Multiple system atrophy (MSA) is a rare neurodegenerative disease with complex clinical manifestations, presenting substantial challenges in clinical diagnosis and treatment. Its symptoms and the eight extraordinary meridians are potentially correlated; therefore, this article explores the association between MSA symptom clusters and the eight extraordinary meridians based on their circulation and physiological functions, as well as their treatment strategies. The progression from deficiency to damage in the eight extraordinary meridians aligns with the core pathogenesis of MSA, which is characterized by "the continuous accumulation of impacts from the vital qi deficiency leading to eventual damage". Liver and kidney deficiency and the emptiness of the eight extraordinary meridians are required for the onset of MSA; the stagnation of qi deficiency and the gradual damage to the eight extraordinary meridians are the key stages in the prolonged progression of MSA. The disease often begins with the involvement of the yin and yang qiao mai, governor vessel, thoroughfare vessel, and conception vessel before progressing to multiple meridian involvements, ultimately affecting all eight extraordinary meridians simultaneously. The treatment approach emphasizes that "the direct method may be used for joining battle, but indirect method will be needed in order to secure victory" and focuses on "eliminate pathogenic factors and reinforce healthy qi". Distinguishing the extraordinary meridians and focusing on the primary symptoms are pivotal to improving efficacy. Clinical treatment is aimed at the target, and tailored treatment based on careful clinical observation ensures precision in targeting the disease using the eight extraordinary meridians as the framework and core symptoms as the specific focus. Additionally, combining acupuncture, daoyin therapy, and other method may help prolong survival. This article classifies clinical manifestations based on the theory of the eight extraordinary meridians and explores treatment.

OBJECTIVE To offer a reference for the treatment of Mycobacterium iranicum infection by analyzing the diagnosis and management of a single case alongside literature-reported cases. METHODS Through case report and literature reviews， this study synthesized the clinical features， therapeutic regimens， and patient outcomes of those infected with M. iranicum. RESULTS In the single case documented in this report， subsequent to clinical pharmacists’ involvement in the consultation， the patient was prescribed a therapeutic regimen comprising levofloxacin （0.5 g， qd， ivgtt）+Clarithromycin sustained-release tablets （1 000 mg， qd， po） + Ethambutol tablets （0.75 g， qd， po）. The patient exhibited clinical improvement and was discharged after treatment. This article integrated 12 published studies， encompassing 13 patients （7 male and 6 female）， of whom 69.23% were aged ≥50 years. Patients infected with M. iranicum exhibited non-specific clinical manifestations and imaging features， with pulmonary infection as the primary presentation. Antimicrobial susceptibility test revealed that M. iranicum was susceptible to multiple agents， including amikacin， clarithromycin， linezolid， and ethambutol. The three-drug combination therapy was the most frequently employed regimen. In terms of clinical outcomes， there were 9 cases （69.23%） of clinical cure， 3 cases （23.08%） of bacteriological negativity conversion， and 1 case （7.69%） of treatment failure. CONCLUSIONS For M. iranicum infection， a triple-drug therapeutic regimen consisting of three agents with distinct mechanisms of action selected from amikacin， clarithromycin， moxifloxacin， levofloxacin， minocycline， ethambutol， and other relevant drugs may represent a relatively optimal strategy.

In order to explore the role of pre-basic course teaching in the standardized training of residents in clinical pathology, we have independently designed and constructed a pre-basic course teaching system mainly focusing on anatomy and histoembryology, consisting of two levels of theoretical teaching (small lectures by students and systematic lectures by instructors) and two dimensions of practical training (sample collection teaching and case teaching). This teaching model centering on participatory lecturing, practice, summarization, assessment, and feedback has been demonstrated effective. The results showed that the theoretical and practical assessment scores of the experimental group [(458.80±17.60) and (415.40±19.30), respectively] were significantly higher than those of the control group [(444.50±20.90) and (398.80±23.70), respectively]. Among 28 students of grades 2019 to 2021 surveyed for teaching effectiveness, 96.43% were satisfied with the teaching model. The established teaching model provides new ideas for the reform of teaching methods in the standardized training of residents in clinical pathology.

