Valproic acid can reduce the frequency of seizures through various mechanisms and is widely used in clinical practice as a monotherapy or adjunctive treatment for various types of epilepsy and epileptic syndromes. In addition, valproic acid has significant therapeutic effects on comorbidities associated with epilepsy, such as migraines and psychiatric disorders. It can also be effective in terminating status epilepticus and is commonly used as a broad-spectrum antieseizure medication in clinical settings. However, valproic acid has side effects such as teratogenicity, infertility, and menstrual disorders. Additionally, when used in combination with other drugs, the interactions between medications should be carefully considered. Therefore, in clinical practice, it is necessary to strictly adhere to the indications and dosage regimens for the use of valproic acid. This article provides a comprehensive review of the use of valproic acid in different types of seizures, epileptic syndromes, comorbidities associated with epilepsy, post-craniotomy cases, status epilepticus, and special populations. It also summarizes the combination therapy of valproic acid with other drugs, providing a basis for the rational use of valproic acid and individualized drug treatment selection for epilepsy patients.
目的:评价双醋瑞因联合玻璃酸钠治疗骨关节炎的临床疗效。方法:采用回顾性临床对照研究方案设计,65例膝骨关节炎患者应用关节腔内注射玻璃酸钠治疗为对照组,69例膝骨关节炎患者在玻璃酸钠基础治疗的同时合用双醋瑞因6个月作为联合治疗组,通过VAS评分、WOMAC评分、ESR和CRP在治疗前、治疗后1个月、3个月和后3个月3个时段四个时间断面的病情改变作为疗效判断指标。结果:与治疗前相比,两组的关节触痛、20米步行痛评分、WOMAC评分、ESR和CRP有明显改善(Plt;0.001);在治疗后的3个月,各个观察指标联合治疗组明显优于对照组(χ2=5.256,Plt;0.05);在治疗后的第2、3个月和治疗后的后3个月两个时段,应用NSAIDs的患者例数上,联合治疗组明显少于对照组(P=0.022;χ2=10.428,P=0.001),在治疗初的1个月内两组无差异(χ2=0.137,P=0.711),并且未发生严重不良事件。结论:双醋瑞因和玻璃酸钠二者对骨关节炎治疗都有临床疗效;在对OA采用玻璃酸钠治疗的基础上,同时合用和维持治疗,临床疗效更持久有效,值得临床推广。
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, with insidious onset, insensitive to chemotherapy and poor prognosis, which make its clinical treatment face an enormous challenge. In recent years, with the rapid development of nanotechnology, increasing kinds of nanomedicine come to the forefront in biomedical fields. Through rational design, nanomedicine can be prepared in suitable size and modified with specific liver targeting ligands. Moreover, various therapeutic agents of different mechanisms can be co-loaded into the same nanosystem, thus achieving the synergistic therapeutic effects towards HCC. Nanomedicine is able to enhance drug bioavailability and liver-targeting effect as well as reduce the side effects to normal tissues, which provide a great potential in HCC therapy. This review summarizes the recent progress in the application of nanomedicine for HCC therapy from two aspects: their liver-targeting design strategies and the recent progress in combination therapy of HCC.
