Regulated cell death (RCD) has long been conceptualized as an elaborate program orchestrated by the nucleus and mitochondria in eukaryotic cells. However, this paradigm was fundamentally changed in 2025 by two independent studies published in Cell. One revealed that mature, enucleated erythrocytes execute a cytoskeletal disintegration-driven lysis via a miniNLRP3-ASC-caspase-8‑β‑spectrin axis, termed spectrin-dependent death (spectosis), wherein caspase-8 undergoes a functional switch from an initiator to an executioner, reflecting an evolutionary adaptation in protein economy. The other uncovered mitoxypterilysis, a modality in which metabolic distress and innate immune signals converge to trigger mTORC2-mediated aberrant mitochondrial-plasma membrane contacts, culminating in localized lipid peroxidation and membrane rupture. Mitoxypterilysis shows a logic defined by dual metabolic-immune regulation. This paper systematically dissects the molecular architectures of both modalities, and through comparative analysis, delineates their distinctions from classical RCD pathways as well as their divergent dependencies on organellar integrity, triggering contexts, and executional programs. In parallel, we integrate the recent discovery of reductive death, which underscores a central metabolic checkpoint to contextualize these findings within an emerging framework. Finally, we evaluate their therapeutic implications in hemolytic diseases, oncology, and inflammatory pathologies, while critically reflecting on current limitations and future directions, with the aim of providing a renewed conceptual foundation for targeted intervention strategies.

To study the effect of self-assembled nanoparticles from Shaoyao Gancao Decoction(SGD-SAN) on the encapsulation, in vitro release and intestinal absorption of the main components of Baishao. Particle size analysis and morphological observation were used to verify the formation of SGD-SAN in the decoction. The entrapment efficiency(EE) of SGD-SAN on the main components of Baishao was determined by ultrafiltration centrifugation. The dialysis bag method was used to study the in vitro release of the main components of Baishao with pH 6.8 phosphate buffer solution as the release media. Single-pass intestinal perfusion study was performed to investigate the effect of SGD-SAN on the absorption of the main components of Baishao. The results showed that there were nanoparticles in the SGD, and the particle sizes and PDI of SGD-SAN were about 200 nm and 0.38, respectively. SGD-SAN was irregularly spherical under transmission electron microscope(TEM). The EEs of albiflorin, paeoniflorin and benzoylpaeoniflorin in SGD-SAN were 33.78%±1.03%,33.61%±0.90%,88.53%±0.58%, respectively. The release characteristics of albiflorin, paeoniflorin and benzoylpaeoniflorin from SGD-SAN showed a slow-release effect on pH 6.8 phosphate buffer solution media. SGD-SAN could significantly enhance the absorption of albiflorin, paeoniflorin and benzoylpaeoniflorin in the ileum. The results of this study indicated that SAN could be formed during the mixed decoction of Baishao and Gancao, and SGD-SAN could encapsulate the components of Baishao, with a certain slow-release effect, and the formation of SAN facilitated the absorption of drugs in the ileum.
Drugs, Chinese Herbal ; Intestinal Absorption ; Intestines ; Nanoparticles

ObjectiveTo analyze the timeliness of health science popularization during the outbreak of coronavirus disease 2019 （COVID-19） and its correlation with the epidemic situation and policies. MethodsThe original reports of health science popularization by 26 major media in Shanghai during the COVID19 outbreak between January 19 and March 25 of 2020 were retrieved， and the timeliness of the number of reports， media sources and categories， and contents were analyzed. ResultsDuring the epidemic of COVID-19， public media reported timely. Online media accounted for 63.35%， and text-based reports accounted for 85.90%. There was a correlation between the trend of the number of reports and the development of COVID-19 and the prevention and control policy issued by the government. After the change in the epidemic or the release of policy， the number of reports increased. The top four topics were personal protection， disease treatment， healthy lifestyle and psychological health， accounting for 18.62%， 18.54%， 12.96% and 11.74%， respectively. Reports focused on different aspects at different stages of COVID-19 epidemic， and the number of reports tended to increase one week after the occurrence of major events. ConclusionDuring the COVID-19 epidemic， the coverage of health science on media is timely and targeted. For future similar public health emergencies， it is suggested to respond quickly to major events according to the trend， to carry out publicity timely， to innovate the report forms， and thus make it easy for the public to accept and implement.

