ObjectiveTo investigate the potential machanism of Xiaozhong Zhitong Mixture （消肿止痛合剂， XZM） in the treatment of diabetes foot ulcer （DFU）. MethodsFifty SD rats were randomly divided into blank group， model group， XZM group， inhibitor group， XZM plus inhibitor group （combination group）， with 10 rats in each group. Except for the blank group， rats were fed with high-sugar， high-fat， high-cholesterol diet， intraperitoneally injected with streptozotocin， and subjected to skin defect to establish DFU model. After successful modeling， the XZM group and the combination group were given 1 ml/（100 g·d）of XZM by gavage， while the blank group， model group， and inhibitor group were all given an equal volume of 0.9% sodium chloride injection by gavage. Thirty minutes later， the inhibitor group and the combination group were intraperitoneally injected with 5 mg/（kg·d） of Notch1 inhibitor DAPT. All groups were treated once a day. After 14 days of administration， the skin tissue from the dorsal foot of the blank group rats and wound tissue from the other groups were collected. The pathological changes of granulation tissue in the wound were detected using hematoxylin eosin （HE） staining. The microvascular density （MVD） in wounds was detected through immunohistochemical staining. Real time fluorescence quantitative polymerase chain reaction （RT-PCR） and western blotting were used to detect the mRNA and protein levels of Notch1 homolog （Notch1）， Delta-like ligand 4 （Dll4）， Delta-like ligand 4 （VEGF）， and angiopoietin 2 （Ang-2）， respectively. ResultsHistological results showed that the epidermal structure in the dorsal foot skin tissue of the rats in the blank group was intact. In the wound tissue of the model group， the epidermis exhibited excessive keratinization， vacuolar cytoplasm， and a large number of inflammatory cells infiltrating the tissue， while in the XZM group， a large amount of scab formation was observed in the epidermis， with no significant inflammatory cell infiltration and a noticeable increase in fibroblasts. In the combination group and the inhibitor group， partial epidermal scab formation was observed in the wound tissue with a small amount of inflammatory cell infiltration. Compared to those in the blank group， the MVD in the wound tissue increased in the model group， as well as the mRNA expression and protein levels of Notch1 and Dll4， while VEGFA and Ang-2 mRNA expression and protein levels significantly decreased （P＜0.05 or P＜0.01）. Compared to those in the model group， the MVD in the wound tissue of all medication groups significantly increased， and the mRNA and protein levels of Notch1 and Dll4 decreased， while VEGFA and Ang-2 mRNA expression and protein levels increased （P＜0.05 or P＜0.01）. Compared to the XZM group， the inhibitor group and the combination group showed decreased MVD in wound tissue， increased Notch1 and Dll4 mRNA and protein levels， and decreased expression of VEGFA and Ang-2 mRNA and proteins （P＜0.05 or P＜0.01）. ConclusionXZM can effectively promote wound healing in DFU rats， and its mechanism of action may be related to the inhibition of Dll4/Notch1 signaling pathway in the wound tissue， therey promoting angiogenesis.

Fifty whitespotted bamboo sharks (Chiloscyllium playgiosum) of both sexes were used to establish a large capacity variable domain of the new antigen receptor (VNAR) library with a total capacity of over 10⁹ colony-forming units (CFU). It was applied to screen VNARs against human serum albumin (HSA) and human transcription factor EB (TFEB), respectively. Meanwhile, VNAR libraries specific to HSA and TFEB with capacities above 10⁸ CFU were obtained following conventional immunization. These two approaches were systematically studied in terms of VNAR yield and composition. By comparing the VNAR sequences obtained from naïve and antigen-immunized libraries, we found that the complementary-determining region 3 (CDR3) of the former differs in composition from that of the latter. It shares a higher degree of homology with the naïve library. Meanwhile, the binding efficiency assessed by ELISA is also different between the naïve and antigen-immunized libraries. The binding of VNARs from the TFEB-immunized library appeared to surpass that observed with the naïve libraries, whereas the performance of VNARs from the HSA-immunized library indicated that both the immunized and naïve libraries for HSA had positive binding responses in polyclonal and monoclonal ELISA. The results are useful to develop novel diagnostic and therapeutic products based on shark VNARs.

