From Pb6(HPO3)(H2PO3)Cl9 to Pb6(HPO3)2Br8(H2O)·H2O: Halogen Regulation to Achieve Inorganic Metal Phosphite Halide Nonlinear Optical Material with Unprecedented Pb-Centered Polyhedral Units.

Nonlinear optical (NLO) crystals are widely used in various fields. The introduction of lone-pair cations is regarded as an effective strategy to explore NLO crystals. In this work, two novel lead phosphite halides, centrosymmetric Pb6(HPO3)(H2PO3)Cl9 and noncentrosymmetric Pb6(HPO3)2Br8(H2O)·H2O, were obtained via a hydrothermal method. Pb6(HPO3)(H2PO3)Cl9 is the first reported lone-pair metal phosphite with two kinds of phosphite groups (HPO32- and H2PO3-) and Pb6(HPO3)2Br8(H2O)·H2O is the first inorganic NLO phosphite halide with a phase-matchable SHG effect of 1.02 × KDP. In addition, the Pb-centered polyhedral units of PbOCl4, PbOCl6, PbO2Cl5, PbO2Br5, PbOBr6, and PbO3(H2O)Br3 in these two structures have never been reported before. An in-depth study on the structure-property relationship of the two compounds with halogen substitution is also performed.

Abnormal circadian rhythm of heart rate variability and their association with symptoms in patients with major depressive disorder.

BACKGROUND: Heart rate variability (HRV) is often reduced in patients with major depressive disorder (MDD) and is linked to symptoms. However, prior studies have mainly focused on short-term HRV, with limited exploration of the 24-h HRV circadian rhythm, despite its ability to comprehensively capture overall HRV distribution and dynamic fluctuations. In this study, we investigated the circadian rhythms of 24-h HRV indices in patients with MDD and their associations with symptom severity. METHODS: We recorded 24-h electrocardiograms in 73 patients with MDD (53 in major depressive episode and 20 in remission period) and 31 healthy controls. An extended cosine model was used to model the circadian rhythm of six HRV indices by five parameters: the mesor, amplitude, duty cycle, curve smoothness, and acrophase. Symptom severity was evaluated using the Hamilton Depression Scale and Hamilton Anxiety Scale. RESULTS: Compared with the control group, patients with MDD had a significantly smaller SampEn mesor, higher HF duty cycle, and lower heart rate (HR) duty cycle. They also had a significantly higher curve smoothness for HR, RMSSD, and HF. The mesor for SampEn, along with the curve smoothness for HR and ln RMSSD, were associated with certain symptoms in patients with MDD. LIMITATIONS: The cross-sectional design and psychiatric treatment of most patients with MDD limited our findings. CONCLUSION: Patients with MDD exhibit abnormal HRV circadian rhythms that are associated with symptoms. Moreover, 24-h ECG monitoring may potentially serve as an adjunct value to objectively evaluate clinical symptoms in these patients.

Comparative pharmacokinetics of multi-components in normal and stomach cold syndrome rats after oral administration of Zingiberis Rhizoma - Jujubae Fructus herb pair and its single herb extracts by UHPLC-MS/MS.

The Zingiberis Rhizoma - Jujubae Fructus herb pair (ZJHP) is a classic herb pair in traditional Chinese medicine. The herb pair shows the effect of dispelling cold, harmonizing the middle and improving gastrointestinal function, and is widely used for patients with stomach cold syndrome (SCS), stomachache and anemofrigid cold. The gingerols, shogaols, flavonoids and triterpenic acids are the important bioactive ingredients of ZJHP. However, few pharmacokinetic studies have been investigated in vivo for the above compounds. To comprehend the kinetics of active components and promote their curative application, a fast and sensitive ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS/MS) method was established for simultaneous determination of 12 analytes in normal and SCS rats in this study. The results showed that the pharmacokinetic parameters (Cmax, Tmax, t1/2z, MRT0-t, AUC0-t and AUC0-∞) in SCS model were significantly different from those in normal rats. In addition, the pharmacokinetics of rats given ZJHP were also varied from single herb oral administration, especially in model condition. These results indicated that the in vivo processes of the above analytes changed under pathological conditions and the compatibility of the herb pair could significantly influence the absorption of active components, which might provide an insight and further supports for the clinical application of ZJHP.

