OBJECTIVE: To evaluate the efficacy and safety of Cidan Capsule combined with adjuvant transarterial chemoembolization (TACE) in patients with a high risk of early recurrence after curative resection of hepatocellular carcinoma (HCC). METHODS: A multicenter, randomized controlled trial was conducted in patients with high-risk recurrence factors after curative resection of HCC from 9 medical centers between July 2014 and July 2018. Totally 249 patients were randomly assigned to TACE with or without Cidan Capsule administration groups by stratified block in a 1:1 ratio. Postoperative adjuvant TACE was given 4-5 weeks after hepatic resection in both groups. Additionally, 125 patients in the TACE plus Cidan group were administrated Cidan Capsule (0.27 g/capsule, 5 capsules every time, 4 times a day) for 6 months with a 24-month follow-up. Primary endpoints included disease-free survival (DFS) and tumor recurrence rate (TRR). Secondary endpoint was overall survival (OS). Any drug-related adverse events (AEs) were observed and recorded. RESULTS: As the data cutoff in July 9th, 2018, the median DFS was not reached in the TACE plus Cidan group and 234.0 days in the TACE group (hazard ratio, 0.420, 95% confidence interval, 0.290-0.608; P<0.01). The 1- and 2-year TRR in the TACE plus Cidan and TACE groups were 31.5%, 37.1%, and 60.8%, 63.4%, respectively (P<0.01). Median OS was not reached in both groups. The 1- and 2-year OS rates in TACE plus Cidan and TACE groups were 98.4%, 98.4%, and 89.5%, 87.9%, respectively (P<0.05). The most common grade 3-4 AEs included fatigue, abdominal pain, lumbar pain, and nausea. One serious AE was reported in 1 patient in the TACE plus Cidan group, the death was due to retroperitoneal mass hemorrhage and hemorrhagic shock, and was not related to study drug. CONCLUSIONS Cidan Capsule in combination with TACE can reduce the incidence of early recurrence in HCC patients at high-risk of recurrence after radical hepatectomy and may be an appropriate option in postoperative anti-recurrence treatment. (Registration No. NCT02253511).

The study aims to analyze the outcome indicators of randomized controlled trial(RCT) of traditional Chinese medicine(TCM) in the treatment of hypertensive intracerebral hemorrhage(HICH) in recent three years, and thus provide suggestions for the future studies in this field. Four English databases, four Chinese databases and two online registration websites of clinical trials were searched. The RCTs published between January 2018 and September 2020 were screened. The risk of bias was assessed and outcome measures were classified. A total of 151 839 articles were retrieved, of which 44 RCTs were included for analysis after screening. The outcome measures of the included RCTs were classified into 7 categories, among which the symptoms/signs category showed the highest reporting rate. National Institute of Health stroke scale(72.73%) was the most frequently reported outcome indicator, while the vo-lume of intracerebral hemorrhage determined by computerized tomography(36.36%) was the most frequently reported lab test outcome. Most studies collect the outcomes at the end of treatment, while 9 studies reported long-term outcomes 3 months or more after onset. Compared with those of international clinical trials, the application of some of the outcomes was reasonable, focusing on patients' symptoms, quality of life and objective outcomes. However, there were still several problems: unclear primary and secondary outcome measures, insufficient attention to long-term prognosis, insufficient attention to social function, few TCM outcomes, lack of measurement blindness and the use of unreasonable composite outcomes. It is recommended that researchers should rationally design the outcome indicators of clinical trials and develop the core outcome set.
Drugs, Chinese Herbal/therapeutic use* ; Humans ; Intracranial Hemorrhage, Hypertensive/drug therapy* ; Medicine, Chinese Traditional ; Quality of Life ; Randomized Controlled Trials as Topic

