OBJECTIVE: Based on the PTEN-induced hypothetical kinase 1 (PINK1)/Parkin pathway, the effect of acupuncture pretreatment on the expression of mitochondrial autophagy-related proteins in gastrocnemius muscle tissue of rats with exercise-induced muscle damage (EIMD) was observed, and the underlying mechanism of acupuncture pretreatment for the prevention and treatment of EIMD was explored. METHODS: Of 88 SD male rats, aged 6 weeks, 8 rats were randomly selected as a blank group, and the remaining 80 rats were randomized into a model group and an acupuncture pretreatment group, with 40 rats in each group. Either the model group or the acupuncture pretreatment group was subdivided randomly into 5 subgroups with 8 rats in each one according to the time points of sample collection, 0 h, 12 h, 24 h, 48 h and 72 h after modeling. An intermittent downhill running centrifugal exercise was carried out on an animal experimental treadmill to establish the EIMD model in the model group and the acupuncture pretreatment group. The rats in the acupuncture pretreatment group received acupuncture at "Guanyuan" (CV6) and bilateral "Zusanli" (ST36), once a day for 20 min each time, for 7 consecutive days before EIMD model preparation. Transmission electron microscopy was used to observe the ultrastructure of gastrocnemius muscle tissue in each group. The contents of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in serum were detected by ELISA. Western blot was used to detect the protein expression of PINK1, Parkin, sequestosome 1 (p62) and microtubule-associated protein light chain 3B (LC3B) in rat gastrocnemius muscle tissue. Real-time PCR was adopted to detect the mRNA expression of PINK1, Parkin, p62 and LC3B in rat gastrocnemius muscle tissue. RESULTS: Compared with the blank group, the mitochondria of gastrocnemius muscles showed obvious swelling in the 0 h, 12 h, 24 h, and 48 h model subgroups , autophagosomes were formed in the 12 h and 24 h model subgroups, and the mitochondrial morphology returned to normal gradually in the 72 h model subgroup. The serum MDA contents of rats in 5 model subgroups increased (P<0.01, P<0.05). The contents of SOD and CAT in the subgroups of 0 h, 12 h, 24 h and 48 h decreased (P<0.05, P<0.01). The protein and mRNA expression levels of PINK1, Parkin and LC3B in gastrocnemius muscle tissue of rats in 0 h, 12 h and 24 h subgroups were elevated (P<0.01); and the protein and mRNA expression levels of p62 in the 0 h, 12 h, 24 h and 48 h subgroups were reduced (P<0.01, P<0.05). Compared with the model subgroup at the same time point, the myofibril damage and the degree of mitochondrial swelling were mild in each acupuncture pretreatment subgroup, and the numbers of autophagosomes were fewer. The contents of MDA in the acupuncture pretreatment subgroups decreased at 0 h, 12 h, 24 h, and 48 h (P<0.05, P<0.01). The contents of SOD and CAT in the 12 h acupuncture pretreatment subgroup increased (P<0.05, P<0.01). The protein and mRNA expression levels of PINK1 and Parkin in the 0 h, 12 h, and 24 h acupuncture pretreatment subgroups decreased (P<0.01, P<0.05). The protein and mRNA expression levels of LC3B in the 12 h acupuncture pretreatment subgroup decreased (P<0.01), and that of p62 in the 0 h and 24 h acupuncture pretreatment subgroups increased (P<0.01, P<0.05). CONCLUSION The intermittent downhill running centrifugal exercise induces the excessive mitochondrial autophagy. Acupuncture pretreatment may attenuate EIMD, and the underlying mechanism is related to the regulation of PINK1/Parkin signaling pathway expression, reducing oxidative stress damage in skeletal muscle cells, and inhibiting mitochondrial autophagy overactivation.
Animals ; Ubiquitin-Protein Ligases/genetics* ; Male ; Rats ; Acupuncture Therapy ; Protein Kinases/genetics* ; Rats, Sprague-Dawley ; Mitophagy ; Humans ; Muscle, Skeletal/metabolism* ; Physical Conditioning, Animal ; Muscular Diseases/physiopathology* ; Signal Transduction

