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.

Objective To explore the changes in neural activity in patients with type 2 diabetes mellitus(T2DM)and their corre-lation with executive function,and to analyze the neural mechanisms underlying the decline in executive function in T2DM patients.Methods Thirty-one T2DM patients(T2DM group)and thirty-two healthy controls(HC)(HC group)matched for body mass index(BMI)underwent resting-state functional magnetic resonance imaging(rs-fMRI)scans and N-back task tests were included.Differ-ences in the amplitude of low-frequency fluctuation(ALFF),regional homogeneity(ReHo),and seed-based functional connectivity(FC)between the two groups were compared,and partial correlation analyses were performed between the difference results and N-back task performance.Results The T2DM group showed prolonged reaction time(RT)in the 1-back and 2-back tasks.T2DM patients exhibited increased ALFF in the bilateral caudate nucleus,left medial superior frontal gyrus,and right postcentral gyrus,as well as elevated ReHo in the right putamen.FC analysis revealed significant alterations in FC between the caudate nucleus,putamen,and multiple brain regions in T2DM patients,with some of these FC changes significantly correlated with RT and accuracy(ACC)in the N-back task.Conclusion The decline in executive function in T2DM patients may be associated with abnormal neural activity in brain regions such as the striatum,salience network,and frontoparietal control network.FC further decreases under increased cognitive load.These findings provide evidence for the study of the neural mechanisms of executive function impairment in T2DM patients.

Objective To investigate the effects of Jinfukang on the growth of human lung cancer H358 cell xenografts in nude mice and its regulatory role in the TRIM52-mediated Wnt/β-catenin signaling pathway.Methods Human lung cancer H358 cells were cultured,and a subcutaneous xenograft model was established in nude mice.The mice were randomly divided into four groups:0.9％sodium chloride solution,cisplatin(3 mg·kg-1,intraperitoneal injection every 3 days),Jinfukang(0.4 mL,daily oral administration),and Jinfukang combined with cisplatin.Each group included 6 mice.After 15 days of continuous treatment,the tumor growth inhibition rate was calculated.Hematoxylin and eosin(H&E)staining was performed to observe tumor histopathological changes.TUNEL assay was used to evaluate apoptosis and calculate the apoptotic index.The relative mRNA expression levels and protein expression of TRIM52,PCNA,c-Myc,β-catenin,and Cyclin D1 were assessed by Real-time PCR and western blot,respectively.Results Compared with the saline group,Jinfukang,cisplatin,and Jinfukang combined with cisplatin treatments significantly inhibited tumor growth(P＜0.05).The combination group exhibited the most pronounced anti-tumor effect,slightly better than cisplatin alone,although the difference was not statistically significant(P＞0.05).Histopathological analysis and apoptosis indices revealed that the combination group showed the most severe necrosis and the highest level of apoptosis compared to other groups(P＜0.05).Furthermore,the combination group significantly downregulated the mRNA(P＜0.05)and protein(P＜0.05)expression levels of Cyclin D1,PCNA,TRIM52,β-catenin and c-Myc.Conclusion Jinfukang effectively inhibits the growth of human lung cancer H358 xenografts,disrupts tumor cell structure,and promotes apoptosis.Its anti-tumor effect is further enhanced when combined with cisplatin.The underlying mechanism may involve the downregulation of TRIM52 expression,leading to the suppression of Wnt/β-catenin signaling pathway activity and augmentation of anti-tumor efficacy.

For TCM to go global,while carrying forward its own characteristics,it should also build a set of measurement methods recognized by the international medical field.PRO scale is more and more widely used in the field of traditional Chinese medicine because there are many confluence points between PRO scale and TCM connotation.The patient-reported outcomes measurement information system(PROMIS)provides a reference for the development of PRO scales in the field of TCM.We can learn from the methods and models relied on by PROMIS and build a PRO evaluation system for TCM diseases based on TCM culture,so as to promote the standardization,standardization and modernization of TCM.

