Background In the context of climate change, the health burden associated with non-optimal temperature is becoming increasingly substantial. Emergency ambulance calls (EACs) are a sensitive indicator of acute health effects. However, most previous studies have relied on daily mean temperature (MT) or a single thermal stress indicator, and it remains unclear whether different temperature indicators yield materially different estimates of the health burden attributable to non-optimal temperature. Objective To compare multiple temperature indicators in evaluating the attributable burden of EACs associated with non-optimal temperature in Dezhou City, Shandong Province. Methods Daily EACs records and corresponding meteorological data in Dezhou from 2014 to 2023 were collected. A time-stratified case-crossover design with conditional logistic regression, combined with distributed lag non-linear models (DLNM), was employed to examine the exposure-response relationships and population attributable burden of EACs associated with the percentiles of daily MT and 12 commonly used thermal stress indicators. Results During the study period, a total of 952989 EACs were recorded in Dezhou. For all temperature indicators, the cumulative exposure-response curves showed a V-shaped pattern. Among the attributable fraction (AF) estimates, only those derived from the universal thermal climate index for outdoor shaded space (UTCI3) and wet-bulb temperature (WBT) were significantly lower than the estimates based on MT (P < 0.05); no statistically significant differences were observed for the other indicators. The AF based on MT was 5.24% (95%CI: 4.34%, 6.16%), and the attributable burden was mainly driven by cold temperatures (AF=3.57%, 95%CI: 2.65%, 4.48%). Spatially, high heat-attributable EACs rates per 1000 population were primarily concentrated in the central and southern Dezhou, whereas areas with high cold-attributable EACs rates were more dispersed. The overall spatial pattern of EACs attributable to non-optimum temperatures was more consistent with the distribution of cold-related risks. Subgroup analysis showed that, across susceptible population groups, the AF estimates derived from most thermal stress indicators did not differ significantly from those based on MT. Conclusion In Dezhou, most thermal stress indicators produce attributable burden estimates for EACs associated with non-optimal temperature that are similar to those based on daily MT, and cold temperatures contribute more to the overall attributable burden. The spatial distribution of EACs attributable to non-optimal temperature is dispersed, whereas heat-attributable hotspots are concentrated in central and southern Dezhou.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

OBJECTIVE: To evaluate the early effectiveness of transosseous suture fixation in treating recurrent acute patellar dislocation with patellar osteochondral fractures (OCFs). METHODS: A retrospective analysis was conducted on 19 patients with recurrent acute patellar dislocation and patellar OCFs, who underwent transosseous suture fixation between January 2018 and December 2022 and were followed up 2 years. The cohort included 8 males and 11 females, aged 13-21 years (mean, 16.2 years). Patients experienced 2-5 times of patellar dislocation (mean, 3.2 times). The interval from the last dislocation to operation ranged from 3 to 15 days (mean, 9.6 days). Preoperative imaging revealed the intra-articular osteochondral fragments and medial patellofemoral ligament (MPFL) injury. Clinical outcomes were evaluated using the visual analogue scale (VAS) score for pain, the International Knee Documentation Committee (IKDC) score, the Hospital for Special Surgery (HSS) knee score, the Lysholm score, and the Tegner score. Postoperative complications were recorded. During follow-up, the knee X-ray films, CT, and MRI were taken to evaluate fragment healing, displacement, and the morphology and tension of the MPFL reconstruction graft. RESULTS: All incisions healed primarily, and no complication occurred such as infection, joint stiffness, patellofemoral arthritis, or redislocation. Patients were followed up 24-60 months (mean, 43.5 months). At 12 months postoperatively and the last follow-up, significant improvements ( P<0.05) were observed in VAS, Lysholm, IKDC, HSS, and Tegner scores compared to preoperative values. Further improvements were observed at last follow-up compared with the 12 months postoperatively, and the differences were significant ( P<0.05). Imaging studies demonstrated satisfactory osteochondral fragment positioning with stable fixation. At last follow-up, all fragments had healed, and MPFL reconstruction grafts exhibited optimal morphology and tension. No joint adhesion or fragment displacement occurred. CONCLUSION For recurrent acute patellar dislocation with patellar OCFs, transosseous suture fixation proves to be both safe and effective, achieving satisfactory early effectiveness.
Humans ; Male ; Female ; Patellar Dislocation/surgery* ; Adolescent ; Young Adult ; Retrospective Studies ; Patella/surgery* ; Suture Techniques ; Treatment Outcome ; Recurrence ; Fracture Fixation, Internal/methods* ; Fractures, Bone/surgery* ; Follow-Up Studies

