This study aimed to investigate the effects of Zhiwei Fuwei Pills on mitochondrial apoptosis in the rat model of precancerous lesions of gastric cancer(PLGC) based on the microRNA-21(miRNA-21)/B-cell lymphoma-2(Bcl-2) signaling pathway. Eighty-five 5-week-old male SPF-grade SD rats were selected, of which 75 were fed with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) for multifactorial modeling, and the PLGC model was established after 26 weeks. The rats were randomly grouped as follows: model, folic acid(0.002 g·kg~(-1)), low-dose(0.42 g·kg~(-1)) Zhiwei Fuwei Pills, medium-dose(0.84 g·kg~(-1)) Zhiwei Fuwei Pills, and high-dose(1.67 g·kg~(-1)) Zhiwei Fuwei Pills, with 15 rats in each group. Additionally, 10 rats were assigned to a blank group and administrated with an equivalent volume of normal saline by gavage. After four weeks of continuous drug administration, the gastric mucosal tissue was collected. Hematoxylin-eosin(HE) staining was performed to reveal the pathological changes in the gastric mucosa. Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) was employed to detect apoptosis in gastric mucosal epithelial cells. RT-PCR was adopted to determine the mRNA levels of miRNA-21, phosphatase and tensin homolog(PTEN), Bcl-2, Bcl-2-associated X protein(Bax), and cysteinyl aspartate-specific protease 3(caspase-3). Western blot was employed to determine the protein levels of PTEN, Bcl-2, Bax, and caspase-3. Immunohistochemistry(IHC) was used to detect the positive expression of PTEN, Bcl-2, and Bax in the gastric mucosal tissue. Transmission electron microscopy(TEM) was employed to observe the morphological and structural changes in mitochondria. The results showed that compared with model group, the drug administration groups showed alleviated pathological changes, with increased apoptotic cells, down-regulated mRNA levels of miRNA-21 and Bcl-2, up-regulated mRNA and protein levels of PTEN, Bax, and caspase-3, and down-regulated protein level of Bcl-2. In addition, the drug administration groups exhibited mitochondrial swelling and rupture and reduction of cristae, which indicated mitochondrial apoptosis. These findings suggest that Zhiwei Fuwei Pills can effectively improve mitochondrial apoptosis in PLGC cells by regulating the miRNA-21/Bcl-2 signaling pathway.
Animals ; MicroRNAs/metabolism* ; Male ; Apoptosis/drug effects* ; Stomach Neoplasms/physiopathology* ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Rats ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; Mitochondria/genetics* ; Signal Transduction/drug effects* ; Precancerous Conditions/drug therapy* ; Humans ; PTEN Phosphohydrolase/genetics*

OBJECTIVE: To investigate the effectiveness of digital three-dimensional (3D) assisted unilateral biportal endoscopy (UBE) in the treatment of highly isolated lumbar disc herniation (LDH) with translaminar approach. METHODS: The clinical data of 59 patients who met the selection criteria and underwent UBE treatment due to highly isolated LDH between January 2022 and December 2023 were retrospectively analyzed. Among them, 25 cases were treated with digital 3D assisted translaminar approach (observation group) and 34 cases were treated with interlaminar approach (control group). There was no significant difference in gender, age, disease duration, surgical segment, and preoperative visual analogue scale (VAS) score and Oswestry disability index (ODI) between the two groups ( P>0.05). The operation time, intraoperative blood loss, and lateral articular surface preservation rate were recorded and compared between the two groups. VAS score and ODI were used to evaluate the improvements of pain and function before operation and at 3 and 6 months after operation. The modified MacNab criteria was used to evaluate the effectiveness at last follow-up. RESULTS: One patient in the control group had dural tear, and the other patients had no nerve injury, infection, dural tear, or other related complications. There was no significant difference in operation time and intraoperative blood loss between the two groups ( P>0.05). Patients in both groups were followed up 6-13 months, with an average of 8.3 months. The lateral articular surface preservation rate in the observation group was significantly higher than that in the control group ( P<0.05). Three patients in the observation group and 2 patients in the control group had calf muscle venous thrombosis, which was cured after anticoagulant treatment with rivaroxaban and delayed exercise time. There was no recurrence or second operation during the follow-up period. The VAS score and ODI of the two groups at 3 and 6 months after operation significantly improved when compared with those before operation ( P<0.05). There was no significant difference between the two groups at each time point after operation ( P>0.05). At last follow-up, the effectiveness was evaluated according to the modified MacNab criteria, and there was no significant difference in the evaluation grade and excellent and good rate between the two groups ( P>0.05). CONCLUTION UBE via translaminar approach is safe and effective for the treatment of highly isolated LDH, which is beneficial to protect the facet joint, maintain spinal stability, and reduce soft tissue injury. With the assistance of digital 3D technique, preoperative planning can be performed accurately.
Humans ; Intervertebral Disc Displacement/diagnostic imaging* ; Lumbar Vertebrae/diagnostic imaging* ; Male ; Retrospective Studies ; Female ; Endoscopy/methods* ; Treatment Outcome ; Middle Aged ; Adult ; Imaging, Three-Dimensional ; Operative Time ; Pain Measurement

