Tumor immunotherapy has achieved breakthroughs in the treatment of malignant tumors by activating the host immune system’s antitumor response mechanism. Among various strategies, Toll-like receptor (TLR) agonists have garnered substantial attention due to their unique immunomodulatory capabilities. This work reviews the research progress on the combination of TLR agonists with radiotherapy in tumor immunotherapy, focusing on the clinical translational potential of intratumoral injection strategies. Clinical studies have shown that the in-situ injection of TLR agonists in combination with radiotherapy can effectively suppress primary and metastatic lesions by inducing immunogenic cell death, releasing tumor antigens, activating local immune responses, and triggering abscopal effects. Moreover, novel extended-release formulations and “endogenous vaccine” designs further enhance the safety and durability of treatment. Despite several challenges such as tumor microenvironment suppression and dose optimization, TLR agonists hold promise for the treatment of “cold” tumors lacking innate immunity through combinations with immune checkpoint inhibitors, nanodelivery technologies, and precise biomarker screening.

The anterior cingulate cortex (ACC) has recently been proposed as a key player in the representation of itch stimuli. However, to date, little is known about the contribution of specific ACC interneuron populations to itch processing. Using c-Fos immunolabeling and in vivo Ca²⁺ imaging, we reported that both histamine and chloroquine stimuli-induced acute itch caused a marked enhancement of vasoactive intestinal peptide (VIP)-expressing interneuron activity in the ACC. Behavioral data indicated that optogenetic and chemogenetic activation of these neurons reduced scratching responses related to histaminergic and non-histaminergic acute itch. Similar neural activity and modulatory role of these neurons were seen in mice with chronic itch induced by contact dermatitis. Together, this study highlights the importance of ACC VIP⁺ neurons in modulating itch-related affect and behavior, which may help us to develop novel mechanism-based strategies to treat refractory chronic itch in the clinic.
Animals ; Pruritus/physiopathology* ; Vasoactive Intestinal Peptide/metabolism* ; Interneurons/metabolism* ; Gyrus Cinguli/metabolism* ; Mice ; Male ; Mice, Inbred C57BL ; Histamine ; Chloroquine ; Optogenetics ; Mice, Transgenic

Objective:To explore the clinical efficacy and risk factors of umbilical cord mesenchymal stem cells (UCMSCs) infusion at an early stage (i.e.gross hematuria) for hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:The relevant clinical data were retrospectively reviewed for 300 patients undergoing allo-HSCT from January 2016 to July 2021.According to the presence or absence of HC, they were assigned into two groups of HC (n=89) and non-HC (control, n=211). According to whether or not receiving an infusion of UCMSCs, 51 patients of HC degree Ⅱ-Ⅳ were divided into two groups of UCMSC infusion and non-infusion.The risk factors of HC after allo-HSCT were analyzed by χ2 test.Logistic regression was employed for multivariate analysis of P<0.05.Mann-Whitney U test was utilized for statistically analyzing the duration of gross hematuria and urinary tract irritation symptoms and evaluating the clinical efficacy of UCMSCs infusion for HC. Results:Among them, 89 (29.67%) developed HC post-allo-HSCT.Clinical grades were Ⅰ (n=38, 42.70%), Ⅱ (n=36, 40.45%), Ⅲ (n=13, 14.61%) and Ⅳ (n=2, 2.25%). The median occurrence time was 29 (21.5-35.0) days post-allo-HSCT.In univariate analysis, age ≤30 years, haploid transplantation, antithymocyte globulin (ATG), acute graft-versus-host disease (aGVHD), CMV-DNA positive pretreatment significantly boosted the risk of HC ( P<0.05). In multivariate analysis, aGVHD was an independent risk factor for HC ( OR=10.281, 95% CI: 1.606-65.813, P=0.014). Among 89 HC patients, 38 grade Ⅰ patients were complete remission(CR). Among 51 patients of grade Ⅱ-Ⅳ HC, the outcomes were CR (n=48) and non-remission(NR)(n=3). And 24/51 of them received UCMSCs plus conventional treatment.The duration of gross hematuria was shorter in UCMSCs infusion group than that in UCMSCs non-infusion group [12(9-17) vs 17(12.0-26.5) day] and the difference was statistically significant ( P=0.045). And the duration of urinary tract irritation symptoms was shorter in UCMSCs infusion group than that in UCMSCs non-infusion group [18(11-30) vs 27(18.0-35.5) days] and the difference was statistically significant ( P=0.048). Conclusions:Indicated for post-ALLO-HSCT HC, infusion of UCMSCs may significantly shorten the course of disease.Age ≤30 years, haploid transplantation and preconditioning with positive ATG, aGVHD and CMV-DNA may boost the risks of HC post-allo-HSCT.And aGVHD is an independent risk factor for HC after allo-HSCT.

