Analysis of Medication Rules of Traditional Chinese Medicine for Malaria Treatment Based on Data Mining.

Objective To analyze the medication rules of traditional Chinese medicine (TCM) for malaria treatment.Methods Statistical analysis was conducted on the basic attributes of TCM drugs with regard to property, therapeutic methods, flavor, and meridian tropism. A complex network of TCM drug associations was constructed. Cluster analysis was applied to obtain the core drugs for malaria treatment. The Apriori algorithm was applied to analyze the association rules of these core drugs.Results A total of 357 herbs were used 3,194 times in 461 prescriptions for malaria treatment. Radix Glycyrrhizae (), Rhizoma Pinelliae (), Radix Bupleuri (), and Radix Dichroae () were the frequently used herbs through supplementing, exterior-releasing, heat-clearing, qi-rectifying, and damp-resolving therapeutic methods. Such herbs had warm, natural, and cold herbal properties; pungent, bitter, and sweet flavors; and spleen, lung, and stomach meridian tropisms. Cluster analysis showed 61 core drugs, including Radix Glycyrrhizae, Rhizoma Pinelliae, Radix Bupleuri, and Radix Scutellariae (). Apriori association rule analysis yielded 12 binomial rules (herb pairs) and 6 trinomial rules (herb combinations). Radix Bupleuri plus Radix Scutellariae was the core herbal pair for treating malaria. This pair could be combined with Rhizoma Atractylodis Macrocephalae () for treating warm or cold malaria, combined with Pericarpium Citri Reticulatae () or Radix Dichroae () for treating miasmic malaria, or combined with turtle shells () for treating malaria with splenomegaly.Conclusions TCM can be used to classify and treat malaria in accordance with the different stages of development. As the core herbal pair, Radix Bupleuri and Radix Scutellariae can be combined with other drugs to treat malaria with different syndrome types.

Guizhi Decoction () Inhibits Cholinergic Transdifferentiation by Regulating Imbalance of NGF and LIF in Salt-Sensitive Hypertensive Heart Failure Rats.

OBJECTIVE: To observe the imbalance of anatomical and functional innervation factors of sympathetic nerves, nerve growth factor (NGF) and leukemia inhibitory factor (LIF), in salt-sensitive hypertensive heart failure rats and to explore the effects of treatment with Guizhi Decoction () on sympathetic remodeling by inhibiting cholinergic transdifferentiation. METHODS: SS-13BN and Dahl salt-sensitive (DS) rats were divided into 3 groups: SS-13BN group (control group, n=9), DS group (model group, n=9) and GS group (Guizhi Decoction, n=9). After 10 weeks of a high-salt diet, the GS group rats were given Guizhi Decoction and other two groups were given saline at an equal volume as a vehicle. After 4 weeks' intragastric administration, rats were executed to detect the relevant indicators. Echocardiography and plasma n-terminal pro-B type natriuretic peptide (NT-proBNP) levels were used to assess cardiac function. Noradrenaline (NA) levels in the plasma and myocardium were detected to evaluate the sympathetic function. NGF and LIF expression were detected in the myocardium by Western blot or quantitative real-time PCR. Double immunofluorescence or Western blot was used to detect tyrosine hydroxylase (TH), choline acetyltransferase (CHAT) and growth associated protein 43 (GAP43) in order to reflect anatomical and functional changes of sympathetic nerves. RESULTS: DS group had anatomical and functional deterioration of sympathetic nerves in the decompensation period of heart failure compared with SS-13BN group. Compared with the DS group, Guizhi Decoction significantly decreased the expression of LIF mRNA/protein (P<0.01), increased the expression of NGF (P<0.05 or P<0.01), enhanced the levels of TH+/GAP43+ and TH+/CHAT+ positive nerve fibers (P<0.01), and improved the protein expression of TH and GAP43 in left ventricle, but had no effect on CHAT (P>0.05). Guizhi Decoction inhibited inflammatory infiltration and collagen deposition of myocardial injury, increased the content of myocardial NA (P<0.05), reduced the plasma NA level (P<0.01), improved cardiac function (P<0.01), and improved weight and blood pressure to some extent (P<0.05), compared with DS group. CONCLUSIONS: Guizhi Decoction could inhibit cholinergic transdifferentiation of sympathetic nerves, improve the anatomical and functional denervation of sympathetic nerves, and delay the progression of decompensated heart failure. The mechanism may be associated with the correction of the imbalance of NGF and LIF.