Aim To explore the role of Takeda G pro-tein-coupled receptor 5(TGR5)in the proliferation and migration of vascular smooth muscle cells(VSMCs)within the intimal layer of mice.Methods Mouse VSMCs were stimulated for proliferation and migration with PDGF-BB,followed by administration of INT-777 for activation of TGR5.CCK-8 assay and Ki-67 immunofluorescence staining were employed to eval-uate cell proliferation.The scratch assay was utilized to assess migration.Western blot analysis was conducted to monitor TGR5 protein expression.To further investi-gate the role of TGR5 in intimal hyperplasia in vivo,20 male wild-type C57BL/6J mice were randomly divided into four groups:sham group,carotid artery endothelial injury group,sham+UDCA(ursodeoxy-cholic acid,a TGR5 agonist)group,and carotid artery endothelial injury+UDCA group(n=5 in each group).After the establishment of endothelial injury model,mice were orally fed with regular maintenance feed containing 0.5％UDCA for 21 days.Subsequent-ly,samples were collected for Hematoxylin and Eosin(HE)staining to assess the neointimal hyperplasia.Immunofluorescence(IF)staining was used to exam-ine the proliferation of VSMCs within the carotid inti-ma.Results The specific activation of TGR5 marked-ly diminished cell viability,the proportion of Ki-67-positive cells,and slowed down the rate of wound-heal-ing.Notably,the specific activation of TGR5 increases the expression of UCP2 in cells and reduces the levels of reactive oxygen species(ROS).The inhibitory effect of TGR5 on VSMC proliferation and migration was neutralized upon the restoration of intracellular ROS level with H2O2.Activation of TGR5 was found to mitigate intimal thickening following carotid artery inju-ry.Conclusion TGR5 may inhibit the proliferation and migration of mouse VSMCs by attenuating intracel-lular oxidative stress.

Aim To investigate the effect of homocys-teine(Hcy)on the permeability of pulmonary micro-vascular endothelial cells(PMVECs)and the role and mechanism of RASAL1.Methods CBS+/-mice were fed a high methionine diet(HMD)for 16 weeks to replicate an animal model of hyperhomocysteinemia(HHcy).HE staining was used to observe the changes in lung tissue structure.qRT-PCR was used to detect the levels of RASAL1 and DNMT1 mRNA in lung tis-sue.Western blot was used to detect the expression of RASAL1,DNMT1,ZO-1,and VE cadherin proteins.Methylation specific PCR was used to detect methyla-tion in the RASAL1 promoter region.PMVECs were transfected with Ad-RASAL1 to detect the expression of ZO-1 and VE cadherin.The si-DNMT1 interference fragment was transfected into PMVECs,and the ex-pression of the RASAL1 was detected by qRT-PCR and Western blot.Results Serum Hcy level of HMD mice was significantly raised,and HE staining showed severe structural disorder in lung tissue.The expres-sion of RASAL1,ZO-1,and VE cadherin was de-creased,while the expression of DNMT1 was in-creased.The degree of methylation in the RASAL1 promoter region was raised.The expression of ZO-1 and VE cadherin increased after PMVECs were trans-fected with Ad-RASAL1.After knocking down DN-MT1,RASAL1 expression was increased.Conclusion Hcy can increase the permeability of PMVECs,and its mechanism is related to the upregulation of RASAL1 methylation level.

Objective To construct and validate a risk prediction model for delayed healing of venous leg ulcer(VLU),so as to provide a reference basis for early identification of people at high risk of delayed healing.Methods Using a convenience sampling method,331 VLU patients attending vascular surgery departments in 2 tertiary A hospitals in Sichuan Province from January 2018 to December 2022 were selected as a modeling group and an internal validation group,and 112 patients admitted to another tertiary A hospital were selected as an external validation group.Risk factors for delayed healing in VLU patients were screened using univariate analysis,LASSO regression,and multivariate logistic regression analysis,and a risk prediction model was constructed using R software,and the predictive effects of the models were examined using the area under the receiver operating characteristic curve,the Hosmer-Lemeshow test,decision curve,and the bootstrap resampling for internal validation and spatial external validation were performed,respectively.Results The predictors that ultimately entered the prediction model were diabetes(OR=4.752),deep vein thrombosis(OR=4.104),lipodermatosclerosis(OR=5.405),ulcer recurrence(OR=3.239),and ankle mobility(OR=5.520).The model had good discrimination(AUC:0.819 for internal validation and 0.858 for external validation),calibration(Hosmer-Lemeshow test:χ2=13.517,P=0.095 for internal validation and χ2=3.375,P=0.909 for external validation)and clinical validity.Conclusion The model constructed in this study has good differentiation and calibration,and it can effectively predict people at high risk of delayed healing of VLU,which facilitates targeted clinical interventions to improve ulcer outcomes and reduce the risk of delayed ulcer healing.

