Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease that is often accompanied by mental health disorders. However, the potential mechanisms underlying the heterogeneous clinical presentation of CP/CPPS remain uncertain. This study analyzed widely targeted metabolomic data of expressed prostatic secretions (EPS) and plasma to reveal the underlying pathological mechanisms of CP/CPPS. A total of 24 CP/CPPS patients from The Second Nanning People's Hospital (Nanning, China), and 35 asymptomatic control individuals from First Affiliated Hospital of Guangxi Medical University (Nanning, China) were enrolled. The indicators related to CP/CPPS and psychiatric symptoms were recorded. Differential analysis, coexpression network analysis, and correlation analysis were performed to identify metabolites that were specifically altered in patients and associated with various phenotypes of CP/CPPS. The crucial links between EPS and plasma were further investigated. The metabolomic data of EPS from CP/CPPS patients were significantly different from those from control individuals. Pathway analysis revealed dysregulation of amino acid metabolism, lipid metabolism, and the citrate cycle in EPS. The tryptophan metabolic pathway was found to be the most significantly altered pathway associated with distinct CP/CPPS phenotypes. Moreover, the dysregulation of tryptophan and tyrosine metabolism and elevation of oxidative stress-related metabolites in plasma were found to effectively elucidate the development of depression in CP/CPPS. Overall, metabolomic alterations in the EPS and plasma of patients were primarily associated with oxidative damage, energy metabolism abnormalities, neurological impairment, and immune dysregulation. These alterations may be associated with chronic pain, voiding symptoms, reduced fertility, and depression in CP/CPPS. This study provides a local-global perspective for understanding the pathological mechanisms of CP/CPPS and offers potential diagnostic and therapeutic targets.
Humans ; Male ; Prostatitis/blood* ; Adult ; Pelvic Pain/blood* ; Metabolomics ; Prostate/metabolism* ; Middle Aged ; Chronic Pain/blood* ; Metabolome ; Case-Control Studies ; Tryptophan/blood* ; Depression/blood* ; Oxidative Stress/physiology* ; Chronic Disease ; Lipid Metabolism/physiology*

Three-dimensional ordered porous carbon materials exhibit potential application prospects as excellent drug supports in drug delivery systems due to their high specific surface area, tunable pore structure, and excellent biocompatibility. In this study, three-dimensional ordered porous carbon materials were prepared using Acanthopanax senticosus herbal residues as raw material and KOH as activating agent through a one-step pyrolysis method. The prepared carbon-based material was systematically characterized by powder X-ray diffraction, scanning electron microscopy, N₂ adsorption-desorption and Fourier-transform infrared spectroscopy. The results show that the three-dimensional ordered porous carbon materials prepared with KOH as the activator via pyrolysis possess abundant functional groups, high porosity, and high specific surface area, with a specific surface area of 1 471.6 m²·g^-1. The three-dimensional ordered porous carbon materials prepared at 800 ℃ exhibits a high drug loading capacity (78.0%) and drug release rate (86.8%) for 5-fluorouracil. Three-dimensional orderly porous carbon materials show significant application advantages in drug construction, and their high specific surface area and adjustable pore size structure significantly improve the drug load rate and drug release rate, providing a solid foundation for the development of efficient and accurate drug delivery system.

