OBJECTIVE To explore the application effects of the multi-disciplinary treatment （MDT）-based continuous pharmaceutical care system in patients undergoing anti-infection treatment. METHODS This research team innovatively developed an MDT continuous pharmaceutical care system， which was applied to cases of anti-infection treatment following MDT due to infection， aiming to innovate the continuous medication supervision model. A retrospective analysis method was used to collect data from 150 patients in the intensive care unit who underwent conventional anti-infection MDT consultations from January to October 2021 in Banan Hospital Affiliated to Chongqing Medical University， serving as the control group， and 130 patients in the intensive care unit who were under the MDT continuous pharmaceutical care system from January to October 2022 were selected as the intervention group. The general information of the patients， the information continuous tracking management， the outcomes of anti- infection treatment， adverse drug reactions， antibacterial drug management indicators， and the degree of satisfaction of relevant medical staff with the clinical pharmacists’ pharmaceutical services were compared between the two groups. RESULTS Comparison of general information between the two groups showed no statistically significant differences （P＞0.05）. The proportion of continuous tracking management in the intervention group was significantly higher than in the control group （P＜0.01）， and the differences in the initiators and reasons for continuous tracking management between the two groups were statistically significant （P＜0.05）. The intervention group had better outcomes in anti-infection treatment compared to the control group （P＜0.05）. The antibacterial drug management indicators （total length of hospital stay， duration of antibacterial drug use， total drug costs， and amount of antibacterial drugs used） in the intervention group were significantly lower than in the control group， while overall degree of satisfaction among medical staff was significantly higher in the intervention group than in the control group （P＜0.05）. No statistically significant differences were found in adverse reaction occurrence and antibacterial drug costs between the two groups （P＞0.05）. CONCLUSIONS The application of this system in patients who underwent anti-infection treatment after MDT can achieve continuous multi-disciplinary tracking management with clinical pharmacists at the core， which is beneficial for promoting the follow-up efficiency of the MDT team， raising the quality of clinical pharmacists’ pharmaceutical services， strengthening treatment outcomes， and promoting the rational use of antibacterial drugs in clinical practice.

Aim To study the resistance of SIRT3 ex-pression in dopaminergic neurons against the inflamma-tory damage caused by microglia activation and its re-lated mechanism.Methods Dopaminergic neurons(MN9D cells)and microglia(BV-2 cells)were co-cultured to establish an inflammatory injury model in vitro.MN9D cells were divided into the control group,model group,SIRT3 group and SIRT3+PJ34 group.mRNA levels were analyzed by real-time quantitative polymerase chain reaction,cell apoptosis rate was de-tected by flow cytometry,changes in mitochondrial membrane potential were tested by JC-1 method,and the opening of mitochondrial permeability transport pore(mPTP)was analyzed by co-incubation of calce-in-AM and CoCl2.The protein expression was detected by Western blot.Results Compared to the model group,overexpression of SIRT3 in the SIRT3 group significantly reduced the apoptosis rate of MN9D cells.It also led to a significant increase in the expression of SIRT3 and SOD2 genes,as well as a notable decrease in PARP-1,tumor necrosis factor-α,and interleukin 1β(IL-1β)protein expressions.Moreover,it resulted in a substantial reduction in the p-NF-κB p65/NF-κB p65 ratio.There was an improvement observed in mito-chondrial membrane potential along with decreased mPTP opening and ROS production in the SIRT3 group.These differences among these groups were sta-tistically significant(all P＜0.05).After inhibiting PARP-1 activity of MN9D cells in the SIRT3+PJ34 group,except for the insignificant changes in SIRT3 and IL-1 β protein expression,the changing trend of other indicators was further enhanced on the basis of SIRT3 group.The differences between two groups re-mained statistically significant(all P＜0.05).Con-clusions SIRT3 expression can attenuate the inflam-matory damage of dopaminergic neurons induced by microglia activation,and the mechanism may be relat-ed to improving mitochondrial function,inhibiting PARP-1 activity and NF-κB signaling pathway caused by the reduction of ROS production.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

