ObjectiveTo evaluate the effects of Tongnaoyin on the blood-brain barrier status and neurological impairment in acute ischemic stroke （AIS） patients with the syndrome of phlegm-stasis blocking collaterals by dynamic contrast-enhanced magnetic resonance imaging （DCE-MRI）. MethodsA total of 63 patients diagnosed with AIS in the Jiangsu Province Hospital of Chinese Medicine from October 2022 to December 2023 were enrolled in this study. According to random number table method，the patients were assigned into a control group （32 cases） and an observation group （31 cases）. The control group received conventional Western medical treatment，and the observation group took 200 mL Tongnaoyin after meals，twice a day from day 2 of admission on the basis of the treatment in the control group. After 7 days of treatment，the patients were examined by DCE-MRI. The baseline data for two groups of patients before treatment were compared. The National Institute of Health Stroke Scale （NIHSS） score and modified Rankin Scale （mRS） score were recorded before treatment and after 90 days of treatment for both groups. The rKtrans，rKep，and rVe values were obtained from the region of interest （ROI） of the infarct zone/mirror area and compared between the two groups. ResultsThere was no significant difference in the NIHSS or mRS score between the two groups before treatment. After 90 days of treatment，the NIHSS and mRS scores declined in both groups，and the observation group had lower scores than the control group （P<0.05）. After treatment，the rKtrans and rVe in the observation group were lower than those in the control group （P<0.01）. ConclusionCompared with conventional Western medical treatment alone，conventional Western medical treatment combined with Tongnaoyin accelerates the repair of the blood-brain barrier in AIS patients，thereby ameliorating neurological impairment after AIS to improve the prognosis.

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Tic disorders in children refer to the neurodevelopmental disorders usually occurring in childhood and adolescence.Guided by the theory of five-zang-organ correlation,Professor Li Yirui approaches the treatment of tic disorders in children and comorbidities primarily from the perspective of liver-spleen disharmony,and points out that the pathogenesis is due to liver-spleen disharmony,wind-phlegm disturbance,and mutual involvement of the five zang organs.In clinical practice,Professor Li established the therapeutic principle of regulating the liver and spleen,extinguishing wind,and resolving phlegm,and adopted the four liver-regulating methods(calming liver,soothing liver,clearing liver,and softening liver)to extinguish wind and stop tics,as well as the four spleen-regulating methods(replenishing spleen,activating spleen,awakening spleen,and dredging spleen)to strengthen body resistance and support healthy qi.The self-formulated Fupi Xifeng Decoction(composed of Pseudostellariae Radix,Atractylodis Macrocephalae Rhizoma,Poria,Glycyrrhizae Radix et Rhizoma,Bupleuri Radix,Paeoniae Radix Alba,Uncariae Ramulus cum Uncis,Gastrodiae Rhizoma,Pinelliae Rhizoma Praeparatum,Citri Reticulatae Pericarpium,Os Draconis,etc.)serves as the basic formula,herbs directing to the affected regions were flexibly used,and insect drugs were occasionally adopted for refractory cases.The treatment for tic disorders in children focus on simultaneous regulation of the five zang-organs by modified use of herbs for dispersing wind and benefiting lung,tranquilizing heart and calming spirit,and supplementing liver and kidney to address comorbidities and secondary symptoms.Additionally,integrated internal-external treatment,relieving the discomforts physically and mentally,and family-centered comprehensive care are also taken into account to achieve optimal outcomes.

As a common clinical disease, fracture is often accompanied by pain, swelling, bleeding as well as other symptoms and has a high disability rate, even threatening life, seriously endangering patients' physical and psychological health and quality of life. Medical practitioners take many strategies for the treatment of fracture healing, including Traditional Chinese Medicine (TCM). In the early stage of fracture healing, the local fracture is often in a state of hypoxia, accompanied by the expression of hypoxia inducible factor-1α (HIF-1α), which is beneficial to wound healing. Through literature mining, we thought that hypoxia, HIF-1α and downstream factors affected the mechanism of fracture healing, as well as dominated this process. Therefore, we reviewed the local characteristics and related signaling pathways involved in the fracture healing process and summarized the intervention of TCM on these mechanisms, in order to inspirit the new strategy for fracture healing, as well as elaborate on the possible principles of TCM in treating fractures based on the HIF molecular mechanism.

