Effectiveness and Safety of Different Postoperative Adjuvant Regimens in Patients with Low-Grade Gliomas: A Network Meta-Analysis.

OBJECTIVE: This study aimed to investigate the effectiveness and safety of various adjuvant regimens in patients with low-grade gliomas and to further explore the optimal adjuvant treatment for patients with low-grade gliomas and the differences in the efficacy of each treatment regimens in different tumor types. METHODS: A comprehensive search of the PubMed, Cochrane Library, Ovid, Embase, and Web of Science databases was conducted to screen randomized and nonrandomized controlled trials related to adjuvant therapy in patients with low-grade gliomas. The Cochrane quality assessment method and the Newcastle-Ottawa Scale were used to assess the quality of the included randomized and nonrandomized controlled trials, respectively. The data from previous studies were extracted using Excel and GetData Graph Digitizer 2.26 software, and network meta-analysis was performed using RevMan 5.3 and Stata 16.0 statistical software. RESULTS: The specific ranking of 5-year progression-free survival (5-year PFS) for each treatment regimen from the best to the worst in patients with low-grade gliomas was surgery (S) combined with procarbazine, lomustine, and vincristine (S + PCV); surgery combined with standard radiotherapy and PCV multidrug chemotherapy (S + RT + PCV); surgery combined with standard radiotherapy and temozolomide monotherapy (S + RT + TMZ); surgery combined with enhanced radiotherapy (S + H-RT); surgery combined with standard radiotherapy (S + RT); surgery combined with TMZ (S + TMZ); and S. The 5-year overall survival (OS) ranking was S + RT + TMZ, S + RT + PCV, surgery combined with enhanced radiotherapy and TMZ monotherapy (S + H-RT + TMZ), S + H-RT, S + RT, and S. The 2-year progression-free survival ranking was S + RT + TMZ, S + PCV, S + RT, S + RT + PCV, S + TMZ, S + H-RT, and S. The 2-year overall survival ranking was S + RT + TMZ, S + H-RT + TMZ, S + RT, S + RT + PCV, S + H-RT, and S. The incidence of adverse events (≥3) was ranked from highest to lowest as follows: S + RT + PCV, S + RT + TMZ, S + PCV, S + H-RT, S + TMZ, and S + RT. In the isocitrate dehydrogenase 1/2 mutation nonchromosome 1p and 19q chromosome whole arm codeletion (IDHmt/noncoder) group, the S + RT + PCV and S + H-RT regimens had better 5-year PFS and 5-year OS. In the isocitrate dehydrogenase 1/2 mutation and chromosome 1p and 19q chromosome whole arm codeletion (IDHmt/coder) group, the 5-year PFS of each treatment regimen ranked from the best to the worst was S + RT + TMZ, S + RT + PCV, S + H-RT, S + RT, S + TMZ, and S. The order of 5-year OS from the best to the worst was S + H-RT, S + RT + TMZ, S + RT + PCV, S + RT, and S. In the isocitrate dehydrogenase 1/2 wild-type (IDHwt) group, the S + H-RT and S + TMZ regimens had better 5-year PFS. CONCLUSIONS: This study revealed that both the S + RT + TMZ and S + RT + PCV regimens might be effective therapies for treating patients with low-grade gliomas. Among these, the S + RT + TMZ regimen seemed to be safer but might lead to tumor deterioration. In the IDHmt/coder type, the S + RT + TMZ scheme might have a significant advantage. In the IDHmt/noncoder type, the S + RT + PCV scheme might be more dominant, while in the IDHwt type, the S + H-RT and S + TMZ schemes also might be good treatment options.

Effect Western Medicines Combined With Nao-Xue-Shu in Patients With Hypertensive Intracerebral Hemorrhage: A Network Meta-Analysis.