Tropane alkaloids (TAs) are a class of anticholinergic drugs widely used in clinical practice and mainly extracted from plant, among which Atopa belladonna is the main commercial drug source. It is of great industrial value to obtain TAs in large quantities by plant metabolic engineering. In TAs pathway, cytochrome oxidase CYP82M3 catalyze the synthesis of tropinone and then tropinone reductase I (TRI) compete with TRII for tropinone to form tropine leading to the TAs synthesis (drainage). In this study, based on the "increasing flow and drainage" metabolic engineering strategy, two genes, namely HnCYP82M3 and DsTRI from Hyoscyamus niger and Datura stramonium, respectively, were overexpressed in the hair roots of A. belladonna, with a view to promote the TAs accumulation. The HnCYP82M3 gene was cloned from the root of H. niger, and it encoded amino acid with 91.7% sequence identity with AbCYP82M3 from A. belladonna. Overexpression of HnCYP82M3 alone did not affect the content of TAs in hair roots of A. belladonna, indicating that CYP82M3 was not a key enzyme in TAs biosynthesis. Simultaneous overexpression of HnCYP82M3 and DsTRI greatly promoted the accumulation of the three TAs, and the contents of hyoscyamine, anisodamine and scopolamine were 4.97 times, 2.83 times and 2.19 times that of the control, respectively, and the increase amplitude was greater than that of single overexpression of DsTRI. This study showed that the "increasing flow and drainage" strategy of enzyme genes co-expression at branch points was a promising metabolic engineering method to effectively improve the biosynthesis of TAs in A. belladonna, and laid a theoretical and technical foundation for the large-scale industrial acquisition of TAs.

Objective To establish an ultra-high performance liquid phase tandem triple quadrupole mass spectrometry method for the determination of L-synephrine in rat plasma and to study its pharmacokinetics.Methods The plasma samples were precipitated by acetonitrile vortex,centrifuged,dried by nitrogen,dissolved by mobile phase,and then analyzed.Chromatographic column:Shiseido CAPCELL PAK CR(1∶4)column(2.0 mm × 150.0 mm,5 μm),temperature:25 ℃.Mobile phase:Acetonitrile:0.1％formic acid solution(containing 10 mmoL·L-1 ammonium formate)(73∶27)with flow rate:0.3 mL·min-1 and injection volume was 2 μL.The electrospray ion source ionization and positive ion multiple reaction monitoring mode were used for mass spectrometry detection,and biological sample methodology verification was carried out according to requirements.After intragastric administration with 5 mg·kg-1 dose of L-synephrine,blood samples were collected at different time points to investigate the pharmacokinetic characteristics of L-synephrine in rats.Results L-synephrine showed a good linear relationship in the range of 2-800 ng·mL-1,the lowest limit of quantification of L-synephrine was 2 ng·mL-1.Precision,extraction recovery,matrix effect,accuracy,dilution effect and residual effect all meet the requirements all met the requirements.The main pharmacokinetic parameters:Cmax were(464.83±76.68)ng·L-1,tmax were(0.67±0.26)h,t1/2z were(1.89±0.48)h,AUC0-t were(602.26±42.25)ng·mL-1·h-1,AUC0-∞ were(612.28±41.18)ng·mL-1·h-1.Conclusion The established ultra high performance liquid chromatography-tandem triple quadrupole mass spectrometry method for the determination of L-synephrine in rat plasma is simple and rapid,and can be used for the determination of L-synephrine in plasma.