Highly Selective Protic-Solvent-Mediated Organic-Inorganic Hybrid Cuprous Bromides Achieving Structural Transformation.

The potential application of stimuli-responsive hybrid copper halides in information storage and switch devices has generated significant interest. However, their transformation mechanism needs to be further studied deeply. Herein, two zero-dimensional (0D) organic-inorganic hybrids, namely, (TBA)CuBr2 (1) with linear [CuBr2]- units and (TBA)2Cu4Br6 (2) with [Cu4Br6]2- clusters (TBA+ = (C4H9)4N+), are synthesized using simple solvent evaporation approaches. Interestingly, upon exposure to distinct protic solvents, such as methanol, ethanol, ethylene glycol, or hot water, 1 undergoes a transformation into 2 with varying degrees of transition, accompanied by a change in luminescence color from cyan to orange (or mixed color) under high-energy emission (e.g., 254 nm) excitation. Hot water can trigger 1 to completely transform into 2 because of its large contact angle difference in the solvents. Furthermore, 2 can be converted back to 1 through a simple solid-state mechanochemical reaction. Additionally, the structure of 2 remains unchanged even after immersion in 80 °C H2O for 168 h due to the dense organic framework. This study provides valuable insights for exploring reversible structural transformation materials in the 0D metal halide system.

Integrated mRNA-miRNA transcriptome profiling of blood immune responses potentially related to pulmonary fibrosis in forest musk deer.

Background: Forest musk deer (FMD, Moschus Berezovskii) is a critically endangered species world-widely, the death of which can be caused by pulmonary disease in the farm. Pulmonary fibrosis (PF) was a huge threat to the health and survival of captive FMD. MicroRNAs (miRNAs) and messenger RNAs (mRNAs) have been involved in the regulation of immune genes and disease development. However, the regulatory profiles of mRNAs and miRNAs involved in immune regulation of FMD are unclear. Methods: In this study, mRNA-seq and miRNA-seq in blood were performed to constructed coexpression regulatory networks between PF and healthy groups of FMD. The hub immune- and apoptosis-related genes in the PF blood of FMD were explored through Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Further, protein-protein interaction (PPI) network of immune-associated and apoptosis-associated key signaling pathways were constructed based on mRNA-miRNA in the PF blood of the FMD. Immune hub DEGs and immune hub DEmiRNAs were selected for experimental verification using RT-qPCR. Results: A total of 2744 differentially expressed genes (DEGs) and 356 differentially expressed miRNAs (DEmiRNAs) were identified in the PF blood group compared to the healthy blood group. Among them, 42 DEmiRNAs were negatively correlated with 20 immune DEGs from a total of 57 correlations. The DEGs were significantly associated with pathways related to CD molecules, immune disease, immune system, cytokine receptors, T cell receptor signaling pathway, Th1 and Th2 cell differentiation, cytokine-cytokine receptor interaction, intestinal immune network for IgA production, and NOD-like receptor signaling pathway. There were 240 immune-related DEGs, in which 186 immune-related DEGs were up-regulated and 54 immune-related DEGs were down-regulated. In the protein-protein interaction (PPI) analysis of immune-related signaling pathway, TYK2, TLR2, TLR4, IL18, CSF1, CXCL13, LCK, ITGB2, PIK3CB, HCK, CD40, CD86, CCL3, CCR7, IL2RA, TLR3, and IL4R were identified as the hub immune genes. The mRNA-miRNA coregulation analysis showed that let-7d, miR-324-3p, miR-760, miR-185, miR-149, miR-149-5p, and miR-1842-5p are key miRNAs that target DEGs involved in immune disease, immune system and immunoregulation. Conclusion: The development and occurrence of PF were significantly influenced by the immune-related and apoptosis-related genes present in PF blood. mRNAs and miRNAs associated with the development and occurrence of PF in the FMD.

