Elevated glucose metabolism is a prominent characteristic of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). However, the efficacy of inhibiting a single target of glucose metabolism in FLS using small molecular inhibitors is limited for RA treatment. Herein, the synergistic inhibition of FLS' survival, proliferation, and activation by combining two glucose metabolism inhibitors, diclofenac (DC) and lonidamine (LND) was first verified. Subsequently, DC and LND were individually conjugated to cystamine-modified hyaluronic acid (HA) to prepare two polymer-prodrug conjugates. A HAP-1 peptide-modified dual polymer-prodrug conjugates-assembled nanoparticles system (^HAP-1NP_DC+LND) was further tailored in the optimal synergistic ratio for targeted and synergistic metabolic modulation of FLS to alleviate RA symptoms. Upon targeted uptake by FLS in inflamed joints, ^HAP-1NP_DC+LND released DC and LND within the intracellular reductive microenvironment, where DC hinders glucose uptake and LND suppresses glycolytic enzymes to eliminate FLS synergistically. Additionally, the secretion of lactic acid and pro-inflammatory factors from FLS were reduced, thereby disrupting the crosstalk between FLS and pro-inflammatory macrophages. Finally, ^HAP-1NP_DC+LND demonstrated promising efficacy in a mouse model of collagen-induced arthritis (CIA). Overall, this research provides valuable insights into novel therapeutic strategies for the safe and effective of treatment RA through targeted and synergistic metabolic modulation of FLS.

Objective:To investigate the effect of dexmedetomidine combined with chloroprocaine on epidural anesthesia for cesarean section.Methods:A total of 133 women who underwent epidural anesthesia for cesarean section at the Department of Anesthesiology, Jinhua People's Hospital between January 2020 and December 2022 were included in this prospective case-control study. These women were divided into a ropivacaine group ( n = 66) and a chloroprocaine group ( n = 67) using a random number table method. The ropivacaine group received epidural anesthesia with dexmedetomidine combined with ropivacaine, while the chloroprocaine group received epidural anesthesia with dexmedetomidine combined with chloroprocaine. The anesthesia effect (anesthesia onset time, anesthesia duration, peak effect time), changes in blood pressure (systolic blood pressure, diastolic blood pressure), adverse reactions (shivering, nausea and vomiting, urinary retention, skin itching, numbness of lower limbs), and satisfaction with muscle relaxation were observed in the two groups. Results:The anesthesia onset time, anesthesia duration, and peak effect time in the chloroprocaine group were (6.91 ± 1.54) minutes, (61.54 ± 5.31) minutes, and (11.79 ± 4.12) minutes, respectively, which were significantly shorter than those in the ropivacaine group [(9.65 ± 1.92) minutes, (83.57 ± 6.69) minutes, (18.32 ± 4.81) minutes, t = 9.08, 21.05, 8.41, all P < 0.001). The systolic and diastolic blood pressure increased in both groups after 10 minutes of anesthesia and at the end of the procedure; however, the increments observed in the chloroprocaine group were relatively smaller. There were significant differences in systolic and diastolic blood pressure, measured at 10 minutes of anesthesia and at the end of the procedure, between the two groups ( F = 7.36, P < 0.001; F = 5.12, P = 0.001). There were significant differences in systolic and diastolic blood pressure between different time points ( F = 10.03, P < 0.001; F = 6.72, P < 0.001). The group-by-time interaction effect on systolic and diastolic blood pressure was also highly significant ( F = 9.83, P < 0.001; F = 8.01, P < 0.001). The chloroprocaine group exhibited a significantly lower incidence of adverse reactions compared with the ropivacaine group [4.48% (3/67) vs. 15.15% (10/66), χ2 = 4.29, P < 0.05). Additionally, the chloroprocaine group had a significantly higher satisfaction rate with muscle relaxation compared with the ropivacaine group [94.03% (63/66) vs. 81.82% (54/66), Z = 5.73, P < 0.05]. Conclusion:The combination of dexmedetomidine and chloroprocaine offers remarkable benefits in epidural anesthesia for cesarean sections. This combined approach not only enhances epidural anesthesia but also stabilizes the blood pressure of puerperants, reduces adverse reactions, and provides exceptional muscle relaxation. It deserves consideration for clinical application.