Objective To investigate the effects of regular dose and toxic dose of quetiapine (QTP) on PXR signaling and downstream CYP3A4 and P-gp mRNA expression in rat brain and liver and also further investigate the effects of PXR agonist (dexamethasone,DEX) on the mRNA expression of PXR,CYP3A4 and P-gp in these tissues in context of drug overdose to illustrate the potential detoxication mechanisms of PXR activation in the brain and liver.Methods Normal group was intraperitoneally injected with QTP 10 mg · kg-1 once,intoxication modeling group was intraperitoneally injected with QTP 100 mg · kg-1 once,and the PXR activation experimental group was intraperitoneally injected with DEX 2.5 mg · kg-1 · d-1 for consecutive 4 days.SD rats were randomly divided into 4 groups:blank group,normal group,model group,and experimental group.SD rats were dosed daily by the vehicle or dexamethasone 2.5 mg · kg-1 · d-1 for 4 days,and were intraperitoneally injected with the vehicle or QTP 10 or 100 mg · kg-1 on the fourth day.After the 4 days of drug treatment,the rats were sacrificed 12,24,48 h after the last dose.The mRNA expression of PXR,cytochrome P4503A4(CYP3A4) and P-glycoprotein (P-gp) of rats in 4 groups were assessed by Real-time PCR method.Results After administration QTP for 24 h,the expression of PXR mRNA in liver in blank group,normal group,model group,and experimental group were (15.8 ± 0.8) × 10-3,(27.8 ± 2.4) × 10-3,(33.3 ± 1.4) × 10-3,(49.2 ± 2.0) × 10-3,the difference between blank group and normal group was statistically significant (P ＜ 0.05),the difference between normal group and model group was statistically significant (P ＜ 0.05),and the difference between model group and experimental group was statistically significant (P ＜ 0.05).The factors in CYP3A4 and P-gp in liver of rats were same with PXR in liver,and the factors in prefrontal cortex and hippocampus of rats were same with in liver.Our data showed that QTP dose-dependently increased the expression of PXR,CYP3A4 and P-gp in both brain and liver.In addition,we found that the combination use of DEX along with the toxic dose of QTP accelerated the drug-induced mRNA expression of PXR,CYP3A4 and P-gp.Conclusion QTP itself could induce the signaling pathway of PXR-CYP3A4/P-gp,which was accelerated by the adjunctive use of PXR agonist,indicating that activation of PXR signaling pathway could activate detoxification system quickly and effectively,resulting in quick detoxification of xenobiotic and protection of organs.

OBJECTIVETo investigate the expression of vasoactive intestinal peptide (VIP) in peripheral blood of children with hand, foot and mouth disease and its significance.

METHODSAccording to the condition of the disease, 86 children with hand, foot and mouth disease were classified into phase 1 group (19 children) and phase 2 group (67 children). ELISA was used to measure the concentrations of plasma VIP, interferon-γ (IFN-γ), and interleukin-4 (IL-4) in peripheral blood. Flow cytometry was used to measure CD3, CD4, and CD8T lymphocyte subsets. RT-PCR was used for qualitative detection of enterovirus 71 (EV71) RNA in stool.

RESULTSCompared with the phase 1 group, the phase 2 group had a significantly higher positive rate of EV71-RNA (P<0.05) and significantly higher serum levels of IgG, IgA, IgM, and C3 (P<0.05). The phase 2 group had significantly lower proportions of peripheral CD3, CD4, and CD8T lymphocyte subsets than the phase 1 group (P<0.05), as well as significantly lower proportion of peripheral B cells and CD4/CD8ratio than the phase 1 group (P<0.05). The phase 2 group also had a significantly lower concentration of VIP in peripheral blood than the phase 1 group (P<0.05). In the 86 children with hand, foot and mouth disease, the concentration of VIP in peripheral blood was positively correlated with the proportion of CD4T lymphocyte subset and CD4/CD8ratio (r=0.533 and 0.532 respectively; P<0.05).

CONCLUSIONSVIP may be an important marker of the severity of hand, foot and mouth disease.