Objective To observe the sedative and analgesic effects of bupivacaine hydrochloride injection combined with neostigmine methylsulfate injection in critically ill patients after general anesthesia operation.Methods Acute and critical patients who were to undergo general anesthesia were randomly divided into control group and treatment group.Two groups received general anesthesia combined with epidural block anesthesia.After operation,the control group was continuously pumped 0.75％bupivacaine hydrochloride injection 45 mL through the epidural catheter,the treatment group was given 2 μg·kg-1 neostigmine methylsulfate injection on the basis of continuous pumping of bupivacaine injection through epidural catheter in the control group.Comparing the pain numerical rating scale(NRS)for 12 h,24 h,48 h,and 72 h of postoperative analgesia and the Ramsay sedation scores(Ramsay),hemodynamic index and safety in the two groups.Results Treatment group were enrolled 32 cases,2 cases dropped out,and 30 cases were finally included in the statistical analysis.Control group were enrolled 32 cases,2 cases dropped out,and 30 cases were finally included in the statistical analysis.The 12-hour Ramsay in the control group and the treatment group were(2.62±0.46)and(2.58±0.51)points;the 24-hour Ramsay were(2.32±0.45)and(2.27±0.39)points;the 48-hour Ramsay were(2.12±0.36)and(2.04±0.32)points;and the 72-hour Ramsay were(1.68±0.34)and(1.57±0.29)points,respectively;the 12-hour NRS were(1.64±0.26)and(1.53±0.28)points;the 24-hour NRS were(2.14±0.37)and(2.23±0.34)points;the 48-hour NRS were(2.57±0.39)and(2.44±0.42)points;the 72-hour NRS were(2.89±0.46)and(2.61±0.51)points,respectively.The NRS score at 72 h after operation in the treatment group was significantly lower than that in the control group(P＜0.05).The 12 h heart rate(HR)in the control group and treatment group were(75.90±6.45)and(75.42±6.24)time·min-1;24 h HR were(76.37±6.28)and(76.43±5.34)times·min-1,48 h HR(78.57±5.14)and(76.95±5.27)time·min-1;72 h HR were(76.49±4.41)and(78.17±4.64)time·min-1,respectively.The 12 h mean arterial pressure(MAP)in the control group and treatment group were(94.34±7.86)and(95.24±7.45)mmHg;24 h MAP were(95.71±7.55)and(96.56±7.29)mmHg;48 h MAP were(96.58±7.36)and(97.64±7.69)mmHg;72 h MAP were(97.63±8.15)and(96.77±8.53)mmHg,respectively the differences of the above indexes between the control group and the treatment group were not statistically significant(all P＞0.05).The extubation time of control group and treatment group were(63.42±16.34)and(59.56±17.27)h,respectively,with no statistical significance(P＞0.05).The adverse drug reactions of two groups were nausea and vomiting,use of rescue analgesics 12 h after surgery,and wound infection.The incidences of postoperative adverse drug reactions in the control group and the treatment group were 26.67％and 23.33％,respectively,with no statistical significance(P＞0.05).Conclusion Bupivacaine hydrochloride injection combined with neostigmine methylsulforte injection can significantly enhance the epidural analgesia effect in acute and critical patients undergoing general anesthesia,and the safety is better.

Aim To investigate the effects of puerarin on the proliferation,migration,and apoptosis of glio-blastoma cells and the underlying mechanisms.Meth-ods Differentially expressed genes associated with gli-oma and mitochondrial disease were analyzed using the GEO database.Cytotoxicity was detected by CCK-8 as-say.Cell migration was detected by the scratch wound healing assay and Transwell assay.Cell proliferation was assessed by EdU assay.Apoptosis level was meas-ured by TUNEL assay.Mitochondrial membrane poten-tial was detected by Mito-Tracker assay.ATP contents were detected using the ATP kit.The protein expres-sion levels were detected by Western blot.Antitumor efficacy of puerarin was analyzed using subcutaneous xenograft.Results There were 178 genes co-related differentially expressed genes in glioma and mitochon-drial disease.Core genes of co-related differentially ex-pressed genes were screened by GO and KEGG enrich-ment analyses,and the interaction networks.Among them,ubiquitin C(UBC)level was highly expressed in tissues of glioma patients.Puerarin could bind to UBC and reduce UBC expression at the animal and cell levels.Puerarin treatment inhibited the growth of glio-ma and decreased cell proliferation,migration and pro-moted cell apoptosis signals.Meantime,puerarin treat-ment also reduced mitochondrial membrane potentials and ATP contents,and down-regulated the levels of UBC related proteins.Conclusion Puerarin inhibits the proliferation,migration and promotes apoptosis of glioma cells.The mechanism of induction of mitochon-drial dysfunction is involved.

