High-performance liquid chromatography(HPLC) was used to determine the content of three major components in Citri Reticulatae Semen(CRS), including limonin, nomilin, and obacunone. The chromaticity of the CRS sample during salt processing and stir-frying was measured using a color difference meter. Next, the relationship between the color and content of the salt-processed CRS sample was investigated through correlation analysis. By integrating the oil bath technique for processing simulation with HPLC, the changes in the relative content of nomilin and its transformation products were analyzed, with its structural transformation pattern during processing identified. Additionally, RAW264.7 cells were induced with lipopolysaccharides(LPSs) to establish an inflammatory model, and the anti-inflammatory activity of nomilin and its transformation product, namely obacunone was evaluated. The results indicated that as processing progressed, E~*ab and L~* values showed a downward trend; a~* values exhibited a slow increase over a certain period, followed by no significant changes, and b~* values remained stable with no significant changes over a certain period and then started to decrease. The limonin content remained barely unchanged; the nomilin content decreased, and the obacunone increased significantly. The changing trends in content and color parameters during salt-processing and stir-frying were basically consistent. The content of nomilin and obacunone was significantly correlated with the colorimetric values(L~*, a~*, b~*, and E~*ab), while limonin content showed no significant correlation with these values. By analyzing HPLC patterns of nomylin at different heating temperatures and time, it was found that under conditions of 200-250 ℃ for heating of 5-60 min, the content of nomilin significantly decreased, while the obacunone content increased pronouncedly. The in vitro anti-inflammatory activity results indicated that compared to the model group, the group with a high concentration of nomilin and the groups with varying concentrations of obacunone showed significantly reduced release of nitric oxide(NO)(P<0.01). When both were at the same concentration, obacunone showed better performance in inhibiting NO release. In this study, the obvious correlation between the color and content of major components during the processing of CRS samples was identified, and the dynamic patterns of quality change in CRS samples during processing were revealed. Additionally, the study revealed and confirmed the transformation of nomilin into obacunone during processing, with the in vitro anti-inflammatory activity of obacunone significantly greater than that of nomilin. These findings provided a scientific basis for CRS processing optimization, tablet quality control, and its clinical application.
Mice ; Animals ; Drugs, Chinese Herbal/pharmacology* ; RAW 264.7 Cells ; Limonins/chemistry* ; Chromatography, High Pressure Liquid ; Citrus/chemistry* ; Color ; Benzoxepins/chemistry* ; Anti-Inflammatory Agents/chemistry*

BACKGROUND: At present, biopsy is essential for the diagnosis of prostate cancer (PCa) before radical prostatectomy (RP). However, with the development of prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) and multiparametric magnetic resonance imaging (mpMRI), it might be feasible to avoid biopsy before RP. Herein, we aimed to explore the feasibility of avoiding biopsy before RP in patients highly suspected of having PCa after assessment of PSMA PET/CT and mpMRI. METHODS: Between December 2017 and April 2022, 56 patients with maximum standardized uptake value (SUVmax) of ≥4 and Prostate Imaging Reporting and Data System (PI-RADS) ≥4 lesions who received RP without preoperative biopsy were enrolled from two tertiary hospitals. The consistency between clinical and pathological diagnoses was evaluated. Preoperative characteristics were compared among patients with different pathological types, T stages, International Society of Urological Pathology (ISUP) grades, and European Association of Urology (EAU) risk groups. RESULTS: Fifty-five (98%) patients were confirmed with PCa by pathology, including 49 (89%) with clinically significant prostate cancer (csPCa, defined as ISUP grade ≥2 malignancy). One patient was diagnosed with high-grade prostatic intraepithelial neoplasia (HGPIN). CsPCa patients, compared with clinically insignificant prostate cancer (cisPCa) and HGPIN patients, were associated with a higher level of prostate-specific antigen (22.9 ng/mL vs . 10.0 ng/mL, P = 0.032), a lower median prostate volume (32.2 mL vs . 65.0 mL, P = 0.001), and a higher median SUVmax (13.3 vs . 5.6, P <0.001). CONCLUSIONS It might be feasible to avoid biopsy before RP for patients with a high probability of PCa based on PSMA PET/CT and mpMRI. However, the diagnostic efficacy of csPCa with PI-RADS ≥4 and SUVmax of ≥4 is inadequate for performing a procedure such as RP. Further prospective multicenter studies with larger sample sizes are necessary to confirm our perspectives and establish predictive models with PSMA PET/CT and mpMRI.
Humans ; Male ; Prostatectomy/methods* ; Prostatic Neoplasms/diagnosis* ; Middle Aged ; Aged ; Positron Emission Tomography Computed Tomography/methods* ; Biopsy ; Multiparametric Magnetic Resonance Imaging ; Prostate-Specific Antigen/metabolism*