Xiao-Qing-Long Tang Prevents Cardiomyocyte Hypertrophy, Fibrosis, and the Development of Heart Failure with Preserved Ejection Faction in Rats by Modulating the Composition of the Gut Microbiota.

BACKGROUND: Changes in the gut microbiota are associated with cardiovascular disease progression. Xiao-Qing-Long Tang (XQLT), a traditional herbal formula, has an anti-inflammatory effect and regulates the steady state of the immune system, which is also associated with the progression of heart failure with preserved ejection faction (HFpEF). In this study, we investigated whether XQLT could contribute to prevent the development of HFpEF and whether the modulation of the gut microbiota by this herbal formula could be involved in such effect. METHODS: The gut microbiota, SCFAs, the histology/function of the heart, and systolic blood pressure were examined to evaluate the effect of XQLT on the gut microbiota and the progression of HFpEF after oral administration of XQLT to model rats. Furthermore, we evaluated, through fecal microbiota transplantation experiments, whether the favorable effects of XQLT could be mediated by the gut microbiota. RESULTS: Oral administration of XQLT contributed to the reduction of elevated blood pressure, inflammation, and compensatory hypertrophy, features that are associated with the progression of HFpEF. The gut microbiota composition, SCFA levels, and intestinal mucosal histology were improved after treatment with XQLT. Moreover, fecal transfer from XQLT-treated rats was sufficient to prevent the progression of HFpEF. CONCLUSIONS: These data suggested that XQLT prevented the development of HFpEF in model rats by regulating the composition of the gut microbiota.

Transcriptome-Wide Identification and Prediction of miRNAs and Their Targets in Paris polyphylla var. yunnanensis by High-Throughput Sequencing Analysis.

Long dormancy period of seeds limits the large-scale artificial cultivation of the scarce Paris polyphylla var. yunnanensis, an important traditional Chinese medicine. Characterizing miRNAs and their targets is crucial to understanding the role of miRNAs during seed dormancy in this species. Considering the limited genome information of this species, we first sequenced and assembled the transcriptome data of dormant seeds and their seed coats as the reference genome. A total of 146,671 unigenes with an average length of 923 bp were identified and showed functional diversity based on different annotation methods. Two small RNA libraries from respective seeds and seed coats were sequenced and the combining data indicates that 263 conserved miRNAs belonging to at least 83 families and 768 novel miRNAs in 1174 transcripts were found. The annotations of the predicted putative targets of miRNAs suggest that these miRNAs were mainly involved in the cell, metabolism and genetic information processing by direct and indirect regulation patterns in dormant seeds of P. polyphylla var. yunnanensis. Therefore, we provide the first known miRNA profiles and their targets, which will assist with further study of the molecular mechanism of seed dormancy in P. polyphylla var. yunnanensis.

[Preventive Effect of Different Compatibilities of Ramulus Cinnamomi and Radix Paeomlae alba in Guizhi Decoction on Cardiac Sympathetic Denervation Induced by 6-OHDA].

OBJECTIVE: To observe the preventive effect of different compatibilities of Ramulus Cinnamomi (RC) and Radix Paeomiae alba (RPA) in Guizhi Decoction (GZD) on neurotransmitters and their rate-limiting enzymes, and neurotrophic factors of cardiac sympathetic denervation model rats induced by 6-hydroxydopamine (6-OHDA). METHODS: Totally 54 male Wistar rats were randomly divided into 6 groups, i.e., the blank control group, the model group, the methycobal group, the 2:1 (RC/RPA) Guishao group, the 1:2 Guishao group, and the 1:1 Guishao group, 9 in each group. Sympathetic denervation was induced by intraperitoneal injection of 6-OHDA for three successive days. Rats in the methycobal group and GZD groups were administered with corresponding decoction by gastrogavage 1 week before modeling (methycobal at the daily dose 0.15 mg/kg; GZD at the daily dose of 4.0, 5.5, 5.5 g crude drugs/kg for GZD 1:1, 1:2, and 2:1 groups). All medication lasted for 10 successive days. Levels of norepinephrine (NE), tyrosine hydroxylase (TH), choline acetyl-transferase (ChAT), nerve growth factor (NGF), growth associated protein43 (GAP-43) and ciliary neurotrophic factor (CNTF) in myocar- dial homogenates of right atrium and ventricular septum were detected by ELISA. RESULTS: Compared with the blank control group, levels of NE, TH, TH/ChAT ratio, and GAP-43 in myocardial homogenates of right atrium and ventricular septum decreased in the model group, and level of NGF increased (P < 0.01, P < 0.05). Compared with the model group, levels of NE and GAP-43 increased in the right atrium and interventricular septum; NGF level of the ventricular septum decreased in the methycobal group and each GZD groups. TH and TH/ChAT ratio in the right atrium increased in the 2:1 Guishao group and the 1:2 Guishao group (P < 0.01, P < 0.05); NGF levels in the right atrium and interventricular septum decreased only in the 1:1 Guishao group (P < 0.01, P< 0.05). Compared with the methycobal group, levels of NE, TH, and GAP-43 in the right atrium and interventricular septum increased, and NGF levels in the right atrium and interventricular septum decreased in the 1:1 Guishao group (P < 0.05). Compared with the methycobal group, levels of NE and GAP-43 in interventricular septum increased in the 2:1 Guishao group (P < 0.05). CONCLUSION: GZD (with the proportion between RC and RPA 2:1 and 1:1) could improve contents of neurotransmitters and their rate-limiting enzymes, as well as neurotrophic factors in cardiac sympathetic denervation model rats induced by 6-OHDA, alleviate cardiac sympathetic denervation induced by 6-OHDA, and maintain the balance of sympathetic-vagal nerve system.