Objective To observe the sedative and analgesic effects of bupivacaine hydrochloride injection combined with neostigmine methylsulfate injection in critically ill patients after general anesthesia operation.Methods Acute and critical patients who were to undergo general anesthesia were randomly divided into control group and treatment group.Two groups received general anesthesia combined with epidural block anesthesia.After operation,the control group was continuously pumped 0.75％bupivacaine hydrochloride injection 45 mL through the epidural catheter,the treatment group was given 2 μg·kg-1 neostigmine methylsulfate injection on the basis of continuous pumping of bupivacaine injection through epidural catheter in the control group.Comparing the pain numerical rating scale(NRS)for 12 h,24 h,48 h,and 72 h of postoperative analgesia and the Ramsay sedation scores(Ramsay),hemodynamic index and safety in the two groups.Results Treatment group were enrolled 32 cases,2 cases dropped out,and 30 cases were finally included in the statistical analysis.Control group were enrolled 32 cases,2 cases dropped out,and 30 cases were finally included in the statistical analysis.The 12-hour Ramsay in the control group and the treatment group were(2.62±0.46)and(2.58±0.51)points;the 24-hour Ramsay were(2.32±0.45)and(2.27±0.39)points;the 48-hour Ramsay were(2.12±0.36)and(2.04±0.32)points;and the 72-hour Ramsay were(1.68±0.34)and(1.57±0.29)points,respectively;the 12-hour NRS were(1.64±0.26)and(1.53±0.28)points;the 24-hour NRS were(2.14±0.37)and(2.23±0.34)points;the 48-hour NRS were(2.57±0.39)and(2.44±0.42)points;the 72-hour NRS were(2.89±0.46)and(2.61±0.51)points,respectively.The NRS score at 72 h after operation in the treatment group was significantly lower than that in the control group(P＜0.05).The 12 h heart rate(HR)in the control group and treatment group were(75.90±6.45)and(75.42±6.24)time·min-1;24 h HR were(76.37±6.28)and(76.43±5.34)times·min-1,48 h HR(78.57±5.14)and(76.95±5.27)time·min-1;72 h HR were(76.49±4.41)and(78.17±4.64)time·min-1,respectively.The 12 h mean arterial pressure(MAP)in the control group and treatment group were(94.34±7.86)and(95.24±7.45)mmHg;24 h MAP were(95.71±7.55)and(96.56±7.29)mmHg;48 h MAP were(96.58±7.36)and(97.64±7.69)mmHg;72 h MAP were(97.63±8.15)and(96.77±8.53)mmHg,respectively the differences of the above indexes between the control group and the treatment group were not statistically significant(all P＞0.05).The extubation time of control group and treatment group were(63.42±16.34)and(59.56±17.27)h,respectively,with no statistical significance(P＞0.05).The adverse drug reactions of two groups were nausea and vomiting,use of rescue analgesics 12 h after surgery,and wound infection.The incidences of postoperative adverse drug reactions in the control group and the treatment group were 26.67％and 23.33％,respectively,with no statistical significance(P＞0.05).Conclusion Bupivacaine hydrochloride injection combined with neostigmine methylsulforte injection can significantly enhance the epidural analgesia effect in acute and critical patients undergoing general anesthesia,and the safety is better.

Objective: To investigate current use of oral anticoagulant (OAC) therapy and influencing factors among coronary artery disease (CAD) patients with nonvalvular atrial fibrillation (NVAF) in China. Methods: Results of this study derived from "China Atrial Fibrillation Registry Study", the study prospectively enrolled atrial fibrillation (AF) patients from 31 hospitals, and patients with valvular AF or treated with catheter ablation were excluded. Baseline data such as age, sex and type of atrial fibrillation were collected, and drug history, history of concomitant diseases, laboratory results and echocardiography results were recorded. CHA₂DS₂-VASc score and HAS-BLED score were calculated. The patients were followed up at the 3rd and 6th months after enrollment and every 6 months thereafter. Patients were divided according to whether they had coronary artery disease and whether they took OAC. Results: 11 067 NVAF patients fulfilling guideline criteria for OAC treatment were included in this study, including 1 837 patients with CAD. 95.4% of NVAF patients with CAD had CHA₂DS₂-VASc score≥2, and 59.7% of patients had HAS-BLED≥3, which was significantly higher than NVAF patients without CAD (P<0.001). Only 34.6% of NVAF patients with CAD were treated with OAC at enrollment. The proportion of HAS-BLED≥3 in the OAC group was significantly lower than in the no-OAC group (36.7% vs. 71.8%, P<0.001). After adjustment with multivariable logistic regression analysis, thromboembolism(OR=2.48,95%CI 1.50-4.10,P<0.001), left atrial diameter≥40 mm(OR=1.89,95%CI 1.23-2.91,P=0.004), stain use (OR=1.83,95%CI 1.01-3.03, P=0.020) and β blocker use (OR=1.74,95%CI 1.13-2.68,P=0.012)were influence factors of OAC treatment. However, the influence factors of no-OAC use were female(OR=0.54,95%CI 0.34-0.86,P=0.001), HAS-BLED≥3 (OR=0.33,95%CI 0.19-0.57,P<0.001), and antiplatelet drug(OR=0.04,95%CI 0.03-0.07,P<0.001). Conclusion: The rate of OAC treatment in NVAF patients with CAD is still low and needs to be further improved. The training and assessment of medical personnel should be strengthened to improve the utilization rate of OAC in these patients.
Humans ; Female ; Male ; Atrial Fibrillation/drug therapy* ; Coronary Artery Disease/complications* ; Anticoagulants/therapeutic use* ; Platelet Aggregation Inhibitors/therapeutic use* ; Risk Factors ; China ; Administration, Oral ; Stroke

