Prognostic significance of malignant pleural effusions in patients with advanced luminal B breast cancer.

BACKGROUND: Though the survival of breast cancer (BC) patients with malignant pleural effusion (MPE) has been studied, this has not been specifically studied in the luminal B subtype. Therefore, this study investigated the characteristics and survival of luminal B-BC patients presenting with MPE. METHODS: We retrospectively analyzed 141 patients diagnosed with postoperative advanced Luminal B breast cancer, including 54 cases with MPE and 87 cases without MPE at the Tianjin Cancer Hospital from January 2012 to January 2015. We assessed the clinical characteristics between the groups. RESULTS: The mean age of all patients was 47 years, with no significant difference between the two groups. Altogether, 29 (33%), 24 (28%), 28 (32%), 45 (52%), and 10 (11%) patients had lung, liver, bone, lymph node, and chest wall metastases, respectively. In addition. The difference in overall survival between the two groups was not significant (P>0.05). However, cox regression analysis showed that only the tumor clinical stage at initial diagnosis was related to short overall survival. Further, we conducted a subgroup analysis and found that the higher the clinical stage at initial diagnosis in age < 50 years patients, the shorter the overall survival, while age > 50 years patients was not. (P < 0.05). CONCLUSIONS: There was no difference in the overall survival between luminal B-BC patients with MPE and those without. Clinical stages at initial diagnosis were an independent prognostic factor for age < 50 years luminal B BC with MPE overall survival. Our results may help clinicians make positive decisions regarding personalized treatment of luminal B-BC with MPE.

The clinical impact of serum soluble CD25 levels in children with Langerhans cell histiocytosis.

OBJECTIVE: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm with inflammatory characteristics. This study aims to investigate the correlation between sCD25 levels and clinical characteristics, as well as prognosis, in pediatric LCH. METHODS: Serum sCD25 levels were measured in 370 LCH patients under 18 years old using ELISA assays. The patients were divided into two cohorts based on different treatment regimens. We further assessed the predictive value for the prognosis impact of sCD25 in a test cohort, which was validated in the independent validation cohort. RESULTS: The median serum sCD25 level at diagnosis was 3908 pg/ml (range: 231-44 000pg/ml). sCD25 level was significantly higher in multi-system and risk organ positive (MS RO+) LCH patients compared to single-system(SS) LCH patients (p < 0.001). Patients with elevated sCD25 were more likely to have involvement of risk organs, skin, lung, lymph nodes, or pituitary (all p < 0.05). sCD25 level could predict LCH progression and relapse, with an area under the ROC curve of 60.6 %. The optimal cutoff value was determined at 2921 pg/ml. Patients in the high-sCD25 group had significantly worse progression-free survival compared to those in the low-sCD25 group (p < 0.05). CONCLUSION: Elevated serum sCD25 level at initial diagnosis was associated with high-risk clinical features and worse prognosis. sCD25 level can predict the progression/recurrence of LCH following first-line chemotherapy.

Chirality-Mediated 1D-to-2D Phase Transition in Hybrid Lead Halide Perovskites.

Dimensionality engineering plays a pivotal role in optimizing the performance, ensuring long-term stability, and expanding the versatile applications of lead halide perovskites (LHPs). Currently, the manipulation of LHP dimensions primarily occurs during the synthesis stage, a procedure hampered by constraints, including synthetic complexity and irreversibility. This investigation successfully achieved a transition from one-dimensional (1D) to two-dimensional (2D) structures in chiral LHPs by applying hydrostatic pressure. Remarkably, this pressure-induced transition in dimensionality is absent in the racemic analogue due to the staggered arrangement of inorganic chains and the elevated steric hindrance posed by the organic cations. Notably, the hydrogen bonding between organic cations and the inorganic framework adopts a symmetrical arrangement in the racemic system but a helical configuration along the 1D chain direction in the chiral counterparts. This distinct helical arrangement induces a consequential distortion in the inorganic moiety, resulting in the emergence of a spin-polarized Rashba-Dresselhaus texture that explains the chirality's electronic spin origin. Furthermore, both experimental and density functional theory calculation results demonstrate that the 1D-to-2D phase transition in chiral halide perovskites can induce significant modifications in the electronic structures and associated optical emissions. In summary, the findings unveil novel avenues for manipulating optoelectronic properties in chiral perovskites through dimensionality engineering.

