Parkinson disease is a progressive neurodegenerative disease whose incidence increases year by year as the population ages.TCM compounds for the treatment of Parkinson disease has the characteristics of multiple components,targets,and pathways.Combined treatment with Western medicine can achieve synergistic effects and reduce adverse drug reactions.This article focused on the mechanism of TCM compounds for the treatment of Parkinson disease,reviewed relevant experimental studies in recent years.TCM compounds may exert therapeutic effects on Parkinson disease by regulating oxidative stress,mitochondrial dysfunction,neurotransmitters,neuroinflammation,abnormal protein aggregation,cell apoptosis,stem cell transplantation,neurotrophic factors,second messengers,and other mechanisms,in order to provide basis for clinical treatment of Parkinson disease.

Objective:To investigate the clinical manifestations, treatment, and outcomes of Barth syndrome (BTHS).Methods:A retrospective analysis was conducted on 21 pediatric patients diagnosed with BTHS between January 2010 and December 2023 at Beijing Children′s Hospital, Beijing Anzhen Hospital, and Beijing JingDu Children′s Hospital. Clinical data including gender, age at onset, initial symptoms, clinical manifestations, personal history, family genetic history, and laboratory tests (neutrophil count, echocardiography, electrocardiogram and genetic testing) were reviewed.Results:All the 21 patients were male, with the age of onset at 4.1 (1.1, 9.3) months. Main clinical manifestations included heart failure (18 cases), neutropenia (16 cases), respiratory symptoms (15 cases), 3-methylpentenediuria (7 cases),develop retardation (8 cases), gastrointestinal symptoms (7 cases), fatigue and anorexia (6 cases), and recurrent infection (2 cases). Electrocardiogram abnormalities included ST changes (18 cases), flattened T wave and low voltage of limb leads (2 cases), and abnormal Q waves in lead Ⅰ and avL (1 case). Echocardiographic features showed increased trabeculation, interventricular septum and left ventricular wall thickening, and left ventricular enlargement with reduced ejection fraction. Genetic testing identified TAZ gene variations in all 21 patients: 11 missense mutations, 2 nonsense mutations, 2 frameshift mutations, 2 whole code mutations, 2 exon deletions, 1 splicing mutation, and 1 synonymous mutation. Fifteen mutations were maternally inherited, 2 were de novo, and 4 lacked verified variant origin.In terms of treatment, all 18 patients with heart failure received routine heart failure treatment, of whom 11 patients also received intravenous immunoglobulin and corticosteroids. After the follow-up of 91.0 (75.5, 109.5) months, 15 of the 18 patients showed restoration of cardiac function after 4.5 (3.0, 9.8) months of treatment, with one case of significant improvement, while 2 cases suddenly died.Conclusions:BTHS predominantly affects males with early onset, mainly characterized by abnormal cardiac structure and function, along with clinical features including fatigue, delayed growth and development, and neutropenia. Early diagnosis and intervention, including heart failure treatment, intravenous immunoglobulin, and corticosteroids, can lead to significant improvement in cardiac function, though sudden death remains a risk.

Parkinson disease is a progressive neurodegenerative disease whose incidence increases year by year as the population ages.TCM compounds for the treatment of Parkinson disease has the characteristics of multiple components,targets,and pathways.Combined treatment with Western medicine can achieve synergistic effects and reduce adverse drug reactions.This article focused on the mechanism of TCM compounds for the treatment of Parkinson disease,reviewed relevant experimental studies in recent years.TCM compounds may exert therapeutic effects on Parkinson disease by regulating oxidative stress,mitochondrial dysfunction,neurotransmitters,neuroinflammation,abnormal protein aggregation,cell apoptosis,stem cell transplantation,neurotrophic factors,second messengers,and other mechanisms,in order to provide basis for clinical treatment of Parkinson disease.