Purpose: To explore the efficacy of nimodipine, nifedipine, and edaravone (EDA) combined with Nao-Xue-Shu in patients with hypertensive intracerebral hemorrhage (HICH) and to determine the best western medicine combined with Nao-Xue-Shu for treating HICH patients using a ranking method. Methods: After a comprehensive search of the China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP information database, Chinese Biomedical Database (CBM), PubMed, Embase, and Cochrane Library database from the database establishment 31 December 2021, data extraction and quality assessment were conducted for the included articles. The primary outcome measure was the effectiveness after treatment. Secondary outcome measures were after-treatment the National Institutes of Health Stroke Scale (NIHSS) scores, hematoma volume, perihematoma edema volume, and inflammatory factor expression levels. Statistical analyses were performed using Stata 16.0 and RevMan 5.3.0 software. Results: We included 19 randomized controlled trials (RCTs) and six non-RCTs. The effective rate after treatment was ranked from the best to the worst as follows: routine cure measure (RCM) + nifedipine + Nao-Xue-Shu, RCM + EDA + Nao-Xue-Shu, RCM + Nao-Xue-Shu, RCM + nimodipine + Nao-Xue-Shu, RCM + EDA, and RCM. The post-treatment NHISS scores from lowest to highest were as follows: RCM + EDA + Nao-Xue-Shu, RCM + nifedipine + Nao-Xue-Shu, RCM + EDA, RCM + nimodipine + Nao-Xue-Shu, RCM + Nao-Xue-Shu, RCM + Nao-Xue-Kang, and RCM. The post-treatment hematoma volume from minimum to maximum was as follows: RCM + EDA + Nao-Xue-Shu, RCM + nimodipine + Nao-Xue-Shu, RCM + nifedipine + Nao-Xue-Shu, RCM + Nao-Xue-Shu, RCM + Nao-Xue-Kang, and RCM. The post-treatment perihematoma edema volume from minimum to maximum was as follows: RCM + EDA + Nao-Xue-Shu, RCM + nifedipine + Nao-Xue-Shu, RCM + nimodipine + Nao-Xue-Shu, RCM + Nao-Xue-Shu, and RCM. For inflammatory factor expression levels after treatment, IL-6 concentration levels after treatment from lowest to highest wasas follows: RCM + Nao-Xue-Shu, RCM + nifedipine + Nao-Xue-Shu, RCM + nimodipine + Nao-Xue-Shu, RCM + EDA + Nao-Xue-Shu, and RCM. TNF-α concentration levels after treatment from lowest to highest was as follow: RCM + nimodipine + Nao-Xue-Shu, RCM + nifedipine + Nao-Xue-Shu, RCM + Nao-Xue-Shu, and RCM. Conclusion: Nao-Xue-Shu combined with nifedipine showed better effectiveness after treatment in HICH patients compared with the other combinations. Nao-Xue-Shu combined with EDA was more effective for improving neurological function and reducing both hematoma and edema volumes around the hematoma compared with the other combinations. However, Nao-Xue-Shu alone or Nao-Xue-Shu combined with nimodipine may be more effective for reducing proinflammatory factor expression.

Efficacy and safety of different drug treatments in patients with spinal-cord injury-related neuropathic pain: a network meta-analysis.

STUDY DESIGN: Systematic review with network meta-analysis. OBJECTIVE: We explored the efficacy and safety of different drug treatments in patients with spinal-cord injury (SCI)-related neuropathic pain. We investigated which treatment is most suitable for such patients by judging the efficacy and safety of these drugs. METHODS: We searched the PubMed, Medline, Embase and Cochrane databases from inception to 31 August 2020. The quality of the included studies was assessed. We selected the proportion of patients whose pain was reduced by ≥50% and the prevalence of adverse effects as the outcome indicators of efficacy and safety, respectively. RESULTS: We included 15 randomized controlled clinical trials involving five interventions (anticonvulsants, antidepressants, anesthetics, opioids and botulinum toxin A). Based on the proportion of patients with pain reduction ≥50%, the order (from highest to lowest) was anticonvulsants > anesthetics > antidepressants > botulinum toxin A > opioids > placebo. With regard to the prevalence of adverse effects, the order of safety (from highest to lowest) was placebo > antidepressants > botulinum toxin A > anticonvulsants > opioids > anesthetics. Analyzes of efficacy and safety revealed that anticonvulsant, antidepressant and botulinum toxin A have good efficacy and safety. CONCLUSION: The efficacy of anticonvulsants, anesthetics, antidepressants, opioids and botulinum toxin A was greater than that of placebo for treatment of SCI-related neuropathic pain. However, the prevalence of adverse effects associated with use of these drugs was also higher than that of placebo. Further analyses based on efficacy and safety revealed anticonvulsants to be more suitable for such patients. In addition, antidepressant and botulinum toxin A may be promising treatments for SCI-related neuropathic pain, however, their effects still need to be further explored due to the small sample size.

