sham group, the expressions of COX-2, PGE2, TNF-α, ICAM-1, IL-6, MIP-2, IL-lβ and MCP-1 in hippocampus of the other three groups were significantly higher (P<0.01). Compared with the model group, the expressions of COX-2, PGE2 protein and TNF-α, ICAM-1, IL-6, MIP-2, IL-lβ, MCP-1 mRNA in the hippocampus of the acupoint catgut embedding group and the non acupoint catgut embedding group decreased significantly (P<0.01). Conclusion Acupoint catgut embedding can protect the brain from inflammatory injury by down-regulating the expression of related inflammatory factors in COX-2/PGE2 signaling pathway and reducing the inflammatory response induced by VD rats.

Clinical Significance of FGFR1 Gene Abnormalities in Blood Tumors / 中国实验血液学杂志

OBJECTIVE@#To study the potential significance and clinical application of FGFR1 gene abnormality in the diagnosis, clinical features, pathological mechanism and treatment in hematological tumors.@*METHODS@#Clinical data of total of 29 patient with chromosome of 8 short arm (8P) abnormality who had more comprehensive medical history from 2013 to 2018 were collected. The karyotype analysis of bone marrow chromosomes in patients was carried out by using chromosome R band banding technique. FGFR1 gene was detected by using fluorescence in situ hybridization (FISH).@*RESULTS@#Seven cases of FGFR1 gene abnormalities were decteted, including 3 cases of FGFR1 gene amplification, 2 cases of translocation, and 2 cases of deletion. Five patients with FGFR1 gene amplification or deletion not accompaned with eosinophilia, moreover the chromosome was a complex karyotype with poor prognosis; Two cases of FGFR1 gene translocation were non-complex chromosomal translocation and one of which survived for 6 years after bone marrow transplantation, the other chromosome karyotype showed no rearrangement of 8 short arm. However, FGFR1 gene rearrangement was confirmed by FISH analysis, which was a rare insertional translocation.@*CONCLUSION@#FGFR1 gene amplification or deletion often occur in cases with complex karyotype, which not accompany eosinophilia, moreover have poor prognosis. The patients with FGFR1 gene translocation accompany eosinophilia which is consistent with the clinical characteristics of myeloid / lymphoid neoplasms with FGFR1 abnormality. Karyotype analysis combined with FISH method can improve the detection of abnormal clones.

Effect of consolidation before allogeneic hematopoietic stem cell transplantation for non-favorable acute myeloid leukemia patients with first complete remisson and negative minimal residual disease / 中华血液学杂志

Objective: To probe the prognostic value of consolidation chemotherapy in non-favorable acute myeloid leukemia (AML) patients who were candidates for allogeneic hematopoietic stem cell transplantation (allo-HSCT) with first complete remission (CR(1)) and negative minimal residual disease (MRD(-)) . Methods: A retrospective analysis was conducted on 155 patients with non-favorable AML who received allo-HSCT in CR(1)/MRD(-) from January 2010 to March 2019. The survival data were compared between patients who received and those not received pre-transplant consolidation chemotherapy. Results: A total of 102 patients received pre-transplant consolidation chemotherapy (consolidation group) , and 53 cases directly proceeded to allo-HSCT when CR(1)/MRD(-) was achieved (nonconsolidation group) . The median ages were 39 (18-56) years old and 38 (19-67) years old, respectively. Five-year post-transplant overall survival [ (59.3±7.5) % vs (62.2±6.9) %, P=0.919] and relapse-free survival [ (53.0±8.9) % vs (61.6±7.0) %, P=0.936] were not significantly different between the two groups (consolidation vs nonconsolidation) . There was a weak relationship between consolidation therapy and cumulative incidence of relapse [consolidation: (21.9±5.4) % vs nonconsolidation: (18.3±6.0) %, P=0.942], as well as non-relapse mortality [consolidation: (22.4±4.3) % vs nonconsolidation: (28.4±6.5) %,P=0.464]. Multivariate analysis indicated that pre-transplant consolidation and the consolidation courses (< 2 vs ≥2 courses) did not have an impact on allo-HSCT outcomes. Conclusion: Allo-HSCT for candidate patients without further consolidation when CR(1)/MRD(-) was attained was feasible.