The intestinal absorption properties of the main effective components (glycyrrhizic acid, isoliquiritigenin, 6-gingerol, ginsenoside Rb1, atractylode-I) in Lizhong decoction (LZD) extracts were investigated with an in situ single-pass intestinal perfusion model in rats. UPLC-TQ-MS was used to determine the concentration of the five components in the intestinal perfusion. Animal welfare and experimental procedures were in accordance with the regulations of the Animal Ethics Committee of Nanjing University of Chinese Medicine. As evaluation indexes for the intestinal absorption characteristics, the absorption rate constant (K_a) and the apparent permeability coefficient (P_eff) of the five main ingredients were analyzed. Results showed that the best absorption sites for glycyrrhizic acid, isoliquiritin and 6-gingerol were the ileum, colon and duodenum, respectively, and the differences between different intestinal segments were statistically significant (P <0.05). There was no notable difference in K_a and P_eff between ginsenoside Rb1 and atractylode-I in the different intestinal segments (P > 0.05), suggesting that they were absorbed throughout. The five components were well-absorbed in the whole intestine (P_eff > 1.0×10^-3 cm·min^-1), indicating that LZD is suitable for preparing sustained, controlled release and enteric-coated preparations.

Adult ; Capillary Permeability ; Extracorporeal Membrane Oxygenation ; Extravascular Lung Water ; Humans ; Lung/diagnostic imaging* ; Prognosis ; Respiratory Distress Syndrome/therapy*

This study aims to compare the differences of Paeonia lactiflora from different habitats by establishing fingerprint. The fingerprint of P. lactiflora was established by UPLC. The samples collected from Sichuan,Hebei,Henan,Shanxi and Anhui were analyzed. The common peaks were identified by UPLC-Q-TOF/MS. The relative peak area of the common peaks was analyzed through similarity evaluation system( 2012 edition) for chromatographic fingerprint of traditional Chinese medicine developed by the National Pharmacopoeia Commission. Twelve common peaks were obtained and ten components were identified by reference substance and literature comparison. The similarity of each sample to the reference fingerprint is greater than 0. 900. However,all samples were clearly divided into 5 groups according to habitats after PLS-DA analysis. The peaks 2,6( ethyl gallate),10( galloypaeoniflorin) and 12( benzoyl paeoniflorin) were found to be the main difference components between the samples from five different habitats through the VIP value map. The study found that the variety of ingredients in the different areas are basically similar. But there are some differences in the content of the four components. The results of this study can provide reference at choosing and utilizing P. lactiflora from different places comprehensively.
China ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Ecosystem ; Paeonia ; chemistry ; Phytochemicals ; analysis ; Plant Roots ; chemistry

BackgroundThe pro-inflammatory cytokine, interleukin-6 (IL-6), stimulates the metastasis of several neoplasms. An association of its serum level and the single nucleotide polymorphism (SNP) rs1800795 with neuroblastoma (NB) has been reported in American and Italian cohorts. This study was to clarify whether the same association exists in Chinese children.

MethodsA total of 130 NB patients, with 77 boys (59%), 53 girls (41%), mean age 41 ± 5 months, were assigned to two groups: high risk (HR) versus intermediate-low risk (non-HR), and 50 healthy children were randomly selected as the age- and gender-matched controls. Peripheral blood samples were analyzed to determine serum IL-6 level using enzyme linked immunosorbent assay and rs1800795 SNPs phenotype using polymerase chain reaction and gene sequencing.

ResultsThere were 87 NB patients in the HR group and 43 NB patients in the non-HR group. A comparison of allele and genotype frequencies of the rs1800795 polymorphism between patients and controls found no association with NB risk (P > 0.05). The frequency of GG+GC genotype was higher in HR-NB patients than in non-HR-NB patients (64.4% vs. 48.8%, P = 0.02), and serum IL-6 level was much higher in HR-NB patients with GG+GC genotype than in HR-NB patients with CC genotype (4.36 ± 1.1 pg/ml vs. 1.83 ± 0.5 pg/ml; P = 0.02), but not in Non-HR-NB patients.

ConclusionsThe polymorphism rs1800795 is associated with serum IL-6 level and level of NB risk. GG genotype might indicate that the tumor is highly malignant (prone to metastasis) and associated with poor prognosis.

