ObjectiveMicrotube associated protein-2 （MAP-2）， alpha-tubulin （α-tubulin）， and synaptophysin （SYP） are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein （α-Syn） and its oligomers， MAP-2， α-tubulin， and SYP of patients with liver and kidney deficiency of Parkinson's disease （PD）， analyzed their correlation， and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group （30 cases） and a control group （30 cases）. Both groups were treated on the basis of PD medicine， and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score， TCM syndrome score， and expression of serum α-Syn and its oligomers， MAP-2， α-tubulin， and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment， the TCM syndrome score， UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ score of the treatment group were significantly decreased （P<0.05， P<0.01）. The UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment （P<0.05）. After treatment， the total effective rate of the control group was 63.3% （19/30）， and that of the treatment group was 86.7% （26/30）. The clinical effect of the observation group was better than the control group （Z=-2.03， P<0.05）. The total effective rate of the observation group was better than that of the control group， and the difference was statistically significant （χ²=5.136， P<0.05）. After treatment， the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased （P<0.05， P<0.01）. The levels of serum α-Syn and its oligomers， as well as α-tubulin in the treatment group， were significantly decreased compared with those in the control group after treatment （P<0.05， P<0.01）. Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD （P<0.05， P<0.01） but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin （P<0.05， P<0.01） but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 （P<0.05）. ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.

BACKGROUND:Platelet-rich plasma is used to promote the proliferation of thin endometrial cells,but there are problems with difficult dose control and sampling.Microfluidic-chips have the advantages of high throughput,low consumption,and simplified operation,providing a new approach to simulate the in vivo microenvironment of endometrial cells. OBJECTIVE:To establish a model of promoting endometrial cell proliferation with platelet-rich plasma by the three-channel microfluidic-chip. METHODS:Platelet-rich plasma was extracted from peripheral venous blood of a female.Human endometrial stromal cells were cultured in serum-free cell media with different concentrations of platelet-rich plasma[0%(control),0.5%,1%,and 2%].Cell migration was detected by scratch test.Cell proliferation was detected by CCK-8 assay.A microfluidic chip was prepared by using polydimethylsiloxane adhesive.The microfluidic chip was designed with three channels.The middle channel was the extracellular matrix hydrogel channel.Human endometrial stromal cells and platelet-rich plasma channels were found on the left and right sides.There was an area between the three channels that could communicate with each other and realize material exchange.Human endometrial stromal cells(labeled with green fluorescent protein GFP)and serum-free medium containing 0.5%platelet-rich plasma were added to both sides of the experimental group.Human endometrial stromal cells(labeled with green fluorescent protein GFP)and serum-free cell media were added to both sides of the control group.After co-culture for 48 hours,the cell proliferation and migration were observed by Ki67 immunofluorescence staining. RESLUTS AND CONCLUSION:(1)The results of cell scratch test and CCK-8 assay showed that compared with the control group,platelet-rich plasma at 0.5%,1%,and 2%concentrations could promote the migration and proliferation of human endometrial stromal cells(P<0.05).In addition,the promotion of cell migration and proliferation of platelet-rich plasma with 0.5%concentration was stronger than that of the other two concentrations(P<0.05).(2)Ki67 immunofluorescence staining showed that compared with the control group,the proliferation and migration abilities of endometrial stromal cells were stronger in the experimental group.(3)The experiment proves that the microenvironment of endometrial cells can be simulated by the three-channel microfluidic chip.At the same time,the system has proven that platelet-rich plasma can significantly promote the proliferation and migration of endometrial stromal cells.

