Parkinson's Disease in Traditional Chinese and Western Medicine： A Review / 中国实验方剂学杂志

Parkinson's disease （PD） is a neurodegenerative disease that seriously endangers the health of the middle-aged and elderly people. The main clinical manifestations include motor symptoms such as bradykinesia， static tremor， and myotonia and non-motor symptoms like constipation， mental disorders， sleep disorders， and autonomic nervous dysfunction. Its etiology and pathogenesis have not been fully understood， and the clinical efficacy is not satisfactory. By searching the relevant literature in China and abroad in recent years， this paper summarized the etiology， pathogenesis， and treatment of PD in both traditional Chinese medicine （TCM） and western medicine as well as the integrated TCM and Western medicine treatment. In general， liver and kidney deficiency is recognized by domestic experts in related fields as the main pathogenesis of PD. The abnormal aggregation of α-synuclein， oxidative stress， mitochondrial dysfunction， ubiquitin-proteasome system dysfunction， neuroinflammation， autophagy， microbiota-gut-brain axis regulation， and excitatory neurotoxicity are closely related to the pathogenesis of this disease. At present， treatment based on syndrome differentiation， empirical formulae from famous doctors， single Chinese herbs， and acupuncture and moxibustion are mainly adopted for the tackling of PD in TCM. Western medicine is still dominated by drug replacement therapy， supplemented by such surgical treatments as traditional immunotherapy， neurotrophic factors， and deep brain stimulation （DBS）， rehabilitation and exercise therapy， and scientific nursing. Gene therapy has become a new technical means for the treatment of this disease in recent years. In addition， the combined therapy of TCM and Western medicine has received increasing importance. This paper reviewed the pathogenesis and treatment of PD in TCM and Western medicine， so as to provide reference for its clinical diagnosis and treatment.

Onset and Recurrence Characteristics of Chinese Patients with Noncardiogenic Ischemic Stroke in Chinese Medicine Hospital / 中国结合医学杂志

OBJECTIVE@#To delineate the onset and recurrence characteristics of noncardiogenic ischemic stroke patients in China.@*METHODS@#A prospective, multicenter and registry study was carried out in 2,558 patients at 7 representative clinical sub-centers during November 3, 2016 to February 17, 2019. A questionnaire was used to collect information of patients regarding CM syndromes and constitutions and associated risk factors. Additionally, stroke recurrence was defined as a primary outcome indicator.@*RESULTS@#A total of 327 (12.78 %) patients endured recurrence events, 1,681 (65.72%) were men, and the average age was 63.33 ± 9.45 years. Totally 1,741 (68.06%) patients suffered first-ever ischemic stroke, 1,772 (69.27%) patients reported to have hypertension, and 1,640 (64.11%) of them reported dyslipidemia, 1,595 (62.35%) patients exhibited small-artery occlusion by The Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Specifically, 1,271 (49.69%) patients were considered as qi-deficient constitution, and 1,227 (47.97%) patients were determined as stagnant blood constitution. There were 1,303 (50.94%) patients diagnosed as blood stasis syndrome, 1,280 (50.04%) patients exhibited phlegm and dampness syndrome and 1,012 (39.56%) patients demonstrated qi deficiency syndrome. And 1,033 (40.38%) patients declared intracranial artery stenosis, and 478 (18.69%) patients reported carotid artery stenosis. The plaque in 1,508 (41.36%) patients were of mixed. Particularly, 41.09% of them demonstrated abnormal levels of glycated hemoglobin levels.@*CONCLUSIONS@#Recurrence in minor and small-artery stroke cannot be ignored. Hypertension, dyslipidemia, abnormal HbA1c, intracranial artery stenosis and carotid plaque were more common in stroke patients. Particularly, phlegm-dampness and blood stasis syndromes, as well as qi deficiency and blood stasis constitutions, were still the main manifestations of stroke. (Trial registration at ClinicalTrials.gov No. NCT03174535).

