Objective:To investigate the coupling coordination degree between the medical service capability and financial management level of compact county-level medical consortium in Guangdong,analyze regional disparities and influencing factors,and provide policy recommendations for the high-quality development of county-level medical communities.Methods:By using questionnaire survey,sampling survey and coupling coordination model,the evaluation index system of medical service ability and financial management level of 91 compact county-level medical consortia in Guangdong was constructed,and the coupling coordination degree was calculated to evaluate the collaborative development.Results:It is found that the coupling coordination degree of county medical communities in Guangdong during the period of 2019-2023 shows an overall upward trend,and the coordination level of financial unified medical communities is significantly better than that of financial partitioned medical communities,with a higher degree of coordination in the Pearl River Delta Region,and a relatively lower degree of coordination in the western part of Guangdong;some of the medical communities have the problem of lagging healthcare service capacity or financial management level,and the development of inter-regional and inter-type phenomenon of imbalance between regions and types is more prominent.Conclusion:Compact county-level medical consortium implementing unified financial management can effectively enhance the synergistic efficiency of medical services and financial management through unified management and resource sharing.Future efforts should focus on strengthening financial support,advancing information technology construction,and promoting regional balanced development to further improve the overall synergistic level of county-level medical communities and drive the high-quality development of county-level medical and health services.

Discoidin domain receptor 1(DDR1)is overexpressed in various tumors,such as triple-negative breast cancer(TNBC),and is rarely expressed in normal tissues.These characteristics make DDR1 a preferable target candidate for the construction of an antibody-drug conjugate(ADC)for targeted therapy.Here,we investigated the preparation and preclinical efficacy of DDR1-DX8951,an ADC that includes an anti-DDR1 monoclonal antibody conjugated to DX8951 by a cleavable Gly-Gly-Phe-Gly(GGFG)linker.The anti-DDR1 monoclonal antibody was coupled to DX8951(i.e.,DDR1-DX8951),producing the targeted ther-apy ADC.The antitumor activities of DDR1-DX8951 monotherapy or DDR1-DX8951 plus pembrolizumab were assessed in TNBC mouse models.DDR1-DX8951 can specifically target DDR1,be quickly internal-ized by TNBC cells,and reduce the viability of TNBC cells in vitro.The potent antitumor activity of DDR1-DX8951 was revealed in TNBC xenograft models.Importantly,our investigation demonstrated that DDR1-DX8951 plus pembrolizumab not only revealed the inhibitory efficacy on tumor growth and metastasis but also played an important role in improving the immunosuppressive tumor microenvi-ronment(TME)of TNBC.Taken together,this investigation provides justification for large-sample studies to further assess the safety and efficacy of DDR1-DX8951 plus pembrolizumab for TNBC clinical trials.

Discoidin domain receptor 1 (DDR1) is overexpressed in various tumors, such as triple-negative breast cancer (TNBC), and is rarely expressed in normal tissues. These characteristics make DDR1 a preferable target candidate for the construction of an antibody-drug conjugate (ADC) for targeted therapy. Here, we investigated the preparation and preclinical efficacy of DDR1-DX8951, an ADC that includes an anti-DDR1 monoclonal antibody conjugated to DX8951 by a cleavable Gly-Gly-Phe-Gly (GGFG) linker. The anti-DDR1 monoclonal antibody was coupled to DX8951 (i.e., DDR1-DX8951), producing the targeted therapy ADC. The antitumor activities of DDR1-DX8951 monotherapy or DDR1-DX8951 plus pembrolizumab were assessed in TNBC mouse models. DDR1-DX8951 can specifically target DDR1, be quickly internalized by TNBC cells, and reduce the viability of TNBC cells in vitro. The potent antitumor activity of DDR1-DX8951 was revealed in TNBC xenograft models. Importantly, our investigation demonstrated that DDR1-DX8951 plus pembrolizumab not only revealed the inhibitory efficacy on tumor growth and metastasis but also played an important role in improving the immunosuppressive tumor microenvironment (TME) of TNBC. Taken together, this investigation provides justification for large-sample studies to further assess the safety and efficacy of DDR1-DX8951 plus pembrolizumab for TNBC clinical trials.

Objective:To investigate the coupling coordination degree between the medical service capability and financial management level of compact county-level medical consortium in Guangdong,analyze regional disparities and influencing factors,and provide policy recommendations for the high-quality development of county-level medical communities.Methods:By using questionnaire survey,sampling survey and coupling coordination model,the evaluation index system of medical service ability and financial management level of 91 compact county-level medical consortia in Guangdong was constructed,and the coupling coordination degree was calculated to evaluate the collaborative development.Results:It is found that the coupling coordination degree of county medical communities in Guangdong during the period of 2019-2023 shows an overall upward trend,and the coordination level of financial unified medical communities is significantly better than that of financial partitioned medical communities,with a higher degree of coordination in the Pearl River Delta Region,and a relatively lower degree of coordination in the western part of Guangdong;some of the medical communities have the problem of lagging healthcare service capacity or financial management level,and the development of inter-regional and inter-type phenomenon of imbalance between regions and types is more prominent.Conclusion:Compact county-level medical consortium implementing unified financial management can effectively enhance the synergistic efficiency of medical services and financial management through unified management and resource sharing.Future efforts should focus on strengthening financial support,advancing information technology construction,and promoting regional balanced development to further improve the overall synergistic level of county-level medical communities and drive the high-quality development of county-level medical and health services.