AIM: To evaluate the safety and efficacy of allogeneic intrastromal lenticule implantation combined with corneal collagen cross-linking(CXL)in patients with moderate to advanced keratoconus.METHODS: A retrospective case series analysis was conducted. A total of 19 patients(20 eyes)with moderate to advanced keratoconus who underwent combined allogeneic intrastromal lenticule implantation and CXL at the Jinan Mingshui Eye Hospital from June 2021 to December 2023 were included. The uncorrected distance visual acuity(UCVA), thinnest corneal thickness, central corneal epithelial thickness, anterior corneal flat keratometry(Kf), steep keratometry(Ks), and mean keratometry(Km), as well as the first applanation time(A1T), the first applanation length(A1L), the velocity during the first applanation moment(VIN), the second applanation time(A2T), the second applanation length(A2L), the velocity during the second applanation moment(VOUT), highest concavity time(HCT), highest concavity radius(HCR), peak distance(PD), deformation amplitude(DA), stiffness parameter at first applanation(SP-A1), integrated radius(IR), central corneal thickness(CCT), intraocular pressure(IOP), corneal thickness-corrected IOP, biomechanically intraocular pressure IOP(bIOP), and corneal thickness variation rate(ARTH)were compared between the two groups before surgery and at 1 wk, 1, 3 and 6 mo after surgery.RESULTS: All patients successfully completed the surgery without any intraoperative complications. No significant differences were observed between pre-operative and post-operative measurements for UCVA or the corneal biomechanical parameters, including A1L, A2L, PD, A1T, A2T, VIN, VOUT, DA, IOP, and bIOP(all P>0.05). Significant differences were found between pre-operative and post-operative values for corneal thinnest point thickness, central corneal epithelial thickness, Kf, Ks, Km, and the corneal biomechanical parameters, including HCT, HCR, SP-A1, ARTH, IR, and CCT(all P<0.05). The anterior corneal curvature demonstrated an initial increase followed by a decrease post-operatively. Furthermore, significant differences were observed between pre-operative and post-operative values for HCT, HCR, SP-A1, ARTH, IR, and CCT(all P<0.005).CONCLUSION: Allogenic intrastromal lenticule implantation combined with corneal collagen cross-linking demonstrates favorable safety and stability in treating moderate-to-advanced keratoconus. This combined procedure effectively increases corneal thickness and rigidity, resulting in corneas that are more resistant to deformation postoperatively.

Objective: To explore the feasibility of constructing a lung cancer early-warning risk model based on facial image features, providing novel insights into the early screening of lung cancer. Methods: This study included patients with pulmonary nodules diagnosed at the Physical Examination Center of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from November 1, 2019 to December 31, 2024, as well as patients with lung cancer diagnosed in the Oncology Departments of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine and Longhua Hospital during the same period. The facial image information of patients with pulmonary nodules and lung cancer was collected using the TFDA-1 tongue and facial diagnosis instrument, and the facial diagnosis features were extracted from it by deep learning technology. Statistical analysis was conducted on the objective facial diagnosis characteristics of the two groups of participants to explore the differences in their facial image characteristics, and the least absolute shrinkage and selection operator (LASSO) regression was used to screen the characteristic variables. Based on the screened feature variables, four machine learning methods: random forest, logistic regression, support vector machine (SVM), and gradient boosting decision tree (GBDT) were used to establish lung cancer classification models independently. Meanwhile, the model performance was evaluated by indicators such as sensitivity, specificity, F1 score, precision, accuracy, the area under the receiver operating characteristic (ROC) curve (AUC), and the area under the precision-recall curve (AP). Results: A total of 1 275 patients with pulmonary nodules and 1 623 patients with lung cancer were included in this study. After propensity score matching (PSM) to adjust for gender and age, 535 patients were finally included in the pulmonary nodule group and the lung cancer group, respectively. There were significant differences in multiple color space metrics (such as R, G, B, V, L, a, b, Cr, H, Y, and Cb) and texture metrics [such as gray-levcl co-occurrence matrix (GLCM)-contrast (CON) and GLCM-inverse different moment (IDM)] between the two groups of individuals with pulmonary nodules and lung cancer (P < 0.05). To construct a classification model, LASSO regression was used to select 63 key features from the initial 136 facial features. Based on this feature set, the SVM model demonstrated the best performance after 10-fold stratified cross-validation. The model achieved an average AUC of 0.8729 and average accuracy of 0.799 0 on the internal test set. Further validation on an independent test set confirmed the model’s robust performance (AUC = 0.823 3, accuracy = 0.729 0), indicating its good generalization ability. Feature importance analysis demonstrated that color space indicators and the whole/lip Cr components (including color-B-0, wholecolor-Cr, and lipcolor-Cr) were the core factors in the model’s classification decisions, while texture indicators [GLCM-angular second moment (ASM)_2, GLCM-IDM_1, GLCM-CON_1, GLCM-entropy (ENT)_2] played an important auxiliary role. Conclusion The facial image features of patients with lung cancer and pulmonary nodules show significant differences in color and texture characteristics in multiple areas. The various models constructed based on facial image features all demonstrate good performance, indicating that facial image features can serve as potential biomarkers for lung cancer risk prediction, providing a non-invasive and feasible new approach for early lung cancer screening.