Taxifolin (TAX) is a natural compound known for its liver protection effect, but the mechanism remains unknown. Phosphorylated proteomics analyses discovered that the phosphorylation level of NDRG1 at T328 was a key event of TAX-improved liver fibrosis. We established models with NDRG1 knockout (KO) in vivo and in vitro, demonstrating that NDRG1 KO attenuated the development of hepatocyte injury, and combining NDRG1 KO and TAX administration did not result in a reduction in protection against liver injury. Cellular thermal shift assay and surface plasma resonance analysis showed that TAX directly binds to NDRG1 rather than its upstream kinase, subsequently demonstrating that TAX regulated phosphorylation of NDRG1 at T328 through binding to its C289 site. NDRG1 T328A (phosphorylated mutation) and T328E (mimic phosphorylation) in vivo and in vitro confirmed that pNDRG1_T328 exacerbates hepatocyte injury along with DNA damage, inflammatory response, and apoptosis, thereby contributing to hepatic stellate cells (HSCs) activation. In contrast, TAX can inhibit the above pathological abnormalities and block hepatocyte injury-triggered HSCs activation and fibrosis. Overall, TAX is a potent liver protection drug primarily targeting NDRG1 and inhibiting pNDRG1_T328 in hepatocytes.

In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.

Objective To assess the efficacy of a novel inguinal tourniquet in healthy individuals and to investigate the relationship between localized inguinal compression and femoral artery blood flow occlusion.Methods A self-controlled study was conducted.From November 9 to November 30,2024,11 volunteers were recruited at the Third Medical Center of Chinese PLA General Hospital.Three compression methods--finger pressure,a novel groin tourniquet,and a SAM junction tourniquet(SJT)—were applied bilaterally to the inguinal region until distal blood flow signals disappeared.Each compression method was tested in 22 trials with a 5-minute interval between operations.Differences in hemostatic efficacy between bilateral inguinal regions and across compression methods were compared.Subsequently,the novel tourniquet was incrementally pressurized in 120 mmHg multiples using an integrated pressure device to analyze trends in popliteal artery blood flow velocity.Observational indicators included the internal pressure of the tourniquet pressurization device,peak systolic velocity(PSV)of popliteal artery,inguinal surface pressure magnitude,inguinal surface pressure distribution,and pain scores(assessed using a single-dimensional numerical rating scale).Results No statistically significant difference was observed in the minimum pressure required to occlude femoral artery blood flow bilaterally(P>0.05).The success rates of femoral artery blood flow occlusion at the inguinal region were 100%for the novel inguinal tourniquet,SJT,and finger pressure.The novel inguinal tourniquet induced the highest pain scores,ranging from 5 to 8.A significant reduction in PSV of popliteal artery was noted when the intra-tourniquet pressure reached 360 mmHg and 480 mmHg(P<0.05),with a 95%hemostasis efficacy observed within the range of 360-600 mmHg.No significant association was observed between the recovery of popliteal artery blood flow after limb movement and inguinal pressure distribution(P>0.05).The PSV of popliteal artery exhibited the strongest negative correlation with the average pressure within the inguinal compression area(r=-0.79,P<0.001),with a linear regression fitting line of y=69.69-0.13x(P<0.001,R2=0.58).Conclusions The novel inguinal tourniquet effectively occludes femoral artery blood flow within a pressure range of 360-600 mmHg,accompanied by moderate-to-severe pain.Its hemostatic mechanism mainly relies on increasing the mean pressure within the inguinal compression area.

