Airway management for patients with tracheal stenosis and severe scar contracture of the face and neck via bronchoscopy: a case report.

Both anaesthesiologists and surgeons experience challenges in managing airway stenosis and scar contracture in the face and neck. Herein, we report the case of a 38-year-old woman (BMI 23.1 kg/m2, third-degree burns covering 40% of her body, an American Society of Anaesthesiologists physical status III) with an unusual case of airway constriction. This patient had a predictable difficult airway (mouth opening of 2 cm, bilateral nostril scar hyperplasia, Mallampatti score III, scarring of the head and neck, and severe tracheal stenosis). Tracheal stenosis measuring 5.5 mm in width as observed 8 cm below the glottis, and the bronchoscope could not pass through it. After two failed attempts at laryngeal mask insertion, we decided to instead insert a custom-made tracheal tube under the guidance of a fiberoptic bronchoscope. The operation was successful, and the patient was transferred to the intensive care unit (ICU).

Dehydroevodiamine Alleviates Ulcerative Colitis by Inhibiting the PI3K/AKT/NF-κB Signaling Pathway via Targeting AKT1 and Regulating Gut Microbes and Serum Metabolism.

Ulcerative colitis (UC) is a typical inflammatory bowel disease (IBD), impairing the quality of life of patients. Dehydroevodiamine (DHE) is an active alkaloid isolated from Tetradium ruticarpum that exerts significant anti-inflammatory effects in gastrointestinal diseases. However, the effect and mechanisms of DHE on UC remain unclear. We performed a DSS-induced experimental UC rat model to reveal the efficacy and potential mechanisms of DHE on UC. HE and AB-PAS staining were used for the evaluation of pathologies, and 16S rRNA sequencing was used to detect changes in gut microbes. Metabolomics was used to detect changes in serum metabolites. Network pharmacology and transcriptomics were conducted to reveal the underlying mechanisms of DHE for UC. HuProt proteome microarrays, molecular docking, and SPR were used to reveal the targets of action of DHE. WB, RT-qPCR, and IHC were used to assess the action effects of DHE. DHE demonstrated significant alleviation of DSS-induced colitis symptoms in rats by suppressing inflammatory and oxidative stress responses, amending colonic barrier injury, and inhibiting apoptosis. In terms of gut microbial modulation, DHE decreased the abundance of Allobaculum, Clostridium, Escherichia, Enterococcus, and Barnesiella and increased the abundance of Lactobacillus, Bifidobacterium, and SMB5. Moreover, metabolomics suggested that the regulation of DHE in DSS-induced UC rats mainly involved aminoacyl-tRNA biosynthesis, vitamin B6 metabolism, phenylalanine, tyrosine, and so on. Mechanically, DHE alleviated UC in rats by targeting AKT1, thereby inhibiting the PI3K/AKT/NF-κB signaling pathway.

Synergistic Effect of Two Peptaibols from Biocontrol Fungus Trichoderma longibrachiatum Strain 40418 on CO-Induced Plant Resistance.

Trichoderma longibrachiatum is a filamentous fungus used as a biological control agent against different plant diseases. The multifunctional secondary metabolites synthesized by Trichoderma, called peptaibols, have emerged as key elicitors in plant innate immunity. This study obtained a high-quality genome sequence for the T. longibrachiatum strain 40418 and identified two peptaibol biosynthetic gene clusters using knockout techniques. The two gene cluster products were confirmed as trilongin AIV a (11-residue) and trilongin BI (20-residue) using liquid chromatography coupled with tandem mass spectrometry. Further investigations revealed that these peptaibols induce plant resistance to Pseudomonas syringae pv tomato (Pst) DC3000 infection while triggering plant immunity and cell death. Notably, the two peptaibols exhibit synergistic effects in plant-microbe signaling interactions, with trilongin BI having a predominant role. Moreover, the induction of tomato resistance against Meloidogyne incognita showed similarly promising results.

Dehydroevodiamine targeting IKKß to alleviate acute gastric injury via inhibiting the p65/NLRP3 axis.