[Effects of Different Compatibilities of Ramulus Cinnamomi and Peony in Guizhi Decoction on Diabetic Cardiac Autonomic Neuropathy].

OBJECTIVE: To observe the preventive effect different compatibilities of Ramulus Cinnamomi (RC) and peony in Guizhi Decoction (GD) on diabetic cardiac autonomic neuropathy (DCAN). METHODS: Totally 60 male rats were randomly divided into 5 groups, i.e., the blank control DM group, the model group, the methycobal group, the 1:1 (RC/peony) Guishao group, the 2:1 Guishao group, and the 1:2 Guishao group, 10 in each group. Rats were pretreated with corresponding drugs for 1 week, and then induced diabetes by intraperitoneal injection of STZ. Drugs were administrated by gastrogavage for 4 more weeks after STZ-injection. Enzyme-linked immunosorbent assay (ELISA) was employed to detect levels of tyrosine hydroxylase (TH), choline acetyltransferase (CHAT), nerve growth factor. (NGF), and ciliary neurotrophic factor (CNTF) in myocardial homogenates. RESULTS: After 4-week modeling, body weight (BW) was obviously lower, but blood glucose (BG) was higher in STZ rats than in rats of the blank control DM group. There was no statistical difference in BW or BG among the 5 groups (P >0.05). Compared with the blank control group, TH, TH/CHAT, and NGF in left ventricle and ventricular septum increased, CHAT and CNTF increased in the model group (P < 0.05, P < 0.01). Compared with the model group, TH and TH/CHAT in left ventricle decreased (P < 0.05, P < 0.01), CNTF in left ventricle increased (P < 0.05), CHAT in left ventricle and ventricular septum increased (P < 0.05, P < 0.01) in the methycobal group. TH and TH/CHAT in left ventricle and ventricular septum decreased, CNTF in left ventricle and ventricular septum increased (P < 0.05, P < 0.01), CHAT in left ventricle and ventricular septum increased (P < 0.01), NGF in ventricular septum decreased (P < 0.01) in the 1:1 Guishao group. TH/CHAT in left ventricle decreased (P < 0.01), CHAT and CNTF in left ventricle and ventricular septum increased (P < 0.05, P < 0.01) in the 1:2 Guishao group. Compared with the methycobal group, CHAT in left ventricle decreased, TH and TH/CHAT in left ventricle increased in the 2:1 Guishao group (P < 0.05, P < 0.01). TH and TH/CHAT in ventricular septum decreased (P < 0.05), CHAT and CNTF in left ventricle and ventricular septum increased (P < 0.05, P < 0.01) in the 1:1 Guishao group. Compared with the 1:2 Guishao group and the 2:1 Guishao group, CHAT in left ventricle increased, TH/CHAT in left ventricle decreased, TH and TH/CHAT in ventricular septum decreased, CHAT in ventricular septum increased, CNTF in left ventricle and ventricular septum also increased in the 1:1 Guishao group (all P < 0.01). CONCLUSIONS: STZ model rats had autonomic neural injury, manifested as lowered vagal nerve activity and hyperactive sympathetic nerves. GD could effectively suppress hyperactive cardiac sympathetic nerves and protect the vagus. Besides, GD (1:1) showed the optimal effect in regulating the balance of cardiac autonomic nerves and could be used in early prevention of DCAN.

