ObjectiveTo investigate the mechanism by which Simiao Wan improve intestinal uric acid excretion in hyperuricemic （HUA） rats by inhibiting ferroptosis via the solute carrier family 7 member 11/glutathione peroxidase 4 （SLC7A11/GPX4） signaling pathway. MethodsForty-eight male SD rats were randomly assigned to a normal group， a model group， a low-dose Simiao Wan group （282.6 mg·kg^-1）， a high-dose Simiao Wan group （565.2 mg·kg^-1）， an etoricoxib group （5.4 mg·kg^-1）， and a ferroptosis inhibitor （Fer-1） group （2 mg·kg^-1）. Except for the normal group， rats in all other groups were intraperitoneally injected with potassium oxonate （100 mg·kg^-1） combined with intragastric administration of hypoxanthine （500 mg·kg^-1） to establish the HUA rat model. After 21 days， rats in each administration group received the corresponding dose of drug by gavage， rats in the Fer-1 group received intraperitoneal injection of Fer-1， and rats in the normal and model groups were given an equal volume of normal saline by gavage. After sampling， serum levels of uric acid （SUA）， creatinine （Cr）， and blood urea nitrogen （BUN） were measured using biochemical assays. The content of ferrous ion （Fe²⁺）， reduced glutathione （GSH）， and malondialdehyde （MDA）， as well as superoxide dismutase （SOD） activity in ileal tissues were determined. Hematoxylin and eosin （HE） staining was performed to observe the histopathological changes in the ileum， and transmission electron microscopy was used to observe mitochondrial alterations in the ileal tissue. Immunohistochemistry （IHC） and Western blot were used to detect the protein expression levels of GPX4， ferritin heavy chain 1 （FTH1）， acyl-CoA synthetase long-chain family member 4 （ACSL4）， SLC7A11， and ATP-binding cassette transporter G2 （ABCG2） in ileal tissue. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to determine the mRNA expression of GPX4， FTH1， ACSL4， SLC7A11， and ABCG2 in the ileal tissue. ResultsCompared with the normal group， the model group exhibited significantly elevated serum UA， Cr， and BUN levels （P<0.01）， significantly increased content of MDA and Fe²⁺ in ileal tissue， and significantly decreased GSH content and SOD activity （P<0.01）. HE staining showed extensive shedding of the ileal villous epithelium， disrupted and disorganized villous structure， and incomplete local tissue architecture. Transmission electron microscopy revealed reduced mitochondrial volume， decreased or even vanished cristae， indicating ultrastructural features characteristic of ferroptosis. Molecular and immunohistochemical results demonstrated that the protein and mRNA expression levels of GPX4， FTH1， SLC7A11， and ABCG2 were significantly downregulated， whereas those of ACSL4 were significantly upregulated （P<0.05， P<0.01）. Compared with the model group， after intervention with Simiao Wan， the serum UA， Cr， and BUN levels significantly decreased in all dose groups （P<0.05，P<0.01）， the MDA and Fe²⁺ content in ileal tissues were significantly reduced （P<0.01）， and the GSH content and SOD activity significantly increased （P<0.01）. HE staining showed that the shedding of ileal villous epithelium was markedly alleviated， the villous structure became relatively intact and regularly arranged， and local tissue damage was obviously improved. Transmission electron microscopy showed attenuated mitochondrial damage， improvement in mitochondrial shrinkage， and partial restoration of mitochondrial cristae. Molecular and immunohistochemical results showed that Simiao Wan upregulated GPX4， FTH1， SLC7A11， and ABCG2， and downregulated ACSL4 in a dose-dependent manner. In the high‑dose group， all indices improved significantly （P<0.05，P<0.01）， whereas in the low‑dose group， only improving trends were observed for FTH1， SLC7A11 mRNA， and ABCG2 protein. ConclusionSimiao Wan may inhibit ferroptosis of ileal epithelial cells by regulating the SLC7A11/GPX4 signaling pathway， and upregulate the expression of the uric acid transporter ABCG2， thereby promoting intestinal uric acid excretion and improving HUA.

