Parkinson's disease （PD） is a complex neurodegenerative disease involving multiple systems and neurotransmitters. Due to the high clinical heterogeneity of PD，it is urgent to establish a comprehensive and long-term traditional Chinese medicine （TCM） management model. In this paper，the conceptual framework of full-cycle management of PD is preliminarily constructed：based on the evolution of the pathophysiological mechanisms of protein deposition and neurotransmitter disorder in PD，the three-stage syndrome characteristics of the prodromal stage （predominant healthy Qi with subtle pathogenic factors），the early clinical stage （declining healthy Qi with growing pathogenic factors） and the middle and late stages （overwhelming pathogenic factors with deficient healthy Qi） are longitudinally described. Through the syndrome differentiation of visceral manifestations，the etiology and pathogenesis of PD motor and non-motor symptoms were comprehensively analyzed，while the matching treatment methods and prescriptions were inferred，and the modular scheme of the combining main symptoms，accompanying symptoms and secondary symptoms was proposed. The conceptual gap of TCM regarding motor complications （'variable syndrome'） and PD-related hyperpyrexia syndrome （'critical syndrome'） was explained. This framework reflects the characteristics of combination of disease and syndrome and overall constant motion，and provides new theories and research ideas for individualized and whole-process management of PD in TCM.

Parkinson's disease （PD） is a complex neurodegenerative disease involving multiple systems and neurotransmitters. Due to the high clinical heterogeneity of PD，it is urgent to establish a comprehensive and long-term traditional Chinese medicine （TCM） management model. In this paper，the conceptual framework of full-cycle management of PD is preliminarily constructed：based on the evolution of the pathophysiological mechanisms of protein deposition and neurotransmitter disorder in PD，the three-stage syndrome characteristics of the prodromal stage （predominant healthy Qi with subtle pathogenic factors），the early clinical stage （declining healthy Qi with growing pathogenic factors） and the middle and late stages （overwhelming pathogenic factors with deficient healthy Qi） are longitudinally described. Through the syndrome differentiation of visceral manifestations，the etiology and pathogenesis of PD motor and non-motor symptoms were comprehensively analyzed，while the matching treatment methods and prescriptions were inferred，and the modular scheme of the combining main symptoms，accompanying symptoms and secondary symptoms was proposed. The conceptual gap of TCM regarding motor complications （'variable syndrome'） and PD-related hyperpyrexia syndrome （'critical syndrome'） was explained. This framework reflects the characteristics of combination of disease and syndrome and overall constant motion，and provides new theories and research ideas for individualized and whole-process management of PD in TCM.

Objective To investigate the role of JAK2/STAT3 signaling pathway mediated Treg/Th17 imbalance in children with cow's milk protein allergy and the effect of dietary avoidance on the imbalance.Methods A total of 103 children with cow's milk protein allergy in the hospital were enrolled and divided in-to the IgE-mediated group(n=38)and the non-IgE-mediated group(n=65).All patients underwent a 3-month strict dietary avoidance intervention.A total of 100 healthy children who underwent health checkups at the hospital's physical examination center during the same period,with no history of food allergy or other im-mune-related diseases,were selected as the healthy control group.The percentages of Treg and Th17 cells were measured by flow cytometry.The mRNA expression levels of JAK2,STAT3,SOCS1,and SOCS3 were determined by qPCR.Differences between groups,changes before and after dietary avoidance,and correlations between these indicators and clinical symptoms were analyzed using Pearson's test.Results At baseline,both the IgE-mediated group and the non-IgE-mediated group had significantly lower Treg percentages and SOCS1/SOCS3 mRNA levels,and higher Th17 percentages and JAK2/STAT3 mRNA levels compared to the healthy control group(P＜0.05).After dietary avoidance,Treg percentages and SOCS1/SOCS3 mRNA levels in-creased,while Th17 percentages and JAK2/STAT3 mRNA levels decreased in the IgE-mediated group and the non-IgE-mediated group(P＜0.05).The increase of Treg percentage and the decrease of Th17 percentage in the non-IgE-mediated group were greater than in the IgE-mediated group,whereas the increases of SOCS1 and SOCS3 mRNA levels were smaller in the non-IgE-mediated group(P＜0.05).Logistic regression identified JAK2,STAT3,SOCS1,and SOCS3 mRNA levels as factors influencing Treg and Th17 percentages(P＜0.05).Pearson correlation analysis revealed that allergic symptom scores and serum milk-specific IgE levels were positively correlated with JAK2/STAT3 mRNA levels and Th17 percentage,and negatively correlated with SOCS1/SOCS3 mRNA levels,Treg percentage,and the Treg/Th17 ratio(P＜0.05).Conclusion Dieta-ry avoidance can modulate the activity of JAK2/STAT3 signaling pathway,with a more pronounced improve-ment in non-IgE-mediated cow's milk protein allergy.

