OBJECTIVE To investigate the targeting effect of folic acid-modified crebanine nanoparticles （FA-Cre@PEG- PLGA NPs， hereinafter referred to as “NPs”） combined with ultrasound irradiation on M109 cells in vitro and in vivo after administration， and explore the anti-tumor mechanism. METHODS CCK-8 assay was used to detect the inhibitory effect of NPs combined with ultrasound irradiation on the proliferation of M109 cells， and the best ultrasound time was selected. Using human lung cancer A549 cells as a control， the targeting of NPs combined with ultrasound irradiation to M109 cells was evaluated by free folic acid blocking assay and cell uptake assay. The effects of NPs combined with ultrasound irradiation on the migration， invasion， apoptosis， cell cycle and reactive oxygen species （ROS） levels of M109 cells were detected by cell scratch test， Transwell chamber test and flow cytometry at 1 h after 958401536@qq.com administration； the changes of mitochondrial membrane potential （MMP） were observed by fluorescence inverted microscope. A mouse subcutaneous tumor model of M109 cells was constructed， and the in vivo tumor targeting of NPs combined with ultrasound irradiation was investigated by small animal in vivo imaging technology. RESULTS NPs combined with ultrasound irradiation could significantly inhibit the proliferation of M109 cells， and the optimal ultrasound time was 1 h after administration. The free folic acid could antagonize the inhibitory effect of NPs on the proliferation of M109 cells， and combined with ultrasound irradiation could partially reverse this antagonism. Compared with A549 cells， the uptake rate of NPs in M109 cells was significantly higher （P＜0.01）， and ultrasound irradiation could promote cellular uptake. NPs combined with ultrasound irradiation could inhibit the migration and invasion of M109 cells and block the cell cycle in the G0/G1 and G2/M phases. Compared with control group， the apoptosis rate of M109 cells and ROS level were increased significantly （P＜0.01）， while the MMP decreased significantly （P＜0.01） in the different concentration （100， 200， 300 μg/mL） groups of M109 cells. Compared with the mice in non-ultrasound group， the fluorescence intensity and tumor-targeting index of the tumor site in the 0 h ultrasound group were significantly enhanced （P＜0.05 or P＜0.01）. CONCLUSIONS NPs combined with ultrasound irradiation have a strong targeting effect on M109 cells in vitro and in vivo， the anti-tumor mechanism includes inhibiting cell migration and invasion， blocking cell cycle， and inducing apoptosis.

PURPOSE: To evaluate the diagnostic accuracy of the observational chart for traumatic limb swelling (OCTLS) for osteofascial compartment syndrome (OCS). METHODS: This was a descriptive-longitudinal study. Data of 316 patients who underwent surgical treatment for tibial fractures in our department from January 2015 to December 2023 were collected. Patients with Gustilo type II or higher open fractures, vascular injury, or bilateral fractures were excluded from the study. Two groups of double-blinded investigators independently assessed patients for the presence of OCS using 2 distinct diagnostic methods. Three senior orthopedic trauma surgeons evaluated patients with post-fracture calf swelling for OCS and the need for fasciotomy based on clinical signs and their extensive clinical experience. Subsequently, fasciotomy was performed according to their judgment, followed by postoperative examination of muscle and soft tissue conditions. Additionally, a follow-up evaluation was conducted to assess for complications such as ischemic muscle contracture. Another 3 trained researchers used OCTLS to grade swelling severity and determine the need for fasciotomy. The final diagnostic gold standard of OCS was determined by referring to whether there was escape of muscles at fasciotomy and/or color change in the muscles or muscle necrosis intraoperatively, and neurological abnormality or contracture at the last follow-up. The results of the 2 diagnostic methods were compared with the final diagnostic result. Kappa consistency test, paired χ² test (McNemar test), and receiver operating characteristic curve were used to evaluate the diagnostic efficacy of the 2 diagnostic methods. RESULTS: Of the 316 patients, 211 were finally included in the study, including 160 males and 51 females, with an average follow-up time of (14.5 ± 2.7) months. Among the 211 patients with tibial fracture-associated swelling, 42 were definitively diagnosed with OCS. Based on clinical symptoms and signs judgment, among the 65 fasciotomy patients, 38 were confirmed as correct, while among the 146 non-fasciotomy patients, 4 developed ischemic muscle contractures. Based on the OCTLS for assessment, fasciotomy was correctly recommended in 36 out of 43 cases, while 6 out of 168 non-fasciotomy patients developed OCS. Compared to the use of the gold standard, clinical signs judgment showed moderate consistency (McNemar's test p < 0.001, Kappa = 0.618, p < 0.001), whereas OCTLS demonstrated strong agreement (McNemar's test p = 1.000, Kappa = 0.808, p < 0.001). Receiver operating characteristic analysis revealed higher diagnostic accuracy for OCTLS (area under curve = 0.908, 95% CI: 0.843 - 0.972) compared to clinical signs judgment (area under curve = 0.872, 95% CI: 0.812 - 0.933). OCTLS achieved superior accuracy (93.8% vs. 85.3%, χ² = 8.221, p < 0.001) and a lower fasciotomy rate (20.4% vs. 30.8%, χ² = 6.023, p = 0.014). CONCLUSION Compared to clinical signs judgment, OCTLS significantly reduces unnecessary fasciotomy, improves diagnostic accuracy for OCS, and enables non-invasive, dynamic, and quantitative assessment, making it a valuable tool for clinical practice.
Humans ; Compartment Syndromes/etiology* ; Male ; Female ; Adult ; Tibial Fractures/surgery* ; Middle Aged ; Fasciotomy ; Edema/etiology* ; Longitudinal Studies ; Aged ; Young Adult