Asian Continental Ancestry Group ; Child, Preschool ; Female ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Interleukin-6 ; blood ; genetics ; Male ; Neuroblastoma ; blood ; genetics ; Polymorphism, Single Nucleotide ; genetics ; Promoter Regions, Genetic ; genetics

OBJECTIVETo evaluate the clinical effects of modified lamina osteotomy replantation versus traditional lamina osteotomy replantation in the treatment of lumbar disc herniation with lumbar instability.

METHODSThe clinical data of 146 patients with unilateral lumbar disc herniation with lumbar instability underwent surgical treatment from March 2008 to March 2013 were retrospectively analyzed. Patients were divided into two groups according to osteotomy replantation pattern. There were 77 patients in the traditional group (underwent traditional lamina osteotomy replantation), including 42 males and 35 females with an average age of (49.4±18.5) years;the lesions occurred on L₄,₅ in 46 cases, on L₅5S₁ in 31 cases. There were 69 patients in modified group (underwent modified lamina osteotomy replantation), including 37 males and 32 females with an average age of (49.8±17.9) years;the lesions occurred on L₄,₅ in 40 cases, on L₅S₁ in 29 cases. The operation time, intraoperative blood loss, complication rate during operation, lamina healing rate, recurrence rate of low back and leg pain were compared between two groups. Visual analogue scales (VAS) and Japanese Orthopadic Association (JOA) scores were used to evaluate the clinical effects.

RESULTSThe operation time and intraoperative blood loss were similar between two group (>0.05). There was significantly different in nerve injury rate(5.80% vs 16.9%) and dural injury rate(1.45% vs 9.09%) between modified group and traditional group(<0.05). The recurrent rate of low back pain of modified group was higher (91.30%, 63/69) than that of traditional group (76.62%, 59/77), and the intervertebral fusion rate of modified group was lower(8.70%, 6/69) than that of traditional group (29.9%, 23/77) at 3 years after operation. Postoperative VAS scores of all patients were significantly decreased at 6 months, 1, 2, 3 years, and JOA scores were obviously increased (<0.05). At 1, 2, 3 years after operation, VAS scores of modified group were significantly lower than that of traditional group(<0.05), and JOA scores of modified group were higher than that of traditional group(<0.05).

CONCLUSIONSModified lamina osteotomy replantation has better long-term efficacy(in the aspect of recurrent rate of low back pain, intervertebral fusion rate, VAS and JOA score at three years follow-up) in treating lumbar disc herniation with instability.

OBJECTIVETo compare the clinical effect between the lamina osteotomy and former vertebral plates regraft method and total laminectomy and interbody fusion method in treating single-segment lumbar degenerative disease.

METHODSThe clinical data of 167 patients with single-segment lumbar degenerative disease underwent surgical treatment from January 2010 to December 2014 were retrospectively analyzed. There were 92 males and 75 females, aged from 45 to 75 years old with an average of (59.6±12.4) years. The patients were divided into lamina osteotomy and former vertebral plates regraft group(82 cases) and total laminectomy and interbody fusion group(85 cases) according to the different surgical methods used. The general conditions and clinical effects were compared between two groups. General conditions included the operation time, intraoperative blood loss, postoperative drainage, hospitalization time and the clinical effects included the visual analogue scale (VAS), Japanese Orthopaedic Association(JOA), Oswestry Dability Index(ODI), MacNab results, epidural fibrosis (EF), the incidence of adjacent segment degeneration (ASD).

RESULTSAll the patients were followed for 18 to 36 months with an average of (24.8±5.7) months, furthermore, there was no significant difference in the follow-up time between two groups. There was no significant difference in general conditions such as operation time, intraoperative blood loss, postoperative drainage, or hospitalization time between two groups. At final follow-up, the VAS, ODI, JOA, of all patients were significantly improved (<0.05);and the three factors above in the lamina osteotomy and former vertebral plates regraft group respectively were(2.0±1.1) points, (24.0±1.8) %, (19.8±8.2) point, while the results of total laminectomy and interbody fusion group were(2.5±1.6) points, (23.3±2.0)%, and(22.5±8.5) point;there was statistical difference between two groups(<0.05). According to the standard of MacNab, 59 cases obtained excellent results, 20 good, 3 fair results in the lamina osteotomy and former vertebral plates regraft group;while 47 cases got excellent results, 26 good, and 12 fair results in the total laminectomy and interbody fusion group;there was significant difference between two groups(<0.05). Sixteen patients(19.51%) with EF and 20 patients(24.39%) with ASD were found in lamina osteotomy and former vertebral plates regraft group;and 30 patients(35.29%) with EF and 37 patients(43.53%) with ASD were found in total laminectomy and interbody fusion group; there was significant difference between two groups(<0.05).