Mechanism of Kaixinsan on Learning and Memory Ability and Synaptic Function of APP/PS1 Mice / 中国实验方剂学杂志

Objective:To explore the underlying protective mechanism of Kaixinsan on learning， memory， and synaptic function in APP/PS1 mice. Method:Sixty APP/PS1 mice were randomly divided into a model group， a donepezil （2 mg·kg^-1·d^-1） group， and low- （0.7 g·kg^-1·d^-1）， medium- （1.4 g·kg^-1·d^-1）， and high-dose （2.8 g·kg^-1·d^-1） Kaixinsan groups， and the wild-type mice of the same age in the same litter were assigned to the normal group， with 12 mice in each group. After continuous intragastric administration for two months， the Morris water maze experiment was performed. The ultrastructure of hippocampal neurons was observed by transmission electron microscopy. The colorimetric assay was used to detect serum content of acetylcholine （ACh）， choline acetyltransferase （ChAT）， acetylcholinesterase （AChE）， and levels of hippocampal reactive oxygen species （ROS）， malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione peroxidase （GSH-Px）. Real-time fluorescence-based quantitative polymerase chain reaction （Real- time PCR） was used to detect the mRNA expression of hippocampal brain-derived neurotrophic factor （BDNF）， beta-nerve growth factor （NGFB）， discs large homolog (DLG)2， DLG4， and synaptophysin （SYP）. Result:Compared with the normal group， the model group showed prolonged escape latency， reduced number of crossing platforms， shortened stay in the target quadrant （<italic>P</italic><0.01）， decreased number of mitochondria with different shapes and irregular arrangement， some swollen and deformed mitochondria with broken mitochondrial cristae， endolysis， and cytoplasm vacuole， and more cell debris. Additionally， the model group also displayed reduced serum levels of ACh and ChAT， increased AChE （<italic>P</italic><0.01）， elevated hippocampal ROS and MDA （<italic>P</italic><0.05，<italic>P</italic><0.01）， declining SOD and GSH-Px （<italic>P</italic><0.01）， and diminished hippocampal BDNF， NGFB， DLG2， DLG4， and SYP mRNA levels （<italic>P</italic><0.05，<italic>P</italic><0.01）. Compared with the model group， the donepezil group， and the medium- and high-dose Kaixinsan groups showed shortened escape latency， increased number of crossing platforms， prolonged stay in the target quadrant （<italic>P</italic><0.05，<italic>P</italic><0.01）， improved mitochondrial damage with a regular shape （mainly oval shape）， relieved mitochondrial swelling and deformation， and clear mitochondrial cristae. Furthermore， the donepezil group， and the medium- and high-dose Kaixinsan groups also exhibited increased serum ACh and ChAT levels （<italic>P</italic><0.05，<italic>P</italic><0.01）， blunted AChE activity （<italic>P</italic><0.05）， reduced hippocampal ROS level （<italic>P</italic><0.05，<italic>P</italic><0.01）， declining MDA level （<italic>P</italic><0.05）， potentiated SOD and GSH-Px activities， and up-regulated hippocampal BDNF， NGFB， DLG2， DLG4， and SYP mRNA levels （<italic>P</italic><0.05，<italic>P</italic><0.01）. In the low-dose Kaixinsan group， the stay time in the target quadrant was prolonged and the expression of hippocampal SYP mRNA was elevated significantly （<italic>P</italic><0.05）. There was no statistical difference in swimming speed between the groups. Conclusion:Kaixinsan can improve the learning and memory ability of APP/PS1 mice by increasing the expression of synaptic plasticity-related proteins， reducing the ultrastructural damage to hippocampal neurons， resisting oxidative stress， and regulating cholinergic neurotransmitters， thereby exerting neuroprotective effects.

Evaluation on the efficacy and safety of Chinese herbal medication Xifeng Dingchan Pill in treating Parkinson's disease: study protocol of a multicenter, open-label, randomized active-controlled trial / 中西医结合学报