B-site substitution effects on the mechanical properties of halide perovskites [C4H12N2][BCl3]·H2O (B = NH4+; K+).

The mechanical properties of halide perovskites have been attracting ever-increasing interest for their significant importance in future industrial applications. However, studies focused on the effect of B-site substitution of molecular perovskites on their mechanical properties are rare, which makes it favorable to shed light on their fundamental structure-mechanical property relationships. Here, using isostructural halide perovskites, [C4H12N2][BCl3]·H2O (B = NH4+; K+), constructed by ionic bonds and hydrogen bonds, respectively, as the model systems, we investigate their mechanical properties through high-pressure synchrotron X-ray diffraction experiments and density functional theory calculations. Owing to the similar sizes of NH4+ and K+, the two compounds possess almost identical cell parameters and frameworks. Upon compression, the two perovskites exhibit analogous behavior except for slight differences in the shrinkage ratio of principal axes and the onset pressure of amorphization. The fitted bulk moduli of [C4H12N2][KCl3]·H2O and [C4H12N2][NH4Cl3]·H2O are 43.89 and 27.28 GPa, respectively. These results demonstrate that the simple replacement of K+ by NH4+ can significantly reduce the structural rigidity of the corresponding compounds, which is ascribed to the weaker strength of NH4⋯Cl hydrogen bonds than that of K-Cl bonds.

Inborn errors of immunity and its clinical significance in children with lymphoma in China: a single-center study

Abstract Objective: To investigate the incidence, clinical and genetic characteristics of pediatric lymphoma patients of China with inborn errors of immunity (IEI)-related gene mutations, which have not been fully studied. Method: From Jan. 2020 to Mar. 2023, IEI-related genetic mutations were retrospectively explored in 108 children with lymphomas admitted to Beijing Children's Hospital by NGS. Genetic rule and clinical characteristics as well as treatment outcomes were compared between patients with or without IEI-related gene mutations. Results: A total of 17 patients (15.7 %) harbored IEI-associated mutations, including 4 cases with X-linked lymphoproliferative syndrome (XLP), 3 cases had mutations in tumor necrosis factor receptor superfamily 13B (TNFRSF13B), 2 cases with Activated p110 syndrome (APDS). Patients with IEI all had alteration of immunocompetence with decreased levels of immunoglobulin and lymphocyte subsets. Recurrent infection existed in 41.2 % of patients. The 18-month event-free survival (EFS) and the overall response rate (ORR) of patients with IEI are significantly lower than those without IEI (33.86% vs. 73.26 %, p = 0.011; 52.94% vs. 87.91 %, p = 0.002, respectively). In addition, patients with IEI had a higher progression disease (PD) rate of 23.5 % than those without IEI of 4.4% (p = 0.006). Conclusion: The present study demonstrated that IEI-associated lymphomas were much more common than originally appreciated in pediatric lymphomas, and those were insensitive to treatment and more likely to progress or relapse. The genomic analysis and a thorough review of the medical history of IEI can be used to distinguish them from pediatric lymphomas without IEI, which are beneficial for the early diagnosis and direct intervention.

The Main Failure Modes of Hot-Work Die Steel and the Development Status of Traditional Strengthening Methods and Nano-Strengthening Technology.

