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.

The pathogenesis of central nervous system （CNS） diseases is complex， seriously affecting patients' physical and mental health and imposing a heavy economic burden on society. Western medicine shows limited efficacy in treating CNS diseases and is often associated with numerous adverse reactions and contraindications. Chinese medicine Lycii Fructus exhibits multiple pharmacological effects， including immune regulation， enhancement of hematopoietic function， liver protection， anti-tumor， hypoglycemic， antipyretic， anti-aging， and anti-radiation activities， and has gradually been applied in clinical treatment. In recent years， the active components of Lycii Fructus have attracted considerable attention for their potential therapeutic effects on CNS diseases. Studies indicate that these active components may exert neuroprotective effects through anti-inflammatory and antioxidant actions， inhibition of neuronal apoptosis， and repair of neuronal damage， involving multiple targets and pathways. This review summarizes the therapeutic effects of Lycii Fructus active components in CNS diseases over the past decade by searching PubMed， CNKI， Wanfang Data， and other electronic databases， aiming to provide new treatment strategies and insights for future research on Lycii Fructus in CNS disorders.

Nervous system diseases， also known as neuropathies， encompass a wide range of conditions， primarily including Alzheimer's disease （AD）， Parkinson's disease （PD）， Huntington's disease， and other neurodegenerative disorders， as well as depression， subarachnoid hemorrhage， cerebral ischemia-reperfusion injury， vascular dementia， and other neurological diseases. These diseases pose serious threats to the health and lives of patients， bringing heavy burdens to society and families. The pathogenesis of nervous system diseases is highly complex， involving mechanisms such as neuroinflammation， oxidative stress， apoptosis， endoplasmic reticulum stress， mitochondrial dysfunction， brain-derived neurotrophic factor deficiency， reduced cholinergic activity， axonal injury， and demyelination. In recent years， the incidence and mortality of nervous system diseases have been rising annually. Currently， western medicine primarily focuses on symptomatic treatment， often accompanied by many adverse reactions， including lethargy， excessive sedation， dizziness， headaches， tachycardia， liver function damage， metabolic disorders， and incomplete recovery after surgery. As a traditional Chinese medicine， Salviae Miltiorrhizae Radix et Rhizoma has effects such as promoting blood circulation， removing blood stasis， cooling the blood， clearing the heart， nourishing the blood， and calming the nerves. It can play a role in the treatment and protection against nervous system diseases through multiple targets， pathways， and mechanisms. Studies have found that the water-soluble phenolic acids and fat-soluble diterpenoid quinones in Salviae Miltiorrhizae Radix et Rhizoma are the main active ingredients for the treatment of nervous system diseases. This paper summarized the effects of the active components and compounds of Salviae Miltiorrhizae Radix et Rhizoma on nervous system diseases over the past ten years， aiming to provide a theoretical basis and research ideas for the development and application of active components and compounds of Salviae Miltiorrhizae Radix et Rhizoma in nervous system diseases.

Chronic pancreatitis （CP） is a chronic disease characterized by recurrent inflammation and progressive damage to pancreatic tissue， and its deterioration may increase the risk of pancreatic cancer in patients with CP， which seriously threatens the health of patients with CP. In recent years， studies on the pathogenesis of CP have mostly focused on the activation of pancreatic stellate cells （PSCs） and its role in pancreatic fibrosis. This article elaborates on the mechanism of action of PSCs in CP， summarizes the current status of research on effective traditional Chinese medicine components and prescriptions for intervention of PSCs in the treatment of chronic CP， and proposes the future research directions for effective traditional Chinese medicine components and prescriptions， so as to provide a reference for the clinical treatment of CP patients in the future.