ObjectiveTo investigate the changes in cerebral blood perfusion in patients with acute cerebral infarction after taking Tongnaoyin， a traditional Chinese medicine， based on head and neck computed tomography （CT） angiography （CTA） combined with brain CT perfusion imaging （CTP）. MethodA total of 240 patients with cerebral infarction of phlegm and blood stasis syndrome treated in Jiangsu Province Hospital of Traditional Chinese Medicine from March 2018 to September 2023 were randomly divided into a control group （99 cases） and a Tongnaoyin group （141 cases）. Based on the guidelines， the control group was treated with conventional treatment such as anti-aggregation， anticoagulation， lipid-lowering and plaque stabilization， brain protection， and supportive treatment. The Tongnaoyin group was treated with Tongnaoyin of 200 mL in warm conditions in the morning and evening on the basis of the control group. Both groups underwent CTA combined with CTP within 24 hours after admission， and they were reexamined by CTA and CTP in the sixth month after admission. The degree of intracranial artery stenosis was determined according to the North American Symptomatic Carotid Endarterectomy Trial （NASCET） method. The relative cerebral blood volume （rCBV）， relative cerebral blood flow （rCBF）， mean transit time （MTT）， and time to peak （TTP） of the lesion area before and after treatment were compared. The adverse outcomes of the two groups within six months after discharge were compared. ResultCompared with the group before treatment， the degree of vascular stenosis in the Tongnaoyin group was significantly reduced， and the difference was statistically significant （Z=105.369，P<0.05）. Compared with the control group after treatment， the improvement rate of vascular stenosis in the Tongnaoyin group was higher （χ²=84.179，P<0.01）， and the curative effect was better.After treatment， the rCBV and rCBF of patients in the Tongnaoyin group were significantly increased， and the difference was statistically significant （P<0.01）. MTT and TTP showed a trend of shortening， but the difference was not statistically significant. There was no statistically significant difference in rCBV， rCBF， MTT， and TTP in the control group. Compared with those in the control group after treatment， the rCBV and rCBF in the Tongnaoyin group were significantly increased， while MTT and TTP were significantly reduced （P<0.01）. After six months of discharge， the risk of poor prognosis in the Tongnaoyin group was significantly reduced compared with the control group （P<0.05）. ConclusionTongnaoyin has a good effect on improving cerebral blood perfusion in patients with acute cerebral infarction. It can be used as an effective supplement for the conventional treatment of ischemic stroke to improve clinical efficacy.

Objective To construct a nomogram to predict the prognosis of patients with gallbladder cancer(GBC).Methods The clinicopathological data of GBC patients were extracted from the SEER database,and the independent prognostic factors of GBC patients were analyzed by Cox regression,and a nomogram was constructed.Finally,the column diagrams in the training queue and validation queue are verified.Results Age,T stage,M stage,histological grade,radiotherapy,surgery and tumor size were independent prognostic factors in GBC patients,and the differences were statistically significant(P＜0.05).In the training cohort,the C index was 0.735(95％CI=0.721～0.749),and the AUC values at 1,3 and 5 years were 0.821,0.820 and 0.833,respectively.In the verification group,the C index was 0.733(95％CI=0.711～0.755),and the AUC values for 1,3 and 5 years were 0.816,0.807 and 0.827,respectively.The calibration curve shows that the predicted values of the nomogram are in good agreement with the observed values.The decision curve shows that the nomogram model has better prediction ability than TNM staging system.Conclusion The constructed dynamic prognosis nomogram of GBC patients has high accuracy and reliability.