As an important part of die steels, hot-work die steels are mainly used to manufacture molds made of solid metal or high-temperature liquid metal from heating to recrystallization temperature. In view of the requirements for mechanical properties and service life for hot-work die steel, it is conducive to improve the thermal fatigue resistance, wear resistance, and oxidation resistance of hot work die steel. In this review, the main failure modes of hot-work die steel were analyzed. Four traditional methods of strengthening and toughening die steel were summarized, including optimizing alloying elements, electroslag remelting, increasing the forging ratio, and heat treatment process enhancement. A new nano-strengthening method was introduced that aimed to refine the microstructure of hot-work abrasive steel and improve its service performance by adding nanoparticles into molten steel to achieve uniform dispersion. This review provides an overview to improve the service performance and service life of hot work die steel.

BRAF-V600E mutations in plasma and peripheral blood mononuclear cells correlate with prognosis of pediatric Langerhans cell histiocytosis treated with first-line therapy.

BACKGROUND: The clinical relevance of BRAF-V600E alleles in peripheral blood mononuclear cells (PBMCs) and the prognostic impact of the mutants in cell-free (cf) and PBMC DNAs of Langerhans cell histiocytosis (LCH) have not been fully clarified in pediatric LCH. METHODS: We retrospectively determined the levels of BRAF-V600E mutation in paired plasma and PBMC samples at the time of diagnosis of LCH. Subsequently, we performed a separate or combined analysis of the clinical and prognostic impact of the mutants. RESULTS: We assessed BRAF-V600E mutation in peripheral blood from 94 patients of childhood LCH. Our data showed that cfBRAF-V600E was related to young age, multiple-system (MS) disease, involvements of organs with high risk, increased risk of relapse, and worse progression-free survival (PFS) of patients. We also observed that the presence of BRAF-V600E in PBMCs at baseline was significantly associated with MS LCH with risk organ involvement, younger age, and disease progression or relapse. The coexisting of plasma(+)/PBMC(+) identified 36.2% of the patients with the worst outcome, and the hazard ratio was more significant than either of the two alone or neither, indicating that combined analysis of the mutation in plasma and PBMCs was more accurate to predict relapse than evaluation of either one. CONCLUSIONS: Concurrent assessment of BRAF-V600E mutation in plasma and PBMCs significantly impacted the prognosis of children with LCH. Further prospective studies with larger cohorts need to validate the results of this study.

Genetic Landscape and Its Prognostic Impact in Children With Langerhans Cell Histiocytosis.

CONTEXT.­: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm that predominantly affects young children. OBJECTIVE.­: To investigate genetic alterations and their correlation with clinical characteristics and prognosis in pediatric LCH. DESIGN.­: We performed targeted sequencing to detect mutations in LCH lesions from pediatric patients. RESULTS.­: A total of 30 genomic alterations in 5 genes of the MAPK pathway were identified in 187 of 223 patients (83.9%). BRAF V600E (B-Raf proto-oncogene, serine/threonine kinase) was the most common mutation (51.6%), followed by MAP2K1 (mitogen-activated protein kinase kinase 1) alterations (17.0%) and other BRAF mutations (13.0%). ARAF (A-Raf proto-oncogene, serine/threonine kinase) and KRAS (KRAS proto-oncogene, GTPase) mutations were relatively rare (2.2% and 0.9%, respectively). Additionally, FNBP1 (formin-binding protein 1)::BRAF fusion and MAP3K10 (mitogen-activated protein kinase kinase 10) mutations A17T and R823C were identified in 1 case each, with possible constitutive activation of ERK1/2 phosphorylation. BRAF V600E was more frequent in patients with risk organ involvement, while MAP2K1 mutation was more prevalent in patients with single-system LCH (P = .001). BRAF V600E was associated with craniofacial bone, skin, liver, spleen, and ear involvement (all P < .05). Patients with other BRAF mutations had a higher proportion of spinal column involvement (P = .006). Univariate analysis showed a significant difference in progression-free survival among the 4 molecular subgroups for patients treated with first-line therapy (P = .02). According to multivariate analysis, risk organ involvement was the strongest independent adverse prognostic factor (hazard ratio, 8.854; P < .001); BRAF or MAP2K1 mutation was not an independent prognostic factor. CONCLUSIONS.­: Most pediatric patients with LCH carry somatic mutations involving the MAPK pathway, correlating with clinical characteristics and outcomes for first-line chemotherapy.

