Fungal infections have emerged as a critical public health issue endangering human health. However, the existing arsenal of antifungal agents is limited in diversity and is commonly plagued by drawbacks including narrow antimicrobial spectrums and the frequent emergence of drug resistance, which severely compromises the efficacy of clinical treatments. Pathogenic fungi can develop extensive adaptability to currently available drugs through multiple mechanisms, which are mainly manifested in three aspects: drug resistance, tolerance and persistence. The molecular mechanisms and regulatory pathways underlying drug resistance, tolerance and persistence in pathogenic fungi were systematically summarized in this review, and the counteractive strategies such as combination therapy and the development of novel antifungal agents were further discussed, which aimed to provide theoretical basis and practical reference for the precision treatment of fungal infections.

ObjectiveTo evaluate the clinical efficacy and safety of Tengshen Granules in the treatment of grade 1 hypertension with the syndrome of severe liver heat and hyperactive Yang combined with mild kidney Yin deficiency. MethodsA total of 120 patients with grade 1 hypertension presenting with severe liver heat and hyperactive Yang combined with mild kidney Yin deficiency were enrolled in a randomized， double-blind， placebo-controlled， parallel-group clinical trial. Patients were randomly assigned to the observation group （Tengshen granules） and the control group （placebo）， with 60 cases in each group. On the basis of lifestyle intervention， treatment was administered for 8 weeks followed by a 2-month follow-up. During the study period， traditional Chinese medicine （TCM） syndrome scores， blood pressure， antihypertensive efficacy， blood pressure control rate， and other indicators were recorded and analyzed， and safety was evaluated. ResultsA total of 114 patients completed the trial， including 57 in the control group and 57 in the observation group. Compared with baseline， TCM syndrome scores， systolic blood pressure， and diastolic blood pressure in the observation group were significantly reduced after treatment （P<0.01）. Compared with the control group after treatment， systolic blood pressure in the observation group was lower from week 4 of medication （P<0.05）， and this difference persisted until 2 months after drug discontinuation. For diastolic blood pressure， the observation group was superior to the control group at week 8 （P<0.01）， with no statistically significant differences at other time points. Regarding syndrome improvement， the TCM syndrome scores for severe liver heat and hyperactive Yang combined with mild kidney Yin deficiency showed significant improvement at weeks 6 and 8 of treatment， with the observation group superior to the control group （P<0.05）. During the 1-month follow-up after drug discontinuation， the syndrome scores in the observation group remained lower than those in the control group （P<0.01）. The total effective rate of antihypertensive efficacy in the observation group was higher than that in the control group （χ²=11.389， P<0.05）. In addition， the level of urinary microalbumin in the observation group was lower after treatment than before treatment （P<0.05）. ConclusionTengshen granules demonstrate significant clinical efficacy and good safety in the treatment of grade 1 hypertension with severe liver heat and hyperactive Yang combined with mild kidney Yin deficiency. They can effectively reduce blood pressure and improve related TCM syndrome manifestations.

ObjectiveTo evaluate the clinical efficacy and safety of Tengshen Granules in the treatment of grade 1 hypertension with the syndrome of severe liver heat and hyperactive Yang combined with mild kidney Yin deficiency. MethodsA total of 120 patients with grade 1 hypertension presenting with severe liver heat and hyperactive Yang combined with mild kidney Yin deficiency were enrolled in a randomized， double-blind， placebo-controlled， parallel-group clinical trial. Patients were randomly assigned to the observation group （Tengshen granules） and the control group （placebo）， with 60 cases in each group. On the basis of lifestyle intervention， treatment was administered for 8 weeks followed by a 2-month follow-up. During the study period， traditional Chinese medicine （TCM） syndrome scores， blood pressure， antihypertensive efficacy， blood pressure control rate， and other indicators were recorded and analyzed， and safety was evaluated. ResultsA total of 114 patients completed the trial， including 57 in the control group and 57 in the observation group. Compared with baseline， TCM syndrome scores， systolic blood pressure， and diastolic blood pressure in the observation group were significantly reduced after treatment （P<0.01）. Compared with the control group after treatment， systolic blood pressure in the observation group was lower from week 4 of medication （P<0.05）， and this difference persisted until 2 months after drug discontinuation. For diastolic blood pressure， the observation group was superior to the control group at week 8 （P<0.01）， with no statistically significant differences at other time points. Regarding syndrome improvement， the TCM syndrome scores for severe liver heat and hyperactive Yang combined with mild kidney Yin deficiency showed significant improvement at weeks 6 and 8 of treatment， with the observation group superior to the control group （P<0.05）. During the 1-month follow-up after drug discontinuation， the syndrome scores in the observation group remained lower than those in the control group （P<0.01）. The total effective rate of antihypertensive efficacy in the observation group was higher than that in the control group （χ²=11.389， P<0.05）. In addition， the level of urinary microalbumin in the observation group was lower after treatment than before treatment （P<0.05）. ConclusionTengshen granules demonstrate significant clinical efficacy and good safety in the treatment of grade 1 hypertension with severe liver heat and hyperactive Yang combined with mild kidney Yin deficiency. They can effectively reduce blood pressure and improve related TCM syndrome manifestations.

