Objective:To evaluate the role of tumor necrosis factor-α-induced protein 8-like molecule-2 (TIPE2) in the endogenous protective mechanism against acute lung injury in septic mice and the relationship with ferroptosis.Methods:Twenty SPF healthy wild-type male C57BL/6N mice and 20 TIPE2 gene knockout C57BL/6N mice, aged 6-8 weeks, weighing 20-25 g, were assigned to wild-type sham operation group (WT-Sham group), wild-type sepsis group (WT-SEP group), TIPE2 knockout sham operation group (KO-Sham group), and TIPE2 knockout sepsis group (KO-SEP group) using a random number table method, with 10 mice in each group. Acute lung injury was induced by cecal ligation and perforation in anesthetized mice. The animals were sacrificed after anesthesia at 24 h after operation and lung tissues were obtained for examination of the morphological results of lung tissues (with a light microscope) and for determination of wet to dry lung weight (W/D) ratio, contents of ferrous ions (Fe 2+ ), glutathione (GSH) and malondialdehyde (MDA) and expression of solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4) and Acyl-CoA synthetase long-chain family member 4 (ACSL4) (by Western blot). Results:Compared with WT-Sham group, the lung injury score, W/D ratio and contents of Fe 2+ and MDA were significantly increased, the content of GSH was decreased, the expression of GPX4 and SLC7A11 was down-regulated, and the expression of ACSL4 was up-regulated in WT-SEP group ( P<0.05). Compared with WT-SEP group, the lung injury score, W/D ratio and contents of Fe 2+ and MDA were significantly increased, the content of GSH was decreased, the expression of GPX4 and SLC7A11 was down-regulated, and the expression of ACSL4 was up-regulated in KO-SEP group ( P<0.05). Conclusions:TIPE2 is involved in the endogenous protective mechanism against acute lung injury, which may be related to the inhibition of ferroptosis in lung tissues of septic mice.

Temporomandibular joint osteoarthritis (TMJ-OA) is a common disease often accompanied by pain, seriously affecting physical and mental health of patients. Abnormal innervation at the osteochondral junction has been considered as a predominant origin of arthralgia, while the specific mechanism mediating pain remains unclear. To investigate the underlying mechanism of TMJ-OA pain, an abnormal joint loading model was used to induce TMJ-OA pain. We found that during the development of TMJ-OA, the increased innervation of sympathetic nerve of subchondral bone precedes that of sensory nerves. Furthermore, these two types of nerves are spatially closely associated. Additionally, it was discovered that activation of sympathetic neural signals promotes osteoarthritic pain in mice, whereas blocking these signals effectively alleviates pain. In vitro experiments also confirmed that norepinephrine released by sympathetic neurons promotes the activation and axonal growth of sensory neurons. Moreover, we also discovered that through releasing norepinephrine, regional sympathetic nerves of subchondral bone were found to regulate growth and activation of local sensory nerves synergistically with other pain regulators. This study identified the role of regional sympathetic nerves in mediating pain in TMJ-OA. It sheds light on a new mechanism of abnormal innervation at the osteochondral junction and the regional crosstalk between peripheral nerves, providing a potential target for treating TMJ-OA pain.
Animals ; Osteoarthritis/physiopathology* ; Mice ; Sympathetic Nervous System/physiopathology* ; Temporomandibular Joint Disorders/physiopathology* ; Arthralgia ; Sensory Receptor Cells ; Disease Models, Animal ; Norepinephrine ; Male ; Temporomandibular Joint/physiopathology* ; Pain Measurement

Objective:To evaluate the role of tumor necrosis factor-α-induced protein 8-like molecule-2 (TIPE2) in the endogenous protective mechanism against acute lung injury in septic mice and the relationship with ferroptosis.Methods:Twenty SPF healthy wild-type male C57BL/6N mice and 20 TIPE2 gene knockout C57BL/6N mice, aged 6-8 weeks, weighing 20-25 g, were assigned to wild-type sham operation group (WT-Sham group), wild-type sepsis group (WT-SEP group), TIPE2 knockout sham operation group (KO-Sham group), and TIPE2 knockout sepsis group (KO-SEP group) using a random number table method, with 10 mice in each group. Acute lung injury was induced by cecal ligation and perforation in anesthetized mice. The animals were sacrificed after anesthesia at 24 h after operation and lung tissues were obtained for examination of the morphological results of lung tissues (with a light microscope) and for determination of wet to dry lung weight (W/D) ratio, contents of ferrous ions (Fe 2+ ), glutathione (GSH) and malondialdehyde (MDA) and expression of solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4) and Acyl-CoA synthetase long-chain family member 4 (ACSL4) (by Western blot). Results:Compared with WT-Sham group, the lung injury score, W/D ratio and contents of Fe 2+ and MDA were significantly increased, the content of GSH was decreased, the expression of GPX4 and SLC7A11 was down-regulated, and the expression of ACSL4 was up-regulated in WT-SEP group ( P<0.05). Compared with WT-SEP group, the lung injury score, W/D ratio and contents of Fe 2+ and MDA were significantly increased, the content of GSH was decreased, the expression of GPX4 and SLC7A11 was down-regulated, and the expression of ACSL4 was up-regulated in KO-SEP group ( P<0.05). Conclusions:TIPE2 is involved in the endogenous protective mechanism against acute lung injury, which may be related to the inhibition of ferroptosis in lung tissues of septic mice.