The plasma-soluble CSF1R level is a promising prognostic indicator for pediatric Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a rare hematologic neoplasm characterized by the clonal proliferation of Langerhans-like cells. Colony-stimulating factor 1 receptor (CSF1R) is a membrane-bound receptor that is highly expressed in LCH cells and tumor-associated macrophages. In this study, a soluble form of CSF1R protein (sCSF1R) was identified by plasma proteome profiling, and its role in evaluating LCH prognosis was explored. We prospectively measured plasma sCSF1R levels in 104 LCH patients and 10 healthy children using ELISA. Plasma sCSF1R levels were greater in LCH patients than in healthy controls (p < .001) and significantly differed among the three disease extents, with the highest level in MS RO+ LCH patients (p < .001). Accordingly, immunofluorescence showed the highest level of membrane-bound CSF1R in MS RO+ patients. Furthermore, the plasma sCSF1R concentration at diagnosis could efficiently predict the prognosis of LCH patients treated with standard first-line treatment (AUC = 0.782, p < .001). Notably, dynamic monitoring of sCSF1R levels could predict relapse early in patients receiving BRAF inhibitor treatment. In vitro drug sensitivity data showed that sCSF1R increased resistance to Ara-C in THP-1 cells expressing ectopic BRAF-V600E. Overall, the plasma sCSF1R level at diagnosis and during follow-up is of great clinical importance in pediatric LCH patients.

Effects of Environmental Organic Pollutants on Environment and Human Health: The Latest Updates.

This editorial introduces the Special Issue "Effects of Environmental Organic Pollutants on Environment and Human Health: The Latest Updates" [...].

Broadband Emission Induced by Band-Edge Carrier Reconfiguration in 2D Hybrid Lead Halide Perovskites.

Broadband emission in hybrid lead halide perovskites (LHPs) has gained significant attention due to its potential applications in optoelectronic devices. The origin of this broadband emission is primarily attributed to the interactions between electrons and phonons. Most investigations have focused on the impact of structural characteristics of LHPs on broadband emission, while neglecting the role of electronic mobility. In this work, the study investigates the electronic origins of broadband emission in a family of 2D LHPs. Through spectroscopic experiments and density functional theory calculations, the study unveils that the electronic states of the organic ligands with conjugate effect in LHPs can extend to the band edges. These band-edge carriers are no longer localized only within the inorganic layers, leading to electronic coupling with molecular states in the barrier and giving rise to additional interactions with phonon modes, thereby resulting in broadband emission. The high-pressure photoluminescence measurements and theoretical calculations reveal that hydrostatic pressure can induce the reconfiguration of band-edge states of charge carriers, leading to different types of band alignment and achieving macroscopic control of carrier dynamics. The findings can provide valuable guidance for targeted synthesis of LHPs with broadband emission and corresponding design of state-of-the-art optoelectronic devices.

Relationship between subtype-specific minimal residual disease level and long-term prognosis in children with acute lymphoblastic leukemia.

Minimal residual disease (MRD) based risk stratification criteria for specific genetic subtypes remained unclear in childhood acute lymphoblastic leukemia (ALL). Among 723 children with newly diagnosed ALL treated with the Chinese Children Leukemia Group CCLG-2008 protocol, MRD was assessed at time point 1 (TP1, at the end of induction) and TP2 (before consolidation treatment) and the MRD levels significantly differed in patients with different fusion genes or immunophenotypes (P all < 0.001). Moreover, the prognostic impact of MRD varied by distinct molecular subtypes. We stratified patients in each molecular subtype into two MRD groups based on the results. For patients carrying BCR::ABL1 or KMT2A rearrangements, we classified patients with MRD < 10-2 at both TP1 and TP2 as the low MRD group and the others as the high MRD group. ETV6::RUNX1+ patients with TP1 MRD < 10-3 and TP2 MRD-negative were classified as the low MRD group and the others as the high MRD group. For T-ALL, We defined children with TP1 MRD ≥ 10-3 as the high MRD group and the others as the low MRD group. The 10-year relapse-free survival of low MRD group was significantly better than that of high MRD group. We verified the prognostic impact of the subtype-specific MRD-based stratification in patients treated with the BCH-ALL2003 protocol. In conclusion, the subtype-specific MRD risk stratification may contribute to the precise treatment of childhood ALL.