Objective To study the inhibitory effect of secondary metabolites of Pseudomonas aeruginosa(PA)on Candida albicans(CA)and to explore some of the mechanisms.Methods PA and CA strains were i-solated from clinical specimens from the hospital.Then,PA strains with inhibitory effects on CA were screened through cross-line test and co-incubation test,and crude extracts of PA secondary metabolites were prepared,and were tested together with pyocyanin,phenazine-1-carboxylic acid,1-hydroxyphenazine,and 3-ox-ododecyl-l-homoserine lactone(3-oxo-HSL).The inhibitory effects of various PA secondary metabolites on CA were determined through minimum inhibitory concentration test,minimum bactericidal concentration test,time-sterilization curve measurement,and XTT method activity measurement test,and some mechanisms by which PA secondary metabolites inhibited CA were explored.Results The strongest inhibitory effect on CA was 1-hydroxyphenazine,and at a concentration of 6.250 μg/mL,the relative activity of CA decreased to 0.00%.Next were pyocyanin and PA crude extract,and the relative fungal activity of CA decreased to 0.00%at concentrations of 200 and 100 μg/mL.1-hydroxyphenazine,pyocyanin,3-oxo-HSL and PA crude extract all had inhibitory effects on the formation of CA hyphae.Reactive oxygen species(ROS)were generated in CA cells treated with 1-hydroxyphenazine,phenazine 1-carboxylic acid,pyocyanin,and PA crude extract,and the highest levels of ROS were induced by pyocyanin and 1-hydroxyphenazine.Conclusion Phenazine secondary metabolites 1-hydroxyphenazine and pyocyanin have significant inhibitory effects on the growth and activity of CA,and both induce the highest amount of ROS.The quorum-sensing signal molecule 3-oxo-HSL have no in-hibitory effect on CA growth,but have a significant inhibitory effect on the formation of fungal hyphae.

Objective To explore the therapeutic mechanism of maggot for psoriasis-like lesions in mice from the perspective of immune stress and complement activation regulation.Methods Thirty-six male C57BL/6 mice were randomly divided into control group,model group,maggot(1.25%,2.5%,and 5%)groups,and Benvitimod(1%)group.Psoriasis-like lesions were induced by application of imiquimod cream,and the severity of skin lesions was assessed using the modified Psoriasis Area and Severity Index(MPASI)score.Auricular swelling of the mice was observed,and histopathological changes of the skin lesions were examined with HE staining.Scratching behavior of the mice was observed and the spleen index was calculated.Toluidine blue staining was used to detect mast cells in the skin lesions,and serum levels of IgG,IgM,the complements CH50,C1s,C3,C3a,C5 and C5a,and the inflammatory factors IL-23,IL-17A and TNF-α were determined with ELISA.Results In mice with imiquimod-induced psoriasis-like skin lesions,treatment with the maggot at the 3 doses significantly decreased MPASI score,alleviated auricular swelling and pathologies in the skin lesions,reduced scratching behaviors,spleen index,and the number of mast cells in the lesions.Treatment with high-dose maggot significantly lowered serum levels of IgG,C1s,C3a,C5a,IL-23,IL-17A and TNF-α and the levels of C1s,C3,C3a,C5 and C5a in the lesion tissue,and increased serum levels of CH50,C3,and C5.The therapeutic effect of maggot showed a dose-effect dependence.Conclusion Maggot can alleviate psoriasis-like skin lesions in mice by inhibiting immune stress and complement activation.

