Diabetic nephropathy （DN） is one of the most common and serious microvascular complications of diabetes mellitus and represents a major cause of chronic kidney disease progression and end-stage kidney disease， thereby constituting a major public health problem that adversely affects the prognosis and quality of life of patients with diabetes mellitus. The pathogenesis and progression of DN are complex and involve multiple pathological processes， including insulin resistance， inflammation， oxidative stress， lipid deposition， podocyte injury， and renal fibrosis. Although current clinical therapies can delay the progression of DN to some extent， their effectiveness remains limited by marked interindividual variability in therapeutic response and the difficulty of fully reversing renal injury. Therefore， further elucidation of the key molecular mechanisms underlying DN and the exploration of effective therapeutic strategies are of considerable importance. In recent years， with advances in the understanding of DN pathogenesis， peroxisome proliferator-activated receptor γ （PPARγ）， an important nuclear receptor transcription factor involved in the regulation of insulin resistance， inflammation， oxidative stress， and fibrotic processes， has attracted increasing attention for its role in the development and progression of DN. Traditional Chinese medicine （TCM）， characterized by multi-component， multi-target， and multi-pathway synergistic regulation， may ameliorate pathological processes including metabolic abnormalities， inflammation， oxidative stress， lipid deposition， and renal fibrosis in DN by targeting PPARγ and its associated signaling networks. This review systematically summarizes the mechanisms by which PPARγ and its related signaling pathways regulate DN and reviews recent advances in TCM interventions targeting the PPARγ signaling pathway in DN. Such TCM interventions encompass single herbs such as Coptidis Rhizoma， active constituents such as quercetin， astragaloside Ⅳ， and trigonelline， extracts of herbs such as Plantaginis Herba and Dendrobii Nobilis Caulis， and formulas such as Huangkui capsules， Shenshuaining granules， and Mudan granules. This review aims to provide a theoretical basis for the prevention and treatment of DN with TCM.

Objective To observe the clinical efficacy of Bushen Yiliu Formula(mainly composed of Epimedii Folium,Ligustri Lucidi Fructus,Ecliptae Herba,and Paridis Rhizoma)in treating advanced hormone-sensitive prostate cancer accompanied by bone metastasis of kidney deficiency type.Methods A prospective randomized controlled trial was conducted on 45 patients with advanced hormone-sensitive prostate cancer accompanied by bone metastasis of kidney deficiency type,who received treatment at Guangdong Provincial Hospital of Chinese Medicine from January 2022 to February 2024.The patients were randomly divided into an observation group(23 cases)and a control group(22 cases).All patients received complete androgen blockade therapy combined with bone-protective therapy.Additionally,the observation group was treated with the modified Bushen Yiliu Formula for 6 months.The clinical efficacy of Bushen Yiliu Formula was evaluated with the disease control rate(DCR)and objective response rate(ORR)after 3 and 6 months of treatment,and with the changes in the TCM syndrome scores,Karnofsky Performance Status(KPS)scores,Numerical Rating Scale(NRS)pain scores,and serum levels of total prostate-specific antigen(tPSA)and alkaline phosphatase(ALP)before treatment and after 3 and 6 months of treatment.Changes in serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),and creatinine(Scr)levels before treatment and after 3 and 6 months of treatment were observed to assess the clinical safety of the formula.Results(1)After 3 months of treatment,both groups had no complete remission cases.After 6 months,the observation group hand only one complete remission case.After 3 months of treatment,the ORR and DCR in the observation group were 21.74%(5/23)and 95.65%(22/23),respectively,compared to 22.73%(5/22)and 95.45%(21/22)in the control group.The intergroup comparison showed that there were no significant differences between the two groups(P＞0.05).After 6 months of treatment,the ORR and DCR in the observation group were 60.87%(14/23)and 95.65%(22/23),respectively,significantly higher than those in the control group[22.73%(5/22)and 68.18%(15/22),respectively],with statistically significant differences(P＜0.05).(2)After 3 and 6 months of treatment,TCM syndrome scores and NRS pain scores in both groups were significantly decreased(P＜0.01),and KPS scores were significantly increased(P＜0.01).Except for TCM syndrome scores after 3 months of treatment,the observation group had stronger effect on decreasing TCM syndrome scores and NRS pain scores and on increasing KPS scores after 3 and 6 months of treatment than the control group(P＜0.01).(3)The serum level of tumor-related marker tPSA after 3 months of treatment,and serum tPSA and ALP levels after 6 months of treatment were significantly decreased in both groups compared to the baseline level(P＜0.05 or P＜0.01).The observation group had stronger effect on decreasing serum tPSA level after 3 and 6 months compared to the control group(P＜0.05 or P＜0.01).However,no significant differences of serum ALP level were observed between the two groups after 3 and 6 months of treatment(P＞0.05).(4)Serum levels of safety indicators of ALT,AST,and Scr showed no significant changes in either group after 3 or 6 months of treatment compared to the baseline level(P＞0.05).Conclusion Bushen Yiliu Formula combined with endocrine therapy exerts certain efficacy for the treatment of advanced hormone-sensitive prostate cancer accompanied by bone metastasis of kidney deficiency type.The combined therapy is effective in reducing tumor burden of bone metastases,improving objective response rates,alleviating clinical symptoms,decreasing NRS pain scores,enhancing quality of life,and effectively lowering serum tPSA and ALP levels.Its efficacy is significantly superior to endocrine therapy alone.