Trajectories of squamous cell carcinoma antigen and outcomes of patients with advanced penile cancer after chemotherapy based on paclitaxel, ifosfamid, and cisplatin regimen.

INTRODUCTION: Penile cancer (PC) is a lethal malignancy with no effective prognostic biomarker. We aim to investigate associations between trajectories of squamous cell carcinoma antigen (SCC-A) and patient outcomes after chemotherapy based on paclitaxel, ifosfamid, and cisplatin (TIP) regimen. METHODS: Consecutive AJCC staging III/IV PC patients who received TIP chemotherapy and repeated SCC-A measurements in 2014-2022 were analyzed. Latent class growth mixed (LCGM) models were employed to characterize patients' serum SCC-A trajectories. Patient survival, and clinical and pathological tumor responses were compared. Inverse probability treatment weighting was used to adjust confounding factors. RESULTS: Eighty patients were included. LCGM models identified two distinct trajectories of SCC-A: low-stable (40%; n = 32) and high-decline (60%; n = 48). Overall survival (HR [95% CI]: 3.60 [1.23-10.53], p = 0.019), progression-free survival (HR [95% CI]: 11.33 [3.19-40.3], p < 0.001), objective response rate (37.5% vs. 62.5% p = 0.028), disease control rate (60.4% vs. 96.9% p < 0.00), and pathological complete response rate (21.2% vs. 51.9%, p = 0.014) were significantly worse in the high-decline arm. CONCLUSION: PC patients' SCC-A change rate was associated with tumor response and patient survival after TIP chemotherapy. SCC-A might assist tumor monitoring after systemic therapies.

Comprehensive reutilization of Glycyrrhiza uralensis residue by extrusion-biological pretreatment for coproduction of flavonoids, cellulase, and ethanol.

A continuous chemical-free green approach was investigated for the comprehensive reutilization of all components in herbal extraction residues (HERs), taking Glycyrrhiza uralensis residue (GUR) as an example. The GUR structural changes induced by mechanical extrusion which improve the specific surface area and enzyme accessibility of GUR. With 3 % pretreated GUR loading of high-tolerance Penicillium oxalicum G2. The reducing sugar yield of 11.45 g/L was achieved, along with an 81.06 % in situ enzymatic hydrolysis. Finally, 8.23 g/L bioethanol (0.40 g/g total sugar) was produced from GUR hydrolysates after 24 h fermentation of Pichia stipitis G32. The amount of functional medicinal ingredients extracted from GUR after hydrolysis (39.63 mg/g) was 37.69 % greater than that of un-pretreated GUR. In total, 1.49 g flavonoids, 294.36 U cellulase, and 14.13 g ethanol could be produced from 100 g GUR using this process, illustrating that this green and efficient process has the potential for industrial production.

Knowledge mapping of paediatric fever-a visual analysis based on CiteSpace.

Objective: This study aimed to analyse the research hotspots and frontiers in the field of paediatric fever between 2013 and 2023. Methods: The included articles were visually analysed using CiteSpace 6.1.R6 software. Results: A total of 2,662 Chinese-language articles and 1,456 English-language articles were included in the study. Based on the Chinese literature, research groups were identified represented by Xinmin Li, Jinling Hong and Hongshuang Luo. Based on the English literature, research groups were formed represented by Henriette Moll, Santiago Mintegi and Elizabeth Alpern. Tianjin University of Traditional Chinese Medicine was the institution with the largest number of publications in the Chinese literature, and the Centers For Disease Control And Prevention was the institution with the largest number of publications in the English literature. The research on paediatric fever mainly focused on mechanism exploration, green treatment and clinical management. Conclusion: Several relatively stable research groups have been formed. Future studies on the differential diagnosis, rational drug use, standardised management and clinical practice guidelines for paediatric fever are needed.

