Exploring near-infrared autofluorescence properties in parathyroid tissue: an analysis of fresh and paraffin-embedded thyroidectomy specimens.

Significance: Near-infrared autofluorescence (NIRAF) utilizes the natural autofluorescence of parathyroid glands (PGs) to improve their identification during thyroid surgeries, reducing the risk of inadvertent removal and subsequent complications such as hypoparathyroidism. This study evaluates NIRAF's effectiveness in real-world surgical settings, highlighting its potential to enhance surgical outcomes and patient safety. Aim: We evaluate the effectiveness of NIRAF in detecting PGs during thyroidectomy and central neck dissection and investigate autofluorescence characteristics in both fresh and paraffin-embedded tissues. Approach: We included 101 patients diagnosed with papillary thyroid cancer who underwent surgeries in 2022 and 2023. We assessed NIRAF's ability to locate PGs, confirmed via parathyroid hormone assays, and involved both junior and senior surgeons. We measured the accuracy, speed, and agreement levels of each method and analyzed autofluorescence persistence and variation over 10 years, alongside the expression of calcium-sensing receptor (CaSR) and vitamin D. Results: NIRAF demonstrated a sensitivity of 89.5% and a negative predictive value of 89.1%. However, its specificity and positive predictive value (PPV) were 61.2% and 62.3%, respectively, which are considered lower. The kappa statistic indicated moderate to substantial agreement (kappa = 0.478; P < 0.001 ). Senior surgeons achieved high specificity (86.2%) and PPV (85.3%), with substantial agreement (kappa = 0.847; P < 0.001 ). In contrast, junior surgeons displayed the lowest kappa statistic among the groups, indicating minimal agreement (kappa = 0.381; P < 0.001 ). Common errors in NIRAF included interference from brown fat and eschar. In addition, paraffin-embedded samples retained stable autofluorescence over 10 years, showing no significant correlation with CaSR and vitamin D levels. Conclusions: NIRAF is useful for PG identification in thyroid and neck surgeries, enhancing efficiency and reducing inadvertent PG removals. The stability of autofluorescence in paraffin samples suggests its long-term viability, with false positives providing insights for further improvements in NIRAF technology.

A novel stoploss mutation CYB5R3 c.906A>G(p.*302Trpext*42) involved in the pathogenesis of hereditary methemoglobinemia.

Recessive congenital methemoglobinemia (RCM) is a hereditary autosomal disorder with an extremely low incidence rate. Here, we report a case of methemoglobinemia type I in a patient with congenital persistent cyanosis. The condition was attributed to a novel compound heterozygous mutation in CYB5R3, characterized by elevated methemoglobin levels (13.4 % of total hemoglobin) and undetectable NADH cytochrome b5 reductase (CYB5R3) activity. Whole-exome sequencing (WES) revealed two heterozygous mutations in CYB5R3: a previously reported pathogenic missense mutation c.611G>A(p.Cys204Tyr) inherited from the father, and a novel stop codon mutation c.906A>G(p.*302Trpext*42) from the mother, the latter mutation assessed as likely pathogenic according to ACMG guidelines. In cells overexpressing the CYB5R3 c.906A>G mutant construct, the CYB5R3 mRNA level was significantly lower than in cells overexpressing the wild-type (WT) CYB5R3 construct. However, there was no significant difference in protein expression levels between the mutant and WT constructs. Notably, an additional protein band of approximately 55 kDa was detected in the mutant cells. Immunofluorescence localization showed that, compared to wild-type CYB5R3, the subcellular localization of the CYB5R3 p.*302Trpext*42 mutant protein did not show significant changes and remained distributed in the endoplasmic reticulum and mitochondria. However, the c.906A>G(p.*302Trpext*42) mutation resulted in increased intracellular reactive oxygen species (ROS) levels and decreased NAD+/NADH ratio, suggesting impaired CYB5R3 function and implicating this novel mutation as likely pathogenic.

Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery.

JOURNAL/nrgr/04.03/01300535-202501000-00030/figure1/v/2024-05-14T021156Z/r/image-tiff Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery. Our previous in vitro study demonstrated that exosomes/small extracellular vesicles (sEVs) isolated from cerebral endothelial cells (CEC-sEVs) of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a (miR-27a) is an elevated miRNA in ischemic CEC-sEVs. In the present study, we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a (27a-sEVs) further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs. 27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector. Small EVs isolated from CECs transfected with a scramble vector (Scra-sEVs) were used as a control. Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs. An array of behavior assays was used to measure neurological function. Compared with treatment of ischemic stroke with Scra-sEVs, treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side, and significantly improved neurological outcomes. In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth. Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone, while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a, and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone. Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs. Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes. Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.

Exercise preconditioning alleviates ischemia-induced memory deficits by increasing circulating adiponectin.

JOURNAL/nrgr/04.03/01300535-202505000-00027/figure1/v/2024-07-28T173839Z/r/image-tiff Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy. Physical exercise enhances neurogenesis and synaptogenesis, and has been widely used for functional rehabilitation after stroke. In this study, we determined whether exercise training before disease onset can alleviate the severity of cerebral ischemia. We also examined the role of exercise-induced circulating factors in these effects. Adult mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery occlusion. We found that this exercise pre-conditioning strategy effectively attenuated brain infarct area, inhibited gliogenesis, protected synaptic proteins, and improved novel object and spatial memory function. Further analysis showed that circulating adiponectin plays a critical role in these preventive effects of exercise. Agonist activation of adiponectin receptors by AdipoRon mimicked the effects of exercise, while inhibiting receptor activation abolished the exercise effects. In summary, our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.

Machine learning models based on CT radiomics features for distinguishing benign and malignant vertebral compression fractures in patients with malignant tumors.

BACKGROUND: Radiomics has become an important tool for distinguishing benign and malignant vertebral compression fractures (VCFs). It is more clinically significant to concentrate on patients who have malignant tumors and differentiate between benign and malignant VCFs. PURPOSE: To explore the value of multiple machine learning (ML) models based on CT radiomics features for differentiating benign and malignant VCFs in patients with malignant tumors. MATERIAL AND METHODS: This study retrospectively analyzed 78 patients with malignant tumors accompanied by VCFs, 45 patients with benign VCFs, and 33 patients with malignant VCFs. A total of 140 lesions (86 benign lesions, 54 malignant lesions) were ultimately included in this study. All patients were divided into training sets (n = 98) and validation sets (n = 42) according to the 7:3 ratio. The radiomics features were screened and dimensioned, and multiple radiomics ML models were constructed. The receiver operating characteristic (ROC) curve was performed to assess the diagnostic performance. RESULTS: Five radiomics features were included in the model. All the ML models built have good diagnostic efficiency, among which the support vector machine (SVM) model performs better. The area under the curve (AUC), sensitivity, specificity, and accuracy in the training set were 0.908, 0.816, 0.883, and 0.857, respectively, while those in the validation set were 0.911, 0.647, 0.92, and 0.81, respectively. CONCLUSION: A variety of ML models built based on CT radiomics features have good value for differentiating benign and malignant VCFs in malignant tumor patients, and the SVM model has a better performance.

Amino Acid Functionalized SrTiO3 Nanoarrays with Enhanced Osseointegration Through Programmed Rapid Biofilm Elimination and Angiogenesis Controlled by NIR-Driven Gas Therapy.