Objective: To explore the changes of mechanosensitive channels Piezos (Piezo 1 and Piezo 2) in neurogenic bladder (NB) of young rats and their effects，so as to provide reference for clinical search of new therapeutic targets. Methods: A total of 30 female young SD rats were divided into 5 groups based on random number table method：sham operation group (sham)，2-week nerve transection group (NB-2W)，6-week nerve transection group (NB-6W)，2-week nerve transection + Piezos inhibitor group (NB-P-2W) and 6-week nerve transection + Piezos inhibitor group (NB-P-6W)，with 6 rats in each group.The NB models were constructed by transecting the L6 and S1 spinal nerves of young rats.The NB-2W and NB-6W groups were not intervened after modeling，while the NB-P-2W and NB-P-6W groups were intraperitoneally injected with Piezos inhibitor GsMTx4 (10 mg/kg) every 2 days after modeling.Bladder cystometry and ultrasound were performed after 2 and 6 weeks of transection.The expressions of Piezos and fibrosis-related indexes (Collagen Ⅰ and α-smooth muscle actin) were detected in bladder tissues. Results: The results of bladder cystometry showed that the basal bladder pressure in NB-2W group was significantly increased，while it was slightly decreased but was still higher in NB-6W group than in the sham group (P<0.05).Basal bladder pressure was lower in NB-P-2W group than in NB-2W group，but was higher than that in the sham group; basal bladder pressure was lower in NB-P-6W group than in NB-6W group，but higher than that in the sham group (P<0.05).Compared with the sham group，the NB-2W and NB-6W groups had firstly increased and then decreased maximum cystometric capacity (MCC) (P<0.05).Compared with NB-2W group，NB-P-2W group had lower bladder leakage point pressure (BLPP)，but higher MCC and bladder compliance (BC) (P<0.05).Compared with NB-6W group，NB-P-6W group had significantly lower BLPP but higher MCC and BC (P<0.05).HE and MASSON staining and ultrasound results showed that，with the extension of nerve transection time，bladder fibrosis gradually worsened，the bladder wall became rough and thickened，calculi were visible inside，and hydronephrosis gradually appeared; the degree of fibrosis in NB-P-2W and NB-P-6W groups was less than that in NB-2W and NB-6W groups，and no hydronephrosis was observed in the upper urinary tract.In addition，Western blotting and immunohistochemical results showed that NB-2W and NB-6W groups had significantly higher relative expression levels of Piezos，Collagen Ⅰ and α-SMA than the sham group (P<0.01)，while NB-P-2W and NB-P-6W groups had lower relative expression levels of Piezos,Collagen Ⅰ and α-SMA than NB-2W and NB-6W groups (P<0.01). Conclusion: The increased expressions of mechanosensitive channels Piezos in NB young rats may be involved in the progression of bladder fibrosis，but its mechanism needs further study.

BACKGROUND:The application of miniscrew in adolescents is increasing day by day,but at present,there are few studies on bone mass in the external oblique line of the mandible in adolescents at home and abroad,and there is no systematic study on bone mass in the external oblique line of the mandible in adolescents in different growth and development periods. OBJECTIVE:To measure the bone mass in the external oblique line of the mandible in adolescents with different cervical vertebral bone ages using a cone-beam CT and to investigate the difference of bone mass in the external oblique line of the mandible in adolescents with different cervical vertebral bone ages and the correlation between bone mass in this area and the cervical vertebral bone age. METHODS:The cone-beam CT data of 105 adolescent patients before orthodontic treatment were collected and divided into CS3 group(n=24),CS4 group(n=26),CS5 group(n=29)and CS6 group(n=26)using the cervical vertebral maturation method.The adolescent mandibular buccal shelf was reconstructed by Mimics Medical 21.0 software.The width of buccal bone at 6 and 11 mm under the cemento-enamel junction and the bone height at 4 and 5 mm buccal to the cemento-enamel junction of right mandibular first and second molars were measured.The measured data were statistically analyzed.The measurement was made on four planes:plane 1 is the plane where the proximal mesial root of the mandibular right first molar is located;plane 2 is the plane where the distal mesial root of the mandibular right first molar is located;plane 3 is the plane where the proximal mesial root of the mandibular right second molar is located;and plane 4 is the plane where the distal mesial root of the mandibular right second molar is located. RESULTS AND CONCLUSION:In each group,the bone width on the buccal side of the external oblique line increased gradually from the first molar proximally to the second molar distally in adolescents,and the width of buccal bone at 6 and 11 mm under the cemento-enamel junction showed significant difference among different layers(P<0.05).The bone width of buccal bone at 11 mm under the cemento-enamel junction was greater than that at 6 mm.The bone height on the buccal side of the external oblique line increased gradually from the first molar proximally to the second molar distally in all four groups,and the bone height at 4 and 5 mm buccal to the cemento-enamel junction showed significant differences at different layers(P<0.05).The bone height at 4 mm buccal to the cemento-enamel junction was greater than that at 5 mm.On the fourth plane,the bone width at 11 mm buccal to the cemento-enamel junction was smaller in the CS3,CS4,and CS5 groups than in the CS6 group(P<0.05).On the third plane,the bone heights at 4 mm and 5 mm buccal to the cemento-enamel junction were smaller in the CS3 and CS4 groups than in the CS6 group(P<0.05).On the fourth plane,the bone height at 5 mm buccal to the cemento-enamel junction was smaller in the CS3 and CS4 groups than in the CS6 group(P<0.05).On the fourth plane,the bone height at 4 mm buccal to the cemento-enamel junction was smaller in the CS3 group than in the CS6 group(P<0.05).Spearman correlation analysis showed that there was no correlation between bone mass and the cervical vertebral bone age,except that there was a weak correlation between bone mass at some measurement sites and cervical vertebral bone age.To conclude,the bone mass in the external oblique area of the mandible in adolescents does not change significantly with the increase of cervical vertebral bone age.The buccal side of the mesial root and distal root of the mandibular second molar in the external oblique area of CS3-CS6 adolescents meets the requirement of bone mass for miniscrew implantation,which is a site available for miniscrew implantation.

