Objective To investigate the changes of brain networks function in patients with primary dysmenorrhea(PDM)during menstruation based on topological attributes of brain network.Methods Brain resting-state functional MRI of 57 PDM patients(PDM group)and 50 healthy women(health control[HC]group)were prospectively collected within the first or the second day of menstruation.Clinical scores were obtained and compared between groups.Results Visual analogue scale,cox menstrual symptom scale,self-rating anxiety scale and self-rating depression scale scores in PDM group were all higher than those in HC group(all P＜0.05).At the sparsity of 0.04-0.50,brain networks in both groups conformed to the small world attribute characteristics,and no significant difference of global attributes of brain network was found between groups(all P＞0.05).The node efficiency(Ne)and node degree(Dc)of bilateral posterior cingulate gyrus(PCG),as well as De and node betweenness(Bc)of left middle frontal gyrus(MFG)in PDM group were all higher than those in HC group,while Ne and De of left inferior temporal gyrus in PDM group were lower than those in HC group(all P＜0.01).Compared with HC group,the functional connections between left PCG and right calcarine fissure and surrounding cortex,right lingual gyrus and left MFG,as well as between right PCG and right dorsolateral superior frontal gyrus and left MFG,between right insula and left middle occipital gyrus enhanced in PDM group(all P＜0.001).Conclusion In PDM patients,local brain networks function such as default mode network,central executive network and salience network were over-activated during menstruation,yet the overall brain network still had good coordination and organization.

Objective:To explore the impacts of thermotherapy combined with gemcitabine on the biological behavior of tongue squamous cell carcinoma cells.Methods:Human tongue squamous cell carcinoma Tca8113 cells were divided into the control group (blank control), gemcitabine group, thermotherapy group (heated in an incubator at 43℃ for 1 h and then incubated at 37℃ for 24 h) and thermotherapy + gemcitabine group. The proliferation ability of Tca8113 cells was assessed by EdU staining and CCK-8 assay. Cell apoptosis and cell cycle of Tca8113 cells were detected by flow cytometry. The invasion of Tca8113 cells was determined by Transwell chamber assay. The expression levels of cyclin D1 (CyclinD1), Bcl-2-associated X protein (Bax), matrix metalloproteinase (MMP)-9, phosphorylated histone H2AX (γH2AX) and Nijmegen breakage syndrome 1 (NBS1) proteins in Tca8113 cells were measured by Western blot. The changes of tumor mass and volume were detected by xenograft tumor in vivo test in nude mice. Multi-group comparison was performed by one-way ANOVA. Two group comparison was conducted by SNK- q test. Results:Compared with the control group, EdU positive cell percentage, OD 450 value, invasive cell number, CyclinD1, MMP-9 and NBS1 protein expression of Tca8113 cells were decreased, whereas the apoptosis rate, the expression of Bax and γH2AX proteins were increased in the gemcitabine, thermotherapy and thermotherapy + gemcitabine groups ( q=4.45-72.06, all P<0.001). Compared with the control group, the proportion of G 0/G 1 phase cells was decreased, whereas the proportion of S and G 2/M phase cells was increased in the gemcitabine and thermotherapy + gemcitabine groups, the proportion of G 0/G 1 phase cells was decreased and the proportion of G 2/M phase cells was increased in the hyperthermia group ( q=10.36-61.09, all P<0.001). Compared with the gemcitabine and thermotherapy groups, EdU positive cell percentage, OD 450 value, G 0/G 1 phase cell proportion, invasive cell number, CyclinD1, MMP-9 and NBS1 protein expression of Tca8113 cells were decreased, whereas apoptosis rate, S, G 2/M phase cell proportion, Bax and γH2AX protein expression were increased in the thermotherapy + gemcitabine group ( q=4.45-28.73, all P<0.001). Xenograft tumor in vivo test in nude mice showed that the tumor volume and mass of nude mice in the gemcitabine, thermotherapy, and thermotherapy + gemcitabine groups were decreased compared with those in the control group ( q=5.58-73.02, all P<0.001). Compared with the gemcitabine and thermotherapy groups, the tumor volume and mass in the thermotherapy + gemcitabine group were decreased ( q=5.58-21.45, all P<0.001). Conclusion:The combination of thermotherapy and gemcitabine can inhibit the proliferation and invasion, block the cell cycle, and induce cell apoptosis of Tca8113 cells.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

