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

Objective A rat model of pulmonary fibrosis was constructed using a single or two intratracheal drops of bleomycin(BLM)and the modeling rate and stability of the two modeling modalities were compared.Methods A total of 150 specific pathogen-free SD rats were divided randomly into blank control(control),single intratracheal drop of bleomycin(BLM-S),and two intratracheal drops of bleomycin(BLM-M)groups.Rats in the BLM-S group received a single dose of 3 mg/kg BLM by noninvasive intratracheal instillation,and rats in BLM-M group received 3 mg/kg BLM on day 1 and BLM 2 mg/kg on day 14.Rats in the control group were given intratracheal instillation of 0.9％sodium chloride(1 mL/kg).The rats were euthanized on days 28,42,56,and 84 after modelling,respectively.Deep inspiratory capacity(IC),vital capacity(VC),static lung compliance(Cchord),and dynamic lung complication(Cdyn)were measured in all rats.Pathological changes in lung tissue were observed,and the extent of alveolitis and fibrosis was graded.Collagen-Ⅲ(COL-Ⅲ)expression in rat lung tissue was detected by immunohistochemistry.Results(1)The survival rates in the control,BLM-S,and BLM-M groups were 100％,80％,and 66％,respectively.Rats in the BLM-S and BLM-M groups had significantly lower body weights on days 14～42 compared with the control group(P＜0.05,P＜0.01),and rats in the BLM-M group had significantly lower body weight on days 28～42 than rats in the control and BLM-S groups(P＜0.05,P＜0.01).(2)Regarding lung function,IC,VC,Cchord,and Cdyn were all markedly decreased in the BLM-S group compared with the control group(P＜0.05,P＜0.01)and IC,VC,and Cchord were significantly decreased in the BLM-M group(P＜0.05,P＜0.01)on day 28.IC,VC,and Cchord were significantly decreased in rats in the BLM-S group on day 42(P＜0.05,P＜0.01),and were also significantly decreased in rats in the BLM-M group on days 42～84(P＜0.05,P＜0.01).(3)In terms of lung pathology,inflammatory infiltration and fibrous cords appeared in the BLM-S group from days 28～84 and then gradually decreased(P＜0.05,P＜0.01),while fibrosis and alveolitis were relatively stable in the BLM-M group(P＜0.05,P＜0.01).(4)COL-Ⅲ expression levels in lung tissue were significantly higher in rats in the BLM-S and BLM-M groups compared with the control group(P＜0.05,P＜0.01),and the COL-Ⅲ content in the BLM-S group was significantly lower at 42～84 days than at 28 days(P＜0.05).Conclusions Both method are capable of effectively creating pulmonary fibrosis models.The single-dose approach is straightforward,has a lower death rate,and the degree of fibrosis is clearly visible by day 28,but progressively recovers after 42 days.In contrast,the two-dose instillation model has a greater success rate and better stability,with over half the rats still exhibiting visible fibrosis on day 84.

Objective To compare the success rate and stability of rat pulmonary fibrosis(PF)models induced by intratracheal instillation of different doses of bleomycin(BLM).Methods One hundred and fifty Sprague Dawley rats were divided randomly into control,low-dose BLM 3 mg/kg(BL-L),and high-dose BLM 5 mg/kg(BL-H)groups.General status,mortality,and weight changes were observed,and the lung inspiratory capacity(IC),vital capacity(VC),chord compliance(Cchord),and dynamic compliance(Cdyn)were detected on days 28,42,56,and 84.Lung coefficients were recorded and pathological changes in lung tissue were observed by hematoxylin and eosin and Masson staining.The lung hydroxyproline(HYP)content was detected and collagen type Ⅲ(COL Ⅲ)was detected by immunohistochemistry.Results The mortality rates in the BL-L and BL-H groups were 20％and 28％,respectively.Body weight was significantly lower in the BL-L group compared with the control group on days 0～56,and weight recovery after day 56.Body weight was significantly lower in the BL-H group compared with the control and BL-L groups from days 0～56(P＜0.01).Regarding lung function,IC,VC,Cchord,and Cdyn were significantly lower in the BL-L group compared with the control group on day 28(P＜0.01,P＜0.05),and IC and Cdyn were significantly lower in the BL-H group(P＜0.01).IC,VC,and Cchord were significantly decreased in the BL-L group on day 42(P＜0.01,P＜0.05),while IC,VC,Cchord,and Cdyn were significantly decreased in the BL-H group(P＜0.01,P＜0.05),and IC,VC,and Cchord were significantly lower compared with in the BL-L group(P＜0.01).Cchord was significantly lower in the BL-H group compared with the control and BL-L groups on day 56(P＜0.01).The lung coefficients on day 28 were significantly higher in the BL-L and BL-H groups compared with the control group(P＜0.01),and were significantly higher in the BL-H group from days 42～56 compared with the BL-L and control groups(P＜0.01).Regarding lung histopathology and immunohistochemistry,inflammatory infiltration,fibrotic streaks,and COL Ⅲ expression were observed in the BL-L group from days 28～56,and almost complete disappearance of the fibrotic lesions on day 84.In contrast,fibrotic lesions could be observed from days 28～84 in the BL-H group,with significantly elevated COL Ⅲ expression compared with the control group(P＜0.01).The HYP content was significantly higher in the BL-L group compared with the control group from days 28～42(P＜0.05,P＜0.01),and then gradually decreased,and the HYP content was significantly higher in the BL-H group than in the control group from days 28～84(P＜0.01).Conclusions Both 3 and 5 mg/kg BLM can successfully induce PF rat models.Rats treated with 3 mg/kg BLM developed fibrosis on day 28,which lasted until day 42 and then gradually recovered.Rats treated with 5 mg/kg BLM developed fibrosis on day 28,and the degree of fibrosis was more severe with the higher compared with the lower dose,with stable fibrotic lesions up to day 56 and moderate-to-severe fibrosis still present in half of the rats until day 84.

By identifying and analyzing the problems and difficulties in the implementation process of student stratification, goal stratification, practice stratification, and assessment stratification in standardized residency training, this article proposes to fully leverage the main role of professional bases in hierarchical and progressive teaching for standardized residency training and strengthen the specific responsibilities of professional base teaching groups in discussing hierarchical and progressive teaching plans, evaluation standards, and assessments. It is also necessary to scientifically implement student stratification, achieve consistent stratification goals, strengthen the training of hierarchical and progressive teaching concepts and teaching abilities for teachers, enhance the ability for homogeneous and hierarchical evaluation, and develop countermeasures that combine stage training goal process evaluation with dynamic personalized teaching by mentors, so as to provide a useful reference for further promoting the reform of standardized residency training using a hierarchical and progressive teaching model.

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 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.