OBJECTIVES: To explore the effects of acupuncture combined with rehabilitation training for promoting transdifferentiation of astrocytes into neurons in mice after cerebral ischemia. METHODS: Male C57/BL6J mice were subjected to intracerebral microinjection of an adeno-associated virus carrying the GFAP promoter for NeuroD1 and Ngn2 overexpression in the astrocytes, followed 3 or 12 days later by electrocoagulation of the distal middle cerebral artery. After modeling, the mice were randomly divided into model group without interventions and intervention group treated with electroacupuncture at the acupoints Baihui (GV20), left Hegu (LI4), Neiguan (PC6), Zusanli (ST36), and Yanglingquan (GB34) 24 h after surgery. The mice in the intervention group were housed individually in cages with running wheels, and their activity was recorded every 24 h. Neurological function scores of the mice were assessed on the 1st, 14th, and 21st days after modeling. Transdifferentiation of astrocytes in the target brain regions was observed using double immunofluorescence staining. RESULTS: Compared with those in the model group, the mice receiving eletroacupuncture and rehabilitation training showed significant improvement of neurological deficits at 14 and 21 days after modeling. The GFAP promoter of the AAV2/5 vector specifically labeled the local astrocytes, and compared with that that in the model group, the number of AAV-positive cells colabeled with the neuronal marker DCX significantly increased after 14 days of electroacupuncture and rehabilitation intervention, and the number of AAV-positive cells colabeled with the neuronal marker NeuN significantly increased after 21 days of intervention. CONCLUSIONS In mice with cerebral ischemia, electroacupuncture and rehabilitation training can promote transdifferentiation of astrocytes into neurons in the ischemic brain region, and the efficiency of transdifferentiation is positively correlated with the improvement of motor function.
Animals ; Electroacupuncture ; Astrocytes/cytology* ; Cell Transdifferentiation ; Male ; Mice, Inbred C57BL ; Brain Ischemia/physiopathology* ; Mice ; Neurons/cytology* ; Doublecortin Protein

Gout is a metabolic disease closely associated with hyperuricemia and urate deposition. Because of the complex pathogenesis， high morbidity， multiple complications， and increasingly young patients， gout has received worldwide attention. Currently， western medicine mainly treats gout by lowering the uric acid level and reducing inflammation， which， however， causes serious adverse reactions and has contraindications. Phellodendri Chinensis Cortex （PCC） is the dried bark of Phellodendron chinense， with the effects of clearing heat， drying dampness， purging fire， detoxifying， and treating sores. Studies have shown that PCC and its active components have anti-inflammatory， pain-relieving， uric acid-lowering， and anti-gout activities， with extensive sources and high safety. PCC and its active components could prevent and treat gout through multi-targets and multi-pathways， whereas the systematic review remains to be carried out. Therefore， this paper summarized the pharmacological activities and mechanisms of PCC and its active components in the treatment of gout. The available studies have shown that PCC and its active components exert the anti-gout effect by lowering the uric acid level， reducing inflammation， alleviating oxidative stress， and regulationg intestinal flora， and protecting the kidneys. Particularly， the active components represented by alkaloids contribute obviously to the therapeutic effect of of PCC. Herein， we analyzed the problems and future development of the research on PCC， aiming to provide theoretical support and a scientific basis for the research and development of new drugs against gout.