Purpose To explore the pathological characteristics,diagnosis,and differential diagnosis of pure ery-throid leukemia(PEL).Methods A retrospective analysis was conducted on the clinicopathological data of 12 cases of PEL.Immunohistochemical EnVision method and flow cytometry were used to detect PEL-related immune markers,and heat-treated Giemsa R-banding technique was applied to analyze the chromosomal karyotype.Results Peripheral blood and bone marrow smears revealed that 2 out of 7 cases showed presence of proerythroblast in peripheral blood,and 7 out of 12 cases showed atypical proerythroblast in bone marrow samples.After recounting,the average percentage of proerythroblast in the 12 PEL cases was 36.8％(ranging from 2％to 69.5％),with an average of 53.2％of all er-ythroid cells(ranging from 5％to 88％).Among them,9 cases did not meet the diagnostic criteria for PEL.Bone marrow biopsy:11 cases showed hypercellularity,with tumor cells showing diffuse proliferation in 9 cases,accompa-nied by dysplasia of megakaryocytes in 7 cases,and there was increased proliferation of fibrous tissue in 9 cases.Im-munohistochemistry:12 cases exhibited strong staining intensity for CD71 and E-cadherin.11 cases expressed CD117,while 4 cases expressed CD34,3 cases exhibited slight expression of GPA,and 1 case weakly expressed CD61.Flow cytometry:in 8 cases,there was an increased proportion of early-stage erythroid cells,accounting for 3.1％to 80.31％of nucleated cells,with an average of 31.0％.All cases expressed CD117 and CD71 to varying degrees,with 7 out of 8 cases expressing CD36,5 out of 7 cases expressing CD105,and 3 out of 4 cases expressing GPA.A few ca-ses demonstrated aberrant expression of CD123 and CD7.Chromosomal Karyotyping:7 cases exhibited highly complex karyotypes(7/8),with frequent involvement of chromosomes 5,7,8,17,and 19.One case had a normal karyotype.Conclusion The diagnosis of PEL requires a comprehensive assessment combining various methods including bone marrow smears,bone marrow biopsy,immunohistochemistry,and flow cytometry.

Objective:To investigate the therapeutic effects of adeno-associated virus vector 5 (AAV5)-mediated hepatic lipoprotein lipase (LPL) expression on serum triglyceride (TG) metabolism and hypertriglyceridemic acute pancreatitis (HTG-AP) in mice.Methods:Ten male C57BL/6 Lpl+/- mice were randomly divided into two groups by a random number table: the Lpl+/- control group and the Lpl+/- gene therapy group, with five mice in each group. The Lpl+/- control group received a tail vein injection of AAV5 vector carrying the enhanced green fluorescent protein (EGFP) gene (AAV5-EGFP), while the Lpl+/- gene therapy group received a tail vein injection of AAV5 vector carrying the human LPLS447X gene (AAV5-LPLS447X). Oral fat tolerance tests were performed at 14, 28, and 56 days post-injection. Twenty wild-type ICR mice were randomly divided into a control group and a gene therapy group, with ten mice in each group. The ICR control group was injected with AAV5-EGFP, and the ICR gene therapy group was injected with AAV5-LPLS447X. Fourteen days after injection, the mice underwent intraperitoneal injection of P407 solution (0.5 g/kg) and caerulein (200 μg/kg) to induce HTG-AP. Serum TG, total cholesterol (TC), amylase, lipase levels, and plasma LPL activity after heparin injection were measured by microplate reader. Plasma LPL concentration was measured using an enzyme-linked immunosorbent assay (ELISA). LPL mRNA expression levels in the liver, heart, and adipose tissue of Lpl+/- mice were determined by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). LPL protein expression in the liver tissue of ICR mice was detected by immunohistochemistry at 28 days after gene therapy. Histopathological changes in the pancreas were observed using hematoxylin-eosin staining. Results:Compared to the Lpl+/- control group, the Lpl+/- gene therapy group showed a significant decrease in serum TG levels starting from day 21. After oral administration of olive oil, the increase and peak of serum TG levels were significantly lower than those in the control group. Furthermore, hepatic LPL mRNA expression levels were significantly higher (1.96±0.11 vs 1.02±0.12) with statistical significance ( P<0.05). Compared to the ICR control group, the ICR gene therapy group showed a significant decrease in serum TG and TC levels, and plasma LPL activity (0.17±0.05 mEq/L·h -1vs 0.06±0.02 mEq/L·h -1) was significantly higher at 28 days after heparin injection with statistical significance (all P value <0.05). Immunohistochemical results showed high expression of LPL protein on the hepatocyte membrane in the liver of ICR gene therapy group mice. Moreover, pancreatic edema, inflammatory infiltration, and acinar cell necrosis were significantly alleviated compared to the control group. Conclusions:LPLS447X treatment can promote LPL expression in the liver of mice, significantly reduce TG levels, and alleviate the severity of HTG-AP.

Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.