ObjectiveTo investigate the effects of different cultivation modes on the yield of Gentiana crassicaulis and its microbial diversity and secondary metabolite content in the rhizosphere soil. MethodWith G. crassicaulis of different cultivation modes and its rhizosphere soil as the research objects， the composition of bacterial and fungal communities， dominant bacteria， and differential microorganisms in the rhizosphere soil were analyzed by high-throughput sequencing technology. HPLC was used to determine the content of iridoids in G. crassicaulis with different cultivation modes. ResultCompared with plastic film mulching， planting without mulch and intercropping of peony， white kidney bean， potato， and corn increased the yield of fresh products by 16.11%-17.68%， 22.48%-26.34%， 29.37%-32.19%， 34.82%-36.57%， and 35.34%-39.71%， respectively， and increased the yield of dry products by 19.75%-23.17%， 25.86%-29.32%， 30.18%-34.94%， 35.22%-39.87%， and 39.72%-43.73%. The total content of four iridoids， including gentiopicrin， loganic acid， sweroside， and swertiamarin， increased by 10.17%-37.83%， 5.93%-47.44%， 9.09%-28.84%， and 10.71%-28.57%， respectively. The diversity of bacterial and fungal communities in the rhizosphere soil increased significantly （P<0.05）. The relative abundance of pathogenic bacteria such as Sordariomycetes， Leotiomycetes， Tremellomycetes， Eurotiomycetes， Fusarium， and Cladophialophora decreased， and the proportions of beneficial bacteria such as Proteobacteria， Acidobacteria， and Actinobacteriota increased and they gradually became the dominant bacteria. ConclusionDifferent cultivation modes can affect the yield of G. crassicaulis and its microbial diversity and iridoid content in the rhizosphere soil. Cultivation without mulch and intercropping patterns have certain advantages， which can provide theoretical references for the planting of G. crassicaulis.

Inflammatory bowel disease (IBD) is a formidable disease due to its complex pathogenesis. Macrophages, as a major immune cell population in IBD, are crucial for gut homeostasis. However, it is still unveiled how macrophages modulate IBD. Here, we found that LIM domain only 7 (LMO7) was downregulated in pro-inflammatory macrophages, and that LMO7 directly degraded 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) through K48-mediated ubiquitination in macrophages. As an enzyme that regulates glycolysis, PFKFB3 degradation led to the glycolytic process inhibition in macrophages, which in turn inhibited macrophage activation and ultimately attenuated murine colitis. Moreover, we demonstrated that PFKFB3 was required for histone demethylase Jumonji domain-containing protein 3 (JMJD3) expression, thereby inhibiting the protein level of trimethylation of histone H3 on lysine 27 (H3K27me3). Overall, our results indicated the LMO7/PFKFB3/JMJD3 axis is essential for modulating macrophage function and IBD pathogenesis. Targeting LMO7 or macrophage metabolism could potentially be an effective strategy for treating inflammatory diseases.

OBJECTIVE: To investigate the correlation between the human epidermal growth factor receptor-2-related genes (HRGs) and survival prognosis of bladder cancer and to construct a predictive model for survival prognosis of bladder cancer patients based on HRGs. METHODS: HRGs in bladder cancer were found by downloading bladder tumor tissue mRNA sequencing data and clinical data from the cancer genome atlas (TCGA), downloading HER-2 related genes from the molecular signatures database (MsigDB), and crossing the two databases. Further identifying HRGs associated with bladder cancer survival (P < 0.05) by using single and multi-factor Cox regression analysis and constructing HRGs risk score model (HRSM), the bladder cancer patients were categorized into high-risk and low-risk groups accor-ding to the median risk score. Survival analysis of the patients in high- and low-risk groups was conducted using R language and correlation of HRGs with clinical characteristics. A multi-factor Cox regression analysis was used to verify the independent factors affecting the prognosis of the patients with bladder cancer. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) of HRSM was calculated, and a nomogram was constructed for survival prediction of the bladder cancer patients. Analysis of HRSM and patient immune cell infiltration correlation was made using the TIMER database. RESULTS: A total of 13 HRGs associated with patient survival were identified in this study. Five genes (BTC, CDC37, EGF, PTPRR and EREG) were selected for HRSM by multi-factor Cox regression analysis. The 5-year survival rate of the bladder cancer patients in the high-risk group was significantly lower than that of the patients in the low-risk group. High expression of PTPRR was found to be significantly and negatively correlated with tumor grade and stage by clinical correlation analysis, while EREG was found to be the opposite; Increased expression of EGF was associated with high grade, however, the high expression ofCDC37showed the opposite result. And no significant correlation was found between BTC expression and clinical features. Correlation analysis of HRSM with immune cells revealed a positive correlation between risk score and infiltration of dendritic cells, CD8⁺T cells, CD4⁺T cells, neutrophils and macrophages. CONCLUSION HRGs have an important role in the prognosis of bladder cancer patients and may serve as new predictive biomarkers and potential targets for treatment.
Humans ; Epidermal Growth Factor ; Prognosis ; Urinary Bladder Neoplasms/genetics* ; Nomograms ; Urinary Bladder