目的 比较拉米夫定+阿德福韦酯联合治疗与阿德福韦酯单药治疗对阿德福韦酯停药后出现病毒学反弹而无基因型耐药变异患者的疗效及安全性。 方法 回顾研究2007年1月－2012年1月在传染科门诊就诊的67例阿德福韦酯治疗获得病毒学应答但停药后出现病毒学反弹的e抗原阳性慢性乙型肝炎患者，分别给予拉米夫定+阿德福韦酯联合治疗（联合组，n=35）和阿德福韦酯单药治疗（单药组，n=32）。 结果 治疗1年后，联合组（32例，85.7%）较单药组（21例，65.6%）有更多的患者重新获得了丙氨酸转氨酶复常（P=0.009），联合组34例（97.1%）乙型肝炎病毒DNA阴转，单药组22例（68.8%）阴转，两组差异有统计学意义（P=0.002）；在血清学转换方面，联合组和单药组分别有4例（11.4%）和1例（3.1%）患者获得了e抗原的血清学转换。在治疗中所有患者均未发生任何严重不良反应。 结论 阿德福韦酯停药后出现病毒学反弹，选择拉米夫定与阿德福韦酯联合治疗可使患者重新获得较好的生化学和病毒学应答。
ObjectiveTo observe the short-term efficacy and safety of a new strategy of dexamethasone intravitreal implant (DEX) combined with ranibizumab in the treatment of retinal vein occlusion (RVO) secondary to macular edema (ME) (RVO-ME). MethodsA prospective clinical interventional study. From May 2020 to September 2021, 78 RVO-ME patients with 78 eyes diagnosed in the eye examination of Department of Ophthalmology of The First Affiliated Hospital of Anhui University of Science&Technology were included in the study. Among them, there were 35 males and 43 females, all with monocular disease. Branch retinal vein occlusion (BRVO) was found in 40 patients with 40 eyes; central retinal vein occlusion (CRVO) was found in 38 patients with 38 eyes. According to the treatment strategies, patients were randomly divided into DEX and ranibizumab combination therapy group (initial combination therapy group), DEX monotherapy group and ranibizumab monotherapy group, with 29 eyes, 26 eyes and 23 eyes respectively. Different types of RVO were divided into different treatment groups of BRVO and CRVO. Best corrected visual acuity (BCVA) and frequency domain optical coherence tomography were performed. The BCVA examination was carried out using the international standard visual acuity chart, which was converted into the logarithmic minimum angle of resolution (logMAR) visual acuity during statistics. There were no significant differences in logMAR BCVA (χ2=2.376) and central retinal thickness (CRT) (F=0.052) among the three groups (P＞0.05). After treatment, the patients were followed up every month for 6 months. The changes of BCVA, CRT and the incidence of adverse reactions were observed during follow-up. One-way ANOVA and Kruskal-Wallis H test were used to compare the differences. ResultsDuring the follow-up period, compared with the baseline, the BCVA of the eyes in the initial combination treatment group, DEX treatment group and ranibizumab treatment group were significantly improved (Z=110.970, 90.359, 207.303), and CRT was significantly decreased (F=107.172, 88.418, 61.040), the difference was statistically significant (P＜0.01). At 1, 2, 3, 4, 5, and 6 months after treatment, there were significant differences in the mean changes in BCVA between the initial combined treatment group, DEX treatment group, and ranibizumab treatment group (χ2=34.522, 29.570, 14.199, 7.000, 6.434, 6.880; P＜0.05); 1, 2, 3, and 6 months after treatment, the differences were statistically significant (F=4.313, 7.520, 3.699, 3.152; P＜0.05). The time required to improve BCVA by 0.1 logMAR units in the initial combination treatment group, DEX treatment group, and ranibizumab treatment group was 5.73 (3.21, 8.48), 9.97 (6.29, 18.78), and 20.00 (9.41, 37.89) d, respectively; The time required for CRT to drop to 300 μm was 24.31 (21.32, 26.15), 29.42 (25.65, 31.37), and 29.17 (25.28, 36.94) d, respectively. The BCVA improvement of 0.1 logMAR unit and the time required for CRT to decrease to 300 μm in the eyes of initial combined treatment group were shorter than those in the eyes of DEX treatment group and the ranibizumab treatment group, and the differences were statistically significant (Z=－3.533, －4.445, －3.670, －4.030; P＜0.01). Different BRVO treatment groups: 1, 2, 3, 5, and 6 months after treatment, the mean BCVA changes were significantly different (χ2=24.989, 21.652, 11.627, 7.054, 9.698; P＜0.05); CRVO was different treatment group: 1 and 2 months after treatment, there were significant differences in mean BCVA changes (χ2=11.137, 9.746; P＜0.05). Two months after treatment, there were significant differences in CRT changes between BRVO and CRVO groups with different treatment regimens (F=3.960, 3.722; P＜0.01). The time required to improve BCVA by 0.1 logMAR unit in the eyes of BRVO and CRVO combined treatment group was shorter than that in the eyes of BRVO, CRVO DEX treatment group and the BRVO, CRVO ranibizumab treatment group, and the differences were statistically significant (BRVO: Z=－2.687, －3.877; P＜0.05; CRVO: Z=－2.437, －3.575; P＜0.05). The time required for CRT to drop to 300 μm in the CRVO combined treatment group was significantly shorter than that in the CRVO DEX treatment group and the CRVO ranibizumab treatment group, and the difference was statistically significant (F=6.910, P＜0.010); there was no statistically significant difference between the different BRVO treatment groups (F=1.786, P＞0.05). The number of re-treated eyes in the initial combined treatment group and DEX treatment group was less than that in the ranibizumab treatment group, and the difference was statistically significant (χ2=18.330, 7.224; P＜0.05). The retreatment interval of the eyes in the initial combined treatment group was significantly longer than that in the DEX treatment group and the ranibizumab treatment group, and the difference was statistically significant (P＜0.01). There was no significant difference in the incidence of intraocular hypertension among the initial combined treatment group, DEX treatment group and ranibizumab treatment group (χ2=0.058, P＞0.05). ConclusionsThe new strategy of initial combination therapy with DEX and ranibizumab in the treatment of RVO-ME has a better short-term effect. Compared with the monotherapy group, the retreatment interval is shorter, the visual and anatomical benefits are faster, the efficacy lasts longer, and the safety is better.