Sympathectomy, as an emerging treatment method for cardiovascular diseases, has received extensive attention in recent years. Stereotactic radiotherapy (SRT), a precise and noninvasive therapeutic technique, has gradually been introduced into interventions targeting the sympathetic nervous system and has shown promising prospects in the management of cardiovascular conditions. Using three-dimensional imaging, SRT can accurately localize sympathetic ganglia and deliver high-energy radiation to disrupt nerve fibers, thereby achieving effects similar to conventional sympathectomy while reducing surgery-related complications and shortening recovery time. It also offers the advantages of being noninvasive and causing fewer adverse effects, and thus holds potential as an alternative to traditional approaches in the future. The integration of SRT with sympathectomy opens new avenues for the treatment of cardiovascular diseases and presents broad clinical application prospects.
Radiosurgery/methods* ; Cardiovascular Diseases/radiotherapy* ; Humans ; Imaging, Three-Dimensional ; Ganglionectomy/methods* ; Ganglia, Sympathetic/radiation effects* ; Blood Vessels/physiopathology* ; Heart/physiopathology*

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Background: Medicinal plants rich in endophytic fungi are a significant source of natural lead compounds. Meroterpenoids, which are hybrid natural products originating from partially terpenoid pathways, exhibit impressive structural complexity and substantial potential as drug candidates. The structural diversity of meroterpenoids is largely attributed to the functional diversity of terpenoid cyclases, which generate a variety of terpenoid compounds with different ring systems. This enzymatic versatility underscores the biochemical potential of endophytic fungi and their invaluable role in drug discovery. Objective: The aim of the study was to investigate the role of endophytic fungi from Paris polyphylla var. yunnanensis in facilitating diverse cyclization modifications of meroditerpenoids through four terpene cyclases (TCs) from the Pyr4 family. Methods: This study utilized a recombinant strategy to successfully reconstruct four distinct TCs from endophytic fungi in the heterologous host, Aspergillus oryzae NSAR1. The structural characterization of the resulting secondary metabolites was performed using mass spectrometry and NMR techniques. Results: The substitution of TCs from the endophytes Aspergillus felis 0260 and Fusarium graminearum 1962 in Aspergillus oryzae through hydrophobic intermediates 1 and 2, led to the production of meroditerpenoids sartorypyrone C (3) and a new compound, 4′-methylchevalone E (4), respectively. This study demonstrates the critical role of endophytic fungi in enhancing structural diversity. Conclusions: These findings provide valuable insights into the compatibility of pathway combinations and the interchangeability of terpene cyclases derived from endophytic fungi in medicinal plants, which advanced the understanding of meroditerpenoid biosynthesis and highlighted the importance of endophytic fungi in drug discovery.

Background: Medicinal plants rich in endophytic fungi are a significant source of natural lead compounds. Meroterpenoids, which are hybrid natural products originating from partially terpenoid pathways, exhibit impressive structural complexity and substantial potential as drug candidates. The structural diversity of meroterpenoids is largely attributed to the functional diversity of terpenoid cyclases, which generate a variety of terpenoid compounds with different ring systems. This enzymatic versatility underscores the biochemical potential of endophytic fungi and their invaluable role in drug discovery. Objective: The aim of the study was to investigate the role of endophytic fungi from Paris polyphylla var. yunnanensis in facilitating diverse cyclization modifications of meroditerpenoids through four terpene cyclases (TCs) from the Pyr4 family. Methods: This study utilized a recombinant strategy to successfully reconstruct four distinct TCs from endophytic fungi in the heterologous host, Aspergillus oryzae NSAR1. The structural characterization of the resulting secondary metabolites was performed using mass spectrometry and NMR techniques. Results: The substitution of TCs from the endophytes Aspergillus felis 0260 and Fusarium graminearum 1962 in Aspergillus oryzae through hydrophobic intermediates 1 and 2, led to the production of meroditerpenoids sartorypyrone C (3) and a new compound, 4′-methylchevalone E (4), respectively. This study demonstrates the critical role of endophytic fungi in enhancing structural diversity. Conclusions: These findings provide valuable insights into the compatibility of pathway combinations and the interchangeability of terpene cyclases derived from endophytic fungi in medicinal plants, which advanced the understanding of meroditerpenoid biosynthesis and highlighted the importance of endophytic fungi in drug discovery.