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Attenuated Salmonella typhimurium VNP20009 is a widely used natural oncolytic bacterium, which has great application potential given its unique characteristics, including clinical safety, tumor targeting specificity, and explicit genome sequence. Here, we show that tumor progression can be effectively reduced by intraperitoneal administration with VNP20009 in a mouse model of melanoma (all animal experiments were conducted in accordance with the Animal Ethics Committee of China Pharmaceutical University); co-culture experiment in vitro demonstrated that VNP20009 can induce the polarization of macrophage M1, accompanied by expression of inflammation-related factors; flow cytometry analysis showed that VNP20009 induced the increase of immune cell infiltration in tumor. Further analysis showed that T cells infiltration in tumor-draining lymph node (TDLN) increased, and VNP20009 induced the activation of CD4⁺ T cells and CD8⁺ T cells in tumor. Our results demonstrate that VNP20009 treatment significantly inhibited melanoma tumors by remodeling tumor-associated macrophages to an M1-like phenotype, as well as recruiting and activating cytotoxic T cells, combined with its own antigenic activity to exert anti-tumor immunity.

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.
Male ; Humans ; Prostate-Specific Antigen ; Treatment Outcome ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Retrospective Studies

OBJECTIVE: To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). METHODS: In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. RESULTS: Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. CONCLUSIONS In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.

ObjectiveTo explore the effect and mechanism of Xiaojindan extract （XJD） on macrophage polarization. MethodLipopolysaccharide （LPS） and interleukin-4 （IL-4） were used to induce M1 and M2 polarization of RAW264.7 cells. The influence of 10-80 mg·L^-1 XJD on cell proliferation was detected by Cell Counting Kit-8 （CCK-8） assay. Nitric oxide （NO） and interleukin-6 （IL-6） release was explored by Griess assay and enzyme-linked immunosorbent assay （ELISA）， respectively. The mRNA expression of M1 and M2 macrophage markers was measured by real-time quantitative polymerase chain reaction （Real-time PCR）， and the CD206⁺ expression was determined by flow cytometry. The activation of phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） pathway was analyzed by western blot. Result10-80 mg·L^-1 XJD showed no marked cytotoxicity in LPS （0.5 mg·L^-1）- or IL-4 （20 μg·L^-1）-induced RAW264.7 cells. Compared with the control group， LPS significantly promoted the expression of M1 macrophage markers （P<0.01）， including increased NO and IL-6 release （P<0.01） and upregulated mRNA expression of interleukin-1β （IL-1β）， inducible nitric oxide synthase （iNOS）， cyclooxygenase-2 （COX-2） and tumor necrosis factor-α （TNF-α） （P<0.01）. Compared with LPS-induced group， 20-80 mg·L^-1 XJD decreased the release of NO and IL-6 in a dose-dependent manner （P<0.01）， and similarly 10-80 mg·L^-1 XJD suppressed the mRNA expression of IL-1β， iNOS， COX-2 and TNF-α （P<0.01）. Compared with the control group， IL-4 obviously increased the expression of M2 macrophage markers （P<0.01）， including increased CD206⁺ cell population and upregulated mRNA expression of arginine-1 （Arg-1）， interleukin-10 （IL-10）， interleukin-13 （IL-13） and transforming growth factor-β₁ （TGF-β₁）. Compared with IL-4-induced group， 10-80 mg·L^-1 XJD dose-dependently decreased CD206⁺ cell population （P<0.01） and inhibited the mRNA expression of Arg-1， IL-10， IL-13 and TGF-β₁ （P<0.01）. Western blot showed that XJD significantly downregulated the activation of PI3K/Akt pathway as compared to LPS- and IL-4-induced groups （P<0.05， P<0.01）. ConclusionXJD significantly inhibited the macrophage polarization in the LPS- and IL-4-induced RAW264.7 cells by targeting PI3K/Akt pathway.