Predictive value of thrombus enhancement sign for stroke subtype and recanalization in acute basilar-artery occlusion.

BACKGROUND: Thrombus enhancement sign (TES) is associated with cardioembolic stroke and first-pass angiographic failure in anterior ischemic stroke. However, the relationship between TES and stroke subtype and recanalization status after endovascular treatment (EVT) in basilar artery occlusion (BAO) remains unknown. METHODS: This retrospective study included consecutive patients with acute BAO who underwent EVT between January 2020 and September 2023. Each patient underwent baseline non-contrast computed tomography (CT) and CT angiography. Two independent readers assessed the presence of TES. Stroke types were classified according to the Trial of ORG 10172 for Acute Stroke Treatment. Successful recanalization was defined as a modified Thrombolysis in Cerebral Infarction score of 2b-3 after EVT. Clinical and interventional parameters, along with histopathological thrombi examination results, were compared between the TES-positive and TES-negative groups. The associations between TES and stroke subtype and recanalization status were analyzed using univariate and multivariate analyses. RESULTS: A total of 151 patients were included in the analysis, among whom 116 (77%) exhibited TES. TES showed a significant correlation with cardioembolic and cryptogenic strokes (odds ratio [OR]: 8.56; 95% confidence interval: 3.49-22.4; p < 0.001), whereas the TES-positive thrombi were characterized by a higher fibrin/platelet proportion (p = 0.002) and lower erythrocyte proportion (p = 0.044). The TES-positive group demonstrated favorable outcomes compared to the TES-negative group, including a shorter procedure time (p < 0.001), lower number of thrombectomy attempts (p = 0.010), higher incidence of first pass success (p = 0.022), and lower rate of requiring rescue angioplasty and/or stenting (p < 0.001). In multivariate analysis, TES remained independently associated with successful recanalization (OR: 9.63; 95% CI: 2.33, 47.7; p = 0.003) after adjusting for baseline confounders. CONCLUSIONS: Visualization of TES serves as a reliable and easily accessible marker for identifying cardioembolic and cryptogenic strokes and predicting recanalization success in thrombectomy for basilar artery occlusion.

KBa3M2F14Cl (M = Zr, Hf): novel short-wavelength mixed metal halides with the largest second-harmonic generation responses contributed by mixed functional moieties.

The development of short-wavelength nonlinear optical (NLO) materials is indispensable and urgently required for further applications. Halides have been disregarded as potential NLO materials with deep-ultraviolet (DUV) cutoff edges due to their weak second-harmonic generation (SHG) response and poor birefringence. Here, two novel and isostructural halides, KBa3M2F14Cl (M = Zr (KBZFC), Hf (KBHFC)), possess structures that are formed by isolated MF7 monocapped triangular prisms and dissociative K+, Ba2+, and Cl- ions. Compared with reported metal halides that are transparent to the DUV region, KBZFC and KBHFC possess the strongest SHG responses (approximately 1, 0.9 × KH2PO4), which are contributed by the synergistic effect of MF7 (M = Zr, Hf) groups, Ba2+ cations, and Cl- ions. The zero-dimensional structures favour sufficient birefringences (0.12, 0.10 @ 1064 nm) for phase-matchable (PM) behaviours. The discovery of KBZFC and KBHFC showcases the potential of NLO mixed metal halides transparent to the DUV region.

Mechanism of Guigan Longmu Decoction in the Treatment of Arrhythmias Based on Network Pharmacology and Untargeted Metabolomics Assays.