Background: Medicinal plants rich in endophytic fungi are a significant source of natural lead compounds. Meroterpenoids, which are hybrid natural products originating from partially terpenoid pathways, exhibit impressive structural complexity and substantial potential as drug candidates. The structural diversity of meroterpenoids is largely attributed to the functional diversity of terpenoid cyclases, which generate a variety of terpenoid compounds with different ring systems. This enzymatic versatility underscores the biochemical potential of endophytic fungi and their invaluable role in drug discovery. Objective: The aim of the study was to investigate the role of endophytic fungi from Paris polyphylla var. yunnanensis in facilitating diverse cyclization modifications of meroditerpenoids through four terpene cyclases (TCs) from the Pyr4 family. Methods: This study utilized a recombinant strategy to successfully reconstruct four distinct TCs from endophytic fungi in the heterologous host, Aspergillus oryzae NSAR1. The structural characterization of the resulting secondary metabolites was performed using mass spectrometry and NMR techniques. Results: The substitution of TCs from the endophytes Aspergillus felis 0260 and Fusarium graminearum 1962 in Aspergillus oryzae through hydrophobic intermediates 1 and 2, led to the production of meroditerpenoids sartorypyrone C (3) and a new compound, 4′-methylchevalone E (4), respectively. This study demonstrates the critical role of endophytic fungi in enhancing structural diversity. Conclusions: These findings provide valuable insights into the compatibility of pathway combinations and the interchangeability of terpene cyclases derived from endophytic fungi in medicinal plants, which advanced the understanding of meroditerpenoid biosynthesis and highlighted the importance of endophytic fungi in drug discovery.

Objective To analyze the clinical efficacy of low temperature plasma radiofrequency ablation(RFA)combined with nasal irrigation in the treatment of allergic rhinitis(AR)with nasal septal deviation.Methods A total of 120 AR patients with nasal septal deviation who were diagnosed and treated in Taikang Xianlin Drum Tower Hospital from August 2018 to December 2022 were selected as research objects.They were assigned to observation group or control group according to random number table method,with 60 cases in each group.The control group received nasal irrigation,and the observation group received low temperature plasma RFA and nasal irrigation.The efficacy,immunity,inflammation,quality of life,safety and prognosis were compared between the two groups.Results The observation group had better curative effect than the control group(P<0.05).The natural killer(NK)cells were increased,and the levels of immunoglobulin G(IgE),thymic stromal lymphopoietin(TSLP),hypoxia-inducible factor-1(HIF-1)and fractional exhaled nitric oxide(FeNO)were decreased in both groups after treatment.The level of NK cells in the observation group was higher than that in the control group after treatment,and the levels of IgE,TSLP,HIF-1,and FeNO in the observation group were lower than those in the control group(P<0.05).After treatment,the rhinoconjunctivitis quality of life questionnaire(RQLQ)scores decreased in both groups,and the scores in the observation group were lower than those in the control group(P<0.05).There was no significant difference in safety between the two groups(P>0.05).The control group had higher recurrence rate than the observation group(P<0.05).Conclusion Low temperature plasma RFA combined with nasal irrigation can effectively improve the immune function and inflammation of AR patients with nasal septal deviation,thereby improving the efficacy and quality of life,and reducing the recurrence rate,with high safety.

Objective To evaluate the effects of bladder neck preservation on postoperative stress urinary inconti-nence and retrograde ejaculation in patients undergoing transurethral thulium laser enucleation of the prostate(ThuLEP).Methods The clinical data of 203 patients who underwent ThuLEP in our hospital from September 2021 to December 2023 were retrospectively analyzed.According to the operation method,the patients were divided into bladder neck preservation group(n=95)and non-bladder neck preservation group(n=108).The occurrence of postoperative stress urinary inconti-nence and retrograde ejaculation of the two groups were compared.Results The differences between the patients of two groups in operative time(110[80,130]min vs 110[90,140]min),hospital stay(8[8,8]d vs 8[8,8]d),in-dwelling catheter time(7[7,7]h vs 7[7,7]h),and hemoglobin decline(9[6,14]g/L vs 8[4,13]g/L)were not statistically significant(P＞0.05).There were no statistically significant differences between the two groups at 3 months postoperatively in maximum flow rate(20[18,21]mL/s vs 19[18,20]mL/s),scores of International Prostate Symp-tom Scale(5[4,6]vs 5[4,5]),post-void residual urine volume(0[0,8]mL vs 0[0,7.5]mL)and quality of life(2[1,3]vs 2[1,3])(P＞0.05).The differences in the rates of postoperative stress urinary incontinence(2.1％vs 9.3％)and retrograde ejaculation(49.4％vs 74.5％)between the two groups were statistically significant(P＜0.05).Conclusion Bladder neck preservation during ThuLEP reduces the incidence of postoperative stress urinary incontinence and retrograde ejaculation.