OBJECTIVES: To analyze the changes in disease burden and risk factors of atrial fibrillation/atrial flutter (AF/AFL) in China and globally from 1990 to 2021 to provide epidemiological evidence for developing effective preventive measures for AF/AFL in China. METHODS: Based on data from the Global Burden of Disease Study 2021, we analyzed sex- and age-specific AF/AFL burden metrics across 204 countries or territories. Age-standardized incidence rate (ASIR), prevalence, mortality rate (ASMR), and disability-adjusted life-years (DALYs) rate (ASDR) were calculated. Joinpoint regression was employed to compute average annual percentage changes (AAPC) in trends. The risk factors were systematically evaluated and further validated using Mendelian randomization analysis. RESULTS: From 1990 to 2021, China experienced an increase in ASIR of AF/AFL (from 42.63 to 44.93 per 100 000), contrasting with the global decline. While China's ASMR decreased (from 4.93 to 4.33 per 100 000), global ASMR rose slightly (from 4.24 to 4.36 per 100 000). China's ASDR remained stable at 93.29 per 100 000, whereas global ASDR increased marginally (100.81 to 101.40 per 100 000). Significant sex disparities were observed: males showed higher ASIR and ASDR, while females exhibited greater ASMR and ASDR. China had higher incidence and prevalence but lower mortality and DALY rates compared to global averages. In 2021, the key risk factors for AF/AFL included elevated systolic blood pressure, high BMI, smoking, alcohol use, high-sodium diet, and low temperature. Gender-specific patterns emerged: smoking was predominant in males, whereas high BMI disproportionately affected females. CONCLUSIONS AF/AFL incidence and prevalence keep increasing in China, and its large population base and demographic aging pose significant public health challenges. Maintaining healthy lifestyle habits, including smoking cessation, alcohol moderation, and a low-sodium diet can help to lower AF/AFL incidence, and regular screenings is crucial for its early detection and treatment.
Humans ; China/epidemiology* ; Risk Factors ; Atrial Flutter/epidemiology* ; Atrial Fibrillation/epidemiology* ; Mendelian Randomization Analysis ; Male ; Female ; Global Burden of Disease ; Incidence ; Prevalence ; Middle Aged ; Disability-Adjusted Life Years ; Aged

Objective:To understand the cognition of the family caregivers of terminal cancer patients on digital health intervention, to clarify their actual needs, and to analyze the obstacles to their acceptance of digital health intervention, so as to develop a digital health intervention plan for the family caregivers of terminal cancer patients.Methods:From February 2024 to March 2024, the family caregivers of 16 patients with terminal cancer in Hunan Cancer Hospital Pain Hospice Ward were selected by objective sampling, who met the inclusion and exclusion criteria were interviewed in a semi-structured manner about the cognition and needs of digital health intervention, and the interview contents were sorted and analyzed using the Colaizzi7 step method.Results:A total of 16 family caregivers of terminal cancer patients, 4 males and 12 females, aged 26-55 years, were interviewed. Four themes were distilled from the interview results: family caregivers of terminally cancer patients agree on the importance of digital health interventions; lack of awareness of digital health interventions; expectations of digital health interventions; and possible confounders affecting digital health interventions.Conclusions:The family caregivers of terminal cancer patients had insufficient awareness of digital health intervention, but all showed affirmation of the development of digital health intervention services. It is recommended to actively improve the basic conditions of digital health services, strengthen publicity, raise the level of awareness of the family caregivers, and positively overcome the relevant interfering factors, so as to gradually promote the development of digital health services.

Objective:To observe the clinical efficacy of neck Gongfa exercise in intervening people at high risk for cervical spondylosis. Methods:A total of 212 participants from 8 companies at high risk for cervical spondylosis were divided into two groups using the random number table method,with 105 participants in the control group receiving health education and 107 participants in the trial group receiving an additional neck Gongfa exercise.After successive 3-month interventions,the two groups were compared in terms of cervical soft tissue tension and neck disability index(NDI)score.The incidence of cervical spondylosis was observed 3 months later. Results:During the process,10 cases dropped out in the trial group,and the control group had 9 dropout cases.After the intervention,the cervical soft tissue tension value and NDI score improved in both groups(P<0.05)and showed significant differences between the two groups(P<0.05).At the 3-month follow-up,the trial group had a lower incidence rate of cervical spondylosis than the control group(P<0.05). Conclusion:For people at high risk for cervical spondylosis,neck Gongfa exercise can effectively improve cervical soft tissue tension and motor dysfunction and lower the incidence of cervical spondylosis in the short run.