Schimke immuno-osseous dysplasia (SIOD)caused by SMARCAL1 gene mutations is a rare genetic disorder characterized by multi-system involvement, including T-cell dysfunction, skeletal dysplasia, disproportionate short stature, nephrotic syndrome, and kidney failure. This multidisciplinary consultation involved a 9-year-old boy with intrauterine growth retardation, presenting with short stature, T-cell lymphopenia, proteinuria, and degenerative bone and joint disease. Treatment primarily focused on symptomatic and supportive care. Through the multidisciplinary rare disease consultation, holistic support was provided to the patient, offering comprehensive care from various specialtiesx.We also aim to use this case report to enhance clinicians′ under-standing of SIOD and improve the management and treatment of rare diseases.

Background Atmospheric fine particulate matter (PM_2.5) can disrupt the metabolic homeostasis of the liver and accelerate the progression of liver diseases, but there are few studies on the effects of sub-chronic PM_2.5 exposure on the liver metabolome. Objectives To investigate the effects of sub-chronic exposure to concentrated PM_2.5 on hepatic metabolomics in mice by liquid chromatography-mass spectrometry (LC-MS), and to identify potentially affected metabolites and metabolic pathways. Methods Twelve male C57BL/6J (6 weeks old) mice were randomly divided into two groups: a concentrated PM_2.5 exposure group and a clean air exposure group. The mice were exposed to concentrated PM_2.5 using the "Shanghai Meteorological and Environmental Animal Exposure System" at Fudan University. The exposure duration was 8 h per day, 6 d per week, for a total of 8 weeks. The mice's liver tissues were collected 24 h after the completion of exposure. LC-MS was performed to assess changes in the hepatic metabolome. Orthogonal partial least squares discriminant analysis and t-test were employed to identify differentially regulated metabolites between the two groups under the conditions of variable important in projection (VIP)≥1.0 and P<0.05. Metabolic pathway enrichment analysis was performed using MetaboAnalyst 5.0 software and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Results A total of 297 differentially regulated metabolites were identified between the concentrated PM_2.5 exposure group and the clean air group. Among these metabolites, 142 were upregulated and 155 were downregulated. A total of 38 metabolic pathways were altered, with 7 pathways showing significant perturbation (P<0.05). These pathways involved amino acid metabolism, glucose metabolism, nucleotide metabolism, as well as cofactor and vitamin metabolism. The 7 significant metabolic pathways were pantothenic acid and coenzyme A biosynthesis; purine metabolism; amino sugar and nucleotide sugar metabolism; arginine biosynthesis; alanine, aspartate and glutamate metabolism; aminoacyl-tRNA biosynthesis; and fructose and mannose metabolism. Conclusion The results from metabolomics analysis suggest that sub-chronic exposure to PM_2.5 may disrupt hepatic energy metabolism and induce oxidative stress damage. Aspartic acid, succinic acid, ornithine, fumaric acid, as well as purine and xanthine derivatives, were identified as potential early biomarkers of hepatic response to sub-chronic PM_2.5 exposure.