Objective:To investigate the clinical value of AB classification combined with Arima classification for predicting the invasion depth of superficial esophageal squamous cell carcinomas (SESCC).Methods:From July 2017 to December 2022, 76 cases of SESCC receiving endoscopic submucosal dissection and intra-epithelial papillary capillary loops (IPCL) AB classification as type B2 in Ningbo Medical Center Lihuili Hospital and Jiangsu Province Hospital of Chinese Medicine were included in the study. IPCL was reclassified according to Arima classification. The depth of infiltration determined by pathology was the gold standard. The sensitivity, the specificity, the positive predictive value and the negative predictive value of B2-Arima combined classification in predicting the invasion depth of SESCC were analyzed.Results:In the 76 cases of type B2 IPCL lesions, 31 cases (40.79%) were T1a-MM/T1b-SM1 SESCC. The sensitivity, the specificity, the positive predictive value, the negative predictive value and the diagnostic accuracy of type B2 IPCL to predict T1a-MM/T1b-SM1 SESCC were 70.45% (31/44), 79.64% (176/221), 40.79% (31/76), 93.12% (176/189), and 78.11% (207/265), respectively. After Arima classification, the above corresponding indicators of type B2-4ML and type B2-AVA-4M IPCL in predicting T1a-MM/T1b-SM1 SESCC were 61.36% (27/44), 88.24% (195/221), 50.94% (27/53), 91.98% (195/212), 83.77% (222/265) and 38.64% (17/44), 94.57% (209/221), 58.62% (17/29), 88.56% (209/236), 85.28% (226/265), respectively.Conclusion:B2 IPCL combined with Arima classification can improve the diagnostic accuracy of T1a-MM/T1b-SM1 ESSCC.

Objective:To evaluate the status of, differences in, and factors influencing quality of life (QoL) in patients with chronic graft-versus-host disease (GVHD).Methods:From September 2021 to February 2023, a cross-sectional study of 140 patients with chronic GVHD was conducted at our center. Symptom burden was assessed by the Lee Symptomatology Scale (LSS), and QoL was assessed by the Medical Outcome Study 36-Item Short-Form Health Survey (SF-36) (version 1) and five-level EuroQoL five-dimensional questionnaire (EQ-5D-5L).Results:Data from 140 respondents, including 32 (22.9%) with mild chronic GVHD, 87 (62.1%) with moderate chronic GVHD, and 21 (15.0%) with severe chronic GVHD, were analyzed. Of the respondents, 61.4% were male, and the median transplantation age was 34 (15-68) years. The primary diagnoses were acute myeloid leukemia (50.0%), acute lymphoblastic leukemia (20.0%), and myelodysplastic syndrome (15.0%). The common chronic GVHD-affected organs included the skin in 74 patients (52.9%), the eyes in 57 patients (40.7%), and the liver in 50 patients (35.7%). Among the whole cohort, the eye (20.48±23.75), psychological (16.13±17.00), and oral (13.66±20.55) scores were highest in the LSS group. The physiological function (36.07±11.13), social function (36.10±10.68), and role-emotional functioning (38.36±11.88) scores were lowest in the SF-36 group. The EQ-5D index was 0.764. The total LSS scores for mild, moderate, and severe chronic GVHD were 6.51±6.15, 10.07±5.61, and 20.90±10.09, respectively. The SF-36 physical component scores (PCSs) were 43.12±6.38, 40.73±7.14, and 36.97±6.97, respectively, and the mental component scores (MCSs) were 43.00±8.47, 38.90±9.52, and 28.96±9.63, respectively. The EQ-5D values were 0.810±0.124, 0.762±0.179, and 0.702±0.198, respectively. The multivariate analysis showed that the overall symptom burden ( β=-0.517), oral symptom burden ( β=-0.456), National Institute of Health (NIH) criteria for the eyes ( β=-0.376), and nutrition-related symptom burden ( β=-0.211) were significantly negatively correlated with the PCS. The NIH score ( β=-0.260) was negatively correlated with the MCS score. Oral symptom burden ( β=-0.400), joint/fascia NIH criteria ( β=-0.332), number of involved systems ( β=-0.253), overall NIH criteria ( β=-0.205), and number of immunosuppressants taken ( β=-0.171) were significantly negatively correlated with the EQ-5D score (all P<0.05). Medium to strong correlations were found between the EQ-5D score and the SF-36 score (| r|=0.384-0.571, P<0.001). Conclusions:The QoL of patients with chronic GVHD is impaired, and the more severe the disease, the poorer the QoL. Overall symptom burden, severity of eyes, and oral symptom burden were the most important factors affecting QoL.