Objective·To explore the correlation between comorbidities of chronic non-communicable diseases(chronic diseases),phase angle(PhA),and muscle mass decline associated with sarcopenia in the elderly,and the predictive value of chronic disease comorbidities and PhA in muscle mass decline in the elderly.Methods·By retrospectively screening inpatients aged≥60 years who were admitted to the Department of Geriatrics,Renji Hospital,Shanghai Jiao Tong University School of Medicine from August 1,2018 to July 31,2019,basic information and medical history of the patients(gender,age,number of medications used,number of comorbidities,presence of osteoporosis,smoking history,etc.)were collected,as well as laboratory examination indicators(hemoglobin,albumin,serum creatinine,serum uric acid,ferritin,vitamin D,triacylglycerol,total cholesterol,high-density lipoprotein,low-density lipoprotein,etc.).The age-adjusted Charlson comorbidity index(aCCI)was calculated.The InBody S10 bioelectrical impedance body composition detector was used to test the body composition.Body mass index(BMI),skeletal muscle mass index(SMI),and PhA were collected.Some patients underwent measurement of grip strength.Muscle mass decline was diagnosed by using the SMI values recommended by the 2019 Asian Working Group for Sarcopenia(AWGS)(≤7.0 kg/m2 for males and≤5.7 kg/m2 for females).According to the measured SMI values,patients were divided into a group with normal muscle mass and a group with muscle mass decline.Univariate and multivariate Logistic analyses were employed to investigate the risk factors associated with muscle mass decline related to sarcopenia in the elderly.Additionally,the receiver operator characteristic(ROC)curve and the area under the curve were utilized to predict the significance of these factors in muscle mass decline.Results·A total of 359 chronic disease patients were enrolled,including 226 males and 133 females.There were 241 cases in the normal muscle mass group and 118 cases in the muscle mass decline group.The incidence of muscle mass decline related to sarcopenia in the elderly was 32.9%.The univariate Logistic regression analysis showed that age(OR=1.036,95%CI 1.013?1.060),comorbidities(OR=1.117,95%CI 1.025?1.217),aCCI(OR=1.123,95%CI 1.031?1.222),and high-density lipoprotein(OR=3.688,95%CI 2.065?6.622)were positively correlated with the risk of muscle mass decline in the elderly.BMI(OR=0.514,95%CI 0.443?0.597),PhA(OR=0.195,95%CI 0.126?0.303),hemoglobin(OR=0.984,95%CI 0.972?0.996)and triacylglycerol(OR=0.606,95%CI 0.424?0.866)were negatively correlated with the risk of muscle mass decline in the elderly.Multivariate Logistic regression model indicated that PhA(OR=0.338,95%CI 0.119?0.959)and BMI(OR=0.634,95%CI 0.476?0.844)were negatively correlated with the risk of muscle mass decline in elderly.The area under the ROC curve for predicting muscle mass decline related to sarcopenia in elderly by using BMI and PhA was 0.893(95%CI 0.855?0.931)and 0.786(95%CI 0.736?0.837),respectively.The sensitivity was 0.724 and 0.676,respectively.The specificity was 0.916 and 0.762,respectively.When BMI combined with PhA predicted muscle mass decline in the elderly,the area under the ROC curve was 0.917(95%CI 0.883?0.951).The sensitivity was 0.867,and the specificity was 0.860.Conclusion·aCCI is correlated with muscle mass decline associated with sarcopenia in the elderly.As BMI and PhA decrease,the risk of muscle mass decline in the elderly increases.The combination of BMI and PhA has a high predictive value in muscle mass decline in the elderly.No predictive value of chronic diseases comorbidities in muscle mass decline related to sarcopenia in the elderly is found.