Biomarkers ; CD4-CD8 Ratio ; Child, Preschool ; Female ; Hand, Foot and Mouth Disease ; immunology ; Humans ; Infant ; Interferon-gamma ; blood ; Interleukin-4 ; blood ; Male ; Severity of Illness Index ; Vasoactive Intestinal Peptide ; blood

Objective To determine the relationship between estimated glomerular filtration rate (eGFR) and proteinuria with cardiovascular events in subjects aged 80 years or older.Methods Data for this retrospective prognostic study were drawn from the patient database for routine checkup in Beijing hospital between January 2001 to December 2001.Baseline eGFR and proteinuria were evaluated in 340 subjects [mean age:(85.6 ± 4.0) years].eGFR was calculated using the modified abbreviated MDRD equations based on the Chinese chronic kidney disease patients.The subjects were divided into normal renal function group and reduced renal function group (eGFR ＜ 60 ml · min-1 · 1.73 m-2).The subjects were divided into subjects without proteinuria and subjects with proteinuria group.Cardiovascular events included cardiovascular death,nonfatal myocardial infarction,nonfatal stroke.Results The proportion of reduced renal function was 36.8％ (125/340).The proportion of proteinuria was 10.3％ (35/340).The proportion of reduced renal function or proteinuria was 41.8％ (142/340).Follow-up time was 79 months (40-114 months).Cardiovascular events rate was significantly higher in reduced renal function group than in normal renal function group [37.6％ (47/125)vs.26.2％ (55/210),P ＜0.05] and in proteinuria group than in without proteinuria group [50.0％ (17/34) vs.28.2％ (85/301),P ＜ 0.01].Cox multivariate analysis revealed that both eGFR (HR =0.978,95％ CI:0.961-0.994,P ＜ 0.05) and proteinuria (HR =2.049,95％ CI:1.132-3.709,P ＜ O.05) were independent risk factors for cardiovascular events after adjusting for age,gender,triglyceride,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,uric acid,hypertension,coronary heart disease,diabetes mellitus.Conclusions Reduced eGFR and presence of proteinuria are independent risk factors for cardiovascular event in subjects aged 80 years or older.eGFR and proteinuria can thus be used for cardiovascular event risk stratification in subjects aged 80 years or older.

OBJECTIVETo investigate the relationship between 8 endocrine-disrupting chemicals in the serum and insulin resistance in patients with polycystic ovary syndrome (PCOS).

METHODSThis study was conducted among 60 patients with PCOS, including 23 with insulin resistance (PCOS-IR) and 37 without insulin resistance (PCOS-NIR), and 29 non-PCOS women seeking medical attention for infertility or menstrual disorder (control group). The serum levels of 6 phthalic acid esters (PEAs), bisphenol A (BPA) and octylphenol (OP) were measured in all the subjects.

RESULTSThe levels of PAEs, BPA and OP showed no significant differences between PCOS patients and the control group (P>0.05). The serum level of OP was significantly lower in patients PCOS-IR than in those with PCOS-NIR (47.89 ng/ml vs 60.24 ng/ml, P<0.05).

CONCLUSIONPEAs and BPA do not produce obvious effect on the pathogenesis of PCOS or contribute to insulin resistance, but OP may play a role in insulin resistance in PCOS patients.

Adult ; Benzhydryl Compounds ; adverse effects ; blood ; Case-Control Studies ; Endocrine Disruptors ; adverse effects ; blood ; Environmental Pollutants ; adverse effects ; blood ; Female ; Humans ; Insulin Resistance ; Phenols ; adverse effects ; blood ; Phthalic Acids ; adverse effects ; blood ; Polycystic Ovary Syndrome ; blood ; physiopathology ; Young Adult