Objective:To investigate the clinical manifestations, treatment, and outcomes of Barth syndrome (BTHS).Methods:A retrospective analysis was conducted on 21 pediatric patients diagnosed with BTHS between January 2010 and December 2023 at Beijing Children′s Hospital, Beijing Anzhen Hospital, and Beijing JingDu Children′s Hospital. Clinical data including gender, age at onset, initial symptoms, clinical manifestations, personal history, family genetic history, and laboratory tests (neutrophil count, echocardiography, electrocardiogram and genetic testing) were reviewed.Results:All the 21 patients were male, with the age of onset at 4.1 (1.1, 9.3) months. Main clinical manifestations included heart failure (18 cases), neutropenia (16 cases), respiratory symptoms (15 cases), 3-methylpentenediuria (7 cases),develop retardation (8 cases), gastrointestinal symptoms (7 cases), fatigue and anorexia (6 cases), and recurrent infection (2 cases). Electrocardiogram abnormalities included ST changes (18 cases), flattened T wave and low voltage of limb leads (2 cases), and abnormal Q waves in lead Ⅰ and avL (1 case). Echocardiographic features showed increased trabeculation, interventricular septum and left ventricular wall thickening, and left ventricular enlargement with reduced ejection fraction. Genetic testing identified TAZ gene variations in all 21 patients: 11 missense mutations, 2 nonsense mutations, 2 frameshift mutations, 2 whole code mutations, 2 exon deletions, 1 splicing mutation, and 1 synonymous mutation. Fifteen mutations were maternally inherited, 2 were de novo, and 4 lacked verified variant origin.In terms of treatment, all 18 patients with heart failure received routine heart failure treatment, of whom 11 patients also received intravenous immunoglobulin and corticosteroids. After the follow-up of 91.0 (75.5, 109.5) months, 15 of the 18 patients showed restoration of cardiac function after 4.5 (3.0, 9.8) months of treatment, with one case of significant improvement, while 2 cases suddenly died.Conclusions:BTHS predominantly affects males with early onset, mainly characterized by abnormal cardiac structure and function, along with clinical features including fatigue, delayed growth and development, and neutropenia. Early diagnosis and intervention, including heart failure treatment, intravenous immunoglobulin, and corticosteroids, can lead to significant improvement in cardiac function, though sudden death remains a risk.

Nonalcoholic fatty liver disease （NAFLD） is an abnormal lipid metabolic disorder of the liver characterized by accumulation of a large amount of lipids in the liver， and it is currently the most common liver disease around the world. Mendelian randomization （MR） incorporates genomic data into traditional epidemiological study designs to infer the causal relationship between exposure factors and disease risk. In recent years， MR has been widely used in studies on inference of the etiology of NAFLD. This article systematically summarizes the advances in the application of MR in NAFLD research， so as to provide new ideas for understanding the nature of the disease and scientific interventions.

OBJECTIVE To explore the molecular mechanism of Compound Dihuang Granule in treating Parkinson's disease(PD)with yin-deficiency and dynamic wind syndrome by regulating the changes of ubiquitin-proteasome system-related proteins.METHODS SPF male SD rats were randomly selected as normal control group and sham operation group,13 rats in each group.The remaining rats were treated with 6-hydroxydopamine lateral brain injection to damage the substantia nigra to establish PD yin-deficien-cy and dynamic wind syndrome rat model.The established rats were randomly divided into model group,madopar group(150 mg·kg-1),low,medium and high dose groups of Compound Dihuang Granule(1.75,3.5,7 g·kg-1),13 rats in each group.Each group was given drugs by intragastric gavage for 28 d.The general conditions and neurobehavioral manifestations of the rats were observed;the expression of ubiquitin(UB),ubiquitin activating enzyme(UBE1),ubiquitin conjugating enzyme(UBE2A)and ubiquitin carboxyl terminal hydrolase(UCH-L1)positive cells,protein and mRNA expression levels in the damaged lateral stria-tum of the brain of rats were detected by immunohistochemistry,Western blot and qPCR methods;changes of dopamine(DA)content in the damaged lateral striatum of the brain of rats were detected by ELISA.RESULTS There was no significant difference in general conditions between the normal control group and the sham operation group,and there was no significant difference in the number of ro-tations,suspension time and number of moving grids.Compared to the sham-op group,the model group rats showed poor spirit,irrita-bility,limb tremor,slow movement,dark yellow fur,less food intake,reduced body weight;the modeling increased number of rota-tions,decreased hanging time and number of moving grids(P<0.01),significantly decreased expression of UB,UBE1,UBE2A,and UCH-L1 positive cells,mRNA and protein expression levels in the damaged lateral striatum(P<0.01),and significantly decreased DA content(P<0.01).Compared with the model group,the general condition of the rats in the madopar group and Compound Di-huang Granule groups was improved,the number of rotations was reduced,the hanging time and number of moving grids were increased(P<0.05,P<0.01),the expression of UB,UBE1,UBE2A,and UCH-L1 positive cells,mRNA and protein expression levels were increased(P<0.05,P<0.01),and the DA content was increased(P<0.01);behavioral tests and the expression levels of various in-dicators were most significantly improved in the madopar group and the high-dose Compound Dihuang Granule group(P<0.05,P<0.01),and there was no statistical significance between the two groups.CONCLUSION Compound Dihuang Granule may play a role in treating PD yin-deficiency and dynamic wind syndrome by regulating the expression of ubiquitin-proteasome system-related proteins,reducing abnormal protein aggregation,and thus alleviating DA content deficiency,and the high-dose Compound Dihuang Granule has the best effect.

