BACKGROUND: The protective effect of mesenchymal stem cells (MSCs) on cardiac ischemia-reperfusion (I/R) injury has been widely reported. Dental pulp-derived mesenchymal stem cells (DP-MSCs) have therapeutic effects on various diseases, including diabetes and cirrhosis. This study aimed to determine the therapeutic effects of DP-MSCs on I/R injury and elucidate the underlying mechanism. METHODS: Myocardial I/R injury model mice were treated with DP-MSCs or a miR-19a-3p mimic. The infarct volume, fibrotic area, pyroptosis, inflammation level, and cardiac function were measured. Cardiomyocytes exposed to hypoxia-reoxygenation were transfected with the miR-19a-3p mimic, miR-19a-3p inhibitor, or negative control. Pyroptosis and protein expression in the interferon regulatory factor 8/mitogen-activated protein kinase (IRF-8/MAPK) pathway were measured. RESULTS: DP-MSCs protected cardiac function in cardiac I/R-injured mice and inhibited cardiomyocyte pyroptosis. The upregulation of miR-19a-3p protected cardiac function, inhibited cardiomyocyte pyroptosis, and inhibited IRF-8/MAPK signaling in cardiac I/R-injured mice. DP-MSCs inhibited cardiomyocyte pyroptosis and the IRF-8/MAPK signaling by upregulating the miR-19a-3p levels in cardiomyocytes injured by I/R. CONCLUSION DP-MSCs protected cardiac function by inhibiting cardiomyocyte pyroptosis through miR-19a-3p under I/R conditions.
Animals ; MicroRNAs/metabolism* ; Pyroptosis/genetics* ; Mesenchymal Stem Cells/metabolism* ; Myocytes, Cardiac/cytology* ; Mice ; Male ; Mice, Inbred C57BL ; Dental Pulp/cytology* ; Myocardial Reperfusion Injury/therapy* ; MAP Kinase Signaling System/physiology*

Colorectal cancer (CRC) is one of the most prevalent malignant tumors of the digestive system worldwide, characterized by continuously rising incidence and mortality rates. Despite significant advancements in therapeutic approaches, the prognosis for advanced-stage CRC remains unsatisfactory, highlighting the urgent need to explore novel molecular mechanisms and therapeutic strategies. Ferroptosis, a form of programmed cell death driven by iron-dependent lipid peroxidation, plays a crucial role in cancer occurrence, progression, and treatment resistance. Activation of ferroptosis significantly suppresses tumor cell growth. Further investigation into the mechanisms of ferroptosis in CRC occurrence, progression, and treatment could provide valuable insights for both basic and clinical research on CRC.

Rheumatoid arthritis （RA）， as an autoimmune disease， is mainly characterized by persistent synovitis. It often involves multiple joints symmetrically and can lead to joint deformity， joint function loss， and even disability in severe cases. The pathogenesis of RA is complex， and the prevention and treatment are complicated. Therefore， it is difficult to cure the disease completely. Previous studies have validated important targets and mechanisms for the prevention and treatment of RA， including the nuclear factor-κB （NF-κB） signaling pathway that controls the inflammatory process， nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway that regulates oxidative stress， inhibits inflammation， and maintains cell homeostasis， Wnt/β-catenin signaling pathway that plays a key role in cell growth， differentiation， apoptosis， and inflammatory response， anti-inflammatory， anti-oxidation， and silent information regulator 1 （SIRT1） signaling pathway that regulates synovial cells， anti-inflammatory adenylate-activated protein kinase （AMPK） signaling pathway that regulates energy metabolism， and hypoxia-inducible factor-1α （HIF-1α）/vascular endothelial growth factor （VEGF） signaling pathway related to angiogenesis in RA. At the same time， many studies have confirmed that traditional Chinese medicine prevents and treats RA by regulating the above signaling pathways and exerting their related effects， indicating the advantages of traditional Chinese medicine such as multiple regulatory pathways， long-term effects， and less adverse reactions. In this paper， by consulting many research reports， the role of the above-mentioned signaling pathways in RA was clarified， and the latest research results of traditional Chinese medicine intervention in the above-mentioned signaling pathways in the prevention and treatment of RA in recent years were summarized in detail. This paper aims to promote the in-depth study of the pathogenesis of RA and its treatment with traditional Chinese medicine， provide a scientific basis for the rational application of traditional Chinese medicine， and offer useful enlightenment for the development of new drugs and clinical practice for the treatment of RA in the future.