BACKGROUND: Guigan longmu decoction (GGLM), a traditional Chinese medicine compound, has demonstrated efficacy in treating rapid arrhythmia clinically. Nevertheless, its mechanism of action remains elusive. This study aims to elucidate the molecular mechanism underlying the efficacy of GGLM in treating arrhythmia utilizing non-targeted metabolomics, widely-targeted metabolomics, and network pharmacology, subsequently validated through animal experiments. METHODS: Initially, network pharmacology analysis and widely-targeted metabolomics were performed on GGLM. Subsequent to that, rats were administered GGLM intervention, and nontargeted metabolomics assays were utilized to identify metabolites in rat plasma postadministration. The primary signaling pathways, core targets, and key active ingredients of GGLM influencing arrhythmia were identified. Additionally, to validate the therapeutic efficacy of GGLM on arrhythmia rat models, a rat model of rapid arrhythmia was induced via subcutaneous injection of isoproterenol, and alterations in pertinent pathogenic pathways and proteins in the rat model were assessed through qRT-PCR and Western blot following GGLM administration. RESULTS: The results of network pharmacology showed that 99 active ingredients in GGLM acted on 249 targets and 201 signaling pathways, which may be key to treating arrhythmia. Widelytargeted metabolic quantification analysis detected a total of 448 active ingredients in GGLM, while non-targeted metabolomics identified 279 different metabolites and 10 major metabolic pathways in rats. A comprehensive analysis of the above results revealed that the core key active ingredients of GGLM in treating arrhythmia include calycosin, licochalcone B, glabridin, naringenin, medicarpin, formononetin, quercetin, isoliquiritigenin, and resveratrol. These active ingredients mainly act on the relevant molecules and proteins upstream and downstream of the MAPK pathway to delay the onset of arrhythmia. Animal experimental results showed that the heart rate of rats in the model group increased significantly, and the mRNA and protein expression of p38, MAPK, JNK, ERK, NF-kb, IL-1ß, and IL-12 in myocardial tissue also increased significantly. However, after intervention with GGLM, the heart rate of rats in the drug group decreased significantly, while the mRNA and protein expression of p38 MAPK, JNK, ERK1, NF-kb, IL-1ß, and IL-12 in myocardial tissue decreased significantly. CONCLUSION: GGLM, as an adjunctive therapy in traditional Chinese medicine, exhibits favorable therapeutic efficacy against arrhythmia. This can be attributed to the abundant presence of bioactive compounds in the formulation, including verminin, glycyrrhizin B, glabridine, naringenin, ononin, quercetin, isorhamnetin, and kaempferol. The metabolites derived from these active ingredients have the potential to mitigate myocardial inflammation and decelerate heart rate by modulating the expression of proteins associated with the MAPK signaling pathway in vivo.

Genome-wide identification and expression analysis of the KNOX family and its diverse roles in response to growth and abiotic tolerance in sweet potato and its two diploid relatives.

KNOXs, a type of homeobox genes that encode atypical homeobox proteins, play an essential role in the regulation of growth and development, hormonal response, and abiotic stress in plants. However, the KNOX gene family has not been explored in sweet potato. In this study, through sequence alignment, genomic structure analysis, and phylogenetic characterization, 17, 12 and 11 KNOXs in sweet potato (I. batatas, 2n = 6x = 90) and its two diploid relatives I. trifida (2n = 2x = 30) and I. triloba (2n = 2x = 30) were identified. The protein physicochemical properties, chromosome localization, phylogenetic relationships, gene structure, protein interaction network, cis-elements of promoters, tissue-specific expression and expression patterns under hormone treatment and abiotic stresses of these 40 KNOX genes were systematically studied. IbKNOX4, -5, and - 6 were highly expressed in the leaves of the high-yield varieties Longshu9 and Xushu18. IbKNOX3 and IbKNOX8 in Class I were upregulated in initial storage roots compared to fibrous roots. IbKNOXs in Class M were specifically expressed in the stem tip and hardly expressed in other tissues. Moreover, IbKNOX2 and - 6, and their homologous genes were induced by PEG/mannitol and NaCl treatments. The results showed that KNOXs were involved in regulating growth and development, hormone crosstalk and abiotic stress responses between sweet potato and its two diploid relatives. This study provides a comparison of these KNOX genes in sweet potato and its two diploid relatives and a theoretical basis for functional studies.