Objective:To study the protective effects and mechanism of Melastoma sanguineum Sims fruit extract (MSE) on chronic chemical liver injury induced by ethanol, acetaminophen and carbon tetrachloride in mice; To discuss it mechanism.Methods:Totally 96 mice were divided into normal control group, ethanol model group, ethanol+bifendate control group and ethanol+MSE high-, medium- and low-dosage groups, APAP model group, APAP+bifendate control group and APAP+MSE high-, medium- and low-dosage groups, CCl 4 model group, CCl 4+bifendate control group and CCl 4+MSE high-, medium- and low-dosage groups, with 6 mice in each group. Except for the normal control group, the other groups were respectively prepared for the ethanol model, the APAP model and the CCl 4 model. The mice in the MSE high-, medium- and low-dosage groups were intragastrically administrated with 10, 5 and 2.5 g/kg of MSE, respectively; the bifendate control group was intraperitoneally injected with 15 mg/ml bifendate solution at 75 mg/kg; the normal control group was intraperitoneally injected with equal volume of normal saline/peanut oil solution once a day for 25 consecutive days. The levels of GPT, GOT and total bilirubin (TBIL) in serum were detected; the activities of SOD and GSH-Px and the content of MDA in liver tissue were detected; the mRNA expressions of TNF-α, IL-6, alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) were detected by qRT-PCR; the protein expressions of cytochrome P450 CYP1A1, CYP1A2, and CYP3A in liver tissue were detected by Western blot; the pathological changes of the liver tissue were observed by HE staining. Results:Compared with the corresponding ethanol, APAP and CCl 4 model groups, the serum GPT, GOT and TBIL levels of mice in the ethanol+bifendate control group and ethanol+MSE high- and medium-dosage groups, the APAP+bifendate control group and APAP+MSE high- and medium-dosage groups, and the CCl 4+bifendate control group and CCl 4+MSE high- and medium-dosage groups decreased ( P<0.01 or P<0.05), the activities of SOD and GSH-Px in the liver tissue increased ( P<0.01 or P<0.05), and the MDA level decreased ( P<0.01 or P<0.05), and the mRNA levels of IL-6 and TNF-α decreased ( P<0.01); the mRNA levels of ADH and ALDH in the ethanol+MSE high-, medium-, and low-dosage groups decreased ( P<0.01). Compared with the APAP model group, the expressions of CYP1A1 and CYP1A2 in the APAP+MSE groups increased ( P<0.01), and the expression of CYP3A protein decreased ( P<0.05); compared with the CCl 4 model group, the expressions of CYP1A1, CYP1A2 and CYP3A proteins in the CCl 4+MSE groups decreased ( P<0.05). Conclusion:MSE has a protective effect on chronic chemically-induced liver injury induced by ethanol, APAP, and CCl 4 in mice, and its mechanism may be related to antioxidant stress, inhibition of inflammatory response, and regulation of the expression of cytochrome P450-related enzymes.

Objective To modify the method for establishing mouse models of middle cerebral artery occlusion(MCAO)-induced focal cerebral ischemia using electrocoagulation.Methods Forty-six C57/BL6J male mice were divided into MCAO model group(n=34)and sham-operated group(n=12).In the model group,MCAO was induced by permanent coagulation of the right middle cerebral artery(MCA)using a coagulator,and cerebral blood flow perfusion was monitored before and at 20 min and 1 day after modeling.Neurological deficits of the mice at 1,7,and 14 days after modeling were evaluated using Longa score,mNSS score,beam walking test,cylinder test and corner test.TTC staining was used to measure the cerebral infarct size,and Western blotting was performed to detect the expressions of BDNF,GFAP and DCX proteins in the ischemic cortex.Results The mice in the model group showed significantly reduced cerebral blood flow in the MCA on the ischemic side and obvious neurological deficits with increased forelimb use asymmetry on days 1,7 and 14 after modeling(P<0.05).In the cerebral cortex on the ischemic side of the model mice,the expressions of GFAP and DCX increased significantly at 1,7,and 14 days(P<0.05)and the expression of BDNF increased at 1 day after modeling ischemia(P<0.05).Conclusion We successfully prepared mouse models of MCAO using a modified method by changing the electrocoagulation location from the distal location of the junction between the MCA and the inferior cerebral vein to a 2 mm segment medial to the junction between the MCA and the olfactory bundle.