Prognostic value of donor chimerism at +90 days after allogeneic hematopoietic stem cell transplantation in young patients with intermediate-risk acute myeloid leukemia / 中华血液学杂志

Objective: To investigate the relationship between donor chimerism and relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: The clinical data of 105 patients with acute myeloid leukemia (AML) who underwent allo-HSCT and recurrence-free survival>90 days from January 2010 to January 2019 were retrospectively analyzed. The bone marrow samples were collected at 15, 30, 60, 90, 180, 270, 360 days after transplantation. Donor chimerism was detected by single nucleotide polymorphism (SNP) -PCR. Results: Of the 105 patients, 43 cases were male and 62 cases were female, with a median age of 38 (16-60) years. Till April 2019, the median follow-up was 843 (94-3 261) days. Ninety days after transplantation, 18 cases relapsed, 33 cases died, and 72 cases survived. The 3-year overall survival (OS) rate was (66.8±5.1) %, and the recurrence-free survival (RFS) rate was (65.1±5.0) %. Pre-transplant disease status, pre-transplant minimal residual disease (MRD) , and 90 day post-transplantation chimerism were independent risk factors related to RFS. The risk of recurrence was significantly increased in patients with a donor chimerism rate ≤97.24% at 90 days after transplantation[HR=6.921 (95%CI 2.669-17.950) , P<0.001], which was considered as a sign of early relapse. Conclusion: SNP-PCR is an applicable method for detecting donor chimerism in patients after allo-HSCT. Chimerism rate equal or less than 97.24% at 90 days after transplantation predicts a higher risk of relapse.

Efficacy of Hyper-CVAD/MA and CHALL-01 regimens in the treatment of Philadelphia chromosome-positive adult acute lymphoblastic leukemia patients under 60 years old / 中华血液学杂志

Objective: To compare the difference of efficacy between traditional Hyper-CVAD/MA regimen and the adolescents inspired chemotherapy regimen, CH ALL-01, in treatment of adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) . Methods: In this study we retrospectively analyzed 158 Ph(+) ALL patients receiving Hyper-CVAD/MA regimen (n=63) or CHALL-01 regimen (n=95) in our center and Changzheng hospital from January 2007 to December 2017, excluding patients with chronic myeloid leukemia in blast crisis. Tyrosine kinase inhibitor (TKI) was administered during induction and consolidation chemotherapy. Patients who underwent hematopoietic stem cell transplantation received TKI as maintenance therapy. Results: Of them, 91.1% (144/158) patients achieved complete remission (CR) after 1-2 courses of induction. CR rate was 90.5% (57/63) for patients in Hyper-CVAD/MA group and 91.6% (87/95) for patients in CHALL-01 group. There was no difference in CR rates between the two groups (χ(2)=0.057, P=0.811) . The last follow-up was June 2018. A cohort of 134 CR patients could be used for further analysis, among them, 53 patients received Hyper-CVAD/MA regimen and other 81 patients received CHALL-01 regimen. The molecular remission rates were significantly higher in CHALL-01 group (complete molecular response: 44.4%vs 22.6%; major molecular response: 9.9% vs 18.9%) (χ(2)=7.216, P=0.027) . For the patients in Hyper-CVAD/MA group, the 4-year overall survival (OS) was 44.81% (95%CI: 30.80%-57.86%) and the 4-year disease free survival (DFS) was 37.95% (95%CI: 24.87%-50.93%) . For patients received CHALL-01 regimen, the 4-year OS was 55.63% (95%CI: 39.07%-69.36%) (P=0.037) and 4 year DFS was 49.06% (95%CI: 34.24%-62.29%) (P=0.015) , while there was no significant difference in 4 year cumulative incidence of relapse (CIR) (P=0.328) or cumulative incidence of nonrelapse mortality (CI-NRM) (P=0.138) . The rate of pulmonary infection was lower in patients received CHALL-01 regimen compared with patients received Hyper-CVAD regimen (43.4% vs 67.9%, χ(2)=7.908, P=0.005) . Conclusions: Outcome with CHALL-01 regimen appeared better than that with the Hyper-CVAD/MA regimen in Ph(+) ALL, which has lower incidence of pulmonary infection, higher molecular remission rate and better OS and DFS.