Objective To study the effect of Hedysarum polysaccharides(HPS)on the expression of transforming growth factor-β,(TGF-β1),smad homologue 3 recombinant protein(smad3)and smad7 in renal tissue of db/db mice with diabetic nephropathy(DN).Methods According to their body weight,6-week-old male db/db mice were randomly divided into 5 groups:model group(0.9％NaCl 0.2 mL·d-1),positive control group(22.75 mg·kg-1·d-1 irbesartan)and experimental-H,-M,-L groups(200,100,50 mg kg-1·d-1 HPS),with 10 mice in each group;another 10 SPF grade male C57BL/6 mice of the same week were selected as normal group(0.9％NaCl 0.2mL·d-1).The mice in the 6 groups were given intragastric administration once a day for 12 weeks.The blood glucose concentration of mice was measured before treatment and at the 4th,8th and 12th week after treatment.The expression levels of TGF-β1,smad3 and smad7 were detected by Western blotting.Results After treatment,the blood glucose levels of the model group was significantly higher than those of the normal group(all P＜0.01);compared with the model group,the levels of blood glucose in the experimental-H,-M groups decreased significantly,and the differences were statistically significant(P＜0.05,P＜0.01).The relative expression levels of TGF-β,protein in normal group,model group,positive control group and experimental-H,-M groups were 0.71±0.16,1.66±0.18,1.00±0.17,0.88±0.15 and 1.23±0.15;the relative expression levels of smad3 protein were 0.89±0.32,2.26±0.35,1.24±0.31,1.05±0.30 and 1.67±0.35;the relative expression levels of smad7 protein were 1.66±0.03,0.60±0.03,1.10±0.07,1.48±0.08 and 0.97±0.09;there were statistically significant differences between the experimental-H,-M groups and the model group(P＜0.05,P＜0.01).Conclusion Hedysarum polysaccharides can improve renal fibrosis and delay the development of diabetic nephropathy by regulating the level of blood glucose,inhibiting TGF-β1,smad3 and increasing the expression of smad7.

Laminar organization is a hallmark of the mammalian neocortex, where the orderly arrangement of diverse neurons stereotypically forms into six distinct layers. The laminar structure provides a basis for the formation of precise neural circuits responsible for high-level cognitive functions. A deeper understanding of the mechanisms underlying neocortical layer formation and cell assembly in the brain will provide a more comprehensive insight into mammalian and even human physiology and behavior. It will also enable the development of novel diagnostic and therapeutic strategies for neurological disorders. To achieve this, it is imperative to elucidate the molecular regulatory networks that determine the fate of neurons in the neocortex. MicroRNAs (miRNAs) are small non-coding RNAs of 18-25 nucleotides in length that play important roles in the gene expression network. A large number of studies have reported that miRNAs are involved in various developmental processes within the nervous system. This review summarizes the progress of research on miRNAs that have been identified in recent years with regard to neocortical layer formation. We start with a comparative analysis of different Cre-line mediated conditional knockout mice for Dicer, a gene indispensable for the synthesis of almost all miRNAs. The results indicate that miRNAs are essential for the formation of neocortical layers, including the determination of the fate of projection neurons and the migration of these cells. Next, we summarize the regulatory roles of miRNAs in the coordinated execution of a series of developmental events that contribute to neocortical layer formation. First, the temporal patterning of neocortical neural progenitors is regulated by miRNAs. Two types of temporally opposite expression gradients and functionally antagonistic miRNAs modulate the competence of neural progenitors by changing their relative expression levels during neurogenesis, thereby shifting the progressive generation of neocortical neurons. Second, it is described that miRNAs influence lamination by regulating the fate of intermediate progenitor cells (IPCs). In particular, several miRNAs that are specifically expressed in multiple gyrencephalic species have been identified in recent years and are involved in regulating the generation of IPCs as well as the generation of upper layer neurons. Third, the regulatory roles of miRNAs in the migration of cortical projection neurons, including the multipolar to bipolar transition and other processes, were presented. Fourth, we described miRNAs that are expressed in postmitotic neurons but play roles in the further specification of different cortical projection neuron subtype identities, in particular the role of several miRNAs in the Mirg cluster in establishing different subtype identities of projection neurons in layer V, promoting corticospinal motor neuron (CSMN) identity but inhibiting callosal projection neuron (CPN) identity. Finally, we discussed current challenges in the study of miRNAs in neocortical layer formation and looked forward to future directions that deserve further exploration, such as the functions of a large number of newly discovered miRNAs, or whether miRNAs regulate the layer-dependent pattern of other neuronal cells with layer distribution features; the contribution of miRNAs in the rapid evolution of the neocortex, especially in the formation of characteristic structures in the primate neocortex; and the use of miRNAs as an entry point to explore finer regulatory networks.