Saiga antelope horn suppresses febrile seizures in rats by regulating neurotransmitters and the arachidonic acid pathway.

BACKGROUND: Saiga antelope horn (SAH) is a traditional Chinese medicine for treating febrile seizure (FS) with precise efficacy, but its mechanism of action and functional substances are still unclear. Given the need for further research on SAH, our group conducted studies to elucidate its mechanisms and active substances. METHODS: An FS rat pup model was constructed through intraperitoneal injection of LPS and hyperthermia induction. Behavioural indicators of seizures, hippocampal histopathological alterations, serum levels of inflammatory cytokines and hippocampal levels of neurotransmitters were observed and measured to investigate the effects of SAH on FS model rats. Hippocampal metabolomics and network pharmacology analyses were conducted to reveal the differential metabolites, key peptides and pathways involved in the suppression of FS by SAH. RESULTS: SAH suppressed FS, decreased the inflammatory response and regulated the Glu-GABA balance. Metabolomic analysis revealed 13 biomarkers of FS, of which SAH improved the levels of 8 differential metabolites. Combined with network pharmacology, a "biomarker-core target-key peptide" network was constructed. The peptides of SAH, such as YGQL and LTGGF, could exert therapeutic effects via the arachidonic acid pathway. Molecular docking and ELISA results indicated that functional peptides of SAH could bind to PTGS2 target, inhibiting the generation of AA and its metabolites in hippocampal samples. CONCLUSION: In summary, the functional peptides contained in SAH are the main material basis for the treatment of FS, potentially acting through neurotransmitter regulation and the arachidonic acid pathway.

The new CFEM protein CgCsa required for Fe3+ homeostasis regulates the growth, development, and pathogenicity of Colletotrichum gloeosporioides.

Secreted common fungal extracellular membrane (CFEM) domain proteins have been implicated in multiple biological functions in fungi. However, it is still largely unknown whether the ferric iron (Fe3+), as an important trace element, was involved with the biological function of CFEM proteins. In this study, a new CFEM protein CgCsa, with high expression levels at the early inoculation stage on peppers by Colletotrichum gloeosporioides was investigated. Deletion of the targeted gene CgCsa revealed multiple biological roles in hyphal growth restriction, highly reduced conidial yield, delayed conidial germination, abnormal appressorium with elongated bud tubes, and significantly reduced virulence of C. gloeosporioides. Moreover, in CgCsa mutants, the expression levels of four cell wall synthesis-related genes were downregulated, and cell membrane permeability and electrical conductivity were increased. Compared to the wild-type, the CgCsa mutants downregulated expressions of iron transport-related genes, in addition, its three-dimensional structure was capable binding with iron. Increase in the Fe3+ concentration in the culture medium partially recovered the functions of ΔCgCsa mutant. This is probably the first report to show the association between CgCsa and iron homeostasis in C. gloeosporioides. The results suggest an alternative pathway for controlling plant fungal diseases by deplete their trace elements.

Correlation between hemoglobin and the risk of common malignant tumors: a 1999-2020 retrospective analysis and causal association analysis.