Objective:To explore the clinical characteristics of adrenal lesions in unilateral primary aldosteronism.Methods:This is a prospective study. Consecutive patients diagnosed with unilateral primary aldosteronism at the First Affiliated Hospital of Chongqing Medical University from December 2023 to November 2024 were included. Inclusion criteria：① Age is 18 to 80 years old；② The laboratory test indicators are in line with the diagnosis of primary aldosteronism；③ The auxiliary examination proved that only one side was involved；④ Patient undergo unilateral total adrenalectomy. The exclusion criteria are as follows：① Complete biochemical remission was not achieved during the 1-6 month follow-up after the surgery；② Postoperative loss to follow-up；③ No surgical specimens were received or the surgical specimens were incomplete，making continuous sectioning impossible. Patients meeting the inclusion criteria were recruited，and their clinical and biochemical data were recorded. The number of adrenal nodules visible on CT scans and the number of macroscopically visible nodules in the postoperative adrenal gross specimens were documented. Hematoxylin-eosin（HE）staining and aldosterone synthase CYP11B2 immunohistochemical staining were performed on the adrenal tissues after the operation. The number of nodules visible under the light microscope and the number of CYP11B2-positive nodules were recorded.Results:A total of 114 cases were included in this study. The age of the patients was（49.86 ± 9.80）years，the body mass index was（25.49 ± 3.40）kg/m2，the preoperative aldosterone level was 352（2012，556）pg/ml，and the direct renin concentration was 1.63（0.50，4.56）μIU/ml. The aldosterone/renin ratio was 224.9（57.1，641.6）（aldosterone concentration unit was pg/ml，renin concentration unit was μIU/ml），the minimum blood potassium concentration was 2.87（2.50，3.40）mmol/L，and the systolic blood pressure was（144.5 ± 19.5）mmHg. Among the 114 patients，105 had adrenal nodules detected by preoperative CT，of whom 2（1.75%）had multiple nodules. Postoperative gross adrenal specimen evaluation and CYP11B2 immunohistochemical staining revealed that 90 out of 114 cases were solitary nodules，2 cases had no nodules，and 22 cases（19.30%）had multiple nodules detected（17 cases had 2 nodules and 5 cases had 3 nodules）. Among them，12 cases（10.53%）presented as grossly visible multinodular lesions，while 10 cases（8.77%）appeared as solitary nodules macroscopically but demonstrated multinodular patterns on immunohistochemical staining. CYP11B2 staining showed that among the 22 patients with multiple nodules，13 had multiple CYP11B2-positive nodules，while the remaining had only one positive nodule. Among the 22 patients with multiple nodules，preoperative CT showed single nodules in 19 cases，hyperplasia in 1 case，and multiple nodules in 2 cases（9.09%）. Among the 12 patients with grossly visible multinodular lesions，preoperative CT showed single nodules in 9 cases，hyperplasia in 1 case，and multiple nodules in 2 cases（16.67%）.Conclusions:Multiple adrenal nodules associated with unilateral primary aldosteronism are relatively common，and are often not detected by preoperative CT examination. Partial adrenalectomy based solely on CT-visible nodules may fail to achieve complete remission of primary aldosteronism. This study provides evidence supporting total adrenalectomy as the preferred surgical approach for unilateral primary aldosteronism.

Objective To investigate the risk factors of subdelirium syndrome in adult ICU patients,then establish a risk prediction model and have it verified.Method A total of 380 adult ICU patients in our hospital between June 2022 and January 2024 were selected in this study.Among the patients,224(70％)were assigned to the model group and 114(30％)to the validation group.Independent risk factors were screened by comparison of the general data,disease and treatment,laboratory indicators and other relevant data between the patients with and without subdelirium.A risk prediction model was established with Logistic regression.Results A risk prediction model was finalised and established.It composed six risk factors of age(OR=1.023),APACHE Ⅱ score(OR=1.093),critical care pain observation tool(OR=2.216),duration of mechanical ventilation(OR=1.003),constraint(OR=2.615)and sepsis(OR=2.081).In internal validation,it was found that the calibration curve closely overlapped with the ideal curve and the area under the ROC curve was 0.816,with a predictive cut off value of 85 points.In external validation,the calibration curve was found closely overlapped with the ideal curve and the area under ROC curve was 0.808.Conclusion The risk prediction model for subdelirium syndrome in adult ICU patients established in the study has good consistency and prediction efficiency,thereby it provides a basis for early clinical screening and intervention of subdelirium syndrome.

Objective To investigate the risk factors of subdelirium syndrome in adult ICU patients,then establish a risk prediction model and have it verified.Method A total of 380 adult ICU patients in our hospital between June 2022 and January 2024 were selected in this study.Among the patients,224(70％)were assigned to the model group and 114(30％)to the validation group.Independent risk factors were screened by comparison of the general data,disease and treatment,laboratory indicators and other relevant data between the patients with and without subdelirium.A risk prediction model was established with Logistic regression.Results A risk prediction model was finalised and established.It composed six risk factors of age(OR=1.023),APACHE Ⅱ score(OR=1.093),critical care pain observation tool(OR=2.216),duration of mechanical ventilation(OR=1.003),constraint(OR=2.615)and sepsis(OR=2.081).In internal validation,it was found that the calibration curve closely overlapped with the ideal curve and the area under the ROC curve was 0.816,with a predictive cut off value of 85 points.In external validation,the calibration curve was found closely overlapped with the ideal curve and the area under ROC curve was 0.808.Conclusion The risk prediction model for subdelirium syndrome in adult ICU patients established in the study has good consistency and prediction efficiency,thereby it provides a basis for early clinical screening and intervention of subdelirium syndrome.