Study on the angle of needling Yamen (GV 15) in atlanto-axial dislocation patients / 针灸推拿医学（英文版）

Objective: To compare the risk angle and safety angle of needling Yamen (GV 15) between the atlanto-axial dislocation (AAD) patients and healthy subjects. Methods: A total of 177 AAD patients diagnosed and treated at the Center of Upper Cervical Vertebra of Beijing China-Japan Friendship Hospital between January 2010 and January 2018 were included in the AAD group. Another 207 healthy subjects were included in the normal group. There were totally 191 males and 193 females. The MRI scan was performed for the cervical vertebrae to measure the risk angle and safety angle of acupuncture at Yamen (GV 15) on the sagittal image. Results: In the AAD group, the risk angle was (13.14±3.99)° and the relative safety angle was (10.31±3.23)° for the perpendicular needling, while the oblique needling risk angle was (9.09±3.09)° for the male; the risk angle was (12.12±2.74)° and the relative safety angle was (10.56±2.09)° for the perpendicular needling, while the oblique needling risk angle was (9.70±2.95)° for the female. In the normal group, the risk angle was (7.89±1.59)° and the relative safety angle was (10.21±3.55)° for the perpendicular needling, while the oblique needling risk angle was (16.07±1.77)° for the male; the risk angle was (6.93±1.45)° and the relative safety angle was (10.70±2.94)° for the perpendicular needling, while the oblique needling risk angle was (14.89±2.18)° for the female. The perpendicular needling risk angles for the males and females in the AAD group were larger than those in the normal group, and the differences were statistically significant (bothP<0.01); for the inner-group comparison, there was no significant difference in the perpendicular needling risk angle between the male and the female in the AAD group (P>0.05); however, the perpendicular needling risk angle for the male was larger than the female, and the difference was statistically significant in the normal group (P<0.01). There were no significant differences in the relative safety angle for both the male and the female between the AAD group and the normal group (bothP>0.05). For the inner-group comparison, there was no significant difference in the relative safety angle between the male and the female (P>0.05). The oblique needling risk angles for both the males and females were smaller in the AAD group than those in the normal group, and the differences were statistically significant (bothP<0.01); the oblique needling risk angle for the male was not significantly different from that for the female in the AAD group (P>0.05); in the normal group, the oblique needling risk angle for the male was larger than that for the female, and the difference was statistically significant (P<0.01). Conclusion: Under the AAD condition, the risk angle and safety angle of acupuncture at Yamen (GV 15) change significantly, perpendicular needling should be better if performed slightly lower than the horizontal direction, and the oblique needling should be safer across the occipital foramen toward the occipital bone.

Manual reduction combined with percutaneous vertebroplasty for the treatment of osteoporotic vertebral compression fractures with intravertebral clefts / 中国骨伤

OBJECTIVE@#To explore the therapeutic efficacy of manual reduction combined with percutaneous vertebroplasty in treating osteoporotic vertebral compression fractures(OVCFs) with intravertebral clefts.@*METHODS@#The clinical data of 94 patients with osteoporotic vertebral compression fractures with intravertebral clefts treated from January 2014 to January 2017 were retrospectively analyzed. The patients were divided into group A and group B according to different operative methods. In group A, 45 patients were treated with unilateral approach PVP, including 17 males and 28 females, aged (75.35±11.82) years old, with a bone density T-value of (-4.28±0.65) g/cm³; in group B, 49 patients treated with manual reduction combined with unilateral approach PVP, including 19 males and 30 females, aged (76.79±9.64) years old, with a bone density T-value of (-4.33±0.72) g/cm³. The operation time, bone cement injection volume and postoperative complications of two groups were recorded. The VAS and ODI scores of two groups were analyzed respectively at 1, 12, 18 months after operation. Vertebral height and kyphosis Cobb angle of two groups were compared immediately after surgery and 12, 18 months after operation. The distribution of bone cement in the vertebral body was observed and its distribution excellent rate was calculated.@*RESULTS@#There was no significant difference in operation time between two groups. The amount of bone cement injection was(8.42±1.24) ml in group A and(9.19±1.09) ml in group B, and the difference between two groups was statistically significant(0.05), but group A was higher than group B at 12 and 18 months after operation (<0.05). The vertebral height and Cobb angle before surgery, immediately after surgery, and 12, 18 months after surgery in group A were(59.17±1.42)%, (85.95±2.19)%, (75.27±3.45)%, (68.34±2.24)% and(23.83±3.37)°, (15.26±2.61)°, (17.63±2.16)°, (19.46±2.54)°, and in group B were(59.31±1.87)%, (89.19±2.53)%, (88.62±2.51)%, (88.59±2.62)% and(24.72±3.78)°, (14.91±2.28)°, (15.48±2.55)°, (15.86±2.81)°. Vertebral height Immediately after surgery was greater in group B than in group A and Cobb angle in group B was smaller than in group A (<0.05). During follow-up, there was no significant change in vertebral height in group B, while vertebral body recollapse in group A(<0.05).@*CONCLUSIONS@#In the treatment of osteoporotic vertebral compression fractures with intravertebral clefts, the manual reduction combined with PVP is more effective than single PVP, which can effectively prevent vertebral body recollapse and improve the long-term efficacy of patients.