BACKGROUND: The role of hemoglobin (HGB) in common malignant tumors remains unclear. METHODS: A retrospective analysis was conducted to identify the correlation between HGB levels and risk of 15 malignant tumors using 50,085 samples from the National Health and Nutrition Examination Survey. Mendelian Randomization analyses (MRAs) were performed based on genome-wide association study data to assess the causal relationship between HGB levels and these malignant tumors using more than 700,000 samples. The robustness of the MRA results was confirmed through various analytical methods. Fifty-six in-house samples were used to investigate the correlation between HGB levels and the prognosis in prostate cancer (PRCA) using the Kaplan-Meier curve. RESULTS: High HGB levels were associated with a higher risk for patients with cervix cancer, melanoma, and non-melanoma skin cancer (OR > 1.000, p < 0.05). It served as a protective factor for colon cancer, esophagus cancer, stomach cancer, bone cancer, lung cancer, renal cancer, and PRCA (OR < 1.000, p < 0.05). Furthermore, MRAs suggested that elevated HGB levels were correlated with a reduced risk of PRCA (OR = 0.869, p < 0.05), with no significant association observed between this marker and the remaining 14 malignant tumors. No pleiotropy or heterogeneity was found in the ultimate results for MRAs (p-values > 0.05), suggesting the robustness of the results. The results derived from the in-house data revealed a relationship between higher HGB values and a more favorable prognosis in PRCA (p < 0.05). CONCLUSION: High circulating HGB levels may play a protective prognostic role for PRCA and serve as a protective factor against the occurrence of PRCA.

From CaBaM2F12 to K2BaM2F12 (M = Zr, Hf): Heterovalent Cation-Substitution-Induced Symmetry Break and Nonlinear-Optical Activity.

Designing short-wavelength nonlinear-optical (NLO) crystals is of vital importance for laser applications. Here, the combination of alkaline-earth metals, d0 transition metals, and F atom has generated two new and isostructural fluorides, CaBaZr2F12 (CBZF) and CaBaHf2F12 (CBHF), which adopt centrosymmetric space group I4/mmm. Taking CBZF and CBHF as the parents, two new fluorides, K2BaZr2F12 (KBZF) and K2BaHf2F12 (KBHF), with an Imm2 polar structure were obtained via a heterovalent cation substitution strategy. All four compounds feature ZrF8-dodecahedra-built {[Zr2F12]4-}∞ chains and show short ultraviolet cutoff edges (<200 nm). KBZF and KBHF show phase-matchable behavior with moderate second-harmonic-generation responses [0.6 and 0.35 × KH2PO4 (KDP)] under 1064 nm laser radiation. This work enriches fluorides as promising short-wavelength NLO materials.

Analysis of tumor microenvironment alterations in partially responsive rectal cancer patients treated with neoadjuvant chemoradiotherapy.

PURPOSE: Achieving a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (NCRT) remains a challenge for most patients with rectal cancer. Exploring the potential of combining NCRT with immunotherapy or targeted therapy for those achieving a partial response (PR) offers a promising avenue to enhance treatment efficacy. This study investigated the impact of NCRT on the tumor microenvironment in locally advanced rectal cancer (LARC) patients who exhibited a PR. METHODS: This was a retrospective, observational study. Five patients demonstrating a PR after neoadjuvant treatment for LARC were enrolled in the study. Biopsy samples before treatment and resected specimens after treatment were stained with a panel of 26 antibodies targeting various immune and tumor-related markers, each labeled with distinct metal tags. The labeled samples were then analyzed using the Hyperion imaging system. RESULTS: Heterogeneity within the tumor microenvironment was observed both before and after NCRT. Notably, tumor-associated macrophages, CD4 + T cells, CD8 + T cells, CD56 + natural killer cells, tumor-associated neutrophils, cytokeratin, and E-cadherin exhibited slight increase in abundance within the tumor microenvironment following treatment (change ratios = 0.78, 0.2, 0.27, 0.32, 0.17, 0.46, 0.32, respectively). Conversely, the number of CD14 + monocytes, CD19 + B cells, CD45 + CD4 + T cells, collagen I, α-smooth muscle actin, vimentin, and ß-catenin proteins displayed significant decreases post-treatment (change ratios = 1.73, 1.92, 1.52, 1.25, 1.52, 1.12, 2.66, respectively). Meanwhile, Foxp3 + regulatory cells demonstrated no significant change (change ratio = 0.001). CONCLUSIONS: NCRT has diverse effects on various components of the tumor microenvironment in LARC patients who achieve a PR after treatment. Leveraging combination therapies may optimize treatment outcomes in this patient population.