Acute myocardial infarction(AMI)is a common cardiovascular emergency in clinic.Early reperfusion is a typical and effective method for the treatment of AMI.However,the recovery of blood supply after reperfusion therapy will accelerate the damage of ischemic myocardium and cause myocardial ischemia-reperfusion injury(MI/RI).In recent years,studies have found that TCM has the unique advantages of multi-component,multi-channel and multi-target in the intervention of MI/RI.Janus tyrosine kinase/signal transducer and activator of transcription(JAK/STAT)signaling pathway is closely related to MI/RI,which can reduce MI/RI process by regulating inflammation,oxidative stress,cell proliferation,differentiation and apoptosis.This article reviewed the mechanism of JAK/STAT signaling pathway in MI/RI and the research of TCM targeting this pathway,in order to provide references for the prevention and treatment of MI/RI and further drug development.

Myocardial injury is a pathological change of myocardium caused by many factors,which can lead to the decline of cardiac function and the occurrence of cardiovascular events.Astragaloside Ⅳ is one of the main pharmacological components in Astragali Radix,which plays an anti-myocardial injury role by regulating various signaling pathways.This article reviewed the anti-myocardial injury mechanism of astragaloside Ⅳ from five aspects:inhibition of oxidative stress,inhibition of apoptosis,anti-myocardial fibrosis,improvement of myocardial energy metabolism and inhibition of myocardium inflammation,in order to provide reference for the mechanism research and clinical application of astragaloside Ⅳ in the prevention and treatment of myocardial injury.

Objective·To further clarify the mechanism of podocyte damage by studying the expression of cartilage oligomeric matrix protein(COMP)in glomerular podocytes and its relationship with podocyte autophagy under high glucose environment.Methods·The gene expression dataset GSE104948 was downloaded from the GENE EXPRESSION OMNIBUS(GEO)database,and differentially expressed genes(DEGs)were obtained via GEO2R.The molecular functions and signaling pathways related to differential genes were summarized.The most correlated key genes(hub genes)were acquired by Weighted Gene Co-Expression Network Analysis(WGCNA)and the protein-protein interaction network(PPI)of DEGs was constructed with STRING database.The enrichment analysis was performed again.Conditionally immortalized mouse podocyte cells were cultured in vitro.After being fully differentiated,they were stimulated with high glucose,and the expressions of COMP,mammalian target of rapamycin(mTOR),microtubule-associated protein 1 light chain3(LC3)and other proteins in podocytes were detected by Western blotting.The shRNA constructed by lentiviral vector was further used to infect podocytes to inhibit the expression of COMP,and the stable cell strains were screened by puromycin.The expression of COMP,mTOR,and LC3 of stable strains were detected by Western blotting,in order to observe the effect of COMP on autophagy.Results·A total of 362 DEGs were filtered for subsequent analysis.Among these DEGs,284 genes were up-regulated and 78 genes were down-regulated.The results of Gene Onotology(GO)term analysis showed that DEGs in diabetic nephropathy(DN)were mainly enriched in cell surface receptor signaling pathway,receptor binding,etc.The main enriched Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways included phosphatidylinositol 3-kinase(PI3K)/protein kinase B(PKB/AKT)signaling pathway,extracellular matrix(ECM)-receptor interaction,etc.Sixty-four hub genes were refined through the intersection of WGCNA and PPI hub genes,and the hub genes with significantly increased or decreased expression were sifted.The hub genes were annotated with KEGG again,and it was found that most of the hub genes were enriched in"ECM-receptor interaction"and"PI3K/AKT signaling pathway".The PI3K/AKT/mTOR signaling pathway is a classic autophagy pathway,and COMP was absolutely overexpressed(logFC>2)in the 64 hub genes,suggesting that it may affect autophagy through this pathway.Western blotting showed that compared with the mannitol control group and the low glucose group,the expression of COMP in podocytes was significantly increased under high glucose stimulation.Compared with the control group,the expression of LC3-Ⅱ in the high glucose group was significantly decreased,indicating that the autophagy initiation of podocytes was inhibited under the high glucose environment.Compared with the negative control,the expression of LC3-Ⅱ in renal podocytes of mice with knockdown of COMP was significantly increased,and the mTOR decreased with the decrease of the expression of COMP,indicating that inhibiting COMP contributed to the recovery of autophagy in podocytes.Conclusion·COMP is highly expressed in DN patients and highly enriched in ECM receptor and PI3K/AKT signaling pathway.Autophagy in mouse renal podocytes is inhibited under high glucose conditions,and the high expression of COMP induced by high glucose may be a key factor in autophagy inhibition.Inhibiting COMP helps to restore autophagy in mouse renal podocytes.