OBJECTIVE: To investigate the relationship between sleep quality and bone mineral density (BMD) in urban residents. METHODS: Data of 28 756 Han adults (14 355 males and 14 401 females), who completed both Pittsburgh sleep quality index (PSQI) assessment and radial BMD tests by dual energy X-ray absorptiometry in the Health Management Center of Southwest China University from June 2012 to June 2019 were retrospectively analyzed. The degree of sleep disorder was determined based on PSQI scores, while osteopenia and osteoporosis was diagnosed according to BMD T-value. The test and multiple regression model were used to investigate the relationship between sleep quality and BMD. RESULTS: The numbers of normal BMD, osteoponia and osteoporosis were 17 039 (59.3%), 7916(27.5%) and 3801(13.2%), respectively. The mean PSQI score was 5.6±1.4 points. According to PSQI scores, there were 15 936 subjects without sleep disorder (55.4%), 5965 with mild (20.7%), 4897 with moderate (17.0%) and 1958 with severe sleep disorder (6.8%), respectively. There was no significant difference in osteoponia/osteoporosis rate between subjects with mild sleep disorder and normal ones (=0.948, >0.05), while the rate of osteoporosis in moderate sleep disorder group was higher than that in mild group (=525.583, <0.01), and the rate of osteoponia/osteoporosis in severe sleep disorder group was much higher than that in moderate group (=1124.877, <0.01). Multiple regression results showed that female, elders, mental labor, smoking and higher PSQI scores were independently associated with lower T-value (all <0.05), while moderate to intense daily physical activity was associated with higher T-value (<0.05). CONCLUSIONS Sleep disturbances may be a major risk factor for BMD loss in urban residents, indicating that it would be a potential target of osteoporosis prevention.

Translational medicine means that to establish a bridge between fundamental research and clinical medicine through bidirectional translation path in order to promote the translation and application from fundamental research to clinical medicine.The purpose of traditional Chinese medicine (TCM) translational model is to collate and build one multidimensional TCM translational model,rationality carry out the research on TCM translation.Three paths have been confirmed,where are from literature research to clinical verification,from clinical application to clinical verification,and from experiment to clinical verification.In this research,methodology of one path mcntioned above could be established,which is the key technology of translational medicine.Take constipation,insomnia,and post-flu cough as target diseases to investigate the herbal compounds which could be qualified for clinical application based on preliminary work.This research not only provided clinical data to TCM translation,but also established one methodology of TCM translation path--"from experiment to clinical verification".

Objective: To investigate the effect of hypoxia inducible factor 2α (HIF-2α) on regulating CUB domain-containing protein 1 (CDCP1) and its role in hepatocellular carcinoma metastasis. Methods: HIF-2α-knocked down and HIF-2α-stably overexpressing cells (MHCC97H) were prepared by small interfering RNA (siRNA) and lentivirus transfection, respectively. The expression of CDCP1 protein and mRNA in the above cells was detected by western blot and real-time PCR. The effect of HIF-2α on cell invasion ability was determined by Transwell assay. Furthermore, immunohistochemical staining was performed to detect the expression of CDCP1 in human HCC tissue samples. Results: Both HIF-2α and CDCP1 were induced under hypoxic conditions. The activation of CDCP1 under hypoxic conditions was dependent on the expression of HIF-2α.When HIF-2α was overexpressed, the mRNA level of CDCP1 was greatly upregulated (5.92±0.28, P<0.05). When HIF-2α was knocked down by siRNA for 48 h and 72 h, the expression of CDCP1 was significantly downregulated (48 h: 0.25±0.04; 72 h: 0.18±0.02, all P<0.05). Moreover, analysis of human HCC samples showed that CDCP1 expression was correlated with tumor-free survival (P<0.05). Conclusions The results of this study indicate that the expression of CDCP1 is regulated by HIF-2α and is correlated with the progression of HCC. Inhibition of HIF-2α/CDCP1 may play certain inhibitory role in the metastasis of HCC.