We correct some misunderstandings of hypertension therapy and update the knowledge of hypertensive drugs by reviewing the progress of evidence-based research of hypertension in 2004.
Objective To evaluate the effectiveness of PTD regimen (pamidronate disodium + thalidomide + dexamethasone) and TD regimen (thalidomide + dexamethasone) in the treatment of multiple myeloma. Methods The patients meeting the inclusion criteria were randomly treated with PTD and TD regimens from January 2004 to December 2008. The effectiveness and safety of the two groups were observed after 8 weeks and the statistical analyses were performed using SPSS 13.0 software. Results A total of 25 patients were included, of which 13 were treated with PTD regimen and the other 12 were treated with TD regimen. The results showed overall response rates were 84.6% and 83.3% in the PTD and TD groups, respectively, with no significant difference (Pgt;0.05). The complete response rate (5/13 vs. 1/12) and early response rate (within 2 weeks, 4/13 vs. 1/12) for bone pain in the PTD group were better than those of TD group (Plt;0.05). Conclusion Compared with TD regimen, PTD regimen has more dramatic and faster effects on bone pain relief for multiple myeloma, but for overall response rate, further larger sample size randomized controlled trials are needed.
ObjectiveTo systematically evaluate the efficacy of steroids combined with antiepileptic drugs compared with alone antiepileptic drugs in the treatment of children with epileptic electrical status during sleep to provide evidence-based medical basis for its treatment.MethodsElectronic searches were maded in PubMed, Embase database, Cochrane Library, CNKI, Wanfang and the Chinese biomedical literature database for the literature about steroids combined with antiepileptic drugs compared with alone antiepileptic drugs in the treatment, and retrieval time is from January 1990 to October 2020. Two evaluators independently screened literature, extracted data, evaluated literature quality and risk of bias and checked each other. Meta analysis was performed by stata16.0 software.ResultsA total of 679 children with ESES were included in 10 studies, including 9 randomized controlled trials and 1 retrospective cohort study. Meta analysis results showed that there were statistically significant differences in clinical improvement rate [RR=1.31, 95%CI (1.21, 1.42), P<0.01], electroencephalogram discharge improvement rate [RR=1.35, 95%CI (1.25, 1.46), P<0.01] and cognitive intelligence score [SMD=1.19, 95%CI (0.80, 1.57), P<0.01] between steroids combined with antiepileptic drugs group and alone antiepileptic drugs group after 6 months follow-up. The incidence of adverse reactions in steroids combined with antiepileptic drugs group was higher than that in alone antiepileptic drugs group, and the difference was statistically significant [RR=4.13, 95%CI (1.06, 16.13), P<0.01]. All adverse reactions improved or disappeared after drug withdrawal.ConclusionCompared with alone antiepileptic drugs, steroids combined with antiepileptic drugs group has advantages in controlling epileptic seizures, improving electroencephalogram abnormalities and improving cognitive ability, and it is relatively safe.