Effect of Guizhi Decoction ([symbols; see text]) on heart rate variability and regulation of cardiac autonomic nervous imbalance in diabetes mellitus rats.

OBJECTIVE: To observe abnormalities in heart rate variability (HRV) in diabetic rats and to explore the effects of treatment with Guizhi Decoction ([symbols; see text]) on cardiac autonomic nervous (CAN) imbalance. METHODS: A radio-telemetry system for monitoring physiological parameters was implanted into rats to record electrocardiac signals and all indictors of HRV [time domain measures: standard deviation of all RR intervals in 24 h (SDNN), root mean square of successive differences (RMSSD), percentage of differences between adjacent RR intervals greater than 50 ms (PNN50), and standard deviation of the averages of RR intervals (SDANN); frequency domain measures: low frequency (LF), high frequency (HF), total power (TP), and LF/HF ratio]. The normal group was randomly selected, and the remaining rats were used to establish streptozocin (STZ)-induced diabetic model. After 4 weeks, the model rats were divided into the model group, the methycobal group, and the Guizhi Decoction group, 9 rats in each group. Four weeks after intragastric administration of the corresponding drugs, the right atria of the rats were collected for immunohistochemical staining of tyrosine hydroxylase (TH) and choline acetyltransferase (CHAT) to observe the distribution of the sympathetic and vagus nerves in the right atrium. The myocardial homogenate from the interventricular septum and the left ventricle was used for determination of TH, CHAT, growth-associated protein 43 (GAP-43), nerve growth factor (NGF), and ciliary neurotrophic factor (CNTF) levels using an enzyme-linked immunosorbent assay. RESULTS: (1) STZ rats had elevated blood glucose levels, reduced body weight, and decreased heart rate; there was no difference between the model group and the drug treated groups. (2) Compared with the model group, only RMSSD and TP increased in the methycobal group significantly (P<0.05); SDNN, RMSSD, PNN50, LF, HF, and TP increased, LF/HF decreased (P<0.05), and SDANN just showed a decreasing trend in the Guizhi Decoction group (P>0.05). TH increased, CHAT decreased, and TH/CHAT increased in the myocardial homogenate of the model group (P<0.05). Compared with the model group, left ventricular TH reduced in the methycobal group; and in the Guizhi Decoction group CHAT increased, while TH and TH/CHAT decreased (P<0.05). Compared with the model group, CNTF in the interventricular septum increased in the methycobal group (P<0.05); GAP-43 increased, NGF decreased, and CNTF increased (P<0.05) in the Guizhi Decoction group. There were significant differences in the reduction of NGF and elevation of CNTF between the Guizhi Decoction group and the methycobal group (P<0.05). (3) Immunohistochemical results showed that TH expression significantly increased and CHAT expression significantly decreased in the myocardia of the model group, whereas TH expression decreased and CHAT expression increased in the Guizhi Decoction group (P<0.05). CONCLUSION: Guizhi Decoction was effective in improving the function of the vagus nerve, and it could alleviate autonomic nerve damage.

[Anesthesia and operative approach of resection of the trachea].

OBJECTIVE: Review and discuss anesthesia and operative approach of resection of the trachea for different tracheal diseases, especially for the resection of long-segment of trachea. At the same time to introduce the method of reconstruction of long-segment of trachea with Zhao's (two-stage procedure with memory-alloy mesh) artificial trachea. METHODS: Retrospective study of 18 cases of tracheal resection, analysis of the relation between the choice of anesthetic and operative approach. RESULTS: General anesthesia through cut open the trachea with local anesthesia in 2 cases, general anesthesia through previous tracheotomy in 2 cases, extracorporeal circulation in 2 cases, general anesthesia through endotracheal tube in 12 cases. There were no anesthetic or operative death. Local resection in 3 cases, segmental resection in 15 cases. The longest segmental resection was 8.0 cm. Primary anastomosis after segmental resection in 8 cases, Reconstruction with Zhao's artificial trachea in 7 cases. Postoperative follow-up was 5 months to 8 years. Four cases died from systemic metastasis or other reasons at 4, 11 and 12 months, respectively. CONCLUSIONS: Different methods of anesthetic and operative procedures should be used for different patients. Extracorporeal circulation used for patient with highest dangerous condition, or, for which could be inserted endotracheal tube by tracheotomy with local anesthesia. Conservative local resection performed only for patients with very bad general condition. Segmental resection less than 5 cm long could be reconstructed with primary reanastomosis. Resection longer than 5.5 cm could be reconstructed with Zhao's artificial trachea.