Aim To study the regulation and mechanism of phloroglucinol in bladder smooth muscle spasm. Methods In vitro the experiment used bladder muscle strip to verify the relieving effect of phloro-glucinol on bladder spasm by different drugs. At the same time,RT-qPCR and Western blot were used to detect the expression levels of genes involved in the calcium signaling pathway caused by the antispasmodic effect of phloroglucinol. Results Phloroglucinol could relieve bladder spasm, and the antispasmodic effect was enhanced with the increase of concentration, and the expression of calponin 1 and MYLK3 in tissue cells increased. The results of RT-qPCR showed that the expression of Gprc5b G,Ppp2r5a, Chptl, Prkar2b ,Abcd2 and Rasdl genes in mouse bladder tissue significantly decreased, which was consistent with the sequencing results of RNA-seq.Conclusions Phloroglucinol can relieve bladder smooth muscle spasm, and its mechanism is related to calcium signaling pathway. Meanwhile, phloroglucinol also inhibits the expression of Rasdl gene, suggesting that it may be related to cell cycle , protein phosphorylation, choline metabolism, ATP synthesis and tumor-related pathways.

In the wake of the COVID-19 pandemic, only through whole-hearted cooperation and joined efforts can medical institutions, governments, and social organizations cope with emergency, convert the crisis into opportunities, promote modern governance and accomplish high-quality development in the fight against the pandemic. Taking the First Affiliated Hospital of Xi’an Jiaotong University as an example, this paper analyzes the all-media communication matrix of "one network platform, 3W + N" that the hospital established during the pandemic by combining the authoritative official website with WeChat, Wesee, Weibo and that other publicity media. The study explores how to create a publicity brand that is mindful, poignant, compassionate and devoted and maintains its scientific and refined management, so as to achieve the professional goal of educating the public, shouldering the responsibility in the combat against the pandemic, and taking the lead in the research on the pandemic.

OBJECTIVE: To explore the genetic basis of a child with congenital heart disease (CHD). METHODS: Clinical examination of the child was carried out. Chromosomal microarray analysis (CMA) and quantitative PCR were carried out to detect copy number variations. RESULTS: The major features of the child included CHD (ventricular septal defect, severe pulmonary hypertension, tricuspid regurgitation, patent ductus arteriosus, and patent foramen ovale), severe pneumonia and liver failure. A de novo 3.2 Mb deletion encompassing 25 genes in 13q34 and a paternal 2.2 Mb duplication in 19p13.3 were revealed by CMA and qPCR. CONCLUSION The 13q34 region probably contains susceptibility genes for CHD.
Child ; Chromosome Deletion ; Chromosome Disorders ; Chromosomes, Human, Pair 13 ; DNA Copy Number Variations ; Heart Defects, Congenital ; Humans

OBJECTIVE: Pyroptosis is an inflammatory form of programmed cell death. This phenomenon has been recently reported to play an important role in radiation-induced normal tissue injury. Connexin43 (Cx43) is a gap junction protein that regulates cell growth and apoptosis. In this study, we investigated the effect of Cx43 on X-ray-induced pyroptosis in the human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs, Cx43 overexpression, and Cx43 knockdown strains were irradiated with 10 Gy. Proteins were detected using western blot analysis. Cell pyroptosis was evaluated using the fluorescence-labeled inhibitor of caspase assay (FLICA) and propidium iodide staining through flow cytometry and confocal microscopy. Cell morphology and cytotoxicity were detected by scanning electron microscopy and lactate dehydrogenase release assay, respectively. RESULTS: Irradiation with 10 Gy X-ray induced pyroptosis in the HUVECs and reduced Cx43 expression. The pyroptosis in the HUVECs was significantly attenuated by overexpression of Cx43 as it decreased the level of active caspase-1. However, interference of Cx43 expression with siRNA significantly promoted pyroptosis by increasing the active caspase-1 level. Pannexin1 (Panx1), a gap junction protein regulates pyroptosis, and its cleaved form is used to evaluate channel opening and active state. The level of cleaved Panx1 in the HUVECs and Cx43 knockdown strains increased in the presence of X-ray, but decreased in the Cx43 overexpression strains. Furthermore, interference of Panx1 with siRNA alleviated the upregulation of pyroptosis caused by Cx43 knockdown. CONCLUSION Results suggest that single high-dose X-ray irradiation induces pyroptosis in the HUVECs. In addition, Cx43 regulates pyroptosis directly by activating caspase-1 or indirectly by cleaving Panx1.
Caspase 1 ; genetics ; metabolism ; Connexin 43 ; genetics ; metabolism ; Connexins ; genetics ; metabolism ; Gene Expression Regulation ; radiation effects ; Human Umbilical Vein Endothelial Cells ; physiology ; radiation effects ; Humans ; Nerve Tissue Proteins ; genetics ; metabolism ; Pyroptosis ; X-Rays ; adverse effects