As a serious cardiovascular disease, atherosclerosis (AS) causes chronic inflammation and oxidative stress in the body and poses a threat to human health. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a member of the phospholipase A2 (PLA2) family, and its elevated levels have been shown to contribute to AS. Lp-PLA2 is closely related to a variety of lipoproteins, and its role in promoting inflammatory responses and oxidative stress in AS is mainly achieved by hydrolyzing oxidized phosphatidylcholine (oxPC) to produce lysophosphatidylcholine (lysoPC). Moreover, macrophage apoptosis within plaque is promoted by localized Lp-PLA2 which also promotes plaque instability. This paper reviews those researches of Chinese medicine in treating AS via reducing Lp-PLA2 levels to guide future experimental studies and clinical applications related to AS.
Humans ; 1-Alkyl-2-acetylglycerophosphocholine Esterase ; Medicine, Chinese Traditional ; Atherosclerosis/drug therapy* ; Lipoproteins ; Plaque, Atherosclerotic ; Biomarkers

Objective:To develop an efficient and robust method based on three dimensional facial landmarks for evaluating chin region asymmetry at the soft tissue level and to compare it with the tradi-tional mirror-overlap analysis method in order to test its availability.Methods:Standard symmetrical face was used for mental tubercle coordinate transformation so as to filter soft tissue three dimensional spatial angle and construct corresponding three dimensional spatial angle wireframe template.Ten patients aged 12-32 years with clinical chin region asymmetry diagnosis at the Department of Orthodontics of Peking University Hospital of Stomatology from November 2020 to November 2021 were randomly selected.Three dimensional soft tissue face scan data of the patients were collected by three dimensional face scanner and the landmark points were automatically determined by the Meshmonk non-rigid registration algorithm pro-gram,and in this way,the asymmetric three dimensional spatial angle wireframe template and corre-sponding spatial angle parameters were generated.Mirror-overlap analysis of face scan data was also per-formed in Geomagic Studio 2015 software and deviation color maps were generated.This study took mirror-overlap analysis as the gold standard method,the response rate of chin region asymmetry was eva-luated by the outcomes of the mirror-overlap analysis and three dimensional spatial angle wireframe tem-plate analysis.Results:Nine three dimensional spatial angle indicators were selected through coordinate transformation,and the response rate was calculated using mirror-overlap analysis as the gold standard method.Among these ten selected patients,the response rate of the total chin region asymmetry was 90％(9/10).Using the deviation value of mirror-overlap analysis as a reference,the response rate of chin region asymmetry in the X dimension was 86％,the response rate of chin region asymmetry in the Y dimension was 89％,and the response rate of chin region asymmetry in the Z dimension was 100％.Conclusion:The three dimensional soft tissue spatial angle wireframe template proposed in this study has some feasibility in evaluating chin region asymmetry at the soft tissue level,and its ability to recognize asymmetry separately in the three dimensional direction is better than the mirror-overlap analysis method,and the indicators recognition rate still needs to be further improved.

Objective To observe the efficacy and safety of flumatinib conversion in chronic myelogenous leukemia-chronicphase(CML-CP)patients with suboptimal TKI response or intolerance.Methods Patients who did not have the best response or intolerance to first-line imatinib,dasatinib,and nilotinib and switched to flumatinib(600 mg/d)from February 2020 to August 2022 were collected from 5 hospitals from Chongqing and affiliated hospitals of North Sichuan Medical College.The efficacy and safety of flumatinib were observed.The optimal response rate,major molecular response(MMR),cumulative complete cytogenetic response(CCyR)rate,cumulative MMR rate,cumulative deep molecular response(DMR),progression-free survival(PFS),event-free survival(EFS)and adverse reactions in 3,6 and 12 months after treatment were observed and analyzed.Results A total of 100 patients with CML-CP were enrolled,with a median follow-up of 18(3～36)months.The optimal response rate was 92.6％(88/95),94.4％(85/90)and 92.9％(79/85)respectively,at 3,6 and 12 months after treatment.Till August 20,2023,the cumulative CCyR and MMR rate was 98.0％(98/100)and 81.9％(77/94),respectively,the median time to reach CCyR and MMR was 3 months,and cumulative DMR rate was 51.0％(51/100).PFS rate was 100.0％(100/100)and 1-year EFS rate was 85.6％(75/90).The most common non-hematologic adverse reactions of flumatinib were diarrhea and abdominal pain(7.0％),followed by renal dysfunction(6.0％)and musculoskeletal pain(2.0％).The main hematologic adverse reactions were thrombocytopenia(12.0％),anemia(6.0％)and leukopenia(2.0％).Conclusion Flumatinib has better MMR and DMR and is well tolerated in CML-CP patients with TKI resistance or intolerance.