BACKGROUND: Acute gastric injury, a common and recurring global digestive disorder, significantly impairs patient quality of life and overall health. Dehydroevodiamine (DHE), a bioactive natural product derived from Tetradium ruticarpum (A. Juss.) Hartley, shows potential therapeutic effects on acute gastric injury. This study investigates the underlying mechanisms of DHE's alleviating effects on acute gastric injury. METHODS: The gastric mucosal protective effect of DHE was confirmed through in vivo and in vitro acute gastric injury models. Biotin pulldown MS and molecular dynamics simulations identified DHE's target. CETSA and SPR assays validated DHE's affinity for IKKß. Protein site mutation validation and MST pinpointed the direct binding sites of DHE on IKKß. Additionally, the potential mechanism by which DHE ameliorates acute gastric injury was elucidated using WB, IHC, and IF methods, and further confirmed by rescue experiments. RESULTS: DHE effectively ameliorated IDO-induced gastric injury in GES-1 cells and rat gastric mucosa, both in vitro and in vivo. Biotin pulldown MS identified IKKß as the target of DHE in alleviating gastric injury. CETSA and SPR assays confirmed DHE's direct binding to IKKß. Molecular dynamics simulations, protein mutation experiments, and MST results pinpointed GLU-149, GLU-49, and ASP-103 in the ATP-binding pocket as the binding sites of DHE on IKKß. Notably, DHE was found to competitively bind to IKKß with ATP. Mechanistically, DHE attenuated IDO-induced gastric injury by inhibiting the IKKß-p65/NLRP3 signaling pathway. Importantly, exogenous activation of IKKß reversed the therapeutic effect of DHE, indicating that DHE's efficacy depends on IKKß. CONCLUSION: DHE attenuated IDO-induced gastric injury by inhibiting the IKKß-p65/NLRP3 signaling pathway. Notably, DHE is a novel ATP-competitive IKKß inhibitor that prevents phosphorylation by targeting GLU-149, GLU-49, and ASP-103 in the ATP-binding pocket. This study reveals new targets of action for DHE, providing a new molecular basis for using DHE in treating inflammation-related diseases.

Paeoniflorin inhibited GSDMD to alleviate ANIT-induced cholestasis via pyroptosis signaling pathway.

BACKGROUND: Cholestasis (CT) is a group of disorders caused by impaired production, secretion or excretion of bile. This may result in the deposition of bile components in the blood and liver, which in turn causes damage to liver cells and other tissues. If untreated, CT can progress to severe complications, including cirrhosis, liver failure, and potentially life-threatening conditions. OBJECTIVE: This research was intended to elucidate the function and mechanism of Paeoniflorin (PF) in ameliorating ANIT-induced pyroptosis in CT. METHODS: CT models were established in SD rats and HepG2 cells through ANIT treatment. Histological examination was conducted using haematoxylin and eosin (HE) staining to assess the histopathological alterations in the liver. Network pharmacology was employed to identify potential PF targets in CT treatment. To evaluate pyroptosis levels, various methods were used, including serum biochemical analysis, Enzyme-Linked Immunosorbent Assay (ELISA), immunofluorescence (IF), immunohistochemistry (IHC), Western blotting, transmission electron microscopy (TEM), and scanning electron microscopy (SEM). The HuProt™ 20K Chip was utilized to pinpoint potential PF-binding targets. PF's direct mechanisms in CT treatment were explored using molecular docking (MD), molecular dynamics simulations (MDS), Cellular Thermal Shift Assay (CETSA), and Surface Plasmon Resonance (SPR). RESULTS: PF administration was found to alleviate ANIT-induced liver pathology, enhance liver function markers, and improve cell viability. Network pharmacology and pyroptosis inhibitor studies suggested that PF might mitigate CT via the NLRP3-dependent pyroptosis pathway. This hypothesis was further supported by Western blotting, IF, and IHC analyses, which indicated PF's potential to inhibit NLRP3-dependent pyroptosis in CT. GSDMD was identified as a target through HuProt™ 20K Chip screening. The binding affinity of PF to GSDMD was validated through MD, MDS, CETSA, and SPR techniques. Additionally, the regulatory impact of GSDMD on downstream inflammatory pathways was confirmed by ELISA and IHC. CONCLUSION: PF exhibited a hepatoprotective effect in ANIT-induced CT, primarily by targeting GSDMD, thereby suppressing ANIT-induced pyroptosis and the subsequent release of inflammatory mediators.

