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 evaluate the clinical efficacy of Xiaoxuming Decoction combined with conventional Western medicine therapy in the treatment of patients with ischemic stroke in the recovery period.Methods:A randomized controlled clinical study was conducted. A total of the 118 patients with wind phlegm obstructing collaterlas syndrome during the recovery period of ischemic stroke in our hospital from September 2023 to July 2024 were selected as the observation subjects. They were divided into two groups using a random number table method, with 59 patients in each group. The control group was treated with conventional Western medicine therapy, while the TCM group was treated with modified Xiaoxuming Decoction on the basis of the control group. Both groups were treated for 2 months and followed up for 1 month. TCM syndrome scoring was performed before and after treatment, Barthel Index was used to evaluate daily living ability, and carotid artery ultrasound detector was used to evaluate the stability of carotid vascular plaques. Inter group comparisons were performed using t test, χ2 test, or repeated measures analysis of variance (RM-ANOVA). Results:RM-ANOVA showed that the time effect and inter group effect of TCM syndrome integration in the TCM group were significantly different from those in the control group ( Ftime=55.56, Ptime<0.001); Fbetween=18.94, Pbetween<0.001); there was no statistical significance in the interaction effect compared to the control group ( Finteraction=0.24, Pinteraction=0.866); the time effect, inter group effect, and interaction effect of Barthel Index in the TCM group were significantly different from those in the control group ( Ftime=44.57, Ptime<0.001); Fbetween=18.94, Pbetween<0.001; Finteraction=7.45, Pinteraction<0.001). The number of patients with unstable plaques in the TCM group after 3 months of treatment was lower than that in the control group ( χ2=4.52, P=0.033). Conclusion:The combination of modified Xiaoxuming Decoction and conventional Western medicine therapy can effectively improve the clinical symptoms and daily living ability of patients in the recovery period of ischemic stroke, improve the stability of cervical vascular plaques, and the clinical efficacy becomes more significant over time.

Objective:To investigate the effects of insulin-like growth factor-binding protein 3(IGFBP3),which is carried in exosomes released by cisplatin(DDP)-tolerant human lung adenocarcinoma(LUAD)A549/DDP cells,on differentiation of macrophages and its effect on DDP resistance of A549 cells.Methods:The parental A549 and A549/DDP cells were cultured in vitro,and the IC50 values were calculated after treatment with different concentrations of DDP for 48 h.The supernatants of A549 or A549/DDP cells culture were collected,and the exosomes were isolated using ultracentrifugation and named A-exo or A/D-exo,respectively.THP-1 cells were induced to differentiate into M0-type macrophages with PMA(15 μg/mL),mixed with A549 cells at a ratio of 1∶1,and then inoculated in the axillae of nude mice;on the day of tumor cell inoculation,the tumor cells were injected with PBS,A-exo,and A/D-exo at the inoculation site of the tumor cells,respectively,and at the same time,the treatment was carried out by intraperitoneal injection of DDP 1 time every 4 d.On the 35th day of the tumor loading in mice,the recruitment of human CD11b+CD206+or CD11b+CD86+macrophages in transplanted tumor tissues was detected by flow cytometry(FCM).Antibody microarrays were used to screen for proteins carried by A-exo or A/D-exo and validated by detecting the amount of IGFBP3 protein in A-exo and A/D-exo by ELISA method.A549 or A549/DDP cells were treated with different concentrations of rhIGFBP3,and the effects of rhIGFBP3 on the proliferation or migration ability of the cells were detected by MTS assay and Transwell assay,respectively.M0-type macrophages were treated with rhIGFBP3 for 4 d,and the culture