Objective:To explore the clinical characteristics of adrenal lesions in unilateral primary aldosteronism.Methods:This is a prospective study. Consecutive patients diagnosed with unilateral primary aldosteronism at the First Affiliated Hospital of Chongqing Medical University from December 2023 to November 2024 were included. Inclusion criteria：① Age is 18 to 80 years old；② The laboratory test indicators are in line with the diagnosis of primary aldosteronism；③ The auxiliary examination proved that only one side was involved；④ Patient undergo unilateral total adrenalectomy. The exclusion criteria are as follows：① Complete biochemical remission was not achieved during the 1-6 month follow-up after the surgery；② Postoperative loss to follow-up；③ No surgical specimens were received or the surgical specimens were incomplete，making continuous sectioning impossible. Patients meeting the inclusion criteria were recruited，and their clinical and biochemical data were recorded. The number of adrenal nodules visible on CT scans and the number of macroscopically visible nodules in the postoperative adrenal gross specimens were documented. Hematoxylin-eosin（HE）staining and aldosterone synthase CYP11B2 immunohistochemical staining were performed on the adrenal tissues after the operation. The number of nodules visible under the light microscope and the number of CYP11B2-positive nodules were recorded.Results:A total of 114 cases were included in this study. The age of the patients was（49.86 ± 9.80）years，the body mass index was（25.49 ± 3.40）kg/m2，the preoperative aldosterone level was 352（2012，556）pg/ml，and the direct renin concentration was 1.63（0.50，4.56）μIU/ml. The aldosterone/renin ratio was 224.9（57.1，641.6）（aldosterone concentration unit was pg/ml，renin concentration unit was μIU/ml），the minimum blood potassium concentration was 2.87（2.50，3.40）mmol/L，and the systolic blood pressure was（144.5 ± 19.5）mmHg. Among the 114 patients，105 had adrenal nodules detected by preoperative CT，of whom 2（1.75%）had multiple nodules. Postoperative gross adrenal specimen evaluation and CYP11B2 immunohistochemical staining revealed that 90 out of 114 cases were solitary nodules，2 cases had no nodules，and 22 cases（19.30%）had multiple nodules detected（17 cases had 2 nodules and 5 cases had 3 nodules）. Among them，12 cases（10.53%）presented as grossly visible multinodular lesions，while 10 cases（8.77%）appeared as solitary nodules macroscopically but demonstrated multinodular patterns on immunohistochemical staining. CYP11B2 staining showed that among the 22 patients with multiple nodules，13 had multiple CYP11B2-positive nodules，while the remaining had only one positive nodule. Among the 22 patients with multiple nodules，preoperative CT showed single nodules in 19 cases，hyperplasia in 1 case，and multiple nodules in 2 cases（9.09%）. Among the 12 patients with grossly visible multinodular lesions，preoperative CT showed single nodules in 9 cases，hyperplasia in 1 case，and multiple nodules in 2 cases（16.67%）.Conclusions:Multiple adrenal nodules associated with unilateral primary aldosteronism are relatively common，and are often not detected by preoperative CT examination. Partial adrenalectomy based solely on CT-visible nodules may fail to achieve complete remission of primary aldosteronism. This study provides evidence supporting total adrenalectomy as the preferred surgical approach for unilateral primary aldosteronism.

Astrocytes are the largest glial population in the mammalian brain. However, we have a minimal understanding of astrocyte development, especially fate specification in different regions of the brain. Through lineage tracing of the progenitors of the third ventricle (3V) wall via in-utero electroporation in the embryonic mouse brain, we show the fate specification and migration pattern of astrocytes derived from radial glia along the 3V wall. Unexpectedly, radial glia located in different regions along the 3V wall of the diencephalon produce distinct cell types: radial glia in the upper region produce astrocytes and those in the lower region produce neurons in the diencephalon. With genetic fate mapping analysis, we reveal that the first population of astrocytes appears along the zona incerta in the diencephalon. Astrogenesis occurs at an early time point in the dorsal region relative to that in the ventral region of the developing diencephalon. With transcriptomic analysis of the region-specific 3V wall and lateral ventricle (LV) wall, we identified cohorts of differentially-expressed genes in the dorsal 3V wall compared to the ventral 3V wall and LV wall that may regulate astrogenesis in the dorsal diencephalon. Together, these results demonstrate that the generation of astrocytes shows a spatiotemporal pattern in the developing mouse diencephalon.
Mice ; Animals ; Astrocytes ; Neuroglia/physiology* ; Diencephalon ; Brain ; Neurons ; Mammals

Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs. It is critical to inspire new potential to remodel the value of this classical therapeutic strategy. Here, we fabricate bisphosphonate coordination lipid nanogranules (BC-LNPs) and load paclitaxel (PTX) to boost the chemo- and immuno-therapeutic synergism of cytotoxic drugs. Alendronate in BC-LNPs@PTX, a bisphosphonate to block mevalonate metabolism, works as both the structure and drug constituent in nanogranules, where alendronate coordinated with calcium ions to form the particle core. The synergy of alendronate enhances the efficacy of paclitaxel, suppresses tumor metastasis, and alters the cytotoxic mechanism. Differing from the paclitaxel-induced apoptosis, the involvement of alendronate inhibits the mevalonate metabolism, changes the mitochondrial morphology, disturbs the redox homeostasis, and causes the accumulation of mitochondrial ROS and lethal lipid peroxides (LPO). These factors finally trigger the ferroptosis of tumor cells, an immunogenic cell death mode, which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy. Therefore, by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis, BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.