Objective:To investigate the effect of levodopa and benserazide combined with pramipexole in the treatment of Parkinson's disease (PD) and its influence on cognitive function and oxidative stress indicators.Methods:From January 2021 to December 2023, the clinical datas of 110 PD patients in the Neurocritical Rehabilitation Center of Xi'an International Medical Center Hospital were selected for a prospective study. Based on the principle of balanced and comparable baseline features between groups, they were divided into single drug group (odd number, 55 cases, oral levodopa and benserazide, effective dose: 500-1 000 mg/d) and combined group (even number, 55 cases, pramipexole based on single drug group, effective dose: 0.375-4.500 mg/d) according to the simplified randomization method (odd-even number method). The therapeutic effect (Unified Parkinson's Disease Rating Scale (UPDRS)), improvement status of symptoms, cognitive ability (Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA)), oxidative stress indicators (superoxide dismutase (SOD), malondialdehyde) and brain injury indicators (central nervous system specific protein β (S100β), human Parkinson protein 7 (PARK7)) before and after treatment and adverse drug reactions were compared between groups of patients.Results:After treatment, the scores of UPDRS Ⅰ, Ⅱ and Ⅲ dimensions in the two groups were significantly decreased, and the above scores with ((5.53±1.16, 20.43±3.98, 14.37±3.07) points) in combined group were significantly lower than ((7.06±1.64, 24.56±4.37, 17.32±3.83) points) in single drug group ( t values were 5.65, 5.18 and 4.46, respectively; all P<0.001). After treatment, the autonomic disorder and sensory disturbance were significantly improved in both groups, but the proportion of sensory disturbance after treatment in combined group (20.00%, 11/55) was significantly lower than that in single drug group (38.18%, 21/55), and the difference was statistically significant ( χ2=4.41, P=0.036). The MMSE score in the two groups after treatment was decreased significantly while the MoCA score was increased significantly, but the MMSE score in combined group with ((10.38±1.95) points) was significantly lower than ((12.27±2.26) points) in single drug group. The difference was statistically significant ( t=4.70, P<0.001) while the MoCA score with ((18.46±3.21) points) was significantly higher compared with ((16.84±3.07) points) in single drug group.The difference was statistically significant ( t=2.71, P=0.008). After treatment, SOD in the two groups was risen significantly while malondialdehyde was declined significantly, and SOD in combined group with ((82.53±10.63) U/L) was significantly higher than ((76.54±8.85) U/L) in single drug group, while malondialdehyde with ((4.64±0.85) μmol/L) was significantly lower than ((6.46±1.26) μmol/L) in single drug group. The difference is statistically significant ( t values were 3.21 and 8.88, respectively; P values were 0.002 and <0.001). The levels of S100β and PARK7 in both groups were reduced significantly after treatment, and the combined group ((73.64±5.72) ng/L, (78.04±6.93) μmol/L) had significantly lower levels than the single drug group ((15.73±3.25) ng/L, (22.23±3.84) μmol/L). The differences were statistically significant ( t-values were 3.63 and 9.58, respectively; both P<0.001). There was no statistical difference in incidence of adverse drug reactions between groups ( P>0.05). Conclusion:Levodopa and benserazide combined with pramipexole can enhance the cognitive function of PD patients and improve the oxidative stress indicators, with few adverse reactions, safe and effective, and is worthy of application.

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Objective To investigate the therapeutic effect of different combinations of acupuncture and robot training on balance function in patients with Parkinson's disease.Methods A total of 60 patients with Parkinson's disease admitted to Wenzhou Traditional Medicine Hospital from October 2020 to October 2022 were randomly divided into two groups.Group A was given robot training after receiving acupuncture of Baihui and Dazhui points.Group B received those treatments simultaneously.And the balance function of patients was evaluated by Berg balance scale(BBS),Morse fall assessment scale(MFS)and timed up and go test(TUGT).Results In the intra-group comparison,TUGT in group A was significantly improved after 4 weeks of treatment(P<0.01);MFS and TUGT in group B were significantly improved compared with those before treatment(P<0.01).After 8 weeks of treatment,BBS and TUGT in group A were significantly improved compared with those before treatment(P<0.01);BBS,MFS and TUGT in group B were significantly improved compared with those before treatment(P<0.01).At the 12th week,BBS,MFS and TUGT in both groups were significantly improved compared with those before treatment(P<0.01).Comparison between groups:BBS,MFS and TUGT in group B were not significantly different from those in group A at 4 weeks of treatment(P>0.05);After 8 weeks of treatment,MFS in group B was significantly improved compared with that in group A(P<0.05),BBS and TUGT were better than that in group A without significant difference(P>0.05).After 12 weeks of treatment,BBS(P<0.01),MFS(P<0.01)and TUGT(P<0.05)in group B were significantly improved compared with group A.Conclusion Acupuncture at Baihui and Dazhui points combined with robot training simultaneously can improve the balance function and anti-falling ability of Parkinson's disease.