The fusiform skin paddle in fibula free flap: a fusiform-designed skin paddle for maxillofacial soft defect reconstruction and reducing leg wound tension.

Objective: To investigate the feasibility of leg wound closure and reconstruction of maxillofacial soft defect by a fusiform-designed skin paddle in fibula free flap (FFF). Methods: Fifty patients who underwent FFF for reconstruction of maxillofacial soft defect were divided into two groups. The fusiform group (20 patients) was treated using a fusiform-designed skin paddle in FFF (skin paddle width less than 2 cm), and leg wound was closed using primary suturing. Reconstruction of the maxillofacial soft defect or filling of dead space was achieved by folding the fusiform skin paddle. The conventional group (30 patients) was treated using the conventional-designed skin paddle (skin paddle width no less than 2.5 cm). The leg wound was closed using mattress suturing or skin graft, while reconstruction of the maxillofacial soft defect or filling of dead space by conventional way. The average postoperative length of hospital stay, healing time of leg wound, and post-surgical complications were recorded at least 6 months after the surgery. Results: Compared with traditional method, the fusiform-designed skin paddle reduced the average healing time of the leg wound (fusiform group: 11.05 days, conventional group: 14.77 days, P < 0.05). The average length-to-width ratio in fusiform group was significantly greater than that of in conventional group (fusiform group: 5.85, conventional group: 2.93, P < 0.05), and no difference was observed on the graft size of skin paddle between two groups (fusiform group: 23.13, conventional group: 27.13, P > 0.05). The post-surgical early complications of the leg wound in the conventional group were higher than that of in the fusiform group (fusiform group: 0%, conventional group: 6.67%), while the post-surgical late complication of the donor site between the two groups showed no case. Healing disorders of maxillofacial soft reconstruction in the conventional group were higher than that of in the fusiform group (fusiform group: 5.26%, conventional group: 20.69%). Conclusions: Fusiform-designed skin paddle for closure of the leg wound and maxillofacial soft defect is a feasible alternative to the conventional- designed skin paddle. The fusiform- designed skin paddle resulted in the less postoperative length of hospital stay, shorter healing time of leg wound and less complication.

Salvia miltiorrhiza stem-leaf of total phenolic acid conversion products alleviate myocardial ischemia by regulating metabolic profiles, intestinal microbiota and metabolites.

Myocardial ischemia (MI) is a significant contributor to ischemic heart diseases like angina pectoris and myocardial infarction. Reactive oxygen species produced during MI can trigger lipid peroxidation, damaging cell structure and function. Salvia miltiorrhiza (SM) has been widely used clinically in the treatment of cardiovascular diseases. However, in the process of rooting, the aboveground parts of this plant are usually discarded by tons. To make better use of these plant resources, the phenolic acids extracted and purified from the aerial part of SM were studied and chemically transformed, and the potential protective effect and possible mechanism of salvianolic acids containing a higher content of salvianolic acid A on MI were obtained. The transformed products of SM stem-leaves total phenolic acids with 8.16 % salvianolic acid A showed a better protective effect on the isoproterenol (ISO)-induced acute MI injury rat model. It can improve ST segment changes and has good antioxidant, anti-inflammatory and anticoagulant effects. In addition, the dysbiosis of gut microbiota and the related metabolic levels of short chain fatty acids (SCFAs), phenylalanine and glycerophospholipids were improved. This was achieved by reducing the abundance of Bacteroides, Faecalibaculum, and L-phenylalanine levels. In addition, the abundance of probiotics in Butyricoccus, Roseburia, and norank_f_Eubacterium_coprostanoligenes_group, as well as the contents of propionic acid and isobutyric acid, LPCs and PCs were increased. In conclusion, total phenolic acids of SM stem-leaves showed protective effects against ISO-induced rats, especially the strongest effect after conversion, which is a new option for the prevention and treatment of MI.