Objective To explore the correlation of neutrophil/lymphocyte ratio(NLR),monocyte/high density lipoprotein cholesterol ratio(MHR)and mild cognitive impairment(MCI)in patients with type 2 diabetes mellitus(T2DM).Methods 159 T2DM patients hospitalized in the Department of Endocrinology,Affiliated Hospital of Xuzhou Medical University from February 2023 to April 2023 were selected.The subjects were divided into normal cognitive function(Con,n=72)group and MCI group(n=87)based on score of Montreal cognitive assessment scale(MoCA).NLR and MHR were calculated and compared between the two groups.Spearman correlation analysis was used to analyze the correlation between NLR,MHR and MoCA score.Logistic regression analysis of the factors influencing the association between T2DM with MCI.Receiver operator characteristic(ROC)curve was used to evaluate the predictive value of NLR and MHR for DM complicated with MCI.Results Compared with Con group,MCI group showed a significant increase in hemoglobin A1c(HbA1c),fasting plasma glucose,NLR,MHR,neutrophil count,monocyte count,serum creatinine,cystatin C,while high density lipoprotein cholesterol lymphocytes,visual space and executive function,naming,attention,language ability,abstract thinking,delayed memory,orientation and MoCA score decreased(P＜0.05).Spearman correlation analysis showed that there was a negative correlation between MHR,NLR and MoCA score,visuospatial and executive function,delayed recall and attention.Logistic regression analysis showed that NLR,MHR,HbA1c were all risk factors for MCI in T2DM.ROC curve analysis showed that the area under the curve of NLR combined with MHR for diagnosing T2DM with MCI was 0.872,with corresponding sensitivity of 81.6%and specificity of 87.5%.Conclusions NLR and MHR are closely related to MCI in T2DM patients.The combination of NLR and MHR have certain efficacy in prediction T2DM with MCI.

For TCM to go global,while carrying forward its own characteristics,it should also build a set of measurement methods recognized by the international medical field.PRO scale is more and more widely used in the field of traditional Chinese medicine because there are many confluence points between PRO scale and TCM connotation.The patient-reported outcomes measurement information system(PROMIS)provides a reference for the development of PRO scales in the field of TCM.We can learn from the methods and models relied on by PROMIS and build a PRO evaluation system for TCM diseases based on TCM culture,so as to promote the standardization,standardization and modernization of TCM.

Purpose To explore the pathological characteristics,diagnosis,and differential diagnosis of pure ery-throid leukemia(PEL).Methods A retrospective analysis was conducted on the clinicopathological data of 12 cases of PEL.Immunohistochemical EnVision method and flow cytometry were used to detect PEL-related immune markers,and heat-treated Giemsa R-banding technique was applied to analyze the chromosomal karyotype.Results Peripheral blood and bone marrow smears revealed that 2 out of 7 cases showed presence of proerythroblast in peripheral blood,and 7 out of 12 cases showed atypical proerythroblast in bone marrow samples.After recounting,the average percentage of proerythroblast in the 12 PEL cases was 36.8％(ranging from 2％to 69.5％),with an average of 53.2％of all er-ythroid cells(ranging from 5％to 88％).Among them,9 cases did not meet the diagnostic criteria for PEL.Bone marrow biopsy:11 cases showed hypercellularity,with tumor cells showing diffuse proliferation in 9 cases,accompa-nied by dysplasia of megakaryocytes in 7 cases,and there was increased proliferation of fibrous tissue in 9 cases.Im-munohistochemistry:12 cases exhibited strong staining intensity for CD71 and E-cadherin.11 cases expressed CD117,while 4 cases expressed CD34,3 cases exhibited slight expression of GPA,and 1 case weakly expressed CD61.Flow cytometry:in 8 cases,there was an increased proportion of early-stage erythroid cells,accounting for 3.1％to 80.31％of nucleated cells,with an average of 31.0％.All cases expressed CD117 and CD71 to varying degrees,with 7 out of 8 cases expressing CD36,5 out of 7 cases expressing CD105,and 3 out of 4 cases expressing GPA.A few ca-ses demonstrated aberrant expression of CD123 and CD7.Chromosomal Karyotyping:7 cases exhibited highly complex karyotypes(7/8),with frequent involvement of chromosomes 5,7,8,17,and 19.One case had a normal karyotype.Conclusion The diagnosis of PEL requires a comprehensive assessment combining various methods including bone marrow smears,bone marrow biopsy,immunohistochemistry,and flow cytometry.