Association of overall survival benefit of radiotherapy with progression-free survival after chemotherapy for diffuse large B-cell lymphoma: A systematic review and meta-analysis.

Objective: To evaluate whether improved progression-free survival (PFS) from radiotherapy (RT) translates into an overall survival (OS) benefit for diffuse large B-cell lymphoma (DLBCL). Methods: A systematic literature search identified randomized controlled trials (RCTs) and retrospective studies that compared combined-modality therapy (CMT) with chemotherapy (CT) alone. Weighted regression analyses were used to estimate the correlation between OS and PFS benefits. Cohen's kappa statistic assessed the consistency between DLBCL risk-models and PFS patterns. Furthermore, the benefit trend of RT was analyzed by fitting a linear regression model to the pooled hazard ratio (HR) according to the PFS patterns. Results: For both 7 RCTs and 52 retrospective studies, correlations were found between PFS HR (HRPFS) and OS HR (HROS) at trial level (r = 0.639-0.876), and between PFS and OS rates at treatment-arm level, regardless of CT regimens (r = 0.882-0.964). Incorporating RT into CT increased about 18% of PFS, and revealed a different OS benefit profile. Patients were stratified into four CT-generated PFS patterns (>80%, >60-80%, >40-60%, and ≤40%), which was consistent with risk-stratified subgroups (kappa > 0.6). Absolute gain in OS from RT ranged from ≤5% at PFS >80% to about 21% at PFS ≤40%, with pooled HROS from 0.70 (95% CI, 0.51-0.97) to 0.48 (95% CI, 0.36-0.63) after rituximab-based CT. The OS benefit of RT was predominant in intermediate- and high-risk patients with PFS ≤ 80%. Conclusion: We demonstrated a varied OS benefit profile of RT to inform treatment decisions and clinical trial design.

The Respiratory Burst Oxidase Homologue OsRBOHE is crucial for root hair formation, drought resistance and tillering in rice.

Respiratory Burst Oxidase Homologues (RBOHs) are involved in plant growth, development, and stress adaptation. How OsRBOHs affect root hair formation and consequently nutrient acquisition and drought resistance in rice is not well understood. We knocked out six OsRBOH genes in rice that were expressed in roots and identified OsRBOHE as the only one affecting root hair formation. OsRBOHE was strongly expressed in the root epidermis, root hairs and tiller buds. OsRBOHE is localised at the plasma membrane. Knockout of OsRBOHE decreased reactive oxygen species generation in the root hairs and tiller buds, downregulated genes involved in cell wall biogenesis, and decreased root hair length and tillering by 90% and 30%, respectively. Knockout of OsRBOHE decreased phosphorus acquisition only in low available P soil under aerobic conditions, but not in high P soil or under flooded conditions when P was likely not limited by diffusion. Knockout of OsRBOHE markedly decreased drought resistance of rice plants through the effect on root hair formation and the associated rhizosheath. Taken together, OsRBOHE is crucial for root hair formation and tillering and consequently on drought resistance in rice. The contribution of root hairs to P acquisition in rice is limited to aerobic soil.

Paeoniflorin protects hepatocytes from APAP-induced damage through launching autophagy via the MAPK/mTOR signaling pathway.