<p><b>BACKGROUND</b>Parkinson's disease (PD) is a complicated disease, commonly diagnosed among the elderly, which leads to degeneration of the central nervous system. It presently lacks an effective therapy for its complex pathogenesis. Adverse effects from Western drug-based medical intervention prevent long-term adherence to these therapies in many patients. Traditional Chinese medicine (TCM) has long been used to improve the treatment of PD by alleviating the toxic and adverse effects of Western drug-based intervention. Therefore, the aim of this study is to evaluate the efficacy and safety of Xifeng Dingchan Pill (XFDCP), a compound traditional Chinese herbal medicine, taken in conjunction with Western medicine in the treatment of PD patients at different stages in the progression of the disease.</p><p><b>METHODS AND DESIGN</b>This is a multicenter, randomized controlled trial. In total, 320 patients with early- (n = 160) and middle-stage PD (n = 160) will be enrolled and divided evenly into control and trial groups. Of the 160 patients with early-stage PD, the trial group (n = 80) will be given XFDCP, and the control group (n = 80) will be given Madopar. Of the 160 patients with middle-stage PD, the trial group (n = 80) will be given XFDCP combined with Madopar and Piribedil, and the control group (n = 80) will be given Madopar and Piribedil. The Unified Parkinson's Disease Rating Scale scores, TCM symptoms scores, quality of life, change of Madopar's dosage and the toxic and adverse effects of Madopar will be observed during a 3-month treatment period and through a further 6-month follow-up period.</p><p><b>DISCUSSION</b>It is hypothesized that XFDCP, combined with Madopar and Piribedil, will have beneficial effects on patients with PD. The results of this study will provide evidence for developing a comprehensive therapy regimen, which can delay the progress of the disease and improve the quality of life for PD patients in different stages.</p><p><b>TRIAL REGISTRATION</b>This trial has been registered in the Chinese Clinical Trial Registry with the identifer ChiCTR-TRC-12002150.</p>

Correlation between level of metallic elements in urine and childhood acute leukemia / 中华预防医学杂志

<p><b>OBJECTIVE</b>To explore the relation between the level of metallic elements in urine and childhood acute leukemia.</p><p><b>METHODS</b>A total of 71 patients under 15 years old who were newly diagnosed with acute leukemia between September 2007 and August 2008 without Downs' syndrome or other tumors, and 113 gender- and age-matched controls without tumors or congenital diseases were enrolled for the case-control study. The general data and potential risk factors were obtained by questionnaires. Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the metal concentrations in urine, which was collected randomly before chemotherapy. Logistic regression model was performed for univariate and multivariate analysis.</p><p><b>RESULTS</b>The questionnaire showed that there was significant difference in the proportion of children whose mothers had taken iron supplements during or 3 months before pregnancy between case group and control group, which was 28.2% (20/71) and 14.2% (16/113) respectively (Wald χ(2) = 5.438, P = 0.02). Univariate logistic regression analysis showed that levels of vanadium, manganese, iron, cobalt, copper, arsenic, and barium in urine from case group were all higher than those of control group with significant difference. The median values for vanadium in urine from case and control groups were 5.39 and 3.04 ng/mg creatinine (Wald χ(2) = 9.03, P < 0.05); the median values for manganese were respectively 4.46 and 2.44 ng/mg creatinine (Wald χ(2) = 10.57, P < 0.05); the median values for iron were separately 58.69 and 14.09 ng/mg creatinine (Wald χ(2) = 13.41, P < 0.05); the median values for cobalt were respectively 0.98 and 0.77 ng/mg creatinine (Wald χ(2) = 4.46, P < 0.05); the median values for copper were 61.17 and 10.90 ng/mg creatinine (Wald χ(2) = 8.15, P < 0.05); the median values for arsenic were respectively 55.93 and 36.11 ng/mg creatinine (Wald χ(2) = 4.57, P < 0.05); and the median values for barium were 8.55 and 2.87 ng/mg creatinine (Wald χ(2) = 4.82, P < 0.05). Multivariate logistic regression analysis showed that the level of iron in urine had a significantly positive relation with the incidence of childhood acute leukemia (OR = 1.009, 95%CI = 1.002 - 1.016).</p><p><b>CONCLUSION</b>The level of iron in urine might be related to the occurrence of childhood acute leukemia, but its specific role needs further investigation.</p>

Effects of chelation therapy with succimer in young rabbits of moderate lead poisoning / 中华预防医学杂志