Objective To observe the effects of compound Dihuang Granules on striatum PINK1,Parkin and α-syn in rats with Parkinson disease yin-deficiency and wind movement syndrome;To explore the mechanism of compound Dihuang Granules in the treatment of Parkinson disease yin-deficiency and wind movement syndrome.Methods 6-hydroxydopamine was injected into the substantia nigra of the midbrain to prepare the model of PD yin-deficiency and wind movement syndrome.Totally 65 model rats were randomly divided into model group,Madopar(150 mg/kg)group,and TCM low-,medium-,and high-dosage(1.75,3.5,7 g/kg)groups.Another 26 rats were divided into normal control group and sham-operation group,with 13 rats in each group.Each administration group was given corresponding medication solution by gavage,the normal control group,sham-operation group and the model group were given equivalent volume of normal saline,once a day for 28 consecutive days.The behavioral changes of rats were detected,ELISA and biochemical assay kits were used to detect ATP content and COX Ⅳactivity in striatum,HE staining was used to observe the morphological changes of the striatum,immunohistochemistry staining,Western blot and RT-qPCR were used to detect the expression of PINK1,Parkin,α-syn protein and mRNA in striatal tissue.Results Compared with the normal control group and the sham-operation group,the rats in the model group showed increased number of rotations and pole climbing time,decreased swimming score(P<0.01),the ATP content and COX Ⅳ activity in striatum tissue decreased(P<0.01),with disordered arrangement and reduced number of neurons,cell swelling,partial nuclear shrinkage,formation of vacuoles,and blurred boundaries,the expressions of PINK1,Parkin protein and mRNA in striatal tissue decreased(P<0.01),and the expressions of α-syn protein and mRNA increased(P<0.01).Compared with the model group,the number of rotations and pole climbing time of rats in each medication group decreased,swimming scores increased(P<0.01),ATP content and COX Ⅳ activity in striatal tissue increased(P<0.05,P<0.01),the number of neurons increased,the arrangement tended to be neat,and the morphology improved,the expressions of PINK1,Parkin protein and mRNA in striatal tissue increased(P<0.05,P<0.01),the expressions of α-syn protein and mRNA decreased(P<0.05,P<0.01).The improvement was most significant in the Medopar group and TCM high-dosage group(P<0.05,P<0.01),and there was no significant difference between the two groups(P>0.05),and TCM groups showed dosage dependence(P<0.05,P<0.01).Conclusion Compound Dihuang Granules can improve the behavioral symptoms of Parkinson disease yin-deficiency and wind movement syndrome,possibly by regulating the expressions of PINK1,Parkin and α-syn in the striatum tissue,thereby alleviating mitochondrial dysfunction,protecting dopaminergic neurons,and playing a role in treating Parkinson disease.