Objective To investigate the efficacy of Fuzheng Hejie Prescription(composed of Scutellariae Radix,Lonicerae Japonicae Flos,Agastachis Herba,Bupleuri Radix,Atractylodis Rhizoma,Glycyrrhizae Radix et Rhizoma,etc.)in the treatment of respiratory viral infections in children and to observe its effect on inflammatory factors and immune function.Methods A total of 203 children with respiratory viral infection of H1N1 virus were randomly divided into 101 cases in the observation group and 102 cases in the control group.Both groups were given the routine treatment for subsiding fever,maintaining water-electrolyte balance,and ensuring enough sleep.And additionally,the control group was given Ribavirin Granules and Ibuprofen Granules,and the observation group was given Fuzheng Hejie Prescription based on the treatment for the control group.The course of treatment covered 7 days.The changes of traditional Chinese medicine(TCM)syndrome scores and the levels of immunological indicators and inflammatory factors in the two groups were observed before and after the treatment.Moreover,the clinical efficacy,symptom resolution time and the incidence of adverse reactions were compared between the two groups of children.Results(1)In the course of the trial,one case fell off in the observation group and 2 cases fell off in the control group,and eventually 100 children in each group were included in the trial.(2)After 7 days of treatment,the total effective rate of the observation group was 93.00%(93/100),and that of the control group was 88.00%(88/100),and the intergroup comparison showed that the therapeutic effect of the observation group was superior to that of the control group,but the difference was not statistically significant(χ2= 1.454,P = 0.228).(3)After treatment,the scores of primary symptoms and secondary symptoms as well as the total TCM syndrome scores in the two groups were decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the time for the resolution of clinical symptoms such as fever,cough,expectoration and sore throat in the observation group was significantly shorter than that in the control group(P＜0.01).(5)After treatment,the levels of immunological indicators of T lymphocyte subset CD3+ and CD4+ in the two groups were increased compared with those before treatment(P＜0.05),and the levels of CD8+ and B cells were decreased compared with those before treatment(P＜0.05).The intergroup comparison showed that the increase in the levels of CD3+ and CD4+ as well as the decrease in the levels of CD8+ and B cells of the observation group was significantly superior to that of the control group(P＜0.01).(6)After treatment,the levels of inflammatory factors of serum amyloid A(SAA),C-reactive protein(CRP),serum tumor necrosis factor alpha(TNF-α),soluble interleukin 2 receptor(SIL-2R),and interleukin 6(IL-6)in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the levels of interleukin 2(IL-2)and interferon γ(IFN-γ)ls were all significantly increased compared with those before treatment(P＜0.05).The intergroup comparison showed that the decrease of serum SAA,CRP,TNF-α,SIL-2R,and IL-6 levels and the increase of serum IL-2 and IFN-γ levels in the observation group were significantly superior to those in the control group(P＜0.01).(7)The incidence of adverse reactions in the observation group was 2.00%(2/100),which was significantly lower than that of 8.00%(8/100)in the control group,but the difference was not statistically significant(χ2 = 3.789,P = 0.052).Conclusion Fuzheng Hejie Prescription exerts certain effect in treating children with respiratory viral infection of H1N1 virus,which can effectively decrease children's TCM syndrome scores,regulate the inflammatory response,improve the immune function,accelerate the relief of clinical symptoms and shorten the course of the disease.