Objective:To evaluate the effect of low-dose esketamine on intraoperative electroencephalogram (EEG) burst suppression under general anesthesia in elderly patients.Methods:In this prospective randomized controlled trial, 86 elderly patients of either sex, scheduled for elective lumbar fusion surgery at Anhui No. 2 Provincial People′s Hospital from March 15 to June 1, 2024, aged 60-85 yr, with a body mass index of 18-28 kg/m 2, of American Society of Anesthesiologists Physical Status classification ⅡorⅢ, were divided into 2 groups ( n=43 each) using a random number table method: esketamine group (group S) and control group (group C). In group S, esketamine at a dose of 0.25 mg/kg was intravenously injected after anesthesia induction, while the equal volume of normal saline was intravenously injected in group C. The occurrence of EEG burst suppression and frequency of the characteristic density spectral array were recorded using the Masimo Sedline cerebral function monitor. The patient state index was recorded before esketamine administration and at 5, 10, 30 and 60 min after administration and at 5 min before the end of the surgery. Delirium was assessed using the Confusion Assessment Method at 1 and 3 days after operation. The total pressing times of patient-controlled analgesia within 48 h after operation, requirement for rescue analgesia and occurrence of adverse reactions (nausea and vomiting, delayed emergence from anesthesia, agitation, headache) were recorded. The consumption of ephedrine, phenylephrine, sufentanil and remifentanil during operation, emergence time, time of tracheal extubation, length of stay in the post-anesthesia care unit, and length of postoperative hospital stay were also recorded. Results:Compared with group C, the incidence of EEG burst suppression and frequency of the characteristic density spectral array were significantly decreased, the patient state index values were increased at each time point after administration and 5 min before the end of surgery, the consumption of ephedrine, phenylephrine, sufentanil and remifentanil during operation was reduced, the effective pressing times of patient-controlled analgesia, rate of rescue analgesia, and incidence of postoperative delirium within 3 days after operation were decreased, and the length of postoperative hospital stay was shortened in group S ( P<0.05). Conclusions:Low-dose esketamine can reduce intraoperative EEG burst suppression and decrease the development of postoperative delirium under general anesthesia in elderly patients.

Cytochrome P450 (CYP450) enzymes, as versatile biocatalysts with the broadest range of catalytic reactions in nature, play critical roles in the metabolism of medicinal plants. They are involved in various oxidative modification processes of active ingredients, facilitating both the synthesis and degradation of bioactive substances. This review delves into the classification, structure, and catalytic mechanisms of CYP450 enzymes, emphasizing their indispensable roles in plant biosynthesis. Using representative cases, including the biosynthetic pathways of tanshinones, artemisinin, celastrol, paclitaxel, and berberine, this review highlights the functional importance of specific CYP450s. For instance, CYP71AV1 catalyzes the production of artemisinin and artemisinic aldehyde, with its activity directly affecting artemisinin yield. Similarly, CYP76AH1 and CYP76AK1 play pivotal roles in the backbone construction and postmodification of tanshinones, acting as key players in their metabolic network. In the case of celastrol, CYP712K1, CYP712K2, and CYP712K3 initiate the first oxidative reaction, providing a solid foundation for subsequent biosynthetic processes. These examples highlight the pivotal role of CYP450 enzymes in the biosynthesis of medicinal plants, showcasing both their complexity and significance in plant metabolic pathways. Furthermore, this review examines the oxidative metabolism of CYP450 enzymes under aerobic conditions and their reductive metabolism in specific environments, offering deeper insights into their catalytic mechanisms. A comprehensive understanding of these processes lays the groundwork for the effective application of CYP450 enzymes in biotechnology and plant metabolic engineering.