Objective To modify the method for establishing mouse models of middle cerebral artery occlusion(MCAO)-induced focal cerebral ischemia using electrocoagulation.Methods Forty-six C57/BL6J male mice were divided into MCAO model group(n=34)and sham-operated group(n=12).In the model group,MCAO was induced by permanent coagulation of the right middle cerebral artery(MCA)using a coagulator,and cerebral blood flow perfusion was monitored before and at 20 min and 1 day after modeling.Neurological deficits of the mice at 1,7,and 14 days after modeling were evaluated using Longa score,mNSS score,beam walking test,cylinder test and corner test.TTC staining was used to measure the cerebral infarct size,and Western blotting was performed to detect the expressions of BDNF,GFAP and DCX proteins in the ischemic cortex.Results The mice in the model group showed significantly reduced cerebral blood flow in the MCA on the ischemic side and obvious neurological deficits with increased forelimb use asymmetry on days 1,7 and 14 after modeling(P<0.05).In the cerebral cortex on the ischemic side of the model mice,the expressions of GFAP and DCX increased significantly at 1,7,and 14 days(P<0.05)and the expression of BDNF increased at 1 day after modeling ischemia(P<0.05).Conclusion We successfully prepared mouse models of MCAO using a modified method by changing the electrocoagulation location from the distal location of the junction between the MCA and the inferior cerebral vein to a 2 mm segment medial to the junction between the MCA and the olfactory bundle.

Objective·To investigate the current situation and distribution characteristics of chronic comorbidities,and to provide reference for further improving the self-management of comorbidities and implementing the whole course and all-round management of comorbidity.Methods·Two thousand and forty-five inpatients in the Department of Geriatrics,Renji Hospital,Shanghai Jiao Tong University School of Medicine were enrolled in this study from December 2020 to February 2023.The general vital signs,routine laboratory examination and disease status were collected.The epidemiological distribution characteristics of chronic diseases and comorbidities were analyzed.Results·The incidence of chronic diseases in the surveyed population was 99.6％,and the incidence of comorbidities was 94.2％.The top 5 chronic diseases were hypertension(43.68％),diabetes mellitus(24.81％),malignant tumor(21.48％),hyperlipidemia(18.38％)and coronary heart disease(11.99％).The detection rates of hypertension,diabetes mellitus,coronary heart disease,chronic obstructive pulmonary disease,stoke and chronic kidney disease in males were significantly higher than those in females(P＜0.05).The proportion of patients with 5 chronic diseases was the highest(11.99％),followed by 7 chronic diseases(10.26％)and 6 chronic diseases(10.04％).Among the patients of different ages,the comorbidity rate was the highest in the patients aged 50-59 years(27.78％).In different age groups,patients aged 50 to 59 with 2 chronic diseases had the highest incidence of comorbidity,which was as high as 40.82％.Although the overall proportion of comorbidities among male patients(95.37％)was higher than that among females(93.77％),there was no statistically significant difference(P=0.125).However,the proportions of male patients with 2 and 5 chronic diseases were 70.41％and 60.63％,respectively,which were significantly higher than those of female patients(29.59％and 39.37％).The correlations between coronary heart disease and diabetes mellitus,hypertension and coronary heart disease,hypertension and diabetes mellitus were higher(r=0.24,r=0.27,r=0.35,all P＜0.05).Conclusion·The prevalence of chronic diseases and comorbidities is high in the middle-aged and elderly population,and the number of comorbidities increases significantly with the increase of age.