BACKGROUND:There is no consensus on the optimal bone tunnel position in the lateral clavicle,which guides coracoclavicular ligament reconstruction.Postoperative complications such as enlargement of the lateral clavicle bone tunnel,bone osteolysis,clavicle fracture,and failure of internal fixation are likely to occur.Bone mass density plays an important role in the strength and stability of endophytic fixation.Regional differences in the bone mass density of the distal clavicle should not be overlooked in the repair and reconstruction of acromioclavicular dislocation.Currently,there are no quantitative clinical studies in humans regarding the bone mass density of the distal clavicle. OBJECTIVE:To measure the magnitude of bone mass density in different regions of the distal clavicle by quantitative CT to provide a reference for surgeons to repair and reconstruct the coracoclavicular ligament. METHODS:101 patients undergoing quantitative CT checking in Fuyang People's Hospital Affiliated to Anhui Medical University from October to December 2022 were enrolled,from which 1 616 samples of subdivisional bone mass density of the distal clavicle were measured.For each of the quantitative CT samples,firstly,the distal clavicle was divided medially to laterally into the following four regions:conical nodal region(region A),inter-nodal region(region B),oblique crest region(region C)and distal clavicular region(region D).Secondly,each region was divided into the first half and the second half to determine eight subdivisions,then setting semiautomatic region of interest(ROI)in each subdivision:(ROI A1,A2,B1,B2,C1,C2,D1,and D2).Thirdly,each quantitative CT scan was transferred to the quantitative CT pro analysis workstation,and cancellous bone mass density was measured in the distal clavicle ROI.Finally,the clavicular cortex was avoided when measuring. RESULTS AND CONCLUSION:(1)There was no statistically significant difference in bone mineral density on the different sides of the shoulder(P＞0.05).(2)The analysis of bone mineral density in eight sub-areas of the distal clavicle A1,A2,B1,B2,C1,C2,D1,and D2 showed statistically significant differences(P＜0.05).It could be considered that there were differences in bone mineral density in different areas of the distal clavicle.After pairwise comparison,there was no statistically significant difference in bone mineral density between A1 and A2,D1 and D2,A2 and B1(P＞0.05),and there was a statistically significant difference in bone mineral density between the other sub-areas(P＜0.05).(3)The bone mineral density in the region A2 of the anatomical insertion of the conical ligament was significantly higher than that in the inter-nodular area(region B)(P＜0.05).The bone mineral density in the region A1 was higher than that in the region A2,but the difference was not statistically significant(P＞0.05).The bone mineral density in the region C1 of the anatomical insertion of the trapezium ligament was higher than that in regions C2,D1 and D2,and the bone mineral density in the inter-nodular area(region B)was significantly higher than that in regions C and D(P＜0.05).(4)These results have suggested that there are differences in bone mass density in different regions of the distal clavicle;regional differences in bone mass density in the distal clavicle during repair and reconstruction of acromioclavicular dislocation cannot be ignored.Consideration should be given not only to biomechanical factors but also to the placement of implants or bone tunnels in regions of higher bone mass density,which could improve the strength and stability of implant fixation and reduce the risk of complications such as bone tunnel enlargement,osteolysis,fracture and implant failure.

Objective:To explore the characteristics of early postural control disorders in elderly patients with Parkinson's disease(PD). Method:The sensory organization test(SOT),limits of stability(LOS),and adaptation test(ADT)were performed on 15 patients with early-stage PD and 10 healthy elderly patients using a dynamic and static balance training system. Result:Compared with the healthy group,in the SOT,early PD patients showed no significant differences in the comprehensive score of sensory organization,proprioceptive,visual,and visual dependence(P＞0.05).How-ever,there was a significant difference in vestibular balance control(P＜0.05).In the LOS,early PD patients exhibited decreased forward and backward max excursions(MXE)(P＜0.05),increased reaction time(RT)(P＜0.05),and decreased backward directional contro1(DCL)(P＜0.05).There were no significant differences in for-ward DCL,left and right MXE,RT,DCL(P＞0.05).In the ADT,there were no significant differences in the incidence of the first fall and the incidence of the last four falls in PD patients and healthy groups in the for-ward and backward tilt tests(P＞0.05). Conclusion:Early PD elderly patients already have postural control disorders,particularly with decreased limits of stability in forward and backward directions and reduced ability to maintain balance using vestibular input.