supernatant was collected;the effects of different concentrations of rhIGFBP3 on the production of TGF-β and TNF-α content by M0-type macrophages were detected by ELISA;in addition,A549 cells were treated with rhIGFBP3 or culture supernatant of M0-type macrophages pretreated with rhIGFBP3,and again detected the IC50 value of DDP on A549 cells.Results:The IC50 value of DDP on A549/DDP cells was significantly higher than that of A549 cells(P<0.01);A/D-exo significantly promoted the growth of A549 cells xenograft tumors(P<0.05)and facilitated the recruitment of CD11b+CD206+macrophages into tumor tissues(P<0.05),compared with PBS and A-exo groups.Exosomes A-exo and A/D-exo were successfully obtained;high levels of IGFBP3 were carried in A/D-exo compared with A-exo.The analysis showed that the expression level of IGFBP3 was significantly up-regulated in patients with LUAD,and the overall survival rate of patients with high expression of IGFBP3 was reduced compared with those with low expression of IGFBP3.High concentration of rhIGFBP3(100 ng/mL)had a significant pro-proliferative effect on either A549 or A549/DDP cells(both P<0.05),but there was no statistically significant effect on the migratory ability of A549 or A549/DDP cells.High concentrations of rhIGFBP3(100 ng/mL)induced TGF-β1 production by M0-type macrophages(P<0.05),but not TNF-α production.The IC50 value of DDP on A549 cells was significantly increased(P<0.05)after treatment with culture supernatant of M0-type macrophages pretreated with IGFBP3(but not rhIGFBP3).Conclusion:A549/DDP cells mediate M2-type macrophage differentiation and promote secondary drug resistance in A549 cells by secreting IGFBP3-rich exosomes.

Objective To investigate the preparation and evaluation of animal models of depression associated with autoimmune thyroiditis,and to verify the NLRP3/Caspase-1/GSDMD pathway based on this condition.Methods 32 NOD.H-2H4 mice were randomly divided into a normal(N)group,depression(DP)group,autoimmune thyroiditis with depression(AIT+DP)group,autoimmune thyroiditis(AIT)group,with 8 animals in each group.The N group was fed normally,the DP group was subjected to chronic unpredictable mild stress(CUMS)for 5 weeks,the AIT group was given 0.05％sodium iodide water to establish an autoimmune thyroiditis model,and the AIT+DP group was subjected to 5 weeks of CUMS to establish the AIT animal model.We evaluated whether the mouse autoimmune thyroiditis model had been successfully prepared by observing the thyroid tissue structure,lymphocyte infiltration,and serum TGAb and TPOAb levels.Changes in body weight,sugar water preference rate,open field behavior(central quadrant time,central quadrant time proportion,standing rate,frequency of defecation,and hair grooming time),and hippocampal pathological changes were used to evaluate the depression status of the mice.When the model mice met the above-mentioned indicators related to depression and autoimmune thyroiditis,the AIT+DP animal model was considered successfully prepared.Results Compared with the levels in the N group,the AIT group's and AIT+DP group's serum TGAb and TPOAb levels were significantly increased(P＜0.01),and a large number of inflammatory cells had infiltrated the thyroid gland.The central quadrant time and central quadrant time proportion,standing rate,frequency of defecation,and hair grooming time were reduced to varying degrees in the DP group and AIT+DP group.In addition,the numbers of glial cells in the cerebral cortex increased and neuronal cells decreased,accompanied by some nuclear atrophy,and the expression levels of NLRP3,IL-1β,Caspase-1,and GSDMD-N significantly increased,especially in the AIT+DP group(P＜0.01).Conclusions 0.05％sodium iodide water and CUMS create autoimmune thyroiditis with depression model animals that better simulate the external performance and internal index changes of the diseases.These mice can provide an animal model reference for research into autoimmune thyroiditis with depression.