Objective To construct a telemedicine-based home care system of palliative care for end-of-life cancer patients,and to evaluate its application effect.Methods The construction of the system was based on the literature research,interview results of the patients and their caregivers,and expert group meeting discussions.From May to August 2023,a total of 88 patients,who were about to be discharged from the palliative care ward of a cancer hospital in Hunan Province,were selected as the study subjects using a convenient sampling method,and then they were divided into an experimental group and a control group according to the order of admission.The experimental group was given home care services based on the system,while the control group was given routine discharge guidance and follow-up visits.The duration of the intervention was 8 weeks.The Chinese version of the Edmonton Symptom Assessment Scale and the Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 palliative were used to evaluate the symptom burden and quality of life between 2 groups before and after intervention;the Telemedicine Satisfaction Questionnaire was used to evaluate the care satisfaction of the experimental group.Results The system of patient side includes 8 main features,namely personal health record establishment,doctor-patient communication,palliative care knowledge library,medication assistance,smart reporting and monitoring,intelligent Q&A,intelligent follow-up,and intelligent forms.The healthcare professional side includes 7 main functions,namely workbench,case management,follow-up management,warning reminder,popularization push,statistical analysis and user management.A total of 67 patients completed the intervention,with 33 in the experimental group and 34 in the control group.The symptom burden of the experimental group was lower than that of the control group(P＜0.05);the quality of life in the experimental group was better than that in the control group(P＜0.05);the score of care satisfaction was(59.00±6.66),which indicated a high level of satisfaction.Conclusion The system can reduce the symptom burden and improve the quality of life of end-of-life cancer patients with good practicality

Objective To evaluate the effect of Internet-based psychosocial intervention for primary caregivers of patients with terminal stage cancer.Methods The relevant randomized controlled trials of Internet-based psychosocial intervention for primary caregivers of patients with terminal stage cancer were systematically searched from 10 databases,such as Chinese Biomedical Literature Database,CNKI,PubMed,Embase and CINAHL and etc.The search period was from the establishment to December 18,2023,and 2 investigators screened the literature according to inclusion and exclusion criteria and extracted data.Cochrane Manual 5.1.0 was used to assess the quality of the literature.Meta-analysis was performed using Revman 5.4 software.Results A total of 9 pieces of the literature including 592 primary caregivers were included.Meta-analysis showed that Internet-based psychosocial intervention reduced the level of anxiety and depression for primary caregivers of patients with terminal stage cancer[MD=-1.64,95％CI(-2.68,-0.59),P=0.002]and the burden of care[SMD=-0.39,95％CI(-0.60,-0.18),P＜0.001],and improved quality of life[SMD=0.25,95％CI(0.01,0.48),P=0.040];further research is needed to explore the effect of reducing the level of distress[MD=-0.88,95％CI(-1.91,0.16),P=0.100].Conclusion The Internet-based psychosocial intervention is effective in improving the anxiety,depression and the burden of care of the primary caregivers of patients with terminal stage cancer,and it can improve the quality of life;further research is needed to explore the level of distress reduction.

In response to the major national strategic needs of "Healthy China" and "Chengdu-Chongqing Economic Circle", and in strict accordance with the requirements of "New Medicine" construction, Chongqing University builds the medical discipline with a high starting point, develops high-quality medical education, and promotes the exploration and practice of elite education of clinical medical talents in the cross-disciplinary context of medicine and engineering. From the perspective of SWOT, this study analyzed the situations and trends of clinical medical education in "Double First Class" universities which newly established the medical discipline. Combined with the training model of clinical talent class in Chongqing University and the practices of "Four Capacity-Buildings", "Four Integration-Measures", and "Three Optimization-Mechanisms", we discuss the thoughts and strategies of cultivating clinical medical talents in the background of "New Medicine" construction and in the cross-disciplinary context of medicine and engineering.

As a novel and promising antitumor target, AXL plays an important role in tumor growth, metastasis, immunosuppression and drug resistance of various malignancies, which has attracted extensive research interest in recent years. In this study, by employing the structure-based drug design and bioisosterism strategies, we designed and synthesized in total 54 novel AXL inhibitors featuring a fused-pyrazolone carboxamide scaffold, of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions. Notably, compound 59 showed a desirable AXL kinase inhibitory activity (IC₅₀: 3.5 nmol/L) as well as good kinase selectivity, and it effectively blocked the cellular AXL signaling. In turn, compound 59 could potently inhibit BaF3/TEL-AXL cell viability (IC₅₀: 1.5 nmol/L) and significantly suppress GAS6/AXL-mediated cancer cell invasion, migration and wound healing at the nanomolar level. More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development.