In recent years, the development of host-acting antibacterial compounds has gradually become a hotspot in the field of anti-infection. Through research on the interaction mechanism between hosts and pathogenic bacteria, it has been found that the immune system is one of the key targets of host-acting antibacterial compounds. There is a communication system called the quorum sensing system in microorganisms, which mainly adjusts the structure of multi-microbial community and coordinates the group behavior. When the quorum sensing molecules secreted by microorganisms reach a threshold concentration, the quorum sensing system is activated and the overall gene expression of the microorganism is changed. In addition to regulating the density of microorganisms, quorum sensing molecules can also act as a link between pathogenic microorganisms and hosts, entering the host immune system and playing a role in affecting the morphological structure of immune cells, secreting cytokines, and inducing apoptosis, leading to host immune injury and causing host immune dysfunction.The key mechanism of 3-oxo-C12-HSL and other acyl-homoserine lactone (AHL) molecules in the innate immune system has been extensively studied. The lipid solubility allows AHLs to pass through the plasma membrane of host immune cells easily and induce dissolution of lipid domains. Then, it acts through signaling pathways such as p38MAPK and JAK-STAT, further influencing the immune cell’s defense response to bacteria and potentially leading to cell apoptosis. Additionally, the human lactonase paraoxonase 2, which can degrade3-oxo-C12-HSL, has been found in macrophage. It acts as an immune regulator that promotes macrophage phagocytosis of pathogens and is hypothesized to have the ability to reduce bacterial resistance. The mechanism of quorum sensing molecules in the adaptive immune system is less studied, the current results suggest that 3-oxo-C12-HSL is closely related to the mitochondrial pathway in host immune cells. For example, 3-oxo-C12-HSL induces apoptosis of Jurkat cells by inhibiting the expression of three mitochondrial electron transport chain proteins; it can also trigger mitochondrial dysfunction and induce mast cell apoptosis through Ca²⁺ signaling.Among the quorum sensing molecules, the AHLs have the greatest impact on plant immune system. The different effects on plant resistance depends on the chain lengths of acyl groups in bacterial-produced AHLs. Short-chain AHLs (C4-HSL and C8-HSL) induce plant resistance to pathogenic bacteria mainly through the auxin pathway and jasmonic acid pathway. Long-chain AHL (3-oxo-C14-HSL) is commonly used in hosts against fungal pathogens by inducing stomata defense responses, and the reaction process is related to salicylic acid. Diffusible signal factor molecules also interfere with the stomatal immunity caused by pathogens. It may act through the formin nanoclustering-mediated actin assembly and MPK3 pathway to inhibit the innate immunity of Arabidopsis. In summary, AHLs induced different plant pathways and affects the plant-bacteria interactions to trigger plant immunity. As a quorum sensing molecule of fungi, farnesol has similar effects on host immunity as AHLs, such as stimulating cytokine secretion and activating an inflammatory response. It also plays a unique role on dendritic cell differentiation and maturation. In addition, studies have found that farnesol has a protective effect on autoimmune encephalomyelitis, which may be related to its effect on the composition of intestinal microorganisms of the host.Therefore, targeting the host immune system and quorum sensing molecules to develop antibacterial compounds can effectively inhibit the invasion of pathogens and subserve the host to resist the influence of pathogenic bacteria. This article will review the mechanism of host immune responses triggered by important quorum sensing molecules, aiming to explore the targets of host-acting antibacterial compounds and provide new directions for the prevention or treatment of causative infectious sources and the development of related drugs.