Objective To investigate the organ protective role and the underlying mechanism of nafamostat mesylate(NM)in a renal ischemia-reperfusion injury(RIRI)model.Methods A total of 21 healthy male Sprague-Dawley(SD)rats were randomly assigned to 3 groups(n=7 in each group),including the sham operation group(Sham group),the RIRI group,and the NM intervention group(NM group).The RIRI and NM groups underwent ischemia-reperfusion injury(IRI)modeling.The NM group was given an intraperitoneal injection of NM at 0.75 mg/kg before modeling.Venous blood and renal tissue samples were then collected from the rats 24 hours after modeling.The levels of serum creatinine,cystatin C,and serum inflammatory factors were determined using the serum samples.Hematoxylin-eosin(HE)staining and TUNEL stainings were performed on the renal tissues to evaluate the damage of the renal tissues.The localization and expression of HMGB1 were analyzed by immunofluorescence and Western blotting,respectively.Single-cell RNA sequencing of the nuclei was performed to obtain the single-cell transcriptome of the kidneys from the rats in the RIRI and the NM groups and to acquire the RIRI cell profile.The cells were annotated according to the cell marker genes to explore the cell type composition in the disease model and the functional status of immune cells between the groups.Results 1)Compared with those of the Sham group,the levels of cystatin C,creatinine,and inflammatory factors in the RIRI and NM groups were significantly increased,and the expression levels in the NM group were lower than those in the RIRI group(P＜0.05).Compared with those of the RIRI group,the tubular injury score and apoptosis rate in the NM group were significantly decreased(P＜0.05),but those of both the NM and RIRI groups were higher than those of the sham group.Compared with that in the RIRI group,the expression of HMGB1 in the NM group was significantly decreased(P＜0.05),but the expression levels in both the RIRI and NM groups were higher than that in the sham group.Immunofluorescence showed that there was increased cytoplasmic expression of HMGB1 in both the NM and RIRI groups,with the increase being more prominent in the RIRI group.2)A total of 13 major cell populations were identified through the single-nucleus sequencing results.The proportion of tubular cells in the NM group was higher,with the HMGB1 gene being highly expressed in the damaged proximal convoluted tubular cells.The proportion of the polarized Macro3 cell subpopulation in the macrophages in the NM group was lower compared to that in the RIRI group.Conclusion NM may play a protective role in a rat model of RIRI,and its underlying mechanisms may be related to the regulation of the functional abnormalities of HMGB1-mediated macrophages.

[Objective] To analyze the correlation of the distribution and morphological characteristics of breast calcification with the risk of breast malignant tumors, so as to further reveal the important value of the calcification in diagnosis of breast malignant tumors. [Methods] A total of 108 patients who had received concurrent puncture biopsy and surgical treatment of breast calcification at The Second Affiliated Hospital of Xi’an Jiaotong University from January 1, 2019 to December 31, 2019 were recruited, and their imaging data and postoperative pathological results were analyzed. We divided the distribution of breast X calcification into two categories based on segmental/linear calcification and regional/diffuse calcification. We classified the morphology of breast X calcification into punctate, small branching, polymorphic, amorphous, and coarse ones. We then explored the distribution, morphology, and BI-RADS classification of tumor calcification under breast X-ray, and its correlation with the occurrence, age, menopausal status, hormone receptors, and molecular typing of breast malignant tumors. [Results] Among the 108 patients enrolled in the study, 21 cases were malignant and 87 cases were benign. The results showed that the distribution of calcification was segmental/linear (χ²=11.2, P=0.003) and the calcification morphology was of small branching calcification (χ²=9.3, P=0.046). The detection rate in malignant tumors was significantly higher than that in benign tumors. The distribution and morphology of calcification were not significantly correlated with ER, PR, HER2, Ki67, pathological type, or molecular typing (P>0.05). Logistic regression analysis showed that , calcification distribution was segmental/linear [OR=19.94(3.061-129.9), P=0.002], calcification morphology was small branching [OR=3.906(1.141-13.37), P=0.030], and B-RADS classification was 4 grade and above [OR=39.99(2.703-591.7), P=0.007], which were closely related to the occurrence of malignant tumors. [Conclusion] For patients with breast tumors in which calcification can be detected under mammography, their imaging characteristics are closely related to the occurrence of malignant tumors. The distribution of calcification is segmental/linear, and the morphology of calcification is small branching/amorphous, which is more likely to be a malignant tumor and closely related to the occurrence of breast cancer.