ObjectiveTo investigate the effects of Congrong Zonggan capsules （CRZG） on cognitive impairment in the Alzheimer's disease （AD） model of mice and its related mechanisms. MethodsSPF grade 4-week-old 5×FAD mice were divided into a model group， low-dose CRZG （0.819 g·kg^-1） and high-dose CRZG （1.638 g·kg^-1） groups， and Donepezilepezil hydrochloride group （2 mg·kg^-1）， with eight mice in each group. Eight C57 mice with the same background were set as the normal group. After one week of adaptive feeding， mice were orally administered continuously for six months. On the 5th month of drug administration， Y maze， new object recognition， and Morris water maze tests were conducted separately. After administration， mouse brain tissue was taken， and the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in brain tissue were detected by enzyme-linked immunosorbent assay （ELISA）. Immunofluorescence （IF） was used to detect the expression of small glial cell markers Iba1， astrocyte markers GFAP， and amyloid protein 1-42 （Aβ_1-42） in the hippocampus of the brain tissue. The hematoxylin-eosin （HE） staining was used to detect pathological changes in the hippocampus of brain tissue. Western blot was used to detect the expression of nuclear factor-κB （NF-κB） p65， NOD-like receptor protein 3 （NLRP3）， cleaved Caspase-1， apoptosis-associated speck-like protein containing a CARD （ASC）， and other proteins in the brain tissue. ResultsCompared with those in the normal group， the mice in the model group had obvious cognitive impairment. The spontaneous alternation rate of the Y maze was decreased， and the discrimination index of novel object recognition was decreased significantly （P<0.01）. The escape latency in the water maze was shortened significantly （P<0.01）. The contents of IL-6 and TNF-α in brain tissue were increased. The fluorescence levels of Iba1 and Aβ_1-42 in the hippocampus were significantly increased （P<0.01）. There was a significant increase in neuronal lesions， neuronal atrophy， loose arrangement of tissue structure， and abnormal erythrocyte aggregation in the hippocampus. The protein expressions of p-NF-κB p65/NF-κB p65， cleaved Caspase-1， ASC， IL-6， and IL-1β were significantly increased （P<0.05， P<0.01）. Compared with the model group， the spontaneous alternation rate and discrimination index of the high-dose CRZG group were increased significantly （P<0.01）， and the escape latency was shortened significantly （P<0.05， P<0.01）. The content of IL-6 decreased in the brain， and that of TNF-α dropped significantly （P<0.01）. The expression of Iba1 protein and Aβ_1-42 in the hippocampus decreased significantly （P<0.05， P<0.01）. The hippocampal neurons were densely arranged， and the pyramidal nuclei were clear and centered. The abnormal aggregation of red blood cells was alleviated. The value of p-NF-κB/NF-κB proteins and the expression of ASC， cleaved Caspase-1， IL-6， and IL-1β were significantly decreased （P<0.05， P<0.01）. ConclusionCRZG can effectively improve cognitive impairment in 5×FAD mice with Alzheimer's disease， and its mechanism may be related to the regulation of the NF-κB/NLRP3 pathway to reduce the abnormal activation of microglia and inhibit neuroinflammation.

Objective:To evaluate the effect of low-dose esketamine on intraoperative electroencephalogram (EEG) burst suppression under general anesthesia in elderly patients.Methods:In this prospective randomized controlled trial, 86 elderly patients of either sex, scheduled for elective lumbar fusion surgery at Anhui No. 2 Provincial People′s Hospital from March 15 to June 1, 2024, aged 60-85 yr, with a body mass index of 18-28 kg/m 2, of American Society of Anesthesiologists Physical Status classification ⅡorⅢ, were divided into 2 groups ( n=43 each) using a random number table method: esketamine group (group S) and control group (group C). In group S, esketamine at a dose of 0.25 mg/kg was intravenously injected after anesthesia induction, while the equal volume of normal saline was intravenously injected in group C. The occurrence of EEG burst suppression and frequency of the characteristic density spectral array were recorded using the Masimo Sedline cerebral function monitor. The patient state index was recorded before esketamine administration and at 5, 10, 30 and 60 min after administration and at 5 min before the end of the surgery. Delirium was assessed using the Confusion Assessment Method at 1 and 3 days after operation. The total pressing times of patient-controlled analgesia within 48 h after operation, requirement for rescue analgesia and occurrence of adverse reactions (nausea and vomiting, delayed emergence from anesthesia, agitation, headache) were recorded. The consumption of ephedrine, phenylephrine, sufentanil and remifentanil during operation, emergence time, time of tracheal extubation, length of stay in the post-anesthesia care unit, and length of postoperative hospital stay were also recorded. Results:Compared with group C, the incidence of EEG burst suppression and frequency of the characteristic density spectral array were significantly decreased, the patient state index values were increased at each time point after administration and 5 min before the end of surgery, the consumption of ephedrine, phenylephrine, sufentanil and remifentanil during operation was reduced, the effective pressing times of patient-controlled analgesia, rate of rescue analgesia, and incidence of postoperative delirium within 3 days after operation were decreased, and the length of postoperative hospital stay was shortened in group S ( P<0.05). Conclusions:Low-dose esketamine can reduce intraoperative EEG burst suppression and decrease the development of postoperative delirium under general anesthesia in elderly patients.