Objective: To investigate the potential protective effect of Shexiang Tongxin dropping pills (STDP) on ischemia-reperfusion injury and its underlying mechanisms in improving endothelial cell function in coronary microvascular disease (CMVD). Methods: A rat model of myocardial ischemia-reperfusion injury with CMVD was established using ligation and reperfusion of the left anterior descending artery. The effect of STDP (21.6 mg/kg) on cardiac function was evaluated using echocardiography, hematoxylin-eosin staining, and Evans blue staining. The effects of STDP on the microvascular endothelial barrier were assessed based on nitric oxide production, endothelial nitric oxide synthase expression, structural variety of tight junctions (TJs), and the expression of zonula occludens-1 (ZO-1), claudin-5, occludin, and vascular endothelial (VE)-cadherin proteins. The mechanisms of STDP (50 and 100 ng/mL) were evaluated by examining the expression of sphingosine 1-phosphate receptor 2 (S1PR2), Ras Homolog family member A (RhoA), and Rho-associated coiled-coil-containing protein kinase (ROCK) proteins and the distribution of ZO-1, VE-cadherin, and F-actin proteins in an oxygen and glucose deprivation/reoxygenation model. Results: The administration of STDP on CMVD rat model significantly improved cardiac and microvascular endothelial cell barrier functions (all P < .05). STDP enhanced the structural integrity of coronary microvascular positioning and distribution by clarifying and completing TJs and increasing the expression of ZO-1, occludin, claudin-5, and VE-cadherin in vivo (all P < .05). The S1PR2/RhoA/ROCK pathway was inhibited by STDP in vitro, leading to the regulation of endothelial cell TJs, adhesion junctions, and cytoskeletal morphology. Conclusion STDP showed protective effects on cardiac impairment and microvascular endothelial barrier injury in CMVD model rats induced by myocardial ischemia-reperfusion injury through the modulation of the S1PR2/RhoA/ROCK pathway.

The paper introduces one case of intractable beriberi treated with acupuncture of He's three-promotion needling method. The patient visited the hospital because of "repeated redness and swelling of the feet, combined with itching for over 2 years, aggravated in recent 2 days on the left foot". The chief complaints included redness and swelling of the left foot, with the normal walking disturbed, poor appetite, and abdominal distention after meal. The case was identified as beriberi (downward flowing of damp heat, and dysfunction of spleen in transportation due to deficiency). In treatment, using the fire needling technique of acupuncture, Bafeng (EX-LE10) on the left side were stimulated (warming-promotion method). The blood drops were squeezed in the local, if less bleeding was presented, the three-edge needle was used to prick the local area where the acupoint located (strong-promotion method). Afterward, the regular acupuncture was delivered at bilateral Yinlingquan (SP9), Zusanli (ST36) and Sanyinjiao (SP6), as well as Yanglingquan (GB34) and Xuanzhong (GB39) on the left side (mild-promotion method). The therapeutic regimen was adjusted flexibly according to the changes of the symptoms. After treated for 3 weeks, the symptoms disappeared.
Humans ; Acupuncture Therapy/instrumentation* ; Acupuncture Points ; Male ; Beriberi/therapy* ; Middle Aged

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

OBJECTIVES: To explore the mechanism by which Pulsatilla saponin D (PSD) inhibits invasion and metastasis of triple-negative breast cancer (TNBC). METHODS: The public databases were used to identify the potential targets of PSD and the invasion and metastasis targets of TNBC to obtain the intersection targets between PSD and TNBC. The "PSD-target-disease" interaction network was constructed and protein-protein interaction (PPI) analysis was performed to obtain the core targets, which were analyzed for KEGG pathway and GO functional enrichment. Molecular docking study of the core targets and PSD was performed, and the therapeutic effect and mechanism of PSD were verified using Transwell assay and Western blotting in cultured TNBC cells. RESULTS: Network pharmacology analysis identified a total of 285 potential PSD targets and 26 drug-disease intersection core targets. GO analysis yielded 175 entries related to the binding of biomolecules (protein, DNA and RNA), enzyme activities, and regulation of gene transcription. KEGG analysis yielded 46 entries involving pathways in cancer, chemical carcinogenesis-receptor activation, microRNAs in cancer, chemical carcinogenesis-reactive oxygen species, PD-L1 expression and PD-1 checkpoint pathway in cancer. Molecular docking showed high binding affinities of PSD to MTOR, HDAC2, ABL1, CDK1, TLR4, TERT, PIK3R1, NFE2L2 and PTPN1. In cultured TNBC cells, treatment with PSD significantly inhibited cell invasion and migration and lowered the expressions of MMP2, MMP9, N-cadherin and the core proteins p-mTOR, ABL1, TERT, PTPN1, HDAC2, PIK3R1, CDK1, TLR4 as well as NFE2L2 expressionin the cell nuclei. CONCLUSIONS The inhibitory effects of PSD on TNBC invasion and metastasis are mediated by multiple targets and pathways.
Humans ; Triple Negative Breast Neoplasms/metabolism* ; Saponins/pharmacology* ; Pulsatilla/chemistry* ; Female ; Molecular Docking Simulation ; Cell Line, Tumor ; Neoplasm Invasiveness ; Protein Interaction Maps ; Neoplasm Metastasis ; Signal Transduction/drug effects* ; Cell Movement/drug effects*