Objective:To investigate the regulation and possible mechanism of hyperthermia (HT) on the ferroptosis of squamous cell carcinoma of the tongue cell line CAL-27.Methods:Half maximal inhibitory concentration (IC 50) of Fer-1, an inhibitor of ferroptosis, was detected by CCK-8 assay and used for subsequent experiments. CAL-27 cells were divided into the HT, control, Fer-1 and HT+ Fer-1 groups according to experimental design. Reactive oxygen species (ROS) levels and iron ion concentration were determined by corresponding detection kits. The p53 and TfR1 mRNA levels were detected by real-time reverse transcription PCR. Cell migration was detected by cell scratch test and cell apoptosis was detected by flow cytometry. Results:HT significantly up-regulated the ROS levels ( P<0.01) and iron ion concentration ( P<0.001), and significantly increased the expression levels of p53 and TfR1 mRNA (both P<0.01). The cell migration ability was decreased ( P<0.001), whereas cell apoptosis rate was increased by HT ( P<0.01). In the HT+Fer-1 group, the ROS levels ( P<0.001), iron ion concentration ( P<0.001), expression levels of p53 and TfR1 mRNA (both P<0.01) were significantly down-regulated, the cell migration ability was recovered ( P<0.01), and cell apoptosis rate was decreased ( P<0.01) compared with those in the HT group, respectively. Conclusions:HT may induce the ferroptosis of CAL-27 cell line, inhibit cell migration ability and promote cell apoptosis by activating the p53/TfR1 pathway.

Vascular endothelial growth factor (VEGF) plays an important role in promoting tumor vascular growth and changing vascular wall permeability. With the in-depth study of tumor hyperthermia and tumor microenvironment, more and more studies have shown that hyperthermia exerts multiple regulatory effects on VEGF in tumor microenvironment. Combined with current research progress in China and abroad, this article reviews the effect of hyperthermia on VEGF and its related cells and factors in tumor microenvironment, aiming to provide new ideas for the clinical application of tumor hyperthermia combined with immune or targeted therapy.

Conventional tumor culture models include two-dimensional tumor cell cultures and xenograft models. The former has disadvantages including lack of tumor heterogeneity and poor clinical relevance, while the latter are limited by the slow growth, low engraftment successful rate, and high cost. In recent years, in vitro three-dimensional (3D) tumor models have emerged as the tool to better recapitulate the spatial structure and the in vivo environment of tumors. In addition, they preserve the pathological and genetic features of tumor cells and reflect the complex intracellular and extracellular interactions of tumors, which have become a powerful tool for investigating the tumor mechanism, drug screening, and personalized cancer treatment. 3D tumor model technologies such as spheroids, organoids, and microfluidic devices are maturing. Application of new technologies such as co-culture, 3D bioprinting, and air-liquid interface has further improved the clinical relevance of the models. Some models recapitulate the tumor microenvironment, and some can even reconstitute endogenous immune components and microvasculature. In recent years, some scholars have combined xenograft models with organoid technology to develop matched in vivo/in vitro model biobanks, giving full play to the advantages of the two technologies, and providing an ideal research platform for individualized precision therapy for specific molecular targets in certain subtypes of tumors. So far, the above technologies have been widely applied in the field of colorectal cancer research. Our research team is currently studying upon the application of patient-derived tumor cell-like clusters, a self-assembly 3D tumor model, in guiding the selection of postoperative chemotherapy regimens for colorectal cancer. A high modeling success rate and satisfactory results in the drug screening experiments have been achieved. There is no doubt that with the advancement of related technologies, 3D tumor models will play an increasingly important role in the research and clinical practice of colorectal cancer.
Humans ; Organoids/pathology* ; Cell Culture Techniques ; Colorectal Neoplasms/pathology* ; Tumor Microenvironment

Objective: To investigate the association of the levels of high sensitivity C-reactive protein (hs-CRP) with frailty and its components among the elderly over 65 years old in 9 longevity areas of China. Methods: Cross-sectional data from the Health Ageing and Biomarkers Cohort Study (HABCS, 2017-2018) were used and the elderly over 65 years old were included in this study. Through questionnaire interview and physical examination, the information including demographic characteristics, behavior, diet, daily activity, cognitive function, and health status was collected. The association between hs-CRP and frailty and its components in the participants was analyzed by multivariate logistic regression model and restrictive cubic spline. Results: A total of 2 453 participants were finally included, the age was (84.8±19.8) years old. The median hs-CRP level was 1.13 mg/L and the prevalence of frailty was 24.4%. Compared with the low-level group (hs-CRP<1.0 mg/L), the OR (95%CI) value of the high-level group (hs-CRP>3.0 mg/L) was 1.79 (1.35-2.36) mg/L. As for the components, the hs-CRP level was also positively associated with ADL disability, IADL disability, functional limitation and multimorbidity. After adjusting for confounding factors, compared with the low-level group, the OR (95%CI) values of the high-level group for the four components were 1.68 (1.25-2.27), 1.88 (1.42-2.50), 1.68 (1.31-2.14) and 1.39 (1.12-1.72), respectively. Conclusion: There is a positive association between the levels of hs-CRP and the risk of frailty among the elderly over 65 years old in 9 longevity areas of China. The higher hs-CRP level may increase the risk of frailty by elevating the risk of four physical functional disabilities, namely ADL disability, IADL disability, functional limitation and multimorbidity.
Humans ; Aged ; Aged, 80 and over ; C-Reactive Protein/analysis* ; Frailty/epidemiology* ; Cohort Studies ; Cross-Sectional Studies ; China/epidemiology*