Objective To prepare the 99Tcm-survivin mRNA antisense peptide nucleic acid (PNA)and investigate its value as a gene imaging agent in tumor bearing mice and early diagnosis in tumor.Methods Survivin mRNA antisense PNA and mismatch PNA were synthesized.Four amino acids (Gly- (D)Ala-Gly-Gly) and Aba (4-aminobutyric acid) were linked to the 5' end of PNA.Gly- (D)Ala-Gly-Gly served as a chelating moiety for strong chelation of 99Tcm and Aba acted as a spacer to minimize the steric hindrance.PNAs were labeled with 99Tcm by the ligand-exchange method.The labeling efficiency and radiochemical purity were measured by HPLC and ITLC methods.There were five BALB/c nude mice bearing human lung carcinoma ( A549 ) in each of antisense PNA and mismatch PNA groups.Gene imaging of 99Tcm-survivin mRNA antisense and mismatch PNAs were performed at 1,2 and 4 h post the injection,respectively,and the T/NT ratio was measured by the method of ROI.The statistical comparisons of average values were performed with the two-group t-test for independent sample by SPSS 13.0.Results The product kept stable in vitro.The labeling efficiency of 99Tcm-survivin mRNA antisense PNA was (95.48 ±1.92)％ and more than 85％ after the incubation for24 h in serum.The radiochemical purity was ＞ 95％.The labeling efficiency of mismatch PNA was similar to the antisense PNA.99Tcm-survivin mRNA antisense PNA was especially uptaken by tumor lesion,and its accumulation reached the top at 4 h post the injection.T/NT ratios at 1,2,and 4 h were 2.70 ± 0.28,3.44 ± 0.35,4.21 ± 0.63,respectively.In the comparison,the T/NT ratio of 99Tcm-survivin mRNA mismatch PNA at 4 h (3.12 ±0.50) was significantly lower (t =2.918,P =0.019).Conclusions 99Tcm-survivin mRNA antisense PNA has high labeling efficiency,good stability and no need of purification.Its characteristic of especial uptake by tumor lesion provides the potential value in early diagnosis of tumor.

ObjectiveTo investigate the value of 99Tcm labeled survivin mRNA antisense peptide nucleic acid (PNA) as an imaging agent in the specific diagnosis for carcinoma.MethodsSurvivin mRNA antisense PNA was labeled directly with 99Tcm by the ligand-exchange method.Twenty nude mice with lung carcinoma A549 xenografts were randomly divided into 4 groups.Three groups were used for biodistribution study and one group was used for imaging study.Other twenty mice infected by staphylococcus aureus underwent the same procedure.The biodistribution and imaging of 99Tcm-survivin mRNA antisense PNA was studied at 1,2 and 4 h respectively after the intravenous injection in nude mice bearing lung carcinoma A549 xenografts or inflammation models.SPSS 13.0 was used in the study and all data were analyzed by t test.ResultsBiodistribution results showed that the highest radioactivity was found in the liver,and then in the kidney.Four hours after the administration of the imaging agent,the radioactivity ratios of target-tonon target (T/NT,tumor or inflamumatory lesions to the contralateral regions) in tumor model group were significantly higher than those in inflammation model group ( 3.69 ± 1.13 vs 2.03 ± 0.47,t =3.01,P =0.02 ).Tumors were clearly visible in the tumor model groups at 0.5 h and still clearly seen at 4 h after the injection of antisense PNA.On the contrary,inflammatory lesions could not be seen clearly.Conclusion 99Tcm labeled survivin mRNA antisense PNA can be used to distinguish tumor from inflammation and it may provide a new feasible method for specific tumor diagnosis.

OBJECTIVETo investigate the whole sequence of the SLC26A4 gene in moderate to profound sensorineural hearing loss (SNHL) patients with IVS7-2A to G mutation of the gene in China.

METHODSWhole SLC26A4 gene sequence was analyzed by direct sequencing in 80 SLC26A4 gene IVS7-2A to G mutation carriers for the occurrence of a second mutation in the gene.

RESULTSForty-seven out of the 80 patients were found to have a second heterozygous mutation, whereas a single IVS7-2A to G mutation could be responsible for SNHL in the remaining 33 patients. Three novel mutations, 5+ 2T to A, 14-2A to G and 1825del G, were identified. The five most common mutations include H723R (20%), T410M(5%), C.1705+ 5G to A (15+ 5G to A)(5%), L676Q(5%), and N392Y (3.75%). Exon 17 harbored the most types of compound heterozygosity with the IVS7-2A to G mutation.

CONCLUSIONA Chinese specific SLC26A4 diversity was found, and comparable SLC26A4 contributing to deafness. This study suggested that if a heterozygous SLC26A4 mutation is found in a patient with deafness, other exons of the SLC26A4 gene should be analyzed. Furthermore, double heterozygosity of the SLC26A4 gene may also account for some of the disease phenotype.

Adolescent ; Amino Acid Sequence ; Animals ; Base Sequence ; Child ; Child, Preschool ; DNA Mutational Analysis ; methods ; Female ; Hearing Loss, Sensorineural ; genetics ; pathology ; Humans ; Male ; Membrane Transport Proteins ; chemistry ; genetics ; Mice ; Molecular Sequence Data ; Polymorphism, Single Nucleotide ; genetics ; Rats ; Young Adult