Inborn errors of immunity and its clinical significance in children with lymphoma in China: a single-center study.

OBJECTIVE: To investigate the incidence, clinical and genetic characteristics of pediatric lymphoma patients of China with inborn errors of immunity (IEI)-related gene mutations, which have not been fully studied. METHOD: From Jan. 2020 to Mar. 2023, IEI-related genetic mutations were retrospectively explored in 108 children with lymphomas admitted to Beijing Children's Hospital by NGS. Genetic rule and clinical characteristics as well as treatment outcomes were compared between patients with or without IEI-related gene mutations. RESULTS: A total of 17 patients (15.7 %) harbored IEI-associated mutations, including 4 cases with X-linked lymphoproliferative syndrome (XLP), 3 cases had mutations in tumor necrosis factor receptor superfamily 13B (TNFRSF13B), 2 cases with Activated p110 syndrome (APDS). Patients with IEI all had alteration of immunocompetence with decreased levels of immunoglobulin and lymphocyte subsets. Recurrent infection existed in 41.2 % of patients. The 18-month event-free survival (EFS) and the overall response rate (ORR) of patients with IEI are significantly lower than those without IEI (33.86% vs. 73.26 %, p = 0.011; 52.94% vs. 87.91 %, p = 0.002, respectively). In addition, patients with IEI had a higher progression disease (PD) rate of 23.5 % than those without IEI of 4.4 % (p = 0.006). CONCLUSION: The present study demonstrated that IEI-associated lymphomas were much more common than originally appreciated in pediatric lymphomas, and those were insensitive to treatment and more likely to progress or relapse. The genomic analysis and a thorough review of the medical history of IEI can be used to distinguish them from pediatric lymphomas without IEI, which are beneficial for the early diagnosis and direct intervention.

Unusual Pressure-Induced Self-Trapped Exciton to Free Exciton Transfer in Chiral 2D Lead Bromide Perovskites.

The phenomenon of pressure-induced emission alterations related to complex excitonic dynamics in 2D lead halide perovskites (LHPs) has gained considerable attention for understanding their structure-property relationship and obtaining inaccessible luminescence under ambient conditions. However, the well-known pressure-induced emissions are limited to the formation of self-trapped excitons (STEs) due to the structural distortion under compression, which goes against the advantage of the highly pure emission of LHPs. Here, the pressure-induced detrapping from STEs to free excitons (FEs) accompanied by the dramatic transition from broadband orangish emission to narrow blue emission has been achieved in chiral 2D LHPs and R- and S-[4MeOPEA]2PbBr4, (4MeOPEA = 4-methoxy-α-methylbenzylammonium). The combined experimental and calculated results reveal that the distortion level of PbBr6 octahedra of R- and S-[4MeOPEA]2PbBr4 exhibits an unusually significant reduction as the applied pressure increases, which leads to decreased electron-phonon coupling and self-trapped energy barrier and consequently enables the detrapping of STEs to FEs. This work illustrates the dramatic exciton transfer in 2D LHPs and highlights the potential for realizing highly efficient and pure light emissions by manipulating the structural distortion via strain engineering.

Effect of "Tongdu Qishen" acupuncture on expressions of ferroptosis-related factors in the hippocampus of APPswe/PS1dE9 Mice. / "通督启神"针法对APPswe/PS1dE9å°é¼ æµ·é©¬é“æ­»äº¡ç›¸å ³å› å­è¡¨è¾¾çš„å½±å“.