Objective:To evaluate the effect of intraoperative optimization of regional cerebral oxygen saturation(rSO 2C) intervention on postoperative delirium(POD) in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass(CPB). Methods:Two hundred and seventy-three pediatric patients of both sexes, aged 28 days-6 yr, with American Society of Anesthesiologists Physical Status classification ≤Ⅳ, scheduled for elective cardiac surgery under CPB, were divided into intervention group( n=136) and control group( n=137) based on the computer random coding. In intervention group, optimized intervention measures were given when rSO 2C was below 75% of the baseline value for more than 1 min. In control group, rSO 2C was not monitored during operation, and intraoperative management was performed according to the routine monitoring indicators of pediatric cardiac surgery under CPB. The occurrence of POD within 7 days after operation was evaluated, and the duration and first occurrence time of POD were recorded. Results:Compared with control group, no significant change was found in the incidence of POD( P>0.05), the first occurrence time of POD was significantly prolonged, and the duration of POD was shortened in intervention group( P<0.05). Conclusions:Intraoperative optimization of rSO 2C intervention can delay the time to the first occurrence of POD and shorten the duration in pediatric patients undergoing cardiac surgery under CPB.

The European Society for Medical Oncology Asia Congress 2024 was held in Singapore from December 6 to 8,2024.The conference unveiled several groundbreaking studies in the field of hepatobiliary and pancreatic tumors,covering clinical applications related to neoadjuvant and adjuvant therapies,translational treatments,later-line therapies,and tumor biomarkers.These studies provide new insights into the clinical diagnosis and treatment of hepatobiliary and pancreatic malignancies and drive the development of related fields.This article focuses on the key topics in hepatobiliary and pancreatic malignancies presented at the conference,aiming to interpret the latest advances in the field and explore the hot issues and future directions for development in this area.

Objective To explore the nephrotoxic effects of exposure to perfluorobutanoic acid (PFBA) and its mechanism in mice, with a particular focus on analyzing the changes in kidney metabolism and their potential implications. Methods The specific pathogen free C57BL/6 mice were randomly divided into control group, low-dose group, and high-dose group, with 10 mice in each group. Mice in the three groups received intragastric administration of PFBA solution at doses of 0, 35 and 350 mg/kg body weight, once per day for seven consecutive days. The histopathological changes of kidneys of mice in these three groups were evaluated. Metabolomic profiling of mouse kidneys was performed using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Differentially accumulated metabolites (DAMs) were identified based on the Human Metabolome Database, and related metabolic pathways were analyzed through MetaboAnalyst 6.0 and Kyoto Encyclopedia of Genes and Genomes (KEGG). Results Histopathological analysis of kidneys showed that the renal pelvis mucosa of mice in the low-dose group presented focal mild inflammatory changes without marked structural damage, whereas mice in the high-dose group showed severe inflammation and partial destruction of renal structure. The kidney coefficient of mice in both low-dose group and the high-dose group decreased (both P<0.05), and the Paller scores of renal tissues increased (both P<0.05) compared with that in the control group. The Paller score of mouse renal tissue in the high-dose group was higher than that in the low-dose group (P<0.05). Metabolomic profiling identified 46 DAMs (26 upregulated, 20 downregulated) in the low-dose group and 104 DAMs (54 upregulated, 50 downregulated) in the high-dose group, with 26 shared DAMs between the two dose groups. KEGG pathway analysis revealed that DAMs were mainly involved in metabolic pathways such as glycerophospholipid metabolism, glycerolipid metabolism, sphingolipid and steroid hormone synthesis. Conclusion Acute exposure to PFBA can cause kidney injury in mice. Lipid metabolism pathways such as glycerophospholipid and sphingolipid metabolism is involved in the development of acute renal toxicity of PFBA.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective:To evaluate the effect of intraoperative optimization of regional cerebral oxygen saturation(rSO 2C) intervention on postoperative delirium(POD) in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass(CPB). Methods:Two hundred and seventy-three pediatric patients of both sexes, aged 28 days-6 yr, with American Society of Anesthesiologists Physical Status classification ≤Ⅳ, scheduled for elective cardiac surgery under CPB, were divided into intervention group( n=136) and control group( n=137) based on the computer random coding. In intervention group, optimized intervention measures were given when rSO 2C was below 75% of the baseline value for more than 1 min. In control group, rSO 2C was not monitored during operation, and intraoperative management was performed according to the routine monitoring indicators of pediatric cardiac surgery under CPB. The occurrence of POD within 7 days after operation was evaluated, and the duration and first occurrence time of POD were recorded. Results:Compared with control group, no significant change was found in the incidence of POD( P>0.05), the first occurrence time of POD was significantly prolonged, and the duration of POD was shortened in intervention group( P<0.05). Conclusions:Intraoperative optimization of rSO 2C intervention can delay the time to the first occurrence of POD and shorten the duration in pediatric patients undergoing cardiac surgery under CPB.