An increased level of reactive oxygen species is a key factor in neuronal apoptosis and epileptic seizures. Irisin reportedly attenuates the apoptosis and injury induced by oxidative stress. Therefore, we evaluated the effects of exogenous irisin in a kainic acid (KA)-induced chronic spontaneous epilepsy rat model. The results indicated that exogenous irisin significantly attenuated the KA-induced neuronal injury, learning and memory defects, and seizures. Irisin treatment also increased the levels of brain-derived neurotrophic factor (BDNF) and uncoupling protein 2 (UCP2), which were initially reduced following KA administration. Furthermore, the specific inhibitor of UCP2 (genipin) was administered to evaluate the possible protective mechanism of irisin. The reduced apoptosis, neurodegeneration, and spontaneous seizures in rats treated with irisin were significantly reversed by genipin administration. Our findings indicated that neuronal injury in KA-induced chronic epilepsy might be related to reduced levels of BDNF and UCP2. Moreover, our results confirmed the inhibition of neuronal injury and epileptic seizures by exogenous irisin. The protective effects of irisin may be mediated through the BDNF-mediated UCP2 level. Our results thus highlight irisin as a valuable therapeutic strategy against neuronal injury and epileptic seizures.
Rats ; Animals ; Kainic Acid/toxicity* ; Brain-Derived Neurotrophic Factor/metabolism* ; Fibronectins/metabolism* ; Hippocampus/metabolism* ; Rats, Sprague-Dawley ; Epilepsy/metabolism* ; Seizures/prevention & control*

Objective:To retrospectively analyze the epidemiological and clinical characteristics of novel coronavirus pneumonia (COVID-19), and to provide evidence for its further prevention and control.Methods:The epidemiological history, clinical symptoms, pulmonary CT changes, treatment plan (hormone intervention or not), and negative conversion time of nucleic acid were summarized and analyzed in 43 COVID-19 patients.Results:All the 43 patients had clear contact history, among which the number of patients transmitted from conference microphone was the largest (13 cases). There were 2 cases of critical disease, 4 cases of severe disease and 37 cases of common type. The main symptoms were fever (30 cases, 69.8%) and cough (40 cases, 72.1%). Lung CT mainly showed single or multiple ground glass shadows (40 cases), which were all absorbed by the treated lesions, among which 28 cases had a transient aggravation of the lesions during the treatment. All the 43 cases were treated with integrated traditional Chinese and western medicine, 2 cases in critical condition were treated with non-invasive ventilator, and 19 cases were treated with low-dose hormone. The average nucleic acid negative conversion time was 13.28 days, and the use of hormones had no significant effect on the negative conversion time ( P>0.05). Conclusions:COVID-19 of common type is the commonest. Early respiratory support therapy is recommended for critical cases. Hormone intervention makes no obvious influence on the negative conversion time of nucleic acid. Close contact in a closed environment greatly increases the risk of transmission.

Objective? To explore the status of psychological capital of ICU nurses and the correlation between nurses' psychological capital and job burnout, so as to provide the guidance for nursing managers in the management work. Methods? Convenience sampling method was used to select 200 ICU nurses in 4 ClassⅢGrade A Hospitals in Harbin as study subjects. The Nurses' Job Burnout Scale (NBS) and Psychological Capital Scale were used in the study to evaluate the correlation between psychological capital and job burnout. Results? A total of 187 valid questionnaires were collected. The score of Psychological Capital Scale of ICU nurses was (88.38±7.26), the average score of items was (3.68±0.71) , the score of hopefulness was (4.02±0.78) , self-efficacy was (3.84±0.67), flexible anti-resistance was (3.66±0.54) and optimistic was (3.21±0.86). There was a negative correlation between the total score and each dimensional score of ICU nurses Psychological Stress Scale and the scores of NBS including all dimensions (P＜ 0.05). Conclusions? The psychological capital of ICU nurses has negative correlation with their job burnout. Nursing managers should take certain measures based on each nurse's particular situation to improve their psychological capital so as to reduce the occurrence of job burnout.