OBJECTIVES: To investigate the effect of "Tongdu Qishen" acupunctureï¼»dredging the Govern Vessel and normalizing mental activities, electroacupuncture (EA) of "Baihui" (GV20), "Yintang" (EX-HN3) and "Shuigou" (GV26) needlingï¼½on the learning-memory ability and the mechanism of ferroptosis in Alzheimer's disease (AD) mice. METHODS: Twenty-four male APPswe/PS1dE9 mice were randomly and equally divided into model group and EA group, and 12 normal C57BL/6 mice were used as the control group. In the EA group, EA (2 Hz/100 Hz, 20 min) was applied to GV20 and EX-HN3 in combination with manual acupuncture stimulation of GV26. The treatment was performed once a day, for a total of 28 days. The mice in the three groups were given the same fixation and grasping operation. Morris water maze swimming tests were used to assess the mice's learning-memory ability. Nissl staining and transmission electron microscopy were used to observe the morphological changes of neurons in the hippocampus. The activity of superoxide dismutase (SOD) in the hippocampus tissue was detected by superoxide anionic colorimetric assay kit (WST-1), and malondialdehyde (MDA) contents were detected by thiobarbituric acid (TBA) method. The expression levels of prostaglandin endoperoxide synthase 2 (ptgs2) and glutathione peroxidase 4 (GPX4) mRNA in the hippocampus were detected by fluorescent quantitative real-time PCR. RESULTS: Behavioral results showed that compared with the control group, the escape latencies at the 2nd, 3rd, 4th and 5th day of Morris water maze swimming test were significantly increased (P<0.05), and the swimming time in the original platform quadrant and the times of cros-sing the original platform were considerably decreased (P<0.05) in the model group. In comparison with the model group, the escape latencies at the 4th and 5th day were strikingly decreased (P<0.05), and the swimming time in the original platform quadrant and times of crossing the original platform significantly increased (P<0.05) in the EA group. Following modeling, the SOD activity and the expression of GPX4 mRNA were obviously down-regulated (P<0.05), and the content of MDA and the expression of ptgs2 mRNA significantly up-regulated (P<0.05) in the model group rele-vant to the control group. The SOD activity and the expression of GPX4 mRNA were apparently increased (P<0.05), and the content of MDA and the expression of ptgs2 mRNA remarkably down-regulated (P<0.05) in the EA group rele-vant to the model group. Histopathological and ultrastructural results showed scattered arrangement of cells, widened space among cells, reduction in the number of cells, and many shrunk of dissolved nucleoli, shrunking and incomplete mitochondria, and high membrane electron density in the hippocampus of the model group, which was relatively milder in the EA group. CONCLUSIONS: "Tongdu Qishen" acupuncture can improve the learning-memory ability of AD mice, which may be related to its functions in up-regulating SOD activity and GPX4 mRNA expression, and down-regulating MDA content and ptgs2 mRNA expression to reduce the lipid peroxidation in the process of ferroptosis.

Chiral Two-Dimensional Hybrid Organic-Inorganic Perovskites for Piezoelectric Ultrasound Detection.

Hybrid organic-inorganic perovskites (HOIPs) have exhibited striking application potential in piezoelectric energy harvesting and sensing due to their high piezoelectricity, light weight, and solution processability. However, to date, the application of piezoelectric HOIPs in ultrasound detection has not yet been explored. Here, we report the synthesis of a pair of chiral two-dimensional piezoelectric HOIPs, R-(4-bromo-2-butylammonium)2PbBr4 and S-(4-bromo-2-butylammonium)2PbBr4 [R-(BrBA)2PbBr4 and S-(BrBA)2PbBr4], which show low mechanical strength and significant piezoelectric strain coefficients that are advantageous for mechanoelectrical energy conversion. Benefiting from these virtues, the R-(BrBA)2PbBr4@PBAT and S-(BrBA)2PbBr4@PBAT [PBAT = poly(butyleneadipate-co-terephthalate)] composite films show prominent underwater ultrasound detection performance with a transmission effectivity of 12.0% using a 10.0 MHz probe, comparable with that of a polyvinylidene fluoride (PVDF) device fabricated in the same conditions. Density functional theory calculations reveal that R-(BrBA)2PbBr4 and S-(BrBA)2PbBr4 have a beneficial acoustic impedance (5.07-6.76 MRayl) compatible with that of water (1.5 MRayl), which is responsible for the facile ultrasound-induced electricity generation. These encouraging results open up new possibilities for applying piezoelectric HOIPs in underwater ultrasound detection and imaging technologies.