Objective: Explore the association between atrial fibrillation (AF) reoccurrence and new-onset ischemic stroke (IS) in patients with nonvalvular AF, and explore whether there is a high-risk period of IS after recurrent episodes of AF. Methods: A nested case-control study design was used. A total of 565 nonvalvular AF patients with new-onset IS after a follow-up of at least 2 years in the China-AF cohort were enrolled as the case group, and 1 693 nonvalvular AF patients without new-onset IS were matched as the control group at a ratio of 1∶3. Frequency and types of recurrent AF in the previous 1 or 2 years were compared between two groups, and the adjusted associations of AF reoccurrence with new onset IS were explored using conditional logistic regression analysis. The proportion of recurrent AF was compared between the case period and control period, and conditional logistic regression analysis was performed to calculate adjusted associations of case-period AF with IS. Results: The nested case-control study design results showed that the proportion of at least one record of recurrent AF in the previous 1 year was higher in the case group than in the control group (72.0% vs. 60.8%, P<0.05), and the recurrent AF was positively correlated with new-onset IS (adjusted OR=1.80, P<0.001). Similar results were also observed in the previous 2 years period. The case-crossover study design analysis showed that among 565 patients with new-onset IS, recurrent AF in the case period was positively correlated with IS (adjusted OR=1.61, P=0.003). Conclusion: Recurrent AF is associated with IS, and there may be a high-risk period of IS after recurrent episodes of AF.
Humans ; Atrial Fibrillation/epidemiology* ; Case-Control Studies ; Cross-Over Studies ; Ischemic Stroke ; China/epidemiology*

Aim To study the therapeutic effect of Balanophora polysaccharide(BPS)on gastric ulcer(GU)induced by acetic acid in rats and to investigateits mechanisms. Methods Sixty male SD rats were randomly divided into sham-operated group, GU model group, omeprazole positive group(3.6 mg·kg-1), and low, medium and high dose of BPS treatment groups(100, 200 and 400 mg·kg-1). The GU model group was prepared by acetic acid cautery method, and the morphology and pathological changes of ulcers were observed by visual observation combined with HE staining, and the ulcer area and inhibition rate were measured and calculated; superoxide dismutase(SOD)activity, malondialdehyde(MDA)content and glutathione peroxidase(GSH-PX)activity were measured by enzymatic assay; tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)content were detected by ELISA. The expression levels of epidermal growth factor(EGF)and epidermal growth factor receptor(EGFR)were measured by immunohistochemistry staining and Western blot. Results Compared with the sham-operated group, obvious ulcer damage was seen in the model group. Compared with the model group, the BPS-treated group showed a significant reduction in ulcer area, an increase in SOD and GSH-PX activity and EGF and EGFR expression levels, and a significant decrease in MDA, TNF-α and IL-6 content. Conclusions BPS has a therapeutic effect on GU in rats, and its mechanism may be related to the inhibition of oxidative stress, suppression of inflammatory stimuli and promotion of regenerative repair of gastric mucosa.