BACKGROUND: Drug-induced liver injury (DILI) is gradually becoming a common global problem that causes acute liver failure, especially in acute hepatic damage caused by acetaminophen (APAP). Paeoniflorin (PF) has a wide range of therapeutic effects to alleviate a variety of hepatic diseases. However, the relationship between them is still poorly investigated in current studies. PURPOSE: This work aimed to explore the protective effects of PF on APAP-induced hepatic damage and researched the potential molecular mechanisms. METHODS: C57BL/6J male mice were injected with APAP to establish DILI model and were given PF for five consecutive days for treatment. Aiming to clarify the pharmacological effects, the molecular mechanisms of PF in APAP-induced DILI was elucidated by high-throughput and other techniques. RESULTS: The results demonstrated that serum levels of ALP, γ-GT, AST, TBIL, and ALT were decreased in APAP mice by the preventive effects of PF. Moreover, PF notably alleviated hepatic tissue inflammation and edema. Meanwhile, the results of TUNEL staining and related apoptotic factors coincided with the results of transcriptomics, suggesting that PF inhibited hepatocyte apoptosis by regulated MAPK signaling. Besides, PF also acted on reactive oxygen species (ROS) to regulate the oxidative stress for recovery the damaged mitochondria. More importantly, transmission electron microscopy showed the generation of autophagosomes after PF treatment, and PF was also downregulated mTOR and upregulated the expression of autophagy markers such as ATG5, ATG7, and BECN1 at the mRNA level and LC3, p62, ATG5, and ATG7 at the protein level, implying that the process by which PF exerted its effects was accompanied by the occurrence of autophagy. In addition, combinined with molecular dynamics simulations and western blotting of MAPK, the results suggested p38 as a direct target for PF on APAP. Specifically, PF-activated autophagy through the downregulation of MAPK/mTOR signaling, which in turn reduced APAP injury. CONCLUSIONS: Paeoniflorin mitigated liver injury by activating autophagy to suppress oxidative stress and apoptosis via the MAPK/mTOR signaling pathway. Taken together, our findings elucidate the role and mechanism of paeoniflorin in DILI, which is expected to provide a new therapeutic strategy for the development of paeoniflorin.

Trop2-targeted therapy in breast cancer.

Human trophoblastic cell surface antigen 2 (Trop2) is a glycoprotein, a cellular marker of trophoblastic and stem cells, and a calcium signaling transducer involved in several signaling pathways, leading to the proliferation, invasion, and metastasis of tumors. It is expressed at a low level in normal epithelial cells, but at a high level in many tumors, making it an ideal target for cancer therapy. According to previous literature, Trop2 is broadly expressed in all breast cancer subtypes, especially in triple negative breast cancer (TNBC). Several clinical trials have demonstrated the effectiveness of Trop2-targeted therapy in breast cancer. Sacituzumab govitecan (SG) is a Trop2-targeted antibody-drug conjugate (ADC) that has been approved for the treatment of metastatic TNBC and hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer. This article reviews the structure and function of Trop2, several major Trop2-targeted ADCs, other appealing novel Trop2-targeted agents and relevant clinical trials to provide a landscape of how Trop2-targeted treatments will develop in the future.

Synthesis, biological activities and mechanistic studies of C20-ketone pachysandra alkaloids as anti-hepatocellular carcinoma agents.

The pachysandra alkaloids found in Sarcococca ruscifolia demonstrate notable anti-hepatocellular carcinoma activity. Despite their efficacy, the structural diversity of these compounds remains limited, and their precise antitumor mechanism is still unclear. In pursuit of identifying novel lead compounds with high efficacy and low toxicity for combating hepatocellular carcinoma, twenty-three compounds of C20-ketone pachysandra alkaloid derivatives were designed and synthesized by using 3-dimethylamine pachysandra alkaloids as scaffolds. Subsequent in vitro anticancer activity experiments showed that synthetic pachysandra alkaloids had a stronger effect on HepG2 cells than did their natural counterparts, with low toxicity and high selectivity. The most potent derivative, 6k, had an IC50 value of 0.75 µM, demonstrating 25.7-fold greater anticancer activity than sarcovagine D against HepG2 cells. Through network pharmacology and molecular docking analysis, it was revealed that synthetic pachysandra alkaloids may exert their effects by inhibiting the JAK2/STAT3 pathway, thereby preventing the proliferation of liver cancer cells. Further research through scratch tests, immunofluorescence experiments, and Western blot analysis revealed that compound 6k effectively inhibited the migration of HepG2 cells and induced mitochondria-mediated intrinsic apoptosis of HepG2 cells by regulating the JAK2/STAT3 signaling pathway. The aforementioned results indicate that compound 6k could be developed as a potential candidate for the treatment of hepatocellular carcinoma.