CONCLUSIONSBoth two methods can achieve the ideal effects for the treatment of single-segment lumbar degenerative disease, but the lamina osteotomy and former vertebral plates regraft method can reserve the integrity of posterior ligamentous complex, reducing the incidence of EF and ASD, and is a better surgical method.

Adult ; Aged ; Bone Transplantation ; Female ; Humans ; Laminectomy ; Lumbar Vertebrae ; pathology ; surgery ; Lumbosacral Region ; Male ; Middle Aged ; Osteotomy ; Retrospective Studies ; Spinal Fusion ; Treatment Outcome

To explore the flavor and meridian tropism classification of Callianthemum taipaicum by principal components analysis(PCA) and partial least square analysis(PLS). Meanwhile,to establish a high performance liquid chromatography-tandem mass spectrometry(HPLC-ESI-MS) method for the simultaneous determination of 55 active components from 13 kinds of Ranunculaceae of Chinese traditional herbs. Samples were separated on HPLC system by Agilent 5 TC-C₁₈（2）（4.6 mm×250 mm，5 μm）column and eluted with acetonitrile and 0.1% formic acid at the flow rate of 0.6 mL·min⁻¹. The data were performed by HPLC-ESI-MS with multiple reaction monitoring（MRM）scanning mode under positive and negative ion modes and quantified by external standards. The data from 13 Ranunculaceae herbs were analyzed by the PLS-tree and cooman's prediction of PCA and PLS to evaluate the similarities and differences of C. taipaicum in flavor and meridian tropism. The results showed that calibration curves of 55 components all showed good linearity, >0.99,with good precision, repeatability and stability. After compared to other 12 herbs,PCA and PLS results revealed that the C. taipaicum belonged to lung and bladder meridians while its flavor attributive to pungent,warm in nature. In conclusion,the analysis approach of chemometric calculation combined with multi-components quantification is suitable for the classification of meridian tropism and flavor of Chinese traditional medicine,which can be used for alternative research of rare herbs.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; Mass Spectrometry ; Meridians ; Phytochemicals ; analysis ; Plants, Medicinal ; chemistry ; Ranunculaceae ; chemistry ; Tandem Mass Spectrometry

This study established a rapid UPLC-TQ-MS/MS method for determination of eight active ingredients in Lilium lancifolium. The contents range of regaloside E, F, C and B are as follows: 0.604 0×10⁻¹-18.62×10⁻¹, 0.680 0×10⁻²-44.75×10⁻², 0.700 0×10⁻³-29.65×10⁻¹, 0.170 0×10⁻¹-4.724 mg•g⁻¹; the contents of chlorogenic acid, caffeic acid, protocatechualdehyde and ferulic acid, within the range of 6.827×10⁻³-16.07×10⁻³, 0.011 1×10⁻³-79.71×10⁻³, 0.593 7×10⁻³-2.962×10⁻³, 2.606×10⁻²-45.89×10⁻² mg•g⁻¹, respectively. According to PCA (principal components analysis) plotting, 35 batches can be divided into two categories, namely Anhui Huoshan and Hunan Longshan. The main different elements between these two categories are caffeic acid and ferulic acid according to the VIP (variable importance in the projection) points figure. Based on comprehensive principal component values, there are eight batches of L. lancifolium from Huoshan among the comprehensive ranking of ten. The UPLC-TQ-MS method for simultaneous analysis of eight active ingredients is accurate, efficient and convenient. This result can provide scientific basis for quality control of L. lancifolium.