ObjectiveTo explore the mechanism of Buzhong Yiqitang in ameliorating inflammatory injury in autoimmune thyroiditis (AIT) mice based on the Toll-like receptor 4（TLR4）/nuclear transcription factor-kappa B（NF-κB）/absent in melanoma 2（AIM2）inflammasome signaling pathway. MethodThe 120 genetically susceptible 8-week-old NOD.H-2^h4 mice were selected and randomly divided into control group， model group， low， medium and high dose groups of Buzhong Yiqitang （4.78， 9.56， 19.12 g·kg^-1）， and western medicine group （selenium yeast tablets， 3.033×10^-5 g·kg^-1）. The AIT model mice in each group drank ad libitum 0.05% sodium iodide aqueous solution for 8 weeks to establish the AIT model， and the control group drank ad libitum distilled water. Eight weeks later， the mice in each dosing group were divided into groups and gavage. The swelling of thyroid tissue was observed with the naked eye， and the weight of spleen was weighed. The content of serum inflammatory factors interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） was measured by enzyme-linked immunosorbent assay （ELISA）， and Real-time PCR was used to detect the expression of HMGB1， TLR4， AIM2， NF-κB p65，apoptosis-associated speck-like protein（ASC），cysteinyl aspartate-specific protease-1（Caspase-1）， IL-1β mRNA. Western blot was used to detect the expression of high motility group protein 1 （HMGB1）， TLR4， AIM2， NF-κB p65， phosphorylation（p）-NF-κB p65， ASC， Caspase-1， and IL-1β proteins in thyroid tissue， and immunofluorescence staining was used to observe the protein expression of HMGB1， AIM2， and NF-κB p65 in thyroid tissue of mice. ResultCompared with the control group， the thyroid tissue of mice in the model group was significantly swollen， the spleen quality was significantly increased， and the expression of HMGB1， TLR4， NF-κB p65， AIM2， ASC， Caspase-1， IL-1β in thyroid tissue was significantly increased （P<0.01）. Compared with the model group， the swelling of thyroid tissue in mice in each dose group of Buzhong Yiqitang was improved， the quality of spleen was significantly reduced， and the expression of HMGB1， TLR4， AIM2， NF-κB p65， p-NF-κB p65， ASC， Caspase-1， IL-1β in thyroid tissue was significantly reduced （P<0.05， P<0.01）. ConclusionBuzhong Yiqitang can effectively improve the inflammatory injury of AIT， and regulating the abnormal activation of the TLR4/NF-κB/AIM2 inflammasome signal pathway may be one of its intervention mechanisms.

AIM:To test and compare the perceptual eye position and fixation stability of adolescents with emmetropia and adolescents with low myopia, investigating the characteristics of the perceptual eye position and fixation stability of adolescents with low myopia.METHODS: Cross-sectional study. A total of 132 adolescents(264 eyes)who visited in the ophthalmology clinic of our hospital from April to December 2023 were randomly selected as the research subjects. Participants were categorized into normal control group(n=45, 90 eyes), simple low myopia group(n=45, 90 eyes)and low myopia with anisometropia group(n=42, 84 eyes)according to their refractive status and were underwent assessments for perceptual eye position and fixation stability.RESULTS: Compared with the normal control group, the static and dynamic horizontal perceptual eye position deviation of the simple low myopia group and the low myopia with anisometropia group were significantly increased(P<0.05). Compared with the simple low myopia group, the static and dynamic horizontal perceptual eye position deviation of the low myopia with anisometropia group were significantly increased(P<0.05). There was no significant difference in static and dynamic vertical perceptual eye position deviation among the three groups(P>0.05); compared with the normal control group, the horizontal and vertical fixation stability of the simple low myopia group and the low myopia with anisometropia group were significantly worse(all P<0.01), but there was no differences in the simple low myopia group and the low myopia with anisometropia group(P >0.05).CONCLUSION: Abnormalities are observed in perceptual eye position and fixation stability function in adolescents with low myopia compared with those adolescents with emmetropia, even at best corrected visual acuity. The occurrence of anisometropia could lead to an increased degree of horizontal perceptual eye position displacement.