Objective To investigate the effects of emotions(subjective well-being,depressed effect,worry,and guilt)on cancer(colorectal cancer,hepatic cancer,thyroid cancer,lung cancer,and breast cancer).Methods Two-sample bi-directional Mendelian randomization(MR)method was adopted.All data were based on summary data from genome-wide association studies(GWAS).Inverse variance weighting(IVW)was used to generate the main results,and weighted median(WM)and MR-Egger methods were employed to calculate supplementary results.The outcome measure was odds ratio(OR),and sensitivity analysis was conducted.Results For depressed effect,a significant association with lung cancer(OR=1.005,95％CI:1.001-1.009,P=0.015)was found.For worry,a significant association with breast cancer(OR=1.199,95％CI:1.011-1.423,P=0.038)was observed.For guilt,a significant association with thyroid cancer(OR=2.083,95％CI:1.080-4.017,P=0.029)was identified.After removing all potentially pleiotropic SNPs detected by MR PRESSO,the association between worry and breast cancer showed no statistical difference(P=0.064),while the association between worry and colorectal cancer remained significant(OR=0.739,95％CI:0.571-0.956,P=0.021).No causal relationship was found between cancer and emotions.Conclusion There is a causal relationship between depression and increased lung cancer incidence,guilt and increased thyroid cancer incidence,as well as anxiety and decreased colorectal cancer incidence.

Adenosine triphosphate(ATP)is the most common energy supplier in living organisms and also an important signaling molecule.The expression level of ATP is significantly upregulated in the tumor microenvironment.The purinergic receptor ion channel P2X is widely distributed in various tissues.ATP can specifically activate the P2X receptor to induce the opening of gated ion channels in the microenvironment,thereby affecting the downstream signal transduction in regulating the physiological activities.Notably,abnormal purinergic signal plays an important role in tumor progression.This review focuses on the expression,structure,and function of the P2X receptor protein family.It also elucidates the mechanisms by which the P2X receptor family participates in the progression of various solid tumors,as well as research on targeted P2X family for tumor therapy.These studies will enrich the basic research theory related to purinergic signaling and provide the new targets and strategies for clinical therapy of solid tumors by targeting P2X family.

Urothelial carcinoma (UC) is one of the most common malignant tumors. The development of omics technologies has provided new perspectives for the diagnosis and treatment of UC. Genomics, transcriptomics, and proteomics have unveiled the molecular mechanisms and biological characteristics of UC, which are conducive to the discovery of new therapeutic targets and biomarkers. Single-cell omics and spatial transcriptomics have further deepened the understanding of cellular heterogeneity and the tumor microenvironment. These technologies show great potential in molecular typing, non-invasive diagnosis, early screening, and personalized treatment of UC. This article, in response to the national key strategy, will delve into how omics technologies can drive new developments in the diagnosis and treatment of UC, as well as the application and translation prospects of these technologies in UC.

Urothelial carcinoma (UC) is one of the most common malignant tumors. The development of omics technologies has provided new perspectives for the diagnosis and treatment of UC. Genomics, transcriptomics, and proteomics have unveiled the molecular mechanisms and biological characteristics of UC, which are conducive to the discovery of new therapeutic targets and biomarkers. Single-cell omics and spatial transcriptomics have further deepened the understanding of cellular heterogeneity and the tumor microenvironment. These technologies show great potential in molecular typing, non-invasive diagnosis, early screening, and personalized treatment of UC. This article, in response to the national key strategy, will delve into how omics technologies can drive new developments in the diagnosis and treatment of UC, as well as the application and translation prospects of these technologies in UC.

Carbocisteine is a commonly used expectorant drug.Currently,the reported detection methods for carbocisteine mainly include the electrochemical method,potassium bromated titration,kineticmethod,spectrometry,chromatography,HPLC-FLD precolumn derivation determination,HPLC-MS,etc.The advantages and disadvantages of each method were compared and analyzed in this paper,and it is found that HPLC was more suitable for the quality analysis of carbocisteine,which could serve as a reference for upgrading standard of carbocisteine content determination.