Objective To evaluate the effects of bladder neck preservation on postoperative stress urinary inconti-nence and retrograde ejaculation in patients undergoing transurethral thulium laser enucleation of the prostate(ThuLEP).Methods The clinical data of 203 patients who underwent ThuLEP in our hospital from September 2021 to December 2023 were retrospectively analyzed.According to the operation method,the patients were divided into bladder neck preservation group(n=95)and non-bladder neck preservation group(n=108).The occurrence of postoperative stress urinary inconti-nence and retrograde ejaculation of the two groups were compared.Results The differences between the patients of two groups in operative time(110[80,130]min vs 110[90,140]min),hospital stay(8[8,8]d vs 8[8,8]d),in-dwelling catheter time(7[7,7]h vs 7[7,7]h),and hemoglobin decline(9[6,14]g/L vs 8[4,13]g/L)were not statistically significant(P＞0.05).There were no statistically significant differences between the two groups at 3 months postoperatively in maximum flow rate(20[18,21]mL/s vs 19[18,20]mL/s),scores of International Prostate Symp-tom Scale(5[4,6]vs 5[4,5]),post-void residual urine volume(0[0,8]mL vs 0[0,7.5]mL)and quality of life(2[1,3]vs 2[1,3])(P＞0.05).The differences in the rates of postoperative stress urinary incontinence(2.1％vs 9.3％)and retrograde ejaculation(49.4％vs 74.5％)between the two groups were statistically significant(P＜0.05).Conclusion Bladder neck preservation during ThuLEP reduces the incidence of postoperative stress urinary incontinence and retrograde ejaculation.

Objective To investigate the sleep structure of Parkinson's disease (PD) patients with rapid eye movement sleep behavior disorder (RBD) and its correlations with cognitive function, depressive state and motor function. Methods A total of 120 PD patients were enrolled in this study, and divided into PD+RBD group (n=45) and PD group (n=75) based on the presence or absence of RBD. Sleep structure was recorded for both groups. The scores of the Montreal Cognitive Assessment (MoCA), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Unified Parkinson's Disease Rating Scale Part Ⅲ (UPDRS-Ⅲ) and Scales for Outcomes in Parkinson's Disease-Autonomic (SCOPA-AUT) were compared between the two groups. The correlations of MoCA, HAMA, HAMD, UPDRS-Ⅲ and SCOPA-AUT scores with sleep structure in the PD+RBD group were analyzed. Results The PD+RBD group showed significantly higher percentage of non-rapideye movement (NREM) at stage 1, arousal index, periodic limb movements during sleep (PLMS) and apnea-hypopnea index (AHI) compared to the PD group, while the percentages of NREM at stage 3, rapid eye movement (REM) sleep, sleep efficiency and lowest oxygen saturation were significantly lower (P < 0.05). The PD+RBD group also had significantly higher HAMA, HAMD, UPDRS-Ⅲ and SCOPA-AUT scores, and significantly lower MoCA scores compared to the PD group (P < 0.05). In the PD+RBD group, the percentages of NREM at stage 1, arousal index, PLMS and AHI were positively correlated with HAMA, HAMD, UPDRS-Ⅲ and SCOPA-AUT scores, and negatively correlated with MoCA scores (P < 0.05). Conversely, the percentages of NREM at stage 3, REM sleep, sleep efficiency and lowest oxygen saturation were negatively correlated with HAMA, HAMD, UPDRS-Ⅲ and SCOPA-AUT scores, and positively correlated with MoCA scores (P < 0.05). Conclusion PD patients with RBD exhibit disrupted sleep structure, which is closely associated with cognitive function, depressive state, motor function, and autonomic nervous system function.