Conservation and specialization of the Ycf2-FtsHi chloroplast protein import motor in green algae.

The protein import motor in chloroplasts plays a pivotal role in their biogenesis and homeostasis by driving the translocation of preproteins into chloroplasts. While the Ycf2-FtsHi complex serves as the import motor in land plants, its evolutionary conservation, specialization, and mechanisms across photosynthetic organisms are largely unexplored. Here, we isolated and determined the cryogenic electron microscopy (cryo-EM) structures of the native Ycf2-FtsHi complex from Chlamydomonas reinhardtii, uncovering a complex composed of up to 19 subunits, including multiple green-algae-specific components. The heterohexameric AAA+ ATPase motor module is tilted, potentially facilitating preprotein handover from the translocon at the inner chloroplast membrane (TIC) complex. Preprotein interacts with Ycf2-FtsHi and enhances its ATPase activity in vitro. Integrating Ycf2-FtsHi and translocon at the outer chloroplast membrane (TOC)-TIC supercomplex structures reveals insights into their physical and functional interplay during preprotein translocation. By comparing these findings with those from land plants, our study establishes a structural foundation for understanding the assembly, function, evolutionary conservation, and diversity of chloroplast protein import motors.

Cadmium Minimization in Grains of Maize and Wheat Grown on Smelting-Impacted Land Ameliorated by Limestone.

Cadmium (Cd) contamination in agricultural soils has emerged as a significant concern, particularly due to its potential impact on plant-based food. Soil pH reductions can exacerbate Cd mobility, leading to excessive accumulation in crops. While liming has been demonstrated as an effective method to mitigate Cd accumulation in rice grains in acid soils of southern China, its efficacy in remediating acid soils in northern China remains unclear. In this study, a multi-year field experiment was conducted on farmland impacted by zinc ore smelting at coordinates of 33.92° N 112.46° E to investigate the use of limestone for controlling Cd accumulation in wheat and maize grains. The results indicated that applying 7.5 t ha-1 of limestone significantly raised the soil pH from 4.5 to 6.8 as anticipated. Different rates of limestone application (2.25, 4.45, and 7.50 t ha-1) reduced Cd bioavailability in the soil by 20-54%, and Cd accumulation in wheat grains by 5-38% and maize grains by 21-63%, without yield penalty. The remediation effects were sustained for at least 27 months, highlighting limestone as a promising ameliorant for smelting-affected farmland in northern China.

CCL5/CCR5/CYP1A1 pathway prompts liver cancer cells to survive in the combination of targeted and immunological therapies.

Combination therapy of anti-programmed cell death protein-1 (PD-1) antibodies and tyrosine kinase inhibitors (TKIs) has significantly improved the prognosis for hepatocellular carcinoma (HCC), but many patients still have unsatisfactory outcomes. CD8 T cells are known to exert a pivotal function in the immune response against tumors. Nevertheless, most CD8 T cells in HCC tissues are in a state of exhaustion, losing the cytotoxic activity against malignant cells. Cytokines, mainly secreted by immune cells, play an important role in the occurrence and development of tumors. Here, we demonstrated the changes in exhausted CD8T cells during combination therapy by single-cell RNA sequencing (scRNA-seq) analysis on tumor samples before and after treatment. Combination therapy exerted a substantial impact on the exhausted CD8T cells, particularly in terms of cytokine expression. CCL5 was the most abundantly expressed cytokine in CD8T cells and exhausted CD8T cells, and its expression increased further after treatment. Subsequently, we discovered the CCL5/CCR5/CYP1A1 pathway through RNA sequencing (RNA-seq) on CCL5-stimulated Huh7 cells and verified through a series of experiments that this pathway can mediate the resistance of liver cancer cells to lenvatinib. Tissue experiments showed that after combination therapy, the CCL5/CCR5/CYP1A1 pathway was activated, which can benefit the residual tumor cells to survive treatment. Tumor-bearing mouse experiments demonstrated that bergamottin (BGM), a competitive inhibitor of CYP1A1, can enhance the efficacy of both lenvatinib and combination therapy. Our research revealed one mechanism by which hepatoma cells can survive the combination therapy, providing a theoretical basis for the refined treatment of HCC.