Meta Analysis of Risks of Cardiocerebral Vascular Events in Patients with Primary Biliary Cholangitis / 中国医学科学院学报

To systematically evaluate the risks of cardiocerebral vascular events in patients with primary biliary cholangitis(PBC). Methods We carried out a Meta analysis by RevMan 5.3 software to investigate literatureon the risk of cardiocerebral vascular events in patients with PBC and controls. Results Compared with non-PBC controls,PBC patients had significantly higher risk of coronary events(=1.56,=0.0002);however,the risk of cerebrovascular events showed no significant difference between these two groups(=1.01,=0.94).Subgroup analysis demonstrated a significantly lower risk of transient ischemic attack or carotid stenosis in PBC patients(=0.63,=0.03);however,there was no significant difference in the risk of stroke(=1.11,=0.40). Conclusion Patients with PBC have an increased risk of coronary events but may have a lower risk of transient ischemic attack or carotid stenosis.

Safety depth of acupuncture at Yamen (GV 15) in patients with atlantoaxial dislocation / 中国针灸

OBJECTIVE@#To explore and compare the safety depths of perpendicular and oblique acupuncture at Yamen (GV 15) in patients with atlantoaxial dislocation (AAD) and healthy volunteers.@*METHODS@#One bundred and seventy-seven patients with atlantoaxial dislocation were selected as an AAD group, and 207 patients without atlantoaxial dislocation and with normal anatomical structure were selected as a normal group. All participants were moderately sized. The MRI scanning of the cervical vertebra was performed, and the safety depth of perpendicular and oblique acupuncture at Yamen (GV 15) was calculated on the sagittal image.@*RESULTS@#In the AAD group, the safety depth of men was (45.33±5.17) mm for perpendicular acupuncture and (48.58±4.41) mm for oblique acupuncture; the safety depth of women was (44.17±7.80) mm for perpendicular acupuncture and (47.49±7.32) mm for oblique acupuncture. In the normal group, the safety depth of men was (47.72±5.06) mm for perpendicular acupuncture and (42.69±5.53) mm for oblique acupuncture; the safety depth of women was (44.63±5.85) mm for perpendicular acupuncture and (39.88±6.18) mm for oblique acupuncture. The safety depth of men and women for oblique acupuncture was longer than that for perpendicular acupuncture in the AAD group (0.05); the safety depth of perpendicular and oblique acupuncture for men was longer than that for women in the normal group (0.05), while the safety depth of oblique acupuncture in the AAD group was longer than that in the normal group (<0.01).@*CONCLUSION@#The safe depth of acupuncture at Yamen (GV 15) has significantly changed under AAD, so during the clinical acupuncture the needle insertion should be less than its safe depth.

Clinical study on spinal cord decompression combined with traditional Chinese medicine for the treatment of cervical spondylotic myelopathy / 中国骨伤