Automotive antifreeze, being colorless and odorless, can easily cause acute poisoning if ingested. Acute poisoning can lead to damage to the central nervous system, digestive system, and kidney function, and may even result in death. This article analyzes the clinical data, diagnostic and therapeutic processes, and outcomes of two patients admitted to the Department of Poisoning and Occupational Diseases, Emergency Medicine of Qilu Hospital, Shandong University, who suffered acute poisoning due to ingesting antifreeze. The findings aim to provide a reference for clinicians in the diagnosis and treatment of antifreeze poisoning.

BACKGROUND:Polyamines play a crucial role in tissue calcification.Spermidine/spermine N1-acetyltransferase 1(SAT1),as a key rate-limiting enzyme regulating intracellular polyamine metabolism,has been associated with various pathological processes.However,its role in vascular calcification remains unclear.OBJECTIVE:To investigate the role of SAT1 in rat vascular smooth muscle cell calcification.METHODS:(1)Bioinformatics analysis:Differential expression of SAT1 in human carotid atherosclerotic plaques and their surrounding healthy carotid artery tissues were using GEO datasets.PanglaoDB database was used to analyze SAT1 expression abundance and localization across different cell types through single-cell sequencing.(2)Rat vascular smooth muscle cells were divided into three groups:a control group cultured in DMEM medium,a calcification group induced by DMEM medium containing 10 mmol/L β-glycerophosphate sodium and 3 mmol/L calcium chloride,and the 50,100 μmol/L diacetylaminotriazamidine groups treated with the SAT1 inhibitor,diacetylaminotriazamidine,in addition to the calcification medium.After 7-10 days of culture,alizarin red S staining was performed,and cellular calcium content and alkaline phosphatase activity were assessed.Western blot was used to detect the protein expression of Runt-related transcription factor 2,bone morphogenetic protein 2,alpha-smooth muscle actin,and SAT1.Immunofluorescence staining was conducted to examine the expression of Runt-related transcription factor 2 and SAT1.RESULTS AND CONCLUSION:(1)Bioinformatics analysis revealed significantly upregulated expression of SAT1 and Runt-related transcription factor 2(P<0.05)in carotid atherosclerotic plaques compared with healthy carotid tissues(P<0.05).Single-cell sequencing database analysis confirmed SAT1 expression in vascular smooth muscle cells.(2)Compared with the control group,the calcification group showed significantly increased Runt-related transcription factor 2,bone morphogenetic protein 2,SAT1,calcium content,and alkaline phosphatase activity,while alpha-smooth muscle actin expression was significantly decreased(all P<0.05).Compared with the calcification group,the 50 and 100 μmol/L diacetylaminotriazamidine groups showed significantly decreased Runt-related transcription factor 2,bone morphogenetic protein 2,calcium content,and alkaline phosphatase activity,while alpha-smooth muscle actin expression was significantly increased(all P<0.05).(3)Immunofluorescence experiments demonstrated that compared with the calcification group,the expression intensity of Runt-related transcription factor 2 was significantly reduced in the 50 and 100 μmol/L diacetylaminotriazamidine groups.Overall,SAT1 may promote vascular smooth muscle cell calcification by upregulating Runt-related transcription factor 2 expression.

Objective:To investigate the level of rehabilitation exercise adherence in patients undergoing anterior cruciate ligament (ACL) reconstruction within 6 months post-surgery, analyze its trajectory, and provide a reference for clinical nursing interventions.Methods:Using a convenience sampling method, 150 patients who underwent arthroscopic ACL reconstruction at the First Affiliated Hospital of Zhengzhou University from June 2022 to August 2023 were selected. Rehabilitation exercise adherence was assessed monthly from postoperative 1 month (M 1) to 6 months (M 6) using the Orthopedic Functional Exercise Adherence Scale. A latent class growth model was employed to analyze adherence trajectory categories, and Logistic regression was used to identify influencing factors for different adherence trajectories. Results:A total of 144 patients completed follow-up (follow-up rate was 96.00%). Exercise adherence scores gradually declined over the 6 months post-surgery, with scores of (50.30±5.39), (45.92±3.85), (39.48±5.27), (35.83±6.19), (31.85±7.59), and (29.88±7.88) from M 1 to M 6, respectively. The difference in scores across time points was statistically significant ( F=85.467, P<0.01). Three potential categories were identified through the latent class growth model: the moderate-high level rapid decline group ( n=65, 45.14%), the moderate-low level stable group ( n=32, 22.22%), and the moderate-low level slow decline group ( n=47, 32.64%). Logistic regression analysis revealed that gender and age were significant factors influencing adherence trajectory categories ( P<0.05) . Conclusions:Dynamic declines in rehabilitation exercise adherence are common among ACL reconstruction patients, with varying degrees of decline. Gender and age may influence adherence trajectories, suggesting that targeted management strategies could be implemented in clinical practice.