Objective To study the effect and mechanism of paeonol(PAE)on renal interstitial fibrosis in rats.Methods The rats were randomly divided into sham operation(Sham)group,unilateral ureteral obstruction(UUO)group,PAE low dose(PAE-L)group,PAE medium dose(PAE-M)group,PAE high dose(PAE-H)group and irbesartan(IRB)group.Except for the Sham group,the UUO model was established in other groups.Each group was given a corresponding intervention for two weeks.Serum creatinine(Scr),blood urea nitrogen(BUN),serum 8-hydroxydeoxyguanosine(8-OHdG)levels,renal tissue superoxide dismutase(SOD),glutathione peroxidase(GPX)activities,α-smooth muscle actin(α-SMA),type Ⅰ collagen(Col-Ⅰ),fibronectin(FN),silent information regulator 1(SIRT1),nuclear factor E2-related factor 2(Nrf2)protein expression were detected;observe pathological changes of kidney tissue and calculate collagen volume fraction(CVF).Results Compared with the UUO group,the serum levels of Scr,BUN,and 8-OHdG in each dose group of PAE were decreased,the activities of SOD and GPX in kidney tissue were increased,the positive expressions of α-SMA,Col-Ⅰ and FN in kidney tissue were decreased,and the protein expressions of SIRT1 and Nrf2 were increased.Masson staining showed a decrease of CVF in renal tissue(all P<0.05),and HE staining showed a different degree of improvement in pathological changes such as inflammatory cell infiltration and tubular dilatation in renal tissue;PAE improves renal interstitial fibrosis in rats in a dose-dependent manner(P<0.05),and the effect of large dose PAE on renal interstitial fibrosis in rats was similar to that of IRB.Conclusion PAE can alleviate UUO-induced rat renal interstitial fibrosis and oxidative stress,and improve rat renal function.And this mechanism may be related to the activation of the SIRT1/Nrf2 signaling pathway.

AIM:This study explores how the combination of rapamycin(Rapa)and flagellin(FliC)affects the inhibition of 4T1 breast cancer cells.The approach involves using mRNA high-throughput sequencing to examine the underlying mechanisms of this combination therapy in vitro.METHODS:4T1 breast cancer cells were divided into four groups:control group,Rapa group,FliC group,and Rapa+FliC group.The changes in cell viability and apoptosis were detected by the CCK-8 method and flow cytometry.Concurrently,the KEGG pathway of differentially expressed genes(DEGs)was analyzed by high-throughput mRNA sequencing.Furthermore,the DEGs between the Rapa+FliC group and Rapa groups were analyzed using STRING.The PPI network of DEGs was then constructed,and the Hub genes were sub-sequently screened.The protein expression of the Hub gene was verified based on the HPA database.RESULTS:CCK-8 assays and flow cytometry analysis revealed that the combination of Rapa and FliC significantly increased both the inhibi-tion and apoptosis rates in 4T1 breast cancer cells compared to the rates observed with Rapa or FliC alone(P<0.05).Transcriptome sequencing indicated 579 DEGs between the Rapa group and the control group,predominantly in the PI3K/Akt signaling pathway.In contrast,DEGs between the FliC group and control were mainly concentrated in signaling path-ways like NOD-like receptor signaling.Additionally,150 DEGs were identified between the Rapa+FliC group and the Ra-pa group,focusing primarily on pathways such as mTOR.From the protein-protein interaction(PPI)network,ten hub genes,including Atm and Itga2,were identified.CONCLUSION:The combination of Rapa+FliC could inhibit the via-bility of 4T1 breast cancer cells in vitro and promote apoptosis,potentially through the PI3K/Akt/mTOR signaling path-way.The genes Atm and Itga2 could be pivotal in mediating the joint effect of this combination therapy.