Metabonomics Analysis of Brain Stem Tissue in Rats with Primary Brain Stem Injury Caused Death.

OBJECTIVES: To explore the potential biomarkers for the diagnosis of primary brain stem injury (PBSI) by using metabonomics method to observe the changes of metabolites in rats with PBSI caused death. METHODS: PBSI, non-brain stem brain injury and decapitation rat models were established, and metabolic maps of brain stem were obtained by LC-MS metabonomics method and annotated to the HMDB database. Partial least square-discriminant analysis (PLS-DA) and random forest methods were used to screen potential biomarkers associated with PBSI diagnosis. RESULTS: Eighty-six potential metabolic markers associated with PBSI were screened by PLS-DA. They were modeled and predicted by random forest algorithm with an accuracy rate of 83.3%. The 818 metabolic markers annotated to HMDB database were used for random forest modeling and prediction, and the accuracy rate was 88.9%. According to the importance in the identification of cause of death, the most important metabolic markers that were significantly up-regulated in PBSI group were HMDB0038126 (genipinic acid, GA), HMDB0013272 (N-lauroylglycine), HMDB0005199 [(R)-salsolinol] and HMDB0013645 (N,N-dimethylsphingosine). CONCLUSIONS: GA, N-lauroylglycine, (R)-salsolinol and N,N-dimethylsphingosine are expected to be important metabolite indicators in the diagnosis of PBSI caused death, thus providing clues for forensic medicine practice.

[Influence of electroacupuncture of "Dazhui"（GV14） and "Mingmen" （GV4） on expressions of NL1 and NF-200 in spinal cord injury rats].

OBJECTIVE: To observe the effect of electroacupuncture(EA) on activities of A2 type astrocytes(A2s)and A1 type astrocytes (A1s) , expressions of neurofilament protein 200 (NF-200, a marker of axon regeneration), nexin 1(NL1, a marker of synaptic regeneration), and regeneration of Nissl bodies in rats with spinal cord injury (SCI), so as to explore its mechanisms underlying improvement of SCI. METHODS: A total of 75 male SD rats were rando-mized into sham operation, model, antibody neutralizing (AN), EA and EA+AN groups, with 15 rats in each group. The SCI model was established by using an infinite field impactor to deliver an about 200 k dyne weight onto the exposed spinal cord after making a dorsal laminectomy at vertebral level T10. EA (2 Hz, 1 mA) was applied to"Dazhui"(GV14) and "Mingmen"(GV4) for 20 min, once daily for 28 days. After modeling, intraspinal injection of neutralizing antibodies IL-1α, TNF-α and complement 1q (C1q, 2 µL) to the injured spinal locus for inhibition of A1 type astrocytes (A1s) was conducted on the 1st, 7th , 14th and 21st day for rats of AN and EA+AN groups. BBB rating scale was used to evaluate hindlimb locomotor function on day 1, 7, 14, 21 and 28 after modeling. The activation of A2s (its specific marker S100a10), astrocyte (its specific marker glial fibrillary acidic protein, GFAP), and A1s (its specific marker C3) in the spinal cord was detected by immunofluorescence, and the protein expressions of NF-200 and NL1 in the spinal cord detected by Western blot and immunohistochemistry, separately, and the neuronal regeneration was observed after Nissl staining. RESULTS: After SCI, the BBB scores at 1 , 7, 14, 21 and 28 day, and the immunoactivity of NL1 and NF-200 were significantly decreased (P<0.01), and the fluorescence intensity of double labelled S100a10 (A2s)/GFAP and C3, and the expression of NF-200 were considerably increased in the model group (P<0.05, P<0.01). In contrast to the model group, the BBB scores at 7, 14, 21 and 28 day, and the immunoactivity of NL1 and NF-200, and the fluorescence intensity of A2s/GFAP in the AN, EA and AN+EA groups, and the expressions of NL1 in the EA and AN+EA groups, and expression of NF-200 protein in the AN+EA group were evidently increased (P<0.05, P<0.01), and the fluorescence intensity of C3 was strikingly decreased in the EA group (P<0.01). The effect of AN+EA was significantly superior to that of single AN and EA in increasing BBB scores at 14, 21 and 28 day, and in up-regulating the immunoactivity of NF-200(P<0.01, P<0.05). Nissl staining showed damaged structure of the gray matter of the spinal cord, atrophy of the Nissl body, and pyknosis of neurons, which was milder in the AN and EA groups, particularly in the AN+EA group. CONCLUSION: EA at GV14 and GV4 may promote activation of A2s and promote regeneration of axons and synapses in SCI model rats.