Objective:To explore the mechanism of long non-coding RNA RP11-79H23.3 in the development and progression of prostate cancer.Methods:The lnCAR database was used to analyze the RP11-79H23.3 content in prostate cancer tissues and adjacent tissues. RP11-79H23.3 content in prostate cancer cell lines C4-2B, LNCaP, DU-145, and 22Rv1 was detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). Taking 22Rv1 as the research target, colony formation experiments and scratch experiments were used to detect the effects of overexpression of RP11-79H23.3 on the proliferation and migration of 22Rv1 cells. The LncRNome and lncACTdb databases were used to predict the downstream gene and binding sequences of RP11-79H23.3. The Cancer Genome Atlas (TCGA) database was used to analyze the correlation between RP11-79H23.3 and miR-410 expression in prostate cancer tissues. The binding of RP11-79H23.3 and miR-410 was confirmed by dual-luciferase reporter gene experiment. The effect of RP11-79H23.3 on the expression of miR-410 was detected by RT-qPCR. Western blotting was used to detect the effect of RP11-79H23.3 on the expression of phosphatase and tensin homolog/protein kinase B/mammalian target of rapamycin (PTEN/AKT/mTOR) signaling pathway proteins in 22Rv1 cells. The measurement data were expressed as mean ± standard deviation ( ± s), paired sample t-test was used for comparison between two groups, and one-way analysis of variance was used for comparison between multiple groups. Results:Compared with adjacent tissues, RP11-79H23.3 was lowly expressed in prostate cancer tissues ( P<0.01). Compared with normal prostate epithelial cells RWPE-1, RP11-79H23.3 was lowly expressed in prostate cancer cell lines C4-2B, LNCaP, DU-145, and 22Rv1 ( P<0.05). The expression of RP11-79H23.3 in 22Rv1 cells in the control group and RP11-79H23.3 group were 1.02 ± 0.30 and 8.94±1.95, respectively. 22Rv1 cells were successfully overexpressed RP11-79H23.3 compared with the control group ( t=4.04, P<0.01). The number of 22Rv1 cell clones in the control group and RP11-79H23.3 group were 166.10 ± 18.35 and 35.03±6.98, respectively. Overexpression of RP11-79H23.3 could inhibit the proliferation of 22Rv1 cells compared with the control group ( t=6.67, P<0.01). The migration rates of 22Rv1 cells in the control group and RP11-79H23.3 group were (67.40 ± 6.29)% and (26.42 ± 6.24)%, respectively. Overexpression of RP11-79H23.3 could inhibit the migration of 22Rv1 cells compared with the control group ( t=5.71, P<0.01) .Dual-luciferase reporter gene experiment showed that RP11-79H23.3 directly binds to miR-410 ( t=6.20, P<0.01). The expression of miR-410 in 22Rv1 cells in the control group and RP11-79H23.3 group were 6.22±1.39 and 1.05±0.23, respectively. RP11-79H23.3 could inhibit the expression of miR-410 in 22Rv1 cells compared with the control group ( t=3.68, P<0.01). At the same time, RP11-79H23.3 can inhibit the transduction of the PTEN/AKT/mTOR signaling pathway in 22Rv1 cells. Conclusion:RP11-79H23.3 blocks the PTEN/AKT/mTOR signaling pathway by inhibiting the expression of miR-410, thereby inhibiting the proliferation and migration of prostate cancer 22Rv1 cells.