Tyrosine Kinase 2 Inhibition With Zasocitinib (TAK-279) in Psoriasis: A Randomized Clinical Trial.

Importance: New, effective, and well-tolerated oral therapies are needed for treating psoriasis. Zasocitinib, a highly selective allosteric tyrosine kinase 2 (TYK2) inhibitor, is a potential new oral treatment for this disease. Objective: To assess the efficacy, safety, and tolerability of zasocitinib in patients with moderate to severe plaque psoriasis. Design, Setting, and Participants: This phase 2b, randomized, double-blind, placebo-controlled, multiple-dose randomized clinical trial was conducted from August 11, 2021, to September 12, 2022, at 47 centers in the US and 8 in Canada. The study included a 12-week treatment period and a 4-week follow-up period. Key eligibility criteria for participants included age 18 to 70 years; a Psoriasis Area and Severity Index (PASI) score of 12 or greater; a Physician's Global Assessment score of 3 or greater; and a body surface area covered by plaque psoriasis of 10% or greater. Of 287 patients randomized, 259 (90.2%) received at least 1 dose of study treatment. Intervention: Patients were randomly assigned (1:1:1:1:1) to receive zasocitinib at 2, 5, 15, or 30 mg or placebo orally, once daily, for 12 weeks. Main Outcomes and Measures: The primary efficacy end point was the proportion of patients achieving 75% or greater improvement in PASI score (PASI 75) at week 12. Secondary efficacy end points included PASI 90 and 100 responses. Safety was also assessed. Results: In total, 259 patients were randomized and received treatment (mean [SD] age, 47 [13] years; 82 women [32%]). At week 12, PASI 75 was achieved for 9 (18%), 23 (44%), 36 (68%), and 35 (67%) patients receiving zasocitinib at 2, 5, 15, and 30 mg, respectively, and 3 patients (6%) receiving placebo. PASI 90 responses were consistent with PASI 75. PASI 100 demonstrated a dose response at all doses, with 17 patients (33%) achieving PASI 100 with zasocitinib, 30 mg. Treatment-emergent adverse events occurred for 23 patients (44%) receiving placebo and 28 (53%) to 31 (62%) patients receiving the 4 different doses of zasocitinib, with no dose dependency and no clinically meaningful longitudinal differences in laboratory parameters. Conclusions and Relevance: This randomized clinical trial found that potent and selective inhibition of TYK2 with zasocitinib at oral doses of 5 mg or more once daily resulted in greater skin clearance than placebo over 12 weeks. Trial Registration: ClinicalTrials.gov Identifier: NCT04999839.

A report of twenty cases of ovarian Brenner tumor and literature review: a case series study.