ObjectiveTo observe the long-term effects of anti-vascular endothelial growth factor (VEGF) drug initiation combined with dexamethasone intravitreal implant (DEX) on the structural integrity of the outer macular region of the eye in patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO). MethodsA retrospective clinical study. From February 2018 to August 2022, 54 patients diagnosed with CRVO combined with ME (CRVO-ME) in Department of Ophthalmology of Central Theater Command General Hospital were included in the study. Among them, there were 30 males and 24 females, all with monocular disease. According to different treatment regiments, patients were divided into anti-VEGF and DEX combination therapy group (initial combination group), anti-VEGF drug monotherapy group (monotherapy group) with 21 eyes and 33 eyes, respectively. Best corrected visual acuity (BCVA), optical coherence tomography (OCT) examination were performed in all eyes. The thickness of foveal retina (CRT) and the deficiency length of outer membrane (ELM), ellipsoid band (EZ) and chimaera band (IZ) in the 1 mm macular area were measured by OCT. The initiating combination group was treated with anti-VEGF agents or DEX as assessed on demand (PRN) after the combination therapy, and the monotherapy group received 3+PRN regimen. Relevant examinations were performed at 1 (V1), 6 (V6), 12 (V12) months and observation cut-off or the last visit (Vf) after treatment using the same equipment before treatment. The deletion length of ELM, EZ and IZ in V1, V6, V12 and Vf after treatment were compared between the two groups. Repeated measurement ANOVA was used to compare BCVA, CRT and deletion length of ELM, EZ and IZ at different follow-up times. Spearman rank correlation test was used to analyze the correlation between the two groups of continuous variables. ResultsThe follow-up time of patients in the initial combination group and monotherapy group was (18.05±5.66) and (21.90±10.80) months, respectively, with no statistical significance (F=13.430, P=0.229). Compared with baseline, the deletion lengths of ELM, EZ and IZ were significantly improved (F=11.848, 10.880, 29.236), BCVA was increased (F=10.541) and CRT was decreased (F=52.278) in the initial combination group and the monotherapy group at different follow-up times after treatment. The differences were statistically significant (P＜0.001). At V1, EZ and IZ deletion lengths were (344.10±413.03), (593.33±372.96) μm and (354.71±321.75), (604.85±385.77) μm in the initial combination group and monotherapy group, respectively. The improvement of EZ and IZ deletion lengths in the initial combination group was better than that in the single drug group, and the difference was statistically significant (F=5.272, 6.106; P=0.026, 0.017). The CRT of the initial combination group and the monotherapy group were (248.86±59.99) and (314.72±214.91) μm, respectively, and the CRT of the initial combination group was significantly lower than that of the monotherapy group, with statistical significance (F=6.102, P=0.017). At V6, V12 and Vf, the deletion length of ELM, EZ and IZ and BCVA and CRT showed no statistical significance (P＞0.05). Correlation analysis showed that ELM, EZ, IZ were positively correlated with BCVA and CRT in the initial combination group and monotherapy group (P＜0.001). In V6, V12 and Vf, the number of anti-VEGF drug injections in the initial combination group and monotherapy group was (2.67±1.32), (4.43±2.27), (6.05±3.51), (4.58±0.90), (7.33±1.93), (11.33±6.10) times, respectively. The number of injections in the initial combination group was significantly lower than that in the monotherapy group, and the difference was statistically significant (F=5.150, 0.646, 3.433; P＜0.001). ConclusionsThe improvement of BCVA and CRT in the initial combination group is similar to that in the monotherapy group. Compared with the monotherapy group, EZ and IZ deletion are improved more significantly in the initial combination group, and CRT decreased more rapidly and significantly. The initial combination group receives fewer anti-VEGF injections than the monocular group.
Objective To summarize the effect of lenvatinib + transarterial chemoembolization (TACE) + programmed cell death protein-1 (PD-1) antibody in the treatment of hepatocellular carcinoma with main portal vein tumor thrombus and cavernous transformation. Methods In this study, we reported the clinical data of four patients with hepatocellular carcinoma with main portal vein tumor thrombus and cavernous transformation who received conversion therapy with lenvatinib combined with TACE and PD-1 antibody in West China Hospital. Results Among the four patients, two patients achieved complete response and two achieved partial response; tumor markers were significantly decreased after combination treatment. However, all four patients failed to undergo hepatectomy. ConclusionsLenvatinib + TACE + PD-1 antibody is effective for hepatocellular carcinoma with main portal vein tumor thrombus and cavernous transformation. However, there are still many problems worthy of further discussion.