Extracting extracts of secondary metabolites from the karst cave fungus Metarhizium anisopliae NHC-M3-2 from the Yilingyan Scenic Area in Guangxi. Ten compounds were isolated and purified from fungal secondary metabolites using thin-layer chromatography and high-performance liquid chromatography. 7-Hydroxy-3-hydroxypropyl-5,6-dimethylisochrome-1-one (1) and 7-hydroxy-3,5,6-trimethyl-isochromen-1-one (2) were new isocoumarin compounds, N-acetyl phenylalanine (3), chaetosumin J (4), 2-one-13-hydroxy-3,5,8,7(11)-eudesmatetraen-12,8-olide (5), 1H-indole-3-carboxaldehyde (6), irpexolaceus B (7), irlactin L (8), cytochalasin K (9), and helvolic acid (10), a total of 8 known compounds. The structure of the compound was determined using methods such as NMR and mass spectrometry. The tumor cytotoxicity of the compound was evaluated using the CCK-8 method. The results showed that the IC₅₀ of compound 2 on HepG2 cells was 29.83 µmol·L^-1, and compound 9 on HCT116 cells was 27.44 µmol·L^-1.

Objective In this study,inbred BALB/c mice infected with the pneumonia virus of mice(PVM)were used to establish an animal model of viral pneumonia,and the changes in the pro-inflammatory alarmin molecule,high mobility group box 1 protein(HMGB1),during PVM infection were observed,as well as the in vivo intervention effects of the HMGB1 inhibitor,glycyrrhizic acid(GA),on PVM-induced lung injury.Methods Three-week-old female BALB/c mice were randomly divided into three groups,each consisting of 6 mice.One group,uninfected by PVM,served as the control group(Control).The other two groups were inoculated intranasally with PVM at a dose of 1×104 50％tissue culture infective dose(TCID50)/25 μL,and subsequently treated with GA saline solution(GA group)or plain saline solution(normal saline,NS group)via gavage for 15 consecutive days.During this period,changes in body weight and appearance were monitored in each group.At the end of the experiment,lung tissue samples were collected from all groups.The distribution of PVM and HMGB1 proteins in the lung tissues was analyzed using hematoxylin-eosin staining and immunohistochemistry.The expression levels of HMGB1 and its Toll-like receptor 4(TLR-4),advanced glycosylation end-product-specific receptor(AGER),and inflammatory cytokines such as interleukin(IL)-1β,IL-2,and tumor necrosis factor-α(TNF-α)in lung tissues of mice were measured using real time fluorescence quantitative PCR.Results Compared with the Control group,the NS group showed a significant weight loss after 6 days(P＜0.05).Histopathological tests revealed pronounced inflammatory lesions in their lungs.Immunohistochemistry results showed that HMGB1 was released from the nucleus to the cytoplasm,and real time fluorescence quantitative PCR results indicated that the expression levels of HMGB1,IL-1β,and IL-2 were significantly upregulated(P＜0.05).In the GA group,there was no significant change in the clinical symptoms or body weight.However,compared with the NS group,the pathological damages of lung tissues in the GA group were significantly reduced,and the expression levels of HMGB1,IL-1 β,IL-2,and interferon-γ(IFN-γ)in lung tissues were also significantly decreased(P＜0.05),although the expression level of AGER was significantly increased(P＜0.05).Conclusion PVM infection can cause significant inflammatory pathological lung damages in mice,and GA can effectively alleviate the damages.Its therapeutic effect may be related to the activation of HMGB1 signaling pathway.