Background Intraseasonal variation in acute health effects of extreme heat remains insufficiently investigated. Emergency ambulance calls (EACs) may offer timely insights into the population's health during such extreme heat events. Objective To analyze intraseasonal variation in the association between extreme heat and hourly EACs during summer in Dezhou City, Shandong Province, China. Methods We collected data on all-cause hourly EACs in Dezhou City from 2021 to 2022 and assigned hourly temperature and humidity data (with a spatial resolution of 0.0625° × 0.0625°) to call addresses. Summer in this study was defined as from June to September each year, with June to July considered as early summer and August to September as late summer. Extreme heat was defined as the 99th percentile of the temperature range during the summer. We employed a time-stratified case-crossover design using conditional logistic regression integrating distributed-lag nonlinear models to compare the association between extreme heat and the risk of hourly EACs in both early and late summer periods. Results A total of 80389 EACs were recorded in Dezhou City during the study period. The analysis revealed a U-shaped association between hourly ambient temperature and EACs during summer, with the most significant effect observed at lag 0-30 h. Using the optimal temperature of 20.0°C as a reference, the cumulative odds ratio (OR) (lag 0-120 h) for extreme heat was 1.55 (95%CI: 1.40, 1.71) throughout summer. The cumulative effect of extreme heat was higher in late summer (OR=2.38, 95%CI: 1.91, 2.97) than in early summer (OR=1.37, 95%CI: 1.22, 1.54) (P<0.0001). Additionally, individuals aged 60 years and above had a higher risk throughout summer (OR=1.98, 95%CI: 1.70, 2.30) compared to those under 60 years (OR=1.23, 95%CI: 1.06, 1.42) (P<0.0001). Conclusion Intraseasonal variation is observed in the strength of association between extreme heat and hourly EACs during summer in Dezhou City. The higher risk observed in late summer than in early summer indicates that repeated exposures to heat may escalate health risks, and older adults are more vulnerable.

Objective To explore the therapeutic mechanism of maggot for psoriasis-like lesions in mice from the perspective of immune stress and complement activation regulation.Methods Thirty-six male C57BL/6 mice were randomly divided into control group,model group,maggot(1.25%,2.5%,and 5%)groups,and Benvitimod(1%)group.Psoriasis-like lesions were induced by application of imiquimod cream,and the severity of skin lesions was assessed using the modified Psoriasis Area and Severity Index(MPASI)score.Auricular swelling of the mice was observed,and histopathological changes of the skin lesions were examined with HE staining.Scratching behavior of the mice was observed and the spleen index was calculated.Toluidine blue staining was used to detect mast cells in the skin lesions,and serum levels of IgG,IgM,the complements CH50,C1s,C3,C3a,C5 and C5a,and the inflammatory factors IL-23,IL-17A and TNF-α were determined with ELISA.Results In mice with imiquimod-induced psoriasis-like skin lesions,treatment with the maggot at the 3 doses significantly decreased MPASI score,alleviated auricular swelling and pathologies in the skin lesions,reduced scratching behaviors,spleen index,and the number of mast cells in the lesions.Treatment with high-dose maggot significantly lowered serum levels of IgG,C1s,C3a,C5a,IL-23,IL-17A and TNF-α and the levels of C1s,C3,C3a,C5 and C5a in the lesion tissue,and increased serum levels of CH50,C3,and C5.The therapeutic effect of maggot showed a dose-effect dependence.Conclusion Maggot can alleviate psoriasis-like skin lesions in mice by inhibiting immune stress and complement activation.