Animals ; SARS-CoV-2 ; Antibodies, Neutralizing ; Macaca mulatta ; COVID-19/prevention & control* ; Antibodies, Viral ; Vaccines

【Objective】 To explore the mutation type, clinical characteristics, molecular genetics and the two-hit type of a patient with familial Von Hippel Lindau (VHL) syndrome. 【Methods】 The data of the patient were collected. DNA was extracted from the peripheral blood and renal cell carcinoma sample. The VHL gene germline mutation site was detected with high throughput sequencing next generation sequencing (NGS). The two-hit site was identified with UCSCXena database, methylation-specific PCR (MSP) and microsatellite stability detection. 【Results】 The mutation site of the embryo line was located in c.500G>A R167Q mutation. The patient had single nucleotide polymorphism, but no clear loss of heterozygosity, methylation or system mutation. 【Conclusion】 The germline mutation in exon 3 is the basis for the clinical features of this familial renal cell carcinoma proband. The identification of the two-hit site is key to the occurrence of the disease, which is significant for the diagnosis and treatment. The use of the databases can guide the screening of mutations and methylation sites in familial renal cell carcinoma.

The incidence of augmented renal clearance (ARC) in intensive care patients (ICU) is exceptionally high, and these patients are often co-morbid with infection. The occurrence of ARC will significantly increase the clearance rate of antibiotics, making it difficult for conventional doses to reach effective therapeutic concentrations and affect the patient's anti-infective treatment effect and prognosis. It can be seen that it is crucial to formulate a reasonable dosing regimen for ICU patients with ARC. Regrettably, few reports in China about the adjustment strategy of antibiotic dosing regimens for ARC patients. Therefore, this article reviews the domestic and foreign literature for reference to provide evidence for medical personnel to adjust the dose of antibacterial drugs for such patients.

Cutaneous T-cell lymphomas are a relatively rare group of mature T-cell lymphomas mainly manifesting in the skin, and its common subtype is mycosis fungoides. Total skin electron irradiation is one of the important conventional treatment methods, but there are many disadvantages, such as uneven dose distribution, poor position repetition, and long treatment time, which affect the clinical efficacy and patient prognosis. With the emergence and gradual popularization of helical tomotherapy in recent years, more and more medical institutions are gradually expanding their applications in total skin irradiation due to their ability to treat ultra-long targets and achieve dose-sculpted distribution, aiming to further explore its good or bad, and confirm whether it can replace the traditional total skin electron irradiation. In this article, research progress on total skin irradiation using helical tomotherapy was reviewed, the development of treatment technology, clinical efficacy and current concerns and controversies were illustrated.

Chronic myeloid leukemia (CML) is a slowly progressing hematopoietic cell disorder. Sphingosine kinase 1 (SPHK1) plays established roles in tumor initiation, progression, and chemotherapy resistance in a wide range of cancers, including leukemia.However, small-molecule inhibitors targeting SPHK1 in CML still need to be developed. This study revealed the role of SPHK1 in CML and investigated the potential anti-leukemic activity of hirsuteine (HST), an indole alkaloid obtained from the oriental plant Uncaria rhynchophylla, in CML cells. These results suggest that SPHK1 is highly expressed in CML cells and that overexpression of SPHK1 represents poor clinical outcomes in CML patients. HST exposure led to G2/M phase arrest, cellular apoptosis, and downregulation of Cyclin B1 and CDC2 and cleavage of Caspase 3 and PARP in CML cells. HST shifted sphingolipid rheostat from sphingosine 1-phosphate (S1P) towards the ceramide coupled with a marked inhibition of SPHK1. Mechanistically, HST significantly blocked SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways. In addition, HST can be docked with residues of SPHK1 and shifts the SPHK1 melting curve, indicating the potential protein-ligand interactions between SPHK1 and HST in both CML cells. SPHK1 overexpression impaired apoptosis and proliferation of CML cells induced by HST alone. These results suggest that HST, which may serve as a novel and specific SPHK1 inhibitor, exerts anti-leukemic activity by inhibiting the SPHK1/S1P/ S1PR1 and BCR-ABL/PI3K/Akt pathways in CML cells, thus conferring HST as a promising anti-leukemic drug for CML therapy in the future.