The European Society for Medical Oncology Asia Congress 2024 was held in Singapore from December 6 to 8,2024.The conference unveiled several groundbreaking studies in the field of hepatobiliary and pancreatic tumors,covering clinical applications related to neoadjuvant and adjuvant therapies,translational treatments,later-line therapies,and tumor biomarkers.These studies provide new insights into the clinical diagnosis and treatment of hepatobiliary and pancreatic malignancies and drive the development of related fields.This article focuses on the key topics in hepatobiliary and pancreatic malignancies presented at the conference,aiming to interpret the latest advances in the field and explore the hot issues and future directions for development in this area.

The orphan nuclear receptor Nur77 is emerging as an attractive target for cancer therapy, and activating Nur77's non-genotypic anticancer function has demonstrated strong therapeutic potential. However, few Nur77 site B ligands have been identified as excellent anticancer compounds. There are no co-crystal structures of effective anticancer agents at Nur77 site B, which greatly limits the development of novel Nur77 site B ligands. Moreover, the lack of pharmaceutical ligands restricts Nur77's therapeutic proof of concept. Herein, we developed a first-in-class Nur77 site B ligand (NB1) that significantly inhibited cancer cells by mediating the Nur77/Bcl-2-related apoptotic effect at mitochondria. The X-ray crystallography suggests that NB1 is bound to the Nur77 site B with a distinct binding mode. Importantly, NB1 showed favorable pharmacokinetic profiles and safety, as evidenced by its good oral bioavailability in rats and lack of mortality, bodyweight loss, and pathological damage at the 512.0 mg/kg dose in mice. Furthermore, oral administration of NB1 demonstrated remarkable in vivo anticancer efficacy in an MDA-MB-231 xenograft model. Together, our work discovers NB1 as a new generation Nur77 ligand that activates the Nur77/Bcl-2 apoptotic pathway with a safe and effective cancer therapeutic potency.

Interactions between brain-resident and peripheral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia. However, conventional bulk sequencing makes it challenging to depict this complex immune network. Using single-cell RNA sequencing, we mapped compositional and transcriptional features of peri-infarct immune cells. Microglia were the predominant cell type in the peri-infarct region, displaying a more diverse activation pattern than the typical pro- and anti-inflammatory state, with axon tract-associated microglia (ATMs) being associated with neuronal regeneration. Trajectory inference suggested that infiltrated monocyte-derived macrophages (MDMs) exhibited a gradual fate trajectory transition to activated MDMs. Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis, with SOX2 and related Akt/CREB signaling as the underlying mechanisms. This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.
Humans ; Ischemic Stroke ; Brain/metabolism* ; Macrophages ; Brain Ischemia/metabolism* ; Microglia/metabolism* ; Gene Expression Profiling ; Anti-Inflammatory Agents ; Neuronal Plasticity/physiology* ; Infarction/metabolism*