Objectives:Fenofibric acid is extracted from the widely used hypolipemic fenofibrate,nowadays being approved for marketing around numerous nations and regions,nonetheless not in China.Present trial evaluated the efficacy and safety in the Chinese hypertriglyceridemia population. Methods:This is a multi-center,randomized,double-blind,placebo-controlled phase Ⅲ clinical trial.Patients from 3 different cohorts,including severe hypertriglyceridemia(HTG),moderate HTG and mixed-dyslipidemia(MD),were randomized at 1:1 ratio to receive fenofibric acid 135 mg or placebo daily for 12 weeks.The primary endpoint was the percentage change of triglyceridemia(TG)from baseline at week 12.Secondary endpoints were the percentage changes of other blood lipid indexes.At the same time,the incidence of medical adverse events was observed. Results:Among the three cohorts of patients with severe HTG(n=52),moderate HTG(n=23)and MD(n=52),the TG levels in the fenofibric acid-treated group decreased by(49.12±29.19)%,(49.95±25.19)%and(49.79±19.28)%,respectively from baseline to 12 weeks,while the corresponding placebo groups decreased by(18.88±40.69)%,(8.11±29.86)%and increased by(10.42±73.04)%,respectively from baseline to 12 weeks.The differences between treatment and placebo groups were statistically significant(P<0.017 for severe HTG cohort,P<0.05 for moderate and MD cohort).The high-density lipoprotein cholesterol(HDL-C)in the fenofibric acid-treated group increased by(25.51±21.45)%,(24.55±24.73)%,and(23.60±27.38)%,and the placebo group increased by(1.91±20.42)%,(2.40±9.32)%and(7.13±19.12)%,respectively,the differences between the two groups were statistically significant(all P<0.05).In the fenofibric acid group,adverse events with incidence>5%included upper respiratory tract infection(10.9%),abdominal pain(6.3%),and increased serum creatinine levels(6.3%),rates of adverse events were similar between the two groups(P>0.05). Conclusions:Fenofibric acid can significantly reduce triglycerides and elevate HDL-C levels safely in Chinese patients with severe to moderate HTG without statin or MD patients on top of statin therapy.

E2F1, a nucleoprotein gene belongs to transcription factor, is closely associated with the development of malignant tumours. Long non-coding RNAs (lncRNAs) are aberrantly expressed in a variety of tumors. In studies of molecular mechanisms associated with lncRNAs and tumours, E2F1 has been identified as a key factor that can play a critical role as an upstream regulator or downstream target of lncRNAs, and even inter-regulate to form a positive feedback loop. This paper reviews the significance of the interaction between E2F1 and lncRNA in malignant tumors in recent years, and aims to provide ideas for the study of tumor mechanisms.

OBJECTIVE: To investigate the effectiveness of arthroscopic autologous iliac bone grafting with double-row elastic fixation in treatment of recurrent anterior shoulder dislocation combined with massive glenoid bone defects. METHODS: Between January 2018 and December 2021, 16 male patients with recurrent anterior shoulder dislocation combined with massive glenoid bone defects were treated with arthroscopic autogenous iliac bone grafting and double-row elastic fixation. The patients were 14-29 years old at the time of the first dislocation, with an average age of 18.4 years. The causes of the first dislocation included falling injury in 5 cases and sports injury in 11 cases. The shoulders dislocated 4-15 times, with an average of 8.3 times. The patients were 17-37 years old at the time of admission, with an average age of 25.1 years. There were 5 left shoulders and 11 right shoulders. The preoperative instability severity index (ISIS) score of the shoulder joint was 5.8±2.1, and the Beighton score was 4.3±2.6. The University of California Los Angeles (UCLA) score, Constant score, American Shoulder and Elbow Surgeons (ASES) score, and Rowe score were used to evaluate shoulder function, and the degree of the glenoid bone defect repair was observed based on CT after operation. RESULTS: All incisions healed by first intention, and no complication such as incision infection or neurovascular injury occurred. The patients were followed up 12 months. At 12 months after operation, UCLA score, Constant score, ASES score, and Rowe score all significantly improved when compared with the scores before operation ( P<0.05). CT imaging showed the degree of glenoid bone defect was significantly smaller at immediate, 6 and 12 months after operation when compared with that before operation ( P<0.05), and the bone blocks healed with the scapula, and bone fusion had occurred at 12 months. CONCLUSION Arthroscopic autologous iliac bone grafting with double-row elastic fixation is a safe treatment for recurrent anterior shoulder dislocation combined with massive glenoid bone defects, with good short-term effectiveness.
Humans ; Male ; Adolescent ; Adult ; Young Adult ; Shoulder Dislocation/surgery* ; Bone Transplantation/methods* ; Arthroscopy/methods* ; Joint Instability/surgery* ; Shoulder Joint/surgery* ; Scapula/surgery* ; Recurrence