Objective To discuss the perioperative care and wound protection of xenotransplantation from genetically edited pigs to monkeys, with the goal of improving the success rate of such experimental procedures. Methods From October 2022 to October 2023, perioperative care and wound protection were performed on 7 recipient rhesus monkeys undergoing xenotransplantation of genetically edited pig tissues and organs. Customized wound protective garments were designed based on monkeys' size and surgical area to protect the wounds, alongside meticulous perioperative care. This included preoperative preparation and medication, intraoperative monitoring of physiological indicators and anesthesia management, and postoperative care comprising wound protection, observation and monitoring, and nutritional support. Results All seven monkeys successfully underwent xenotransplantation. With the aid of protective garments and detailed care, all surgical wounds healed by first intention, and postoperative recovery was satisfactory. Conclusion Proper care and wound protection during xenotransplantation from genetically edited pigs to monkeys not only promote wound healing, but also alleviate pain and harm to animals. This has significant implications for advancing experimental research in pig-monkey xenotransplantation and enhancing animal welfare.

Objective To analyze the structural changes and reasons for hospitalization expenditure among patients with thyroid cancer,so as to provide a reference basis for reasonable control of medical costs,making the structure of hospitalisation costs for patients undergoing surgery for thyroid cancer more rational.Methods The degree of structural change and the grey correlation method were used to quantitatively analyze the changes in the structure of hospitalization expenses and the degree of correlation of patients with thyroid cancer surgery in a hospital in Shanxi Province from 2017 to 2022.Results From 2017 to 2022,the hospitalization expenses of thyroid cancer surgery patients in the hospital showed a decreasing trend,and drug fees and consumables fees accounted for a large proportion.Consumables fees and treatment fees showed positive contribution changes,drug fees and diagnosis fees showed negative contribution changes.Nursing fees and general medical service fees showed positive contribution changes,but were not obvious.During the 6-year period,the top two related factors affecting the hospitalization expenses of thyroid cancer patients were drug fees and consumables fees.Conclusion The structure of hospitalization expenses of per thyroid cancer patients tends to be reasonable,but there is still a large room for improvement.It is suggested to continue to strengthen the control of drugs and medical consumables,and clarify the value composition of technical labor and material consumables,so as to further optimize the structure of hospitalization expenses.

New quality productive forces provides key inpetus for the high-quality development of the health service. As a systematic value assessment tool, health technology assessment (HTA) can play an important role in the development of new quality productive forces of health. This study analyzed the intrinsic relationship between HTA and the new quality productive forces of health by summarizing their connotations. The path framework of HTA to enhance the development of new quality productive forces of health was constructed, and the potential paths were explored from the perspective of technological governance. These paths included establishing a technology governance mode based on evidence-based principles, improving the innovation ecosystem in the field of health, promoting the embedding of innovative technologies and upgrading service mode, and promoting the sustainable and coordinated development of the health system guided by value healthcare, so as to provide references for policy formulation and related research in China′s health field.

Objective:To explore the influencing factors and pathways of home-based exercise rehabilitation compliance in patients after percutaneous coronary intervention (PCI), so as to provide theoretical basis for formulating targeted intervention program.Methods:From July 2022 to February 2023, convenience sampling was used to select 220 patients who underwent PCI at Yantai Yuhuangding Hospital affiliated with Qingdao Medical College, Qingdao University as the study subject. A survey was conducted on patients using the General Information Questionnaires, Self-Efficacy for Exercise Scale, Illness Perception and Behavior Questionnaire in Patients with Coronary Heart Disease after PCI, Social Support Rating Scale, and Exercise Rehabilitation Compliance Follow-up Scale.Results:A total of 220 questionnaires were distributed, and 215 valid questionnaires were collected, with an effective response rate of 97.73% (215/220). The Exercise Rehabilitation Compliance Follow-up Scale in 215 patients after PCI was (11.35±3.85). The mediating effect of exercise self-efficacy between social support and exercise compliance was 0.150 [95% CI (0.055, 0.167), P<0.01], and the mediating effect of disease cognition between social support and exercise compliance after PCI was 0.065 [95% CI (0.016, 0.090), P<0.05]. The direct effect of social support on exercise compliance was 0.238 [95% CI (0.064, 0.278), P<0.01], and the indirect effect was 0.215 [95% CI (0.083, 0.233), P<0.05], and the mediating effect accounted for 47.46% of the total effect. Conclusions:Social support can directly or indirectly affect the compliance of patients with home-based exercise rehabilitation through the mediating effect of exercise self-efficacy and post PCI disease cognition. Medical and nursing staff can improve patient exercise self-efficacy and disease cognition by constructing intervention strategies based on social support, thereby enhancing home-based exercise rehabilitation compliance.