<p><b>OBJECTIVE</b>To explore the effect of chelation therapy with succimer (DMSA) in male rabbits of moderate lead poisoning during juvenile stage.</p><p><b>METHODS</b>Twenty-four 45-day-old male New Zealand rabbits were randomly divided into three groups (therapy group, TG; positive control group, PG and negative control group, NG, n=8). The TG and PG were orally exposed to lead acetate (5 mg x kg(-1) x d(-1)) for 6 weeks. Rabbits in TG were orally supplied DMSA 1050 mg/m2 in the first week and 700 mg/m2 in the next two weeks, while the other two groups wren't blood and urinary samples of all rabbits were collected per week. The tissues and organs of all rabbits were collected after 12 weeks. The blood lead levels (BLLs) were determined by atomic absorption spectrometer. The urine lead levels and the lead contents of tissue and organ were determined by inductively coupled plasma-mass spectrometry. Histopathology of tissue and organ was observed by light microscope.</p><p><b>RESULTS</b>Compared with PG, the lead level in the morning urine of TG with DMSA chelating was increased significantly. The level was peaked at (1246.96 +/- 157.91) microg/L on the first day after chelating. While the base line was (40.97 +/- 1.77) microg/L before chelating. Meanwhile, the BLLs were sharply declined from (429.63 +/- 10.82) microg/L to (238.50 +/- 11.82) microg/L. The urine lead levels of TG decreased through the 3-week chelating and 3-week discontinuation. The urine lead levels of these two groups were significantly different (F=2934.35, P<0.01). Compared to each two groups in these three groups, there were significant difference (P<0.01). The authors found the reversion of BLLs in first week after stop chelating. The BLLs of PG presented the slow course of declining in the same time, were (135.50 +/- 7.09) microg/L, very close to the level of TG for (149.88 +/- 11.39) microg/L. Compared with treatment discontinuation for 3 weeks, the urine lead levels and the body weight gain of the therapy group increased more than that of PG, and the BLLs and the lead concentrations in tissues and organs decreased more than that of PG, and histopathology in the liver tissues and testicle tissues were improved.</p><p><b>CONCLUSION</b>DMSA chelating for the rodent models of moderate lead poisoning might reduce the BLLs and soft tissue lead contents quickly and effectively, decrease toxic effects of lead in a short period of time, thus alleviate the impairment of lead poisoning on tissues and organs by decreasing lead burden, and bring out improvement on the growth retardation caused by lead poisoning.</p>

Effect of carbamazepine and valproate on bone metabolism in children with epilepsy / 中华儿科杂志

<p><b>OBJECTIVE</b>To assess bone health in epileptic children who have been treated with carbamazepine (CBZ) or valproate (VPA) by using quantitative ultrasound (QUS) and determining the biochemical indices of bone metabolism, and to provide a proposal to improve quality of life of epileptic children.</p><p><b>METHODS</b>Ninety-two epileptic children who had been treated with CBZ or VPA for more than two years were evaluated for bone mineral density (BMD) at the mid-shaft tibia and the distal third of the radius. Biochemical indices of bone metabolism including urine deoxypyridinoline (DPD) and serum osteocalcin (OC), and daily calcium intake were also evaluated. Thirty-five age-matched healthy children were used as controls. Reduced BMD was defined as speed of sound (SOS) Z scores of the mid-shaft tibia and (or) the distal third of the radius less than -0.7.</p><p><b>RESULTS</b>BMD was reduced in epileptic children significantly when compared to the controls (P < 0.05). In addition, a negative correlation was found between the duration of anti-epileptic drugs (AEDs) use and BMD (r(s) = -0.21 - -0.31, P < 0.05), the lowest BMD was observed in those who had been treated for the longest time. The serum values of OC in epileptic children were significantly reduced relative to the controls (P < 0.01), children who took VPA had the lowest value of OC. However, the urine values of DPD showed no significant difference between epileptic and healthy children (P > 0.05); children who took CBZ had the highest value of DPD. Thirty-two epileptic children (35%) and five (14%) sex- and age-matched healthy children had reduced BMD, significant difference was found between them (P < 0.05). Moreover, epileptic children with reduced BMD seemed to have higher body mass index (BMI) (P < 0.05), take less daily calcium intake (P < 0.01), and had longer duration of AEDs (P < 0.01). The two risk factors of having reduced BMD in epileptic children were those who had been treated with AEDs for more than five years and higher BMI, while the protective factor was daily calcium intake.</p><p><b>CONCLUSIONS</b>Long-term use of CBZ or VPA is associated with bone metabolism abnormalities, which include reduced BMD and decreased bone turnover (mainly decreased bone formation). Long-term anti-epileptic therapy is an important factor for impaired bone health in epileptic children, and that low calcium intake and high BMI could be two aggravating factors. QUS is a useful method to evaluate BMD of epileptic children who are on long-term anti-epileptic therapy, and to recognize the status of bone health, in helping to promote bone health and improve quality of life in epileptic children by the use of calcium and vitamin D supplementation.</p>