Objective To explore the clinical efficacy of Baihu decoction combined with insulin on type 2 diabetes with acute hyperglycemia patients.Methods A total of 86 cases of type 2 diabetes with acute hyperglycemia patients were randomly divided into experimental group (n=43) and control group (n=43).Two groups of patients underwent conventional exercise and diet adjustment intervention, control group was treated with insulin, continuous injection of 14d, experimental group was treated with Baihu decoction based on control group, 7d was taken for one courses, two course in all.The clinical symptoms of the two groups were compared, and the FPG, 2hPBG, HbAlc levels was detected in two groups pre-and post-reatment, the serum IL-6, hs-CRP, TNF-α, LP, APN, Cor were detected by enzyme linked immunosorbent assay method.Results The total effective rate was 91.7%in experimental group, higher than 76.7% in control group(P<0.05).After treatment, FPG, 2hPBG, HbAlc, IL-6, hs-CRP, TNF-αlevels in two groups were all significantly decreased (P<0.05), and those indexes in experimental group were significantly lower than those in control group (P<0.05).After treatment, APN and LP were significantly decreased, Cor was significantly increased in two groups(P<0.05), and the LP and APN in experimental group were significantly lower and Cor was significantly higher than that in control group (P<0.05).Conclusion Baihu decoction combine with insulin can significantly improve the clinical symptoms in type 2 diabetes with acute hyperglycemia patients, reduce the level of blood glucose and cytokines, and its mechanism may be relate to the increase APN level, reduce the LP and Cor levels.

Objective:To detect the proportion of lymphocyte subsets in peripheral blood of the ad-vanced breast cancer patients before and after chemotherapy with docetaxel and thiotepa,as well as the association between the proportion of peripheral blood lymphocyte subsets with the response rate and prog-nosis.Methods:The proportions of lymphocyte subsets (CD3 +T cell,CD3 +/CD4 +T cell,CD3 +/CD8 +T cell,CD3 -/CD16 +56 +NK cell,CD3 +/CD16 +56 +T cell,CD19 +B cell,CD4 +/CD25 +T cell,CD8 +/CD28 -T cell,CD8 +/CD28 +T cell)in the peripheral blood of 86 patients were analyzed with flowcytometry before and after chemotherapy.The result was analyzed in combination with clinico-pathological data.Results:The proportion of regulatory T cells (Treg)after chemotherapy in the disease control patients decreased significantly compared with that of the progressive patients (P=0.034).The difference of the proportions of Treg before and after chemotherapy affected significantly the overall survi-val (OS).The OS of the patients with decreased proportion of Treg was significantly longer than that of the patients with increased proportion of Treg,which was 23.5 and 9.4 months respectively (P<0.05). Conclusion:The patients with decreased proportion of Treg after chemotherapy had higher response rate and better survival benefit.

Objective To understand college students on-site first aid training demand situation in Chongqing ,in order to provide the basis for college students to carry out on-site first aid training .Methods Using stratified random sampling method ,a question-naire survey was conducted on 1 232 students of 6 university in Chongqing .Results 90 .9% of the students hoped that they could master the on-site first-aid knowledge and skills ,students of different genders had significant differences on learning attitude of field first aid knowledge(P<0 .05) .The on-site first-aid knowledge among college students in Chongqing city most wanted to know was thetrauma emergency stop(74 .8% ) ,the most loving way of learning was to the hospital or emergency center study tour(47 .7% ) ,The love of on-site first aid training and learning style were theory teaching+watch video teaching or teacher demon-stration+classroom practice (63 .6% ) ,The operation way of learning the most love was teacher ,all the students into groups of two ,mutual operation practice(65 .9% ) ,and in both gender and specialty had significant differences(P<0 .05) .The survey of col-lege students in Chongqing city training status display results ,43 .5% of the students never received on-site first aid training .In ad-dition ,college students receive on-site first aid training frequencies were low ,48 .6% students in more than 2 years received 1 ses-sions of training .while the rescue confidence survey of college students after the on-site first aid training ,only 13 .1% of the students“completely had the confidence to do” .Conclusion College students in Chongqing have strong desire to learn on-site first aid training ,and there are differences in gender and major on demand ,past state of first aid training is poor ,in urgent need of the relevant departments give attention ,and formulate the on-site first aid training programs to improve college students′competence .

Objective To understand the basic situation and the current work status of health education staff in Beibei district of Chongqing city and to explore the community health education pattern in Beibei district to provide reference for rational talent strat -egy and personnel policy adjustment .Methods By using the Investigation Questionnaires of Health Education Personal in Beibei District ,35 health education staffs in Beibei district were performed the investigation .Results Most health education staffs in Bei-bei district are young and middle-aged .The average age was 36 .7 years ;71 .4% of them had undergraduate or college degree .Only 3 individuals were full-time staff and the others were part-time;the health education forms were plentiful with various contents . The health education staffs were insufficient in the professional knowledge and the health education skill .The external factors had influence on the health education work .Conclusion The health education staffs rejuvenation ,lack of the professional staffs and in-adequate depth of the theory and practice of the health education work restrict the deep development of the health education work to some extent .It is suggested that the relevant departments introduce the professional health education talents ,conduct the systematic training for enhancing the professional knowledge and working skills ,and give support in terms of policy and funding .