Objective: To analyze the impact of cancer on the recurrence rate of atrial fibrillation (AF) after AF radiofrequency ablation and further evaluate the feasibility of radiofrequency ablation therapy in cancer patients with AF. Methods: This study was a single-center, retrospective study. Cancer patients with AF undergoing radiofrequency ablation for the first time in the First Affiliated Hospital of Dalian Medical University from May 30, 2008 to September 30, 2018 were included (cancer group). AF patients without cancer undergoing radiofrequency ablation for the first time during the same period served as non-cancer group. Clinical data including age, gender, past history, cancer and AF-related parameters, etc. were analyzed. Patients were followed up after radiofrequency ablation. The primary endpoints were AF recurrence or all-cause death. Kaplan-Meier survival analysis was used to analyze the effect of cancers on the recurrence after AF ablation. The multivariate cox regression analysis was further applied to correct for other confounding factors to analyze whether the impact of cancers on the recurrence of atrial fibrillation was statistically significant. Results: A total of 90 patients were enrolled, there were 30 patients in the cancer group (mean age (64.8±6.6) years, 16 (53.3%) males) and 60 patients in the non-cancer group (mean age (63.6±6.2) years, 32 (53.3%) males). Clinical data, such as age, gender, and cancer treatment, were similar between the two groups. During an average follow-up period of (328.7±110.2) days, there were 6 AF recurrences (recurrence rate 20.0%) in the cancer group, and 17 AF recurrences (recurrence rate 28.3%) in the control group. AF recurrence rate was similar between the two groups (P>0.05). During the follow-up period, there was no all-cause death in the two groups. Kaplan-Meier survival analysis showed that cancer was not related to AF recurrence after radiofrequency ablation (P = 0.383). After adjusting for other confounding factors, the multivariate Cox regression analysis showed that cancer was not an independent predictor of AF recurrence after radiofrequency ablation (HR=0.508, 95%CI: 0.192-1.342, P = 0.172). Conclusions: The combination of cancer has no impact on the recurrence of AF after radiofrequency ablation. For cancer patients with AF, radiofrequency ablation therapy can be considered as a feasible heart rhythm control treatment strategy.

Objective:To explore the inhibitory effect and mechanism of Jingulian extract （JGL） on inflammation. Method:The following groups were set up in this study： a control group （10% fetal bovine serum）， a lipopolysaccharide （LPS） model group （0.5 mg·L^-1）， and JGL groups （10， 20， 40， 60， 80， 120， 160， 200， 250， 300 mg·L^-1 + 0.5 mg·L^-1 LPS）. The RAW264.7 cells were cultured for 24 hours. Cell proliferation was detected by cell counting kit-8 （CCK-8） assay. Nitric oxide （NO） release was detected by Griess assay. The release of cytokines interleukin （IL）-1β， IL-6， IL-10， and tumor necrosis factor （TNF）-α was determined by enzyme linked immunosorbent assay （ELISA）. The expression of inducible nitric oxide synthase （iNOS） and intraprostaglandin peroxidase synthase 2 （PTGS2）/cyclooxygenase-2 （COX-2） was measured by real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR） and the activation of key proteins in the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway by Western blot. Result:Compared with the control group， LPS （0.5 mg·L^-1）could promote the proliferation of RAW264.7 cells after stimulation for 24 hours （P<0.01）. Compared with the model group， JGL had no significant effect on cell proliferation. Compared with the control group， LPS （0.5 mg·L^-1）increased the release of NO， IL-1β， IL-6， IL-10， and TNF-α （P<0.01）. Compared with the model group， JGL （20-300 mg·L^-1）inhibited the release of NO in a dose-dependent manner after stimulation for 24 hours （P<0.05） and reduced IL-1β， IL-6， and IL-10 （P<0.05， P<0.01）， but no obvious inhibition on the release of TNF-α was observed. LPS （0.5 mg·L^-1） could induce the expression of iNOS and PTGS2/COX-2 genes as compared with the control group （P<0.05， P<0.01）. JGL could down-regulate the mRNA expression of iNOS and PTGS2/COX-2 genes as compared with the model group （P<0.05， P<0.01）. LPS （0.5 mg·L^-1） could activate the PI3K/Akt pathway （P<0.01） as compared with the control group， while JGL （10， 20， 40， and 80 mg·L^-1） decreased the expression of PI3K-p110， p-p85， and p-Akt （P<0.01）， and inhibited the activation of PI3K/Akt pathway. Conclusion:JGL extract could significantly inhibit the inflammatory response and activation of the PI3K/Akt pathway induced by LPS in RAW264.7 cells. The anti-inflammatory effect was related to the inhibition of the PI3K/Akt pathway.