OBJECTIVE To develop a whole-process intelligent model of pharmaceutical care for peritoneal dialysis （PD） patients， and to provide a reference for clinical pharmacists to provide standardized PD pharmaceutical care. METHODS The pharmaceutical care mode of PD patients at home and abroad was investigated and analyzed. Based on the actual situation of the First Affiliated Hospital of Soochow University （hereinafter referred to as “our hospital”）， with “home→PD center outpatient→ inpatient department” as the main node， the recycling process of medication reconciliation was optimized. The whole-process intelligent pharmaceutical care model of PD was illustrated by improving the Chinese version of the drug-related problems （DRPs） classification tool， developing the corresponding pharmaceutical care process， and presenting specific cases. RESULTS Based on the medication therapy management （MTM） platform， our hospital had built a closed-loop PD whole-process intelligent pharmaceutical care model of “in-hospital pharmaceutical care （building document）-PD outpatient MTM-home pharmaceutical care （online App management）”. A “double cycle” workflow of “admission→discharge→outpatient” medication reconciliation cycle and “discovery-analysis-intervention-follow-up-record-evaluation” DRPs cycle was formed. CONCLUSIONS The establishment of the whole-process intelligent pharmaceutical care model for PD in our hospital provides experience for standardizing pharmaceutical care for PD patients， and can reduce DRPs.

Allergic diseases affect about 40% of the world's population. Environmental factors are important in the occurrence and development of allergic diseases. Dust mites are one of the most important allergens in the indoor environment. The World Health Organization proposes the "four-in-one, combination of prevention and treatment" treatment principle for allergic diseases, in which environmental control to avoid or reduce allergens is the first choice for treatment. Modern people spend much more time at home (including sleeping) than outdoors, and the control of the home environment is particularly critical. This practice introduces the hypoallergenic home visit program, which including home environment assessment, environmental and behavioral intervention guidance, and common household hypoallergenic supplies and service guidance for the patient's home environment. The real-time semi-quantitative testing of dust mite allergens, qualitative assessments of other indoor allergens, record of patients' household items and lifestyle, and precise, individualized patient prevention and control education will be conducted. The hypoallergenic home visit program improves the doctors' diagnosis and treatment data dimension, and becomes a patient management tool for doctors outside the hospital. It also helps patients continue to scientifically avoid allergens and irritants in the environment, effectively build a hypoallergenic home environment, reduce exposure to allergens in the home environment, and achieve the goal of combining the prevention and treatment of allergic diseases.
Humans ; Hospitals ; Life Style ; Sleep

As a recognized rare and highly fatal disease, hereditary angioedema (HAE) is difficult to diagnose and characterized by recurrent edema involving the head, limbs, genitals and larynx, etc. Diagnosis of HAE is not difficult. However, low incidence and lack of clinical characteristics lead to difficulty of doctors on timely diagnosis and correct intervention for HAE patients. Therefore, it is crucial to improve the awareness of this disease and prevent its recurrence. for HAE patients. In view of absent cognition of doctors and the general public on HAE, patients often suffer from sudden death or become disabled due to laryngeal edema which cannot be treated in time. Thus, based on the Internet mobile terminal platform, the team set up an all-day rapid emergency response system which is provided for HAE patients by setting up "one-click help". The aim is to offer optimization on overall management of HAE and designed the intelligent follow-up management to provide timely assistance and specialized suggestion for patients with acute attacks.
Humans ; Angioedemas, Hereditary/drug therapy*

Allergic diseases affect about 40% of the world's population. Environmental factors are important in the occurrence and development of allergic diseases. Dust mites are one of the most important allergens in the indoor environment. The World Health Organization proposes the "four-in-one, combination of prevention and treatment" treatment principle for allergic diseases, in which environmental control to avoid or reduce allergens is the first choice for treatment. Modern people spend much more time at home (including sleeping) than outdoors, and the control of the home environment is particularly critical. This practice introduces the hypoallergenic home visit program, which including home environment assessment, environmental and behavioral intervention guidance, and common household hypoallergenic supplies and service guidance for the patient's home environment. The real-time semi-quantitative testing of dust mite allergens, qualitative assessments of other indoor allergens, record of patients' household items and lifestyle, and precise, individualized patient prevention and control education will be conducted. The hypoallergenic home visit program improves the doctors' diagnosis and treatment data dimension, and becomes a patient management tool for doctors outside the hospital. It also helps patients continue to scientifically avoid allergens and irritants in the environment, effectively build a hypoallergenic home environment, reduce exposure to allergens in the home environment, and achieve the goal of combining the prevention and treatment of allergic diseases.
Humans ; Hospitals ; Life Style ; Sleep