Enhancing Prediction for Tumor Pathologic Response to Neoadjuvant Immunochemotherapy in Locally Advanced Esophageal Cancer by Dynamic Parameters from Clinical Assessments.

To develop accurate and accessible prediction methods for assessing pathologic response following NICT prior to surgery, we conducted a retrospective study including 137 patients with esophageal squamous cell carcinoma (ESCC) who underwent surgery after two cycles of NICT between January 2019 and March 2022 at our center. We collected clinical parameters to evaluate the dynamic changes in the primary tumor. Univariate and multivariate analyses were performed to determine the correlations between these parameters and the pathologic response of the primary tumor. Subsequently, we constructed prediction models for pCR and MPR using multivariate logistic regression. The MPR prediction Model 2 was internally validated using bootstrapping and externally validated using an independent cohort from our center. The univariate logistic analysis revealed significant differences in clinical parameters reflecting tumor regression among patients with varying pathologic responses. The clinical models based on these assessments demonstrated excellent predictive performance, with the training cohort achieving a C-index of 0.879 for pCR and 0.912 for MPR, while the testing cohort also achieved a C-index of 0.912 for MPR. Notably, the MPR prediction Model 2, with a threshold cut-off of 0.74, exhibited 92.7% specificity and greater than 70% sensitivity, indicating a low rate of underestimating residual tumors. In conclusion, our study demonstrated the high accuracy of clinical assessment-based models in pathologic response prediction, aiding in decision-making regarding organ preservation and radiotherapy adjustments after induction immunochemotherapy.

Drug release and solubility properties of two zeolitic metal-organic frameworks influenced by their hydrophobicity/hydrophilicity.

Metal-organic frameworks (MOFs) have shown significant potential for drug delivery applications. However, there remains a scarcity of comprehensive research addressing the influence of surface properties of MOFs on drug release kinetics and drug solubility. This study focuses on examining the influence of MOFs hydrophilicity and hydrophobicity on the controlled release and solubility of drugs. To achieve this, we prepared drug-loaded nanoparticles through in situ synthesis and created a drug-MOF co-amorphous system using the ball milling technique. Under neutral conditions, the hydrophilic MOF-based drug delivery system demonstrated a comparatively slower drug release profile than its hydrophobic counterpart. This observation suggests that the hydrophilic system holds promise in mitigating drug side effects by enabling improved control over drug release. The implementation of hydrophobic MOFs in co-amorphous systems yields a more pronounced effect on enhancing solubility compared to hydrophilic MOFs. This study offers valuable insights for achieving optimal drug release kinetics and solubility by delicately manipulating surface properties of MOFs.