Objective To observe the effect of compound Dihuang Granules on the expressions of DJ-1,IP3R,GRP75 and VDAC1 in liver and colonic tissue of Parkinson disease(PD)rats with yin deficiency and wind movement syndrome.Methods 6-Hydroxydopamine was used to inject into the right substantia nigra to prepare PD with yin deficiency and wind movement syndrome rats model.65 rats that successfully modeled were randomly divided into model group,madopar group(madopar 150 mg/kg)and TCM low-,medium-and high-dosage groups(compound Dihuang Granules 1.75,3.5,7 g/kg),with 13 rats in each group;another 13 rats without intervention were selected as the normal control group,and 13 rats were only injected with ascorbic acid solution as sham-operation group.The administration groups were given corresponding drugs by gavage,and the normal control group,sham-operation group and model group were given normal saline by gavage,once a day for 28 consecutive days.The neurobehavioral changes of rats were observed,and the morphology of liver tissue and colonic tissue were observed by HE staining,the protein and mRNA expressions of DJ-1,IP3R,GRP75 and VDAC1 in liver and colonic tissue were detected by immunohistochemical staining,Western blot and RT-PCR,respectively.Results Compared with the normal control group and the sham-operation group,the number of rotation circles of rats in the model group increased,with granular degeneration of liver tissue,loose cytoplasm of cells,slight hepatic steatosis,edema of colonic mucosal and submucosal layers,loose connective tissue,infiltration of a small number of lymphocytes,and significant vascular dilation,the expressions of DJ-1,IP3R,GRP75 and VDAC1 protein and mRNA in liver and colonic tissue were significantly decreased(P<0.01).Compared with the model group,the number of rotation circles of rats in madopar group and TCM groups were significantly decreased,with mild granular degeneration of liver cells,loose cytoplasm,orderly arrangement of hepatic cords,mild edema of the colon,a small amount of lymphocyte and granulocyte infiltration,and a small amount of vascular dilation,the protein and mRNA expressions of DJ-1,IP3R,GRP75 and VDAC1 in liver and colonic tissue significantly increased(P<0.05).The TCM high-dosage group showing the most obvious changes,there was no statistical significance with the madopar group(P>0.05).Conclusion Compound Dihuang Granules may restore endoplasmic reticulum-mitochondria homeostasis,improve gut-liver-brain axis mitochondrial function,protect dopamine neurons,and delay PD by regulating the expressions of DJ-1,IP3R,GRP75 and VDAC1 in liver tissue and colonic tissue.

OBJECTIVE: To analyze the clinical phenotype and pathogenic variant in a child diagnosed with mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH). METHODS: Clinical phenotype of the child was reviewed. Whole exome sequencing was carried out for the child. Candidate variant was verified by Sanger sequencing of the family member. RESULTS: The proband manifested dyskinesia, development delay, cerebellar hypoplasia and bilateral hearing impairment. WES results revealed that the proband has carried a pathogenic c.1641_1644delACAA (p.Thr548Trpfs*69) variant of the CASK gene, which was verified by Sanger sequencing to be a de novo variant. CONCLUSION The c.1641_1644delACAA (p.Thr548Trpfs*69) variant of the CASK gene probably underlay the MICPCH in the proband. Above finding has provided a basis for genetic counseling. WES should be considered for the diagnosis of neurological dysplasia.
Cerebellum/abnormalities* ; Child ; Developmental Disabilities ; Family ; Humans ; Mental Retardation, X-Linked ; Microcephaly/genetics* ; Nervous System Malformations

Chondroitin sulfate (CS) is a sulfurated glycosaminoglycan, a major component of the extracellular matrix, widely distributed in skin, cartilage and vascular tissue. CS plays an important role in the physiological state regulation of articular cartilage, which affects tensile strength and elasticity of tissues by influencing aggrecan. Previous studies have shown that CS sulfate modification may be related to the growth and development disorders of cartilage tissue and the occurrence of osteoarticular diseases. At the same time, CS is also a common joint supplement, often used in the treatment of osteoarthritis and Kashin-Beck disease. In this paper, the research progress of CS sulfate modification characteristics in Kashin-Beck disease and osteoarthritis and the application of the preparation in the treatment of Kashin-Beck disease and osteoarthritis are reviewed, aiming to provide help for the investigation of the etiology of Kashin-Beck disease and the treatment of osteoarthritis and Kashin-Beck disease.