<p><b>OBJECTIVE</b>To compare the clinical effect between spinal card decompression combined with traditional Chinese medicine and simple spinal card decompression for cervical spondylotic myelopathy.</p><p><b>METHODS</b>From June 2012 to June 2015, 73 patients with cervical spondylotic myelopathy were treated, including 42 males and 31 females, aged from 29 to 73 years old with a mean of 50.9 years old. The patients were divided into the simple operation group (34 cases) and the operation combined with traditional Chinese medicine group(39 cases) according to the idea of themselves. The anterior discectomy or subtotal corpectomy with internal fixation or posterior simple open-door decompression with lateral mass screw fixation were performed in the patients. Among them, 39 cases were treated with traditional Chinese medicine after surgery. The Japanese orthopedic association (JOA) score of spinal cord function, the improvement rate of neural function, the neck dysfunction index (NDI) score and the governor vessel stasis syndrome score were compared between two groups preoperative and postoperative 1 week, 1 month and the final follow-up respectively. The internal fixation and the condition of spinal cord decompression were observed by CT, MRI and X-rays before and after operation.</p><p><b>RESULTS</b>All the operations were successful, no injuries such as dura mater, spinal cord and nerve root were found. All the wounds were healed without infection except one patient had a superficial infection. It was solved after intermittent debridement and anti-infective therapy. Hematoma occurred in 1 case, complicated with spinal cord compression, caused incomplete paralysis, and promptly performed the re-operation to remove the hematoma without any obvious sequelae. All the patients were followed up from 12 to 24 months, (14.6±0.8) months for simple operation group and (13.5±0.7) months for operation combined with traditional Chinese medicine group, and there was no significant difference(>0.05). The scores of JOA, NDI and the governor's vessel stasis syndrome in simple operation group were 8.31±3.15, 29.91±4.52, 6.58±1.31 before operation, and 10.21±2.58, 18.67±4.31, 8.24±1.18 one week after operation, and 11.38±2.85, 16.11±3.18, 8.91±2.11 one month after operation, and 12.21±3.12, 14.61±3.28, 9.12±1.56 at final follow-up, respectively; and in operation combined with traditional Chinese medicine group were 8.29±3.47, 30.83±4.14, 6.38±1.81before operation, and 10.48±2.39, 17.59±5.14, 8.33±1.57 one week after operation, and 12.14±3.12, 13.14±3.21, 9.55±2.49 one month after operation, and 13.85±3.34, 12.11±2.51, 10.33±1.95 at final follow-up, respectively. Postoperative JOA , NDI, and the governor vessel stasis syndrome score of two groups were significantly higher than preoperativee(<0.05). There was no significant difference in JOA, NDI, and the governor vessel stasis syndrome score between two groups one week after operation (>0.05). The above items in operation combined with traditional Chinese medicine group was better than that of simple operation group one month and final follow-up after operation (<0.05). The improvement rate of neural function in simple operation group was (67.59±10.78)%, and in operation combined traditional Chinese medicine group was (66.88±12.15)%, there was no significant difference between two groups(>0.05). There were no complications such as internal fixation failure or re-dislocation of atlas by postoperative CT, MRI and X-rays examination.</p><p><b>CONCLUSIONS</b>Spinal card decompression for the treatment of cervical spondylotic myelopathy can extend the spinal canal, relieve the compression of nerve, achieve the deoppilation of governor vessel, the regulation of qi and blood, the restore of Yangqi, combined with traditional Chinese medicine of activating blood removing stasis, warming yang and activating meridians, reinforcing liver benefiting kidney, which may obtain better clinical effect.</p>

Effects of decompression combined with electro-acupuncture on rat with acute severe upper cervical spinal cord compression injury / 中国骨伤