Background Atmospheric fine particulate matter (PM_2.5) can disrupt the metabolic homeostasis of the liver and accelerate the progression of liver diseases, but there are few studies on the effects of sub-chronic PM_2.5 exposure on the liver metabolome. Objectives To investigate the effects of sub-chronic exposure to concentrated PM_2.5 on hepatic metabolomics in mice by liquid chromatography-mass spectrometry (LC-MS), and to identify potentially affected metabolites and metabolic pathways. Methods Twelve male C57BL/6J (6 weeks old) mice were randomly divided into two groups: a concentrated PM_2.5 exposure group and a clean air exposure group. The mice were exposed to concentrated PM_2.5 using the "Shanghai Meteorological and Environmental Animal Exposure System" at Fudan University. The exposure duration was 8 h per day, 6 d per week, for a total of 8 weeks. The mice's liver tissues were collected 24 h after the completion of exposure. LC-MS was performed to assess changes in the hepatic metabolome. Orthogonal partial least squares discriminant analysis and t-test were employed to identify differentially regulated metabolites between the two groups under the conditions of variable important in projection (VIP)≥1.0 and P<0.05. Metabolic pathway enrichment analysis was performed using MetaboAnalyst 5.0 software and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Results A total of 297 differentially regulated metabolites were identified between the concentrated PM_2.5 exposure group and the clean air group. Among these metabolites, 142 were upregulated and 155 were downregulated. A total of 38 metabolic pathways were altered, with 7 pathways showing significant perturbation (P<0.05). These pathways involved amino acid metabolism, glucose metabolism, nucleotide metabolism, as well as cofactor and vitamin metabolism. The 7 significant metabolic pathways were pantothenic acid and coenzyme A biosynthesis; purine metabolism; amino sugar and nucleotide sugar metabolism; arginine biosynthesis; alanine, aspartate and glutamate metabolism; aminoacyl-tRNA biosynthesis; and fructose and mannose metabolism. Conclusion The results from metabolomics analysis suggest that sub-chronic exposure to PM_2.5 may disrupt hepatic energy metabolism and induce oxidative stress damage. Aspartic acid, succinic acid, ornithine, fumaric acid, as well as purine and xanthine derivatives, were identified as potential early biomarkers of hepatic response to sub-chronic PM_2.5 exposure.

Cornus officinalis,a medicinal and edible plant known for its liver-nourishing properties,has shown promise in inhibiting the activation of hepatic stellate cells(HSCs),crucial indicators of hepatic fibrosis,especially when processed by high pressure wine steaming(HPWS).Herein,this study aims to investigate the regulatory effects of cornus officinalis,both in its raw and HPWS forms,on inflammation and apoptosis in liver fibrosis and their underlying mechanisms.In vivo liver fibrosis models were established by subcutaneous injection of CCl4,while in vitro HSCs were exposed to transforming growth factor-β(TGF-β).These findings demonstrated that cornus officinalis with HPWS conspicuously ameliorated his-topathological injury,reduced the release of proinflammatory factors,and decreased collagen deposition in CCl4-induced rats compared to its raw form.Utilizing ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer(UHPLC-QTOF-MS)combined with network analysis,we identified that the pharmacological effects of the changed components of cornus officinalis before and after HPWS,primarily centered on the adenosine phosphate(AMP)-activated protein kinase(AMPK)pathway.Of note,cornus officinalis activated AMPK and sirtuin 3(SIRT3),promoting the apoptosis of activated HSCs through the caspase cascade by regulating caspase3,caspase6 and caspase9.small interfering RNA(siRNA)experiments showed that cornus officinalis could regulate AMPK activity and its mediated-apoptosis through SIRT3.In conclusion,cornus officinalis exhibited the ability to reduce inflammation and apoptosis,with the SIRT3-AMPK signaling pathway identified as a potential mecha-nism underlying the synergistic effect of cornus officinalis with HPWS on anti-liver fibrosis.

Objective:To analyze the effect of long-term care insurance on the incidence of falls in old people with disability, and the modification effect of different living arrangements.Methods:Based on the discharge diagnosis records of the hospitalization in urban residents who applied for long-term care insurance in Chengdu from July 2014 to June 2021, those who received long-term care insurance were selected as the intervention group and those who received no long-term care insurance were selected as the control group, the changes in the incidence of falls before and after the long-term care were analyzed using difference-in-differences method, and the modification effects of different living arrangements were explored using stratified analysis.Results:Long-term care insurance significantly reduced the risk for monthly incidence of falls in older adults [average treatment effects on treated (ATT) = -1.21% (95% CI: -1.82%--0.60%)], and the effect increased over time (ATT=-1.26%, 95% CI: -1.93%--0.59%). Long-term care insurance had a significant effect on reducing the incidence of falls in old people living with spouses/family members (ATT=-0.92%, 95% CI: -1.47%--0.37%) and in nursing facilities/hospitals (ATT=-2.10%, 95% CI: -3.81%--0.40%), but it had no significant effect in those living alone. Conclusions:Long-term care insurance can effectively reduce the incidence of falls in old people with disability, showing a positive effect. Living with family members or in nursing facilities/hospitals has a modification effect of the implementation of long-term care insurance policy. It is necessary to pay attention to key populations in the future and expand the coverage of long-term care insurance.