Efficacy and Safety of Bevacizumab Combined with Other Therapeutic Regimens for Treatment of Recurrent Glioblastoma: A Network Meta-analysis.

BACKGROUND: Despite the fact that bevacizumab (Bev) has been approved to treat recurrent glioblastoma, patients have failed to demonstrate a significant overall survival (OS) advantage. In recent years, the advent of more Bev combination regimens seems to bring new hope for patients; nevertheless, there is still a lack of intuitive comparison among these therapies. OBJECTIVE: To explore the efficacy and safety of various Bev combination regimens in patients with recurrent glioblastoma and to further explore the differences in the efficacy of each treatment in randomized controlled trials (RCTs) and nonrandomized controlled trials (non-RCTs). METHODS: We comprehensively searched the PubMed, Cochrane Library, and OVID databases for relevant RCTs and non-RCTs of Bev in combined regimens for recurrent glioblastoma. The Cochrane quality assessment method was used to assess the quality of RCTs, and the Newcastle-Ottawa scale was used to assess the quality of non-RCTs. Excel software was used to extract data from the literature, and a network meta-analysis was performed using RevMan 5.3 and Stata 16 statistical software. RESULTS: In patients with recurrent glioblastoma, the 6-month OS of patients receiving bevacizumab combination therapy was ranked from high to low as follows: Bev + rindopepimut, Bev + lomustine (CCNU), CCNU, tumor treating fields + Bev, Bev, Bev + irinotecan (Iri), Bev + temozolomide (TMZ), Bev + vorinostat, Bev + onartuzumab, Bev + dasatinib, Bev + carboplatin, Bev + trebananib, Bev + VB-111, TMZ, PCV, VB-111, and carboplatin. The 6-month progression-free survival from high to low was ranked as follows: Bev + CCNU, Bev + rindopepimut, Bev + dasatinib, Bev + vorinostat, Bev, Bev + Iri, Bev + TMZ, CCNU, Bev + carboplatin, TMZ, Bev + VB-111, PCV, Bev + trebananib, carboplatin, and VB-111. We compared the total incidence of serious adverse events (≥3) and found that Bev + vorinostat and Bev + trebananib were safer than Bev, while other regimens were not as safe as Bev. A descriptive analysis showed that Bev + rindopepimut also appeared to be safer than Bev. In subgroup analysis, among RCTs, Bev + CCNU therapy had the highest 6-month OS and 6-month progression-free survival. Among non-RCTs, Bev + Iri therapy showed the highest 6-month OS and good 6-month progression-free survival. CONCLUSIONS: Both Bev + CCNU and Bev + rindopepimut could be considered as effective therapies for treating the recurrent glioblastoma according to the network meta-analysis results. Among them, Bev + rindopepimut therapy seems to be safer and more effective. Moreover, we found that Bev + Iri also appeared to be an effective therapy in a retrospective study.

Research progress in functional dyspepsia relevant to traditional Chinese medicine based on the theory of brain-gut axis / 中南大学学报(医学版)

The incidence of functional dyspepsia (FD) is closely related to the dysfunction of brain-gut axis (BGA). Brain gut peptide (BGP) is expressed in the brain and gastrointestinal tract, which is important factor involved in BGA. FD is in the category of "stomach cramps" and "small full" in traditional Chinese medicine (TCM). TCM believes that the brain and intestines are closely connected to each other and form a brain-gut interaction. Therefore, the intestinal function is regulated by the brain, which is consistent with the BGA theory of western medicine. Researchers for TCM verified that the clinical symptoms of FD could be alleviated by regulating BGP and/or BGA through experimental research, clinical prescription therapy, and clinical non-drug therapy. Although TCM has a unique therapeutic effect on the treatment of FD, it has not yet to verify that TCM exerts significant clinical efficacy on FD, which still requires high-quality evidence-based medical evidence verification.