Objective:To investigate the morphological difference and clinical significance of bilateral lumbar multifidus muscles in patients with unilateral lumbosacral radiculopathy due to lumbar disc herniation and lumbar spondylolisthesis.Methods:A retrospective analysis was conducted on patients with low back pain, lumbar disc herniation and lumbar spondylolisthesis. Patients with lumbar disc herniation or lumbar spondylolisthesis underwent single segment lesion either at L 4, 5 or L 5S 1, while those accompanied with unilateral lumbosacral radiculopathy underwent percutaneous endoscopic lumbar discectomy or conventional open surgery at Qingdao Municipal Hospital between January 2017 and January 2023. Patients with lumbar spondylolisthesis were subdivided into degenerative lumbar spondylolisthesis and isthmic spondylolisthesis. 53 patients with low back pain met the inclusion criteria. 170 patients with lumbar disc herniation met the inclusion criteria, with 101 at L 4, 5 and 69 at L 5S 1 level. 129 patients with lumbar spondylolisthesis met the inclusion criteria, including 91 of degenerative lumbar spondylolisthesis at L 4, 5 level and 9 at L 5S 1 level, and 11 of isthmic spondylolisthesis at L 4, 5 level and 18 at L 5S 1 level. Cross-sectional images at the mid-disc of L 3, 4, L 4, 5 and L 5S 1 segments in MRI were acquired. Relative total cross-sectional area (rTCSA), relative functional cross-sectional area (rFCSA), fat infiltration rate (FIR), relative fat distance (rFD) and differential value FIR (D-FIR) in bilateral lumbar multifidus muscle were measured respectively by using Image J software, and were then used to evaluate the atrophy and fat infiltration of bilateral lumbar multifidus muscles. Results:No significant difference was found between the both sides of multifidus muscle in low back pain patients. L 4, 5 lumbar disc herniation group had smaller rFCSA (0.34±0.10 and 0.35±0.10) and larger FIR [29.92(22.21, 36.46) and 26.48(17.54, 34.55)] and rFD [0.39(0.29, 0.54) and 0.32(0.21, 0.43)] on the affected side compared to the unaffected side in L 4, 5 segment, and had larger FIR (34.83±11.34 and 31.44±10.94) and rFD [0.59(0.43, 0.77) and 0.51(0.37, 0.69)] on the affected side in L 5S 1 segment. L 5S 1 lumbar disc herniation group had smaller rFCSA (0.41±0.11 and 0.42±0.12) and larger FIR [26.84(22.92, 35.29) and 24.02(20.03, 32.87)] and rFD (0.51±0.28 and 0.42±0.26) on the affected side in L 5S 1 segment. L 4, 5 degenerative lumbar spondylolisthesis group had larger FIR (36.49±9.76 and 34.72±9.86) on the affected side in L 4, 5 segment, and had larger FIR [35.03(28.64, 41.85) and 33.34(26.37, 39.76)] on the affected side in L 5S 1 segment. L 5S 1 degenerative lumbar spondylolisthesis group had larger FIR [42.53(37.94, 46.81) and 40.79(30.84, 43.53)] and rFD (1.12±0.79 and 0.94±0.79) on the affected side in L 5S 1 segment. L 4, 5 isthmic spondylolisthesis group had smaller rFCSA [0.24(0.20, 0.30) and 0.29(0.23, 0.34)]and larger FIR [34.19 31.30, 42.39) and 29.43(28.82, 36.89)] and rFD (0.39±0.15 and 0.29±0.15) on the affected side in L 4, 5 segment, and had larger FIR (43.18±12.71 and 34.12±11.63) on the affected side in L 5S 1 segment. L 5S 1 isthmic spondylolisthesis group had larger FIR (40.24±9.34 and 36.37±10.70) on the affected side in L 5S 1 segment. No significant difference was found of the multifidus muscle between the affected and unaffected sides in the proximal adjacent segment of the responsible segment in lumbar disc herniation or lumbar spondylolisthesis group patients. L 4, 5 isthmic spondylolisthesis group had larger D-FIR (6.75±8.46 and 1.78±5.77) in L 4, 5 segment, and had larger D-FIR (9.06±11.59 and 1.54±7.08) in L 5S 1 segment compared to L 4, 5 degenerative lumbar spondylolisthesis group. Grade Ⅱ L 4, 5 lumbar spondylolisthesis group had larger D-FIR (10.73±13.61 and 1.92±7.43) in L 5S 1 segment compared to grade Ⅰ L 4, 5 lumbar spondylolisthesis group. Conclusion:L 4, 5 or L 5S 1 lumbar disc herniation and lumbar spondylolisthesis patients with unilateral lumbosacral radiculopathy had asymmetric atrophy and fat infiltration of multifidus muscle. The atrophy and fat infiltration on the affected side showed greater. The asymmetry appeared in the responsible segment and its distal adjacent lumbar segment. Lumbar spondylolisthesis patients with a lager degree of slip or with isthmic type could be accompanied by more severe asymmetry of multifidus muscle.

Objective To explore the important factors influencing organ donation willingness and coordination effect of organ donation coordinators. Methods A questionnaire survey was conducted among 349 national organ donation coordinators by convenience sampling, including 145 males and 204 females, aged 27 (23, 36) years. Multiple linear regression and disordered logistic regression were used to investigate the important factors influencing the willingness to donate organs and coordination effects. Results Among 349 organ donation coordinators, 146 (41.8%) were willing to donate organs, including 101 (28.9%) who had signed the consent card for organ donation. Adequate awareness of organ donation laws, high education level, marital experience, and good self-perceived health status all showed positive effects on organ donation willingness of organ donation coordinators (all P < 0.05). High income, long length of service as organ donation coordinators, full-time mode of employment, high willingness to donate organs, and adequate awareness of donation conditions and donation procedures all showed positive effects on the coordination effect of organ donation coordinators (all P < 0.05). Conclusions The willingness to donate organs is increased as the higher awareness of organ donation laws of organ donation coordinators, while enhancing the willingness to donate organs of organ donation coordinators exerts positive impact upon improving the coordination effect of organ donation coordination. Therefore, an all-round organ donation coordinator training system should be established to improve the success rate of organ donation advocacy and promote the development of organ donation.