<p><b>OBJECTIVE</b>To explore the effect and underlying mechanism of decompression(DE)combined with Governor Vessel(GV)electro-acupuncture(EA) on rats with acute severe upper cervical spinal cord compression injury.</p><p><b>METHODS</b>Thirty SPF rats were randomly divided into 5 groups(control group A, B and experiment group C, D, E), 6 rats in each group. The model of acute severe upper cervical spinal cord compression injury were made by forcing a balloon catheter put in atlas pillow clearance. The group A was blank one, the group B put balloon catheter in atlas pillow clearance without forcing, and the group C, D, E sustained compressed for 48 h. The group C received electric acupuncture intervention, selecting the Baihui and Dazhui point, having the continuous wave and frequency of 2 Hz, with the treatment time of 15 min and continuous treatment for 14 d; the group D received methylprednisolone intervention, injected by caudal vein; the group E did not received any intervention again. The arterial blood and injured spinal cord tissue of all the rats were obtained after 14 days' treatment, and BBB score was used to evaluate the change of each group hind limbs motor function, the contents of platelet activating factor(PAF) in injured spinal cord tissue and blood serum were assess by ELISA method; the Caspase-9 expression for each group after 14 days' treatment was assess by Western blot method.</p><p><b>RESULTS</b>BBB scores were(21.000±0.000) points at the 6 time points, that was, 1 h, 48 h after forcing in control group, 24 h, 3 d, 7 d, 14 d after treating in experiment group; the score of experimental groups (group C, D, E) were always lower than control groups(group A, B); compared with group E, group C and D were significantly higher(<0.05); and there was no significant difference between group C and group D(>0.05). The results of PAF by ELISA method to measure:the concentration of serum PAF, there was no statistical difference among group A, B, D, E (>0.05), group C was lower than the other groups (<0.05); the concentration of tissue PAF, there was no significant difference between group A and group B(>0.05), group D was significantly higher than that of group A, B, and C(<0.05), group E was the highest one than that of the other groups(<0.05). Western blot med tests showed that the Caspase-9 protein expression in group A and B was similar (>0.05), group C was higher than that of group A and B(<0.05), group D was higher than group A, B and C(<0.05), group E was the highest than that of group A, B, C and D (<0.05).</p><p><b>CONCLUSIONS</b>Decompression and Governor Vessel electro-acupuncture on acute severe upper cervical spinal cord compression injury had a better effect compare with decompression and methylprednisolone or simple decompression only, its mechanism may be related to lower the PAF levels and downregulating Caspase-9 protein expression in spinal injury tissue.</p>

Effect of Buyanghuanwu decoction on the expression of platelet activating factor after acute spinal cord injury in rats / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the effect and mechanism of Buyanghuanwu decoction on platelet activating factor expression in spinal cord tissue of model of acute upper cervical spinal cord injury in rats.</p><p><b>METHODS</b>Sixty SPF grade 3-month-old female Wistar rats were randomly divided into sham operation group, model group, methylprednisolone group and Buyanghuanwu decoction (Traditional Chinese Medicine group, TCM), with 15 rats in each group. The first day after the modeling, the methylprednisolone group were treated by injection of the tail vein for a total of 24 h, the first dose of 30 mg/kg, followed by a dose of 5.4 mg/kg·h, and 1 time per 4 h. The traditional Chinese medicine group was prepared with a medium dose of Buyanghuanwu decoction granules which were prepared into a solution containing 2 g/ml of granules, 3.5 g/kg per day gavage, was equivalent to 1 time the amount of adult consumption. The model group and the sham operation group were given equal volume of normal saline for 2 times a day for 2 weeks. The recovery of nerve function was evaluated by BBB classification at 1, 3, 7, 14 days after treatment. The expression of PAF in the segment of spinal cord injury was detected by double antibody sandwich (ELISA) method at 1, 7, and 14 d postoperatively.</p><p><b>RESULTS</b>At the first day after treatment, BBB score in model, TCM and methylprednisolone groups were lower than that of sham operation group(<0.01), but there was no difference among the three groups(>0.05). At 7, 14 days afer treatment, BBB score in TCM and methylprednisolone groups were higher than that of model group significantly(<0.01); but there were no significant difference between TCM group and methylprednisolone group(>0.05). PAF expression in TCM group and methylprednisolone group were lower than that of model group at 7, 14 day afer treatment significantly (<0.05); but there were no significant difference between TCM group and methylprednisolone group (>0.05).</p><p><b>CONCLUSIONS</b>Buyanghuanwu decoction treatment after acute upper cervical spinal cord injury can significantly improve locomotor recovery by inhibiting the expression of PAF.</p>

Synthesis and biological evaluation of novel tricyclic matrinic derivatives as potential anti-filovirus agents

Twenty-six novel tricyclic sophoridinic and matrinic derivatives containing a common chlorinated benzene fragment were designed, synthesized and evaluated for their anti-ebolavirus (EBOV) activities. Structure-activity relationship analysis indicated: (i) 12-dichlorobenzyl motif was beneficial for the activity; (ii) the chiral configuration at C5 atom might not affect the activity much. Among the target compounds, compound exhibited the most potent potency against EBOV with an IC value of 5.29 μmol/L and an SI value of over 37.8. Further anti-EBOV assay of identified its high effectiveness, and anti-MARV assay of suggested its inspiring broad-spectrum anti-filovirus activity. The results provided powerful information on further strategic optimization and development of this kind of compounds against filoviruses.