Objective:To analyze the cost-effectiveness simulation of medical services for COVID-19 epidemic in Wuhan city based on the social perspective, for the sake of providing references and suggestions to deal with possible public health emergencies in the future.Methods:Through policy documents and literature review, interview survey and Delphi method, the cost and cost-effectiveness of medical services for COVID-19 in Wuhan were simulated based on the decision-tree model, from December 27, 2019 to April 26, 2020.Results:The average curing cost of per patient diagnosed with COVID-19 in Wuhan was 175 462.10 yuan, a figure calculated in the baseline that these epidemic prevention and control measures were taken on January 23, 2020. In Hypothesis 1 (with epidemic prevention and control measures taken one week before), the cost was 164 552.43 yuan, and in Hypothesis 2 (with epidemic prevention and control measures taken one week later), the cost was 187 542.37 yuan. Compared with the baseline, the incremental cost-effectiveness ratio of the medical service for COVID-19 in Wuhan under Hypothesis 1 was 183 000 yuan per patient, which was more cost effective.Conclusions:The public health prevention and control measures played an important role during the COVID-19 epidemic in Wuhan. With the cost-effectiveness simulation results taken into account, this study can provide decision-makers with better references in likewise events.

The nucleocapsid (N) protein of SARS-CoV-2 has been reported to have a high ability of liquid-liquid phase separation, which enables its incorporation into stress granules (SGs) of host cells. However, whether SG invasion by N protein occurs in the scenario of SARS-CoV-2 infection is unknow, neither do we know its consequence. Here, we used SARS-CoV-2 to infect mammalian cells and observed the incorporation of N protein into SGs, which resulted in markedly impaired self-disassembly but stimulated cell cellular clearance of SGs. NMR experiments further showed that N protein binds to the SG-related amyloid proteins via non-specific transient interactions, which not only expedites the phase transition of these proteins to aberrant amyloid aggregation in vitro, but also promotes the aggregation of FUS with ALS-associated P525L mutation in cells. In addition, we found that ACE2 is not necessary for the infection of SARS-CoV-2 to mammalian cells. Our work indicates that SARS-CoV-2 infection can impair the disassembly of host SGs and promote the aggregation of SG-related amyloid proteins, which may lead to an increased risk of neurodegeneration.
Amyloidogenic Proteins/metabolism* ; Amyotrophic Lateral Sclerosis/genetics* ; Animals ; COVID-19 ; Cytoplasmic Granules/metabolism* ; Mammals ; SARS-CoV-2 ; Stress Granules

Objective:To simulate the cost of medical services for COVID-19 epidemic in Wuhan city from the social perspective, as references and suggestions in case of possible public health emergencies in China in the future.Methods:By such means as policy documents and literature review, interview survey and Delphi method, a cost estimation model was built and confirmed to simulate the cost of medical services for COVID-19 in Wuhan, from December 27, 2019 to April 26, 2020.Results:The total cost of medical services during the COVID-19 epidemic in Wuhan was 8 152 670 867 yuan. 721 800 387 yuan(8.85%) of the medical cost was covered by medical insurance; the medical cost covered by sources other than medical insurance was 434 813 725 yuan(5.34%); the cost of additional measures related to medical service was estimated to be 6 996 056 755 yuan(85.81%).Conclusions:The total cost of medical services during the COVID-19 epidemic in Wuhan was gigantic. The cost estimation results can provide the government with basic information, decision-making basis and suggestions regarding epidemic control.

In the recent years, the damage of the spleen has been increased due to trauma or neoplastic diseases. Traditional view holds the point that the damaged spleen should be completely removed, but with the development of spleen surgery, the important physiological function of the spleen has been widely recognized, and partial splenectomy has been well recognized by the surgeons. This paper summarized the clinical experience in partial splenectomy and raised some technical points.