Objective To evaluate the effect of modified vertical tooth preparation with full zirconium crown resto-ration in molar area.Methods A randomized study was conducted in 84 patients with all-ceramic crown restoration of posterior teeth.90 full crown restorations were collected and randomly divided into two groups:45 teeth in exper-imental group were treated with modified vertical tooth preparation,while 45 teeth in control group were treated with conventional horizontal tooth preparation with full zirconium crown restoration.When patients wore teeth,the resto-ration effects of the two groups were evaluated respectively,and then the marginal and internal fitness of the two groups were measured by silicone rubber replication method;gingival index(GI)and sulcus bleeding index(SBI)scores were recorded 6 months after wearing teeth.Results The results of chair-side evaluation of the two groups showed that the marginal fitness of the experimental group was better than that of the control group,and the differ-ence was statistically significant(P=0.036);the measured value of marginal fitness of prostheses in experimental group was better than that in control group,and the difference was statistically significant(P＜0.001);after 6 months,there was no mechanical complication between the two groups,and there was no significant difference in GI and SBI scores of periodontal soft tissue indexes.Conclusion Modified vertical tooth preparation abutment can significantly improve the marginal fitness of all-ceramic crown,which will not change the health status of peri-crown gingiva.

Objective To analyze the co-expressed genes in blood lipid metabolism,hyperlipidemia and tacrolimus metabolism and their correlation with blood lipid levels in kidney transplant recipients.Methods Co-expressed genes were screened from Comparative Toxicogenomic Database(CTD).Baseline data of 25 kidney transplant recipients were collected.The expression levels of ATP binding cassette subfamily A member 1(ABCA1),peroxisome proliferator activated receptor γ(PPAR-γ)and glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1(GPIHBP1)were measured.All recipients were followed up.The concentrations of fasting blood glucose,glycosylated hemoglobin,triglyceride,total protein,albumin,globulin,cholesterol,high-density lipoprotein,low-density lipoprotein and tacrolimus blood concentration were collected at postoperative 1,3,6 and 12 months,and the incidence of hyperlipidemia in the recipients was analyzed.The correlation between ABCA1,GPIHBP1,PPAR-γ and clinical indexes was assessed.The diagnostic effiiciency of related indexes for hyperlipidemia after kidney transplantation was evaluated.Results Three co-expressed genes including ABCA1,PPAR-γ and GPIHBP1 were screened.ABC Al was positively correlated with cholesterol level at postoperative 6 months and tacrolimus blood concentration at postoperative 3 months,whereas negatively correlated with fasting blood glucose level at postoperative 3 months(all P＜0.05).GPIHBP1 was negatively correlated with preoperative cholesterol and triglyceride levels,whereas positively correlated with tacrolimus blood concentration at postoperative 3 months(all P＜0.05).PPAR-γ was negatively correlated with preoperative globulin and low-density lipoprotein levels(both P＜0.05).ABCA1,GPIHBP1 and PPAR-γ combined with preoperative globulin and blood glucose level at postoperative 1 and 6 months after operation yielded high diagnostic effiiciency for hypertriglyceridemia after kidney transplantation(AUC=0.900).ABCA1,GPIHBP1 and PPAR-γ combined with tacrolimus blood concentrations at postoperative 1 and 6 months and blood glucose level at postoperative 6 months had high diagnostic effiiciency for hypercholesterolemia after kidney transplantation(AUC=0.931).Conclusions ABCA1,GPIHBP1 and PPAR-γ are correlated with blood lipid level and tacrolimus blood concentration after kidney transplantation to different degrees.No definite evidence has been supported for predicting hyperlipidemia after kidney transplantation.Immunity improvement and rational blood glucose management may be beneficial factors for hyperlipidemia control.