BACKGROUND: To explore the clinical characteristics of ovarian Brenner tumors and provide some basis for the treatment regimen of ovarian Brenner tumors. METHODS: A retrospective analysis of the pathology database of surgical specimens at the Huzhou Maternal and Child Health Hospital from September 2008 to February 2023 was conducted. Patients who were pathologically diagnosed with ovarian Brenner tumors were included. Clinical data of patients was collected, and their diagnostic and treatment characteristics were summarized and analyzed. RESULTS: A total of 20 cases were included in this study, all of which were histologically confirmed by surgical pathology. Among them, 8 cases (40%) were combined with serous, mucinous cystadenoma, or simple cyst. One case presented with a benign ovarian Brenner tumor combined with mucinous cystadenoma, underwent right adnexectomy, and relapsed 5 years later as a malignant Brenner tumor (MBT) coexisting with ovarian squamous cell carcinoma. Multiple tumor markers were elevated malignantly, with CA199 being the most significant. Treatments included unilateral adnexectomy in 7 cases, bilateral adnexectomy in 3 cases, total hysterectomy with bilateral adnexectomy in 7 cases, radical hysterectomy in 1 case, and 2 cases underwent ovarian staging surgery. MBT patients received three cycles of postoperative chemotherapy with the carboplatin-paclitaxel (TC) regimen. FOLLOW-UP: One case with concomitant cervical cancer was lost to follow-up after surgery in an external hospital; one case with concomitant ovarian cancer received no further treatment after surgery and was lost to follow-up after 2 years; one case with concomitant endometrial cancer received no further treatment after surgery, and had no recurrence after 4 years of follow-up. Regular follow-up for MBT patients continued for 5 years without recurrence. The remaining 16 cases were followed up for a period ranging from 6 months to 7 years, with no reported recurrences. CONCLUSION: Clinical manifestations and auxiliary examinations of ovarian Brenner tumors lack obvious specificity. When necessary, a combination of tumor markers and imaging examinations can aid in diagnosis. Surgical strategies should be selected according to the patient's menopausal status. TRIAL REGISTRATION: Not applicable.

Large cell neuroendocrine carcinoma of the cervix: a case report.

Large Cell Neuroendocrine Carcinoma (LCNEC) of the cervix is an extremely rare but highly aggressive type of cervical cancer and it requires multimodal therapy to improve their quality of life. At present, there are no established, standardized treatment protocols for managing large cell neuroendocrine carcinoma of the cervix. In this report, we present a case of a patient with cervical LCNEC, Who was a 39-year-old woman who presented with irregular vaginal bleeding accompanied by lower abdominal distension for over a month. Examination revealed a cauliflower-like cervical mass approximately 4cm in diameter, with the normal cervical architecture distorted and partially fused to the vaginal wall. Following further investigations, the stage assigned was IVB, and who was started on neoadjuvant chemotherapy with the TC (paclitaxel + carboplatin) regimen but during neoadjuvant chemotherapy, The patient developed a vaginal urinary leakage. Then, The patient underwent a comprehensive treatment regimen that included pelvic exenteration, urinary system reconstruction, pelvic floor reconstruction, and chemotherapy. Given the patient's positive immunohistochemistry for EGFR, the treatment was combined with the anti-angiogenic drug, bevacizumab. The patient achieved complete remission following the comprehensive treatment. Through this case to explore individualized treatment for cervical LCNEC.

Risk factors for secondary infection after liver failure and effect of comprehensive nursing intervention.

BACKGROUND: In patients with liver failure (LF), the high rate of secondary infections, which are associated with poor prognosis, highlights the clinical significance of understanding the underlying risk factors and implementing targeted intervention programs. AIM: To investigate risk factors for secondary infections in patients with LF and evaluate the effectiveness of comprehensive nursing interventions. METHODS: This retrospective study included 64 patients with LF, including 32 with and 32 without secondary infections. A questionnaire was used to collect data on age; laboratory parameters, including total and direct bilirubin, prothrombin time, blood ammonia, and other biochemical parameters; invasive procedures; and complications. Patients with secondary infections received comprehensive nursing intervention in addition to routine nursing care, whereas those without secondary infections received only routine nursing care to compare the effect of nursing intervention on outcomes. RESULTS: The infection rate, which was not associated with age or complications, was significantly associated with biochemical parameters and invasive procedures (P < 0.05). The infection rate was 61.6% in patients who had undergone invasive procedures and 32.1% in those who had not undergone invasive procedures during the hospital stay. The infection rate was also significantly associated with the type of LF (P < 0.05), with the lowest rate observed in patients with acute LF and the highest rate observed in those with subacute LF. The nursing satisfaction rate was 58.3% in the uninfected group and 91.7% in the infected group, indicating significantly higher satisfaction in the infected group (P < 0.05). CONCLUSION: In patients with LF, the rate of secondary infections was high and associated with biochemical parameters and type of LF. Comprehensive nursing intervention can improve patient satisfaction.