OBJECTIVE To optimize the preparation of Xiakucao Kaiyin Granules(XKG)and control the quality of its intermedi-ates.METHODS The physical characteristics of spray dry powder of XKG were determined by powder evaluation method,and the physical fingerprint composed of 9 secondary physical quality indexes,such as bulk density,tap density,angle of repose and Hausner ratio,was established to determine the stability of the previous process and the quality consistency of spray dry powder.Taking the parti-cle forming rate,dissolution rate,moisture absorption rate and angle of repose as evaluation indexes,dry granulation was carried out,and the auxiliary materials of XKG were screened.The mixture design experiment combined with G1-entropy weight method and neural network method were used to optimize the proportion of the selected excipients,and the best preparation technology of XKG was deter-mined by comparing the two methods.The physical fingerprint of particles was established to evaluate the consistency of particle quality among different batches.RESULTS The similarity of physical fingerprints of 9 batches of spray dry powder was greater than 0.970,and the physical properties were stable.The comprehensive score of the best proportion of auxiliary materials obtained through the anal-ysis of mixture design was higher than that obtained by neural network modeling and optimization,so it was finally determined that the proportion of medicine and auxiliary materials of XKG was 7:3 and 29%maltodextrin and 71%lactose were added for dry granulation.The similarity of physical fingerprints of five batches of granule was greater than 0.994.CONCLUSION The estab-lished physical fingerprint of intermediates can be used to control the quality process of XKG,and the optimized prescription of XKG can improve the physical properties of granules and improve the consistency of granule quality.

Objective To retrieve,evaluate and summarise the best evidence in management of perioperative hyperglycemia in adult non-diabetic kidney transplant recipients so as to provide a reference for clinical nursing practice.Methods According to the evidence resource pyramid"6S"model,the best clinical practices for perioperative glycemic management in adult non-diabetic kidney transplant patients were retrieved from sources including BMJ Best Practice,UpToDate,Joanna Briggs Institute Evidence-Based Practice Database,World Health Organization,the International Guideline Collaboration Network,the National Institute for Health and Clinical Excellence,the National Guidelines Clearinghouse,Yimaitong,MedSci,Canadian Registered Nurses Association,American Diabetes Association,Canadian Diabetes Association,International Diabetes Federation,Australian Diabetes Society,Chinese Diabetes Society,Chinese Urological Society,Chinese Organ Transplantation Society,Cochrane Library,CINAHL,Web of Science,PubMed,Embase,China National Knowledge Infrastructure(CNKI),VIP,Wanfang Data,and SinoMed.The literature was independently screened and evaluated by two researchers trained in evidence-based methodology,and the evidence was extracted and summarised with expert advices.Results A total of 14 articles were included,comprising 2 clinical decisions,5 guidelines,2 evidence summaries,4 expert consensus and 1 systematic review.A total of 27 pieces of the best evidence were summarised and integrated into 6 topics:evaluation and management,goals for control of blood glucose,blood glucose monitoring,prevention and intervention of hyperglycemia,discharge guidance,diagnosis and intervention of new-onset diabetes after kidney transplant.Conclusion This study summarises the best evidence for perioperative hyperglycemia management in adult non-diabetic kidney transplant recipients.Medical staff may apply the evidence individually in conjunction with the actual clinical situations to standardise the practice criteria.

OBJECTIVE To optimize the preparation of Xiakucao Kaiyin Granules(XKG)and control the quality of its intermedi-ates.METHODS The physical characteristics of spray dry powder of XKG were determined by powder evaluation method,and the physical fingerprint composed of 9 secondary physical quality indexes,such as bulk density,tap density,angle of repose and Hausner ratio,was established to determine the stability of the previous process and the quality consistency of spray dry powder.Taking the parti-cle forming rate,dissolution rate,moisture absorption rate and angle of repose as evaluation indexes,dry granulation was carried out,and the auxiliary materials of XKG were screened.The mixture design experiment combined with G1-entropy weight method and neural network method were used to optimize the proportion of the selected excipients,and the best preparation technology of XKG was deter-mined by comparing the two methods.The physical fingerprint of particles was established to evaluate the consistency of particle quality among different batches.RESULTS The similarity of physical fingerprints of 9 batches of spray dry powder was greater than 0.970,and the physical properties were stable.The comprehensive score of the best proportion of auxiliary materials obtained through the anal-ysis of mixture design was higher than that obtained by neural network modeling and optimization,so it was finally determined that the proportion of medicine and auxiliary materials of XKG was 7:3 and 29%maltodextrin and 71%lactose were added for dry granulation.The similarity of physical fingerprints of five batches of granule was greater than 0.994.CONCLUSION The estab-lished physical fingerprint of intermediates can be used to control the quality process of XKG,and the optimized prescription of XKG can improve the physical properties of granules and improve the consistency of granule quality.