As a recognized rare and highly fatal disease, hereditary angioedema (HAE) is difficult to diagnose and characterized by recurrent edema involving the head, limbs, genitals and larynx, etc. Diagnosis of HAE is not difficult. However, low incidence and lack of clinical characteristics lead to difficulty of doctors on timely diagnosis and correct intervention for HAE patients. Therefore, it is crucial to improve the awareness of this disease and prevent its recurrence. for HAE patients. In view of absent cognition of doctors and the general public on HAE, patients often suffer from sudden death or become disabled due to laryngeal edema which cannot be treated in time. Thus, based on the Internet mobile terminal platform, the team set up an all-day rapid emergency response system which is provided for HAE patients by setting up "one-click help". The aim is to offer optimization on overall management of HAE and designed the intelligent follow-up management to provide timely assistance and specialized suggestion for patients with acute attacks.
Humans ; Angioedemas, Hereditary/drug therapy*

OBJECTIVE: To analyze the kinetic characteristics of lymphocyte subsets and myeloid-derived suppressor cell (MDSC) in patients who newly diagnosed intermediate- to high-risk aGVHD and treated with steroids-ruxolitinib as the first line therapy from a single-arm, open clinical trial (NCT04061876). METHODS: We prospectively observed the efficacy of 23 patients having intermediate- to high-risk aGVHD and treated with steroids-ruxolitinib as the first line therapy. The kinetic characteristics of lymphocyte subsets and MDSC were monitored, and then we compared them in steroids-ruxolitinib group (n=23), free-aGVHD group (n=20) and steroids group (n=23). RESULTS: Of the 23 patients, the CR rate was 78.26% (18/23) on day 28 after first-line treatment with steroids-ruxolitinib. On day 28 after treatment, patients had lower level of CD4⁺CD29⁺ T cells (P=0.08) than that of pre-treatment, whereas levels of other lymphocyte subsets in this study were higher than that of pre-treatment; CD4⁺CD29⁺ T cells in CR patients decreased, compared with refractory aGVHD patients. On day 28 of treatment, CD8⁺CD28^- T cells (P=0.03) significantly increased in patients with aGVHD than that in patients without aGVHD, so did CD8⁺CD28^- T / CD8⁺CD28⁺ T cell ratio (P=0.03). Compared with patients without aGVHD, patients with aGVHD had lower level of G-MDSC, especially on day 14 after allo-HSCT (P=0.04). Compared with pre-treatment, M-MDSC was higher in CR patients on day 3 and 7 post-treatment (P₃=0.01, P₇=0.03), e-MDSC was higher on day 28 post-treatment (P=0.01). Moreover, compared with CR patients, M-MDSC was lower in refractory aGVHD patients on day 3 post-treatment (P=0.01) and e-MDSC was lower on day 28 post-treatment (P=0.01). Compared with steroids group, MDSC in steroids-ruxolitinib group was higher, with the most significant difference in M-MDSC (P₃=0.0351; P₇=0.0142; P₁₄=0.0369). CONCLUSION We found that patients newly diagnosed intermediate- to high-risk aGVHD receiving first-line therapy with steroids-ruxolitinib achieved high response rate. Moreover, the novel first-line therapy has a small impact on the immune reconstitution of patients after allo-HSCT. Elevated MDSC might predict a better response in aGVHD patients receiving this novel first-line therapy. M-MDSC responded earlier to steroids-ruxolitinib than e-MDSC, G-MDSC.
Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Kinetics ; Myeloid-Derived Suppressor Cells ; Nitriles ; Pyrazoles ; Pyrimidines ; Retrospective Studies ; Steroids

Felids are the unique definitive host of Toxoplasma gondii. The intestine of felid is the only site for initiating Toxoplasma gondii sexual reproduction. T. gondii excretes millions of infectious oocysts from the intestine, which are the primary source of infection. There are many difficulties in developing vaccines and drugs to control oocyst excretion due to the lack of an appropriate experimental model. Here, we established an in vitro feline intestinal epithelial cell (IEC) infection system and an efficient animal model of T. gondii Chinese 1 genotype, Wh6 strain (TgCtwh6). The Kunming mice brain tissues containing TgCtwh6 cysts were harvested 42-day post-infection. The bradyzoites were co-cultured with cat IECs in vitro at a ratio of 1:10. Five 3-month-old domestic cats were orally inoculated with 600 cysts each. The oocysts were detected by daily observation of cat feces by microscopy and polymerase chain reaction. We found that the parasite adhered and invaded cat IECs in vitro, transformed into tachyzoites, and then divided to form rose-like structures. These parasites eventually destroyed host cells, escaped, and finished the asexual reproduction process. Schizonts associated with sexual reproduction have not been observed during development in vitro cultured cells. However, schizonts were detected in all infected cat intestinal epithelial cells, and oocysts were presented in all cat feces. Our study provides a feasible cell model and an efficient infection system for the following studies of T. gondii sexual reproduction, and also lays a foundation to develop drugs and vaccines for blocking excretion and transmission of oocysts.