Transient receptor potential melastatin 8 contributes to the interleukin-33-mediated cold allodynia in a mouse model of neuropathic pain.

ABSTRACT: Cold allodynia is a common complaint of patients suffering from neuropathic pain initiated by peripheral nerve injury. However, the mechanisms that drive neuropathic cold pain remain elusive. In this study, we show that the interleukin (IL)-33/ST2 signaling in the dorsal root ganglion (DRG) is a critical contributor to neuropathic cold pain by interacting with the cold sensor transient receptor potential melastatin 8 (TRPM8). By using the St2-/- mice, we demonstrate that ST2 is required for the generation of nociceptor hyperexcitability and cold allodynia in a mouse model of spared nerve injury (SNI). Moreover, the selective elimination of ST2 function from the Nav1.8-expressing nociceptor markedly suppresses SNI-induced cold allodynia. Consistent with the loss-of-function studies, intraplantar injection of recombinant IL-33 (rIL-33) is sufficient to induce cold allodynia. Mechanistically, ST2 is co-expressed with TRPM8 in both mouse and human DRG neurons and rIL-33-induced Ca2+ influx in mouse DRG neurons through TRPM8. Co-immunoprecipitation assays further reveal that ST2 interacts with TRPM8 in DRG neurons. Importantly, rIL-33-induced cold allodynia is abolished by pharmacological inhibition of TRPM8 and genetic ablation of the TRPM8-expressing neurons. Thus, our findings suggest that the IL-33/ST2 signaling mediates neuropathic cold pain through downstream cold-sensitive TRPM8 channels, thereby identifying a potential analgesic target for the treatment of neuropathic cold pain.

Magnesium-promoted rapid self-reconstruction of NiFe-based electrocatalysts toward efficient oxygen evolution.

The acceleration of active sites formation through surface reconstruction is widely acknowledged as the crucial factor in developing high-performance oxygen evolution reaction (OER) catalysts for water splitting. Herein, a simple one-step corrosion method and magnesium (Mg)-promoted strategy are reported to develop the NiFe-based catalyst with enhanced OER performance. The Mg is introduced in NiFe materials to preparate a "pre-catalyst" Mg-Ni/Fe2O3. In-situ Raman shows that Mg doping would accelerate the self-reconstruction of Ni/Fe2O3 to form active NiOOH species during OER. In-situ infrared indicates that Mg doping benefits the formation of *OOH intermediate. Theoretical analysis further confirms that Mg doping can optimize the adsorption of oxygen intermediates, accelerating the OER kinetics. Accordingly, the Mg-Ni/Fe2O3 catalyst exhibits excellent OER performance with overpotential of 168 mV at 10 mA cm-2. The anion exchange membrane water electrolyzer achieved 200 mA cm-2 at voltage of 1.53 V, showing excellent stability over 500 h as well. This work demonstrates the potential of Mg-promoted strategy in regulating the activity of transition metal-based OER electrocatalysts.

Address model mismatch and defocus in FZA lensless imaging via model-driven CycleGAN.

Mask-based lensless imaging systems suffer from model mismatch and defocus. In this Letter, we propose a model-driven CycleGAN, MDGAN, to reconstruct objects within a long distance. MDGAN includes two translation cycles for objects and measurements respectively, each consisting of a forward propagation and a backward reconstruction module. The backward module resembles the Wiener-U-Net, and the forward module consists of the estimated image formation model of a Fresnel zone aperture camera (FZACam), followed by CNN to compensate for the model mismatch. By imposing cycle consistency, the backward module can adaptively match the actual depth-varying imaging process. We demonstrate that MDGAN based on either a simulated or calibrated imaging model produces a higher-quality image compared to existing methods. Thus, it can be applied to other mask-based systems.