Objective:To investigate the effects of insulin-like growth factor-binding protein 3(IGFBP3),which is carried in exosomes released by cisplatin(DDP)-tolerant human lung adenocarcinoma(LUAD)A549/DDP cells,on differentiation of macrophages and its effect on DDP resistance of A549 cells.Methods:The parental A549 and A549/DDP cells were cultured in vitro,and the IC50 values were calculated after treatment with different concentrations of DDP for 48 h.The supernatants of A549 or A549/DDP cells culture were collected,and the exosomes were isolated using ultracentrifugation and named A-exo or A/D-exo,respectively.THP-1 cells were induced to differentiate into M0-type macrophages with PMA(15 μg/mL),mixed with A549 cells at a ratio of 1∶1,and then inoculated in the axillae of nude mice;on the day of tumor cell inoculation,the tumor cells were injected with PBS,A-exo,and A/D-exo at the inoculation site of the tumor cells,respectively,and at the same time,the treatment was carried out by intraperitoneal injection of DDP 1 time every 4 d.On the 35th day of the tumor loading in mice,the recruitment of human CD11b+CD206+or CD11b+CD86+macrophages in transplanted tumor tissues was detected by flow cytometry(FCM).Antibody microarrays were used to screen for proteins carried by A-exo or A/D-exo and validated by detecting the amount of IGFBP3 protein in A-exo and A/D-exo by ELISA method.A549 or A549/DDP cells were treated with different concentrations of rhIGFBP3,and the effects of rhIGFBP3 on the proliferation or migration ability of the cells were detected by MTS assay and Transwell assay,respectively.M0-type macrophages were treated with rhIGFBP3 for 4 d,and the culture supernatant was collected;the effects of different concentrations of rhIGFBP3 on the production of TGF-β and TNF-α content by M0-type macrophages were detected by ELISA;in addition,A549 cells were treated with rhIGFBP3 or culture supernatant of M0-type macrophages pretreated with rhIGFBP3,and again detected the IC50 value of DDP on A549 cells.Results:The IC50 value of DDP on A549/DDP cells was significantly higher than that of A549 cells(P<0.01);A/D-exo significantly promoted the growth of A549 cells xenograft tumors(P<0.05)and facilitated the recruitment of CD11b+CD206+macrophages into tumor tissues(P<0.05),compared with PBS and A-exo groups.Exosomes A-exo and A/D-exo were successfully obtained;high levels of IGFBP3 were carried in A/D-exo compared with A-exo.The analysis showed that the expression level of IGFBP3 was significantly up-regulated in patients with LUAD,and the overall survival rate of patients with high expression of IGFBP3 was reduced compared with those with low expression of IGFBP3.High concentration of rhIGFBP3(100 ng/mL)had a significant pro-proliferative effect on either A549 or A549/DDP cells(both P<0.05),but there was no statistically significant effect on the migratory ability of A549 or A549/DDP cells.High concentrations of rhIGFBP3(100 ng/mL)induced TGF-β1 production by M0-type macrophages(P<0.05),but not TNF-α production.The IC50 value of DDP on A549 cells was significantly increased(P<0.05)after treatment with culture supernatant of M0-type macrophages pretreated with IGFBP3(but not rhIGFBP3).Conclusion:A549/DDP cells mediate M2-type macrophage differentiation and promote secondary drug resistance in A549 cells by secreting IGFBP3-rich exosomes.