Objective: To identify the main metals involved in cognitive impairment in the Chinese oldest old, and explore the association between these metal exposures and cognitive impairment. Methods: A cross-sectional study was conducted on 1 568 participants aged 80 years and older from Healthy Aging and Biomarkers Cohort Study (2017 to 2018). Fasting venous blood was collected to measure the levels of nine metals (selenium, lead, cadmium, arsenic, antimony, chromium, manganese, mercury, and nickel). The cognitive function of these participants was evaluated by using the Chinese version of the Mini-Mental State Examination (CMMSE). The random forest (RF) was applied to independently identify the main metals that affected cognitive impairment. The multivariate logistic regression model and restricted cubic splines (RCS) model were used to further verify the association of the main metals with cognitive impairment. Results: The age of 1 568 study subjects was (91.8±7.6) years old, including 912 females (58.2%) and 465 individuals (29.7%) with cognitive function impairment. Based on the RF model (the out-of-bag error rate was 22.9%), the importance ranking of variables was conducted and the feature screening of five times ten-fold cross-validation was carried out. It was found that selenium was the metal that affected cognitive function impairment, and the other eight metals were not included in the model. After adjusting for covariates, the multivariate logistic regression model showed that with every increase of 10 μg/L of blood selenium levels, the risk of cognitive impairment decreased (OR=0.921, 95%CI: 0.889-0.954). Compared with the lowest quartile(Q₁) of blood selenium, the ORs (95%CI) of Q₃ and Q₄ blood selenium were 0.452 (0.304-0.669) and 0.419 (0.281-0.622) respectively. The RCS showed a linear dose-response relationship between blood selenium and cognitive impairment (P_nonlinear>0.05). Conclusion: Blood selenium is negatively associated with cognitive impairment in the Chinese oldest old.
Aged, 80 and over ; Female ; Humans ; Selenium ; Cohort Studies ; Cross-Sectional Studies ; Metals/analysis* ; Cognitive Dysfunction/epidemiology* ; China/epidemiology*

ObjectiveTo explore the application of Brain and Spinal Injury Center (BASIC) score in evaluation of traumatic cervical spinal cord injury. MethodsFrom January, 2015 to December, 2021, 175 patients with traumatic cervical spinal cord injury in Beijing Bo'ai Hospital were analyzed. Gender, age, cause of injury, injury mechanism and American Spinal Injury Association Impairment Scale (AIS) grade were collected. The sagittal and axial T₂ weighted imaging (T₂WI) of the patients were evaluated with BASIC score, single/multi-segment injury, and with/without intramedullary hemorrhage. According to the injury mechanism, the patients were divided into two groups: with fracture/fracture dislocation (n = 92) and without fracture and dislocation (n = 83). The baseline demographic indicators and T₂WI evaluation indicators were compared between the two groups, and the relationship between AIS grade and BASIC score, intramedullary hemorrhage, single/multi-segment injury were investigated. ResultsThere were significant differences in gender, age and AIS grade, BASIC score, and the rates of inntramedullary hemorrhage and single segment injury of T₂WI between two groups (t = -10.276, χ² > 8.703, P < 0.01); however, no difference was found in the cause of injury (P > 0.05). The AIS grade was significantly correlated with the BASIC score (r = 0.790, P < 0.001). There was significant difference in AIS grade between intramedullary hemorrhage or not, and single/multi-segment injury (χ² > 5.516, P < 0.05). ConclusionThe BASIC score of T₂WI is a predictor of the severity of spinal cord injury after traumatic cervical spinal cord injury, and is different with the injury mechanisms.