Effect of human umbilical cord mesenchymal stem cells on CD4+T cells in liver after hepatic ischemia-reperfusion injury in mice / 器官移植

Objective To investigate the effect of human umbilical cord mesenchymal stem cells (HUC-MSCs) on CD4+T cells in liver after hepatic ischemia-reperfusion injury (HIRI) in mice. Methods Two hundred and twenty-five mice were randomly divided into sham group, control group and MSC group, with 75 mice in each group. HIRI model mice were used in MSC group and control group. HUC-MSCs were injected in MSC group through inferior vena cava. Normal saline was injected in control group through inferior vena cava. Only laparotomy and abdominal closure were performed in sham group without blood vessel clipping. At 6, 12 and 24 h after operation, 15 mice of each group were randomly selected to sample eyeball blood and liver tissues, and the 30 mice left in each group were used to extract intrahepatic mononuclear cells. The number of intrahepatic mononuclear cells, percentage, number and positive rate of CD4+T cells in the mice of various groups at different time points were compared. The content of interleukin (IL)-17 in serum and liver tissue as well as expression levels of costimulatory molecules B7-1 and B7-2 messenger RNA (mRNA) in liver tissues of the mice at different time points were compared. Results At 12 and 24 h after operation, the number of intrahepatic mononuclear cells of control group was significantly higher than that of sham group, while the number of intrahepatic mononuclear cells of MSC group was significantly lower than that of control group (P<0.01-0.05). At 6, 12 and 24 h after operation, the percentage, number and positive rate of CD4+T cells of control group were significantly higher than those of sham group (all P<0.01), while the percentage of CD4+T cells of MSC group was significantly lower than that of control group (P<0.01-0.05). At 12 and 24 h after operation, the number and positive rate of CD4+T cells of MSC group were significantly lower than those of control group (P<0.01-0.05). At 6, 12 and 24 h after operation, the IL-17 contents in serum and liver tissues of control group were higher than those of sham group (all P<0.01), while the IL-17 contents in serum and liver tissues of MSC group were lower than those of control group (all P<0.01). At 6 h after operation, the mRNA expression level of B7-2 of control group was higher than that of sham group (P<0.05). At 12 and 24 h after operation, the mRNA expression levels of B7-1 and B7-2 of control group were higher than those of sham group (all P<0.01), while the mRNA expression levels of B7-1 and B7-2 of MSC group were lower than those of control group (all P<0.01). Conclusions HUC-MSCs inhibits the number of CD4+T cells and the secretion of IL-17 in liver after HIRI, as well as decreases the number of intrahepatic mononuclear cells and the mRNA expression of B7-1 and B7-2, thereby alleviating HIRI.

Effects of nitric oxide and cholecystokinin on the sphincter of Oddi of dogs / 中华消化外科杂志

Objective To investigate the effects of nitric oxide (NO) and cholecystokinin (CCK) on the regulation of the motility of sphincter of Oddi (SO).Methods The basal pressure,action rate and contraction range of the SO were examined before and after the injection of CCK,sodium nitroprusside (SNP) and NG-nitroL-argininemethyl ester hydrochloride (L-NAME).The expression of neurons with positive expression of NO synthase was detected by immunohistochemical staining.The measurement data were analyzed by using the t test.Results The basal pressure,contraction rate and contraction range of the SO were (27 + 10)mm Hg (1 mm Hg =0.133 kPa),( 10 ± 3 ) times/minute and (32 + 8 ) mm Hg before injection of CCK,and (61 + 14) mm Hg,(64 +21 ) times/minute,(44 ± 15 ) mm Hg after injection of CCK of 20 ng/kg.After injection of CCK of 100 ng/kg,the basal pressure,contraction range and contraction rate of the SO were (77 ± 31 )mm Hg,(69 ± 18 ) times/minutes,(79 + 14) mm Hg when the inhibition effect of CCK reached peak,and were ( 140 ± 21 ) mm Hg,( 129 ± 25 )times/minutes,( 173 ± 63 ) mm Hg when the excitatory effect of CCK reached peak.After injection of SNP into the common bile duct,the basal pressure,contraction range and contraction rate of the SO decreased significantly ( t =3.706,5.183,P ＜ 0.05),while the 3 indexes increased significantly after injection of SNP (t =5.859,3.588,P ＜O.05).Conclusion Different from physiological dose (20 ng/kg) of CCK,large dose of CCK enhances motility of SO intensively.NO relaxes SO,which may play an important role in the inhibitor pathway of CCK.