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Objective: To investigate the effect of Porphyromonas gingivallis ( Pg) infection of esophageal cancer cells on the polarization of tumor associated macrophages (TAMs) and functional changes. Methods: The secretion of tumor⁃related cytokines in the supernatant of Pg infected and uninfected esophageal squamous cell carcinoma (ESCC) cells was detected by ELISA. A co⁃culture model of ESCC cells and macrophages in vitro was established ,and the changes of TAMs surface markers were detected by qPCR , cellular immunofluorescence and flow cytometry. Cytokines secreted by TAMs after co⁃culture were detected by ELISA. ESCC cells were cultured using conditioned medium of co⁃cultured TAMs , and the effects of TAMs on the proliferation , migration and invasion of esophageal cancer cells were evaluated by CCK⁃8 , Wound⁃healing assay and Transwell assay. Results: The expression quantity of IL⁃6 and IL⁃10 of Pg⁃infected ESCC cells increased (P < 0. 01) . The contents of CD163 and CD206 on the surface of TAMs co⁃cultured with Pg⁃infected ESCC cells increased (P < 0. 001) . The cytokines IL⁃6 and IL⁃10 secreted by TAMs co⁃cultured with Pg⁃infected ESCC cells relatively increased (P < 0. 01) . TAMs co⁃cultured with Pginfected ESCC cells were able to enhance ESCC cells proliferation , migration and invasion (all P < 0. 05) . Conclusion Pg infection of ESCC cells can induce the secretion of cytokines , remodel TAMs to polarize toward the M2type immunosuppressive phenotype , thereby promoting the malignant biological behavior of ESCC cells. This study provides data support for the etiology of esophageal cancer and potential target molecules for clinical immunotherapy targeting TAMs.

Articular cartilage (AC) injuries often lead to cartilage degeneration and may ultimately result in osteoarthritis (OA) due to the limited self-repair ability. To date, numerous intra-articular delivery systems carrying various therapeutic agents have been developed to improve therapeutic localization and retention, optimize controlled drug release profiles and target different pathological processes. Due to the complex and multifactorial characteristics of cartilage injury pathology and heterogeneity of the cartilage structure deposited within a dense matrix, delivery systems loaded with a single therapeutic agent are hindered from reaching multiple targets in a spatiotemporal matched manner and thus fail to mimic the natural processes of biosynthesis, compromising the goal of full cartilage regeneration. Emerging evidence highlights the importance of sequential delivery strategies targeting multiple pathological processes. In this review, we first summarize the current status and progress achieved in single-drug delivery strategies for the treatment of AC diseases. Subsequently, we focus mainly on advances in multiple drug delivery applications, including sequential release formulations targeting various pathological processes, synergistic targeting of the same pathological process, the spatial distribution in multiple tissues, and heterogeneous regeneration. We hope that this review will inspire the rational design of intra-articular drug delivery systems (DDSs) in the future.

Objective To characterize the species of invasive Pomacea snails that were discovered for the first time in Shandong Province. Methods Pomacea snails samples were collected in the field of Jining City, Shandong Province on October 2021 for morphological identification. Pomacea snails were randomly sampled and genomic DNA was extracted from foot muscle tissues of Pomacea snails for multiplex PCR amplification. The PCR amplification product was sequenced. Then, the sequence was aligned and a phylogenetic tree was created using the software MegAlign 7.1.0. In addition, Angiostongylus cantonensis infection was detected in Pomacea snails with the lung microscopy. Results A total of 104 living Pomacea snails were collected, and all were characterized as Pomacea spp. based on morphological features. Of 12 randomly selected adult Pomacea snails, multiplex PCR assay and sequencing identified eleven snails as P. canaliculata and one as P. maculata. No A. cantonensis infection was detected in 104 Pomacea snails. Conclusion This is the first report of invasive Pomacea snails in Shandong Province, where P. canaliculata and P. maculata are found.

Objective To investigate the influence of perceptions and emotional attitudes on the public's willingness to organ donation and its path of promotion. Methods The mediation effect and structural equation models were established through the convenience sampling method and with ABC attitude model as the theoretical basis to analyze the influence of perceptions and emotional attitudes on the public's willingness to organ donation and the path of promotion. Results Among 4 565 investigated subjects, 621 subjects expressly stated that they were not willing to donate their organs after the death, 701 subjects were willing to donate their organs after the death, but only 259 investigated subjects signed the informed content card of organ donation. The differences in the subjects' willingness to donate their organs were statistically significant in terms of different genders, ages, religious beliefs, places of residence and educational degrees (all P < 0.05). The overall Cronbach's α coefficient of the questionnaire was 0.781, KMO=0.842, with good reliability and validity. In the structural equation model, the path coefficient of perceptions on the willingness to donation was 0.39, while that of attitudes on the willingness was 0.25. As such, perceptions and emotional attitudes had positive impacts on the willingness to donate the organs. The results of the mediation effect model indicated that attitudes played significant mediation effects in the causality relationship of perceptions on the willingness to donate organs, and the mediation effect value was 0.035(P < 0.01). The awareness degree of organ donation was the largest determinant to the perception factor, and the path coefficient on the willingness to donation was 0.20. The sense of social honor was the largest determinant to the attitude factor, and the path coefficient was 0.16. Conclusions Both perceptions and emotional attitudes positively impact the willingness to donate organs. The awareness degree of organ donation is the largest determinant to the perception factor, while the sense of social honor is the largest determinant to the attitude factor. To improve the public's perception level towards the organ donation and increase the public's sense of social honor towards organ donation contributes to the improvement of the public's willingness to donate organs.