Bacterial biofilm formation is closely associated with persistent infections of medical implants, which can lead to implantation failure. Additionally, the reconstruction of the vascular network is crucial for achieving efficient osseointegration. Herein, an anti-biofilm nanoplatform based on L-arginine (LA)/new indocyanine green (NICG) that is anchored to strontim titanium oxide (SrTiO3) nano-arrays on a titanium (Ti) substrate by introducing polydopamine (PDA) serving as the interlayer is designed and successfully fabricated. Near-infrared light (NIR) is used to excite NICG, generating reactive oxygen species (ROS) that react with LA to release nitric oxide (NO) molecules. Utilizing the concentration-dependent effect of NO, high power density NIR irradiation applied during the early stage after implantation to release a high concentration of NO, which synergized with the photothermal effect of PDA to eliminate bacterial biofilm. Subsequently, the irradiation power density can be finely down-regulated to reduce the NO concentration in subsequent treatment for accelerating the reconstruction of blood vessels. Meanwhile, SrTiO3 nano-arrays improve the hydrophilicity of the implant surface and slowly release strontium (Sr) ions for continuously optimizing the osteogenic microenvironment. Effective biofilm elimination and revascularization alongside the continuous optimization of the osteogenic microenvironment can significantly enhance the osseointegration of the functionalized Ti implant in in vivo animal experiments.

Efficacy evaluation of zirconia crown on primary molars with caries defects.

OBJECTIVES: This study aimed to estimate the therapeutic effects of preformed metal crown (PMC) and prefabricated zirconia crowns (ZC) on decayed primary morals in children, as well as to analyze the possible influencing factors. METHODS: A retrospective cohort study was performed on the data of 192 patients (aged 3 to 8) in the Stomatological Department of Shenzhen Children's Hospital from October 2021 to December 2021. The decayed mandibular first molars were selected and restored by vital-pulp therapy followed by PMC and ZC, including 96 cases (96 caries) in the PMC group and 96 cases (96 caries) in the ZC group. Oral clinical examination was performed at 3 months, 1 year, and 2 years after treatment, overwiewing the clinical therapeutic effects and periodontal status of PMC and ZC groups, as well as recording the crown integrity, gingival index (GI), probing bleeding index (BI), plaque index (PLI) and various prosthetic indices. RESULTS: No significance differences existed in the periodontal status of PMC and ZC groups at 3 months, 1 year, and 2 years after treatment (P>0.05). However, the GI, BI, and PLI in the PMC group were higher than those in the ZC group at 3 months, 1 year, and 2 years after treatment, and the difference was dramatically significant (P<0.05). No significances difference existed in various prosthetic indices (P>0.05), as well as in the GI, BI, and PLI, between the two groups (P>0.05). No significant differences existed in various prosthetic indices between genders after PMC restoration (P>0.05). The scores of girls in various prosthetic indices after ZC restoration were higher than those of boys (P<0.05). Pearson correlation analysis indicated an inverse correlation between age in the PMC group and the GI, BI, PLI, and FDI indices (P<0.01), rather than in the ZC group (P>0.05). CONCLUSIONS: PMC and ZC can be applied to restore deciduous molar caries. The periodontal status of deciduous teeth in ZC group was superior to that in the PMC group. The periodontal status of deciduous teeth in PMC group may be stable with increased age.

A longitudinal study on the effect of PM2.5 components on blood pressure in the hypertensive patients from 2011 to 2019.

Extensive research has established the link between PM2.5 exposure and blood pressure (BP) levels among normal individuals. However, the association between PM2.5 components and BP levels in hypertensive patients has not been fully explored. In this study, 12 971 hypertensive cases from Jinchang cohort (in Jinchang City, China) with nearly 9 years of follow-up were enrolled. Based on the linear mixed-effect model, the effects of fine particulate matter (PM2.5) and five major components [sulfate (SO42-), nitrate (NO3-), ammonium (NH4+), black carbon (BC) and organic matter (OM)]on BP [systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure (PP)]were evaluated by single-component model, component-joint model and component-residual model, respectively. A positive correlation was found between PM2.5 as well as its components (SO42-, NO3-, NH4+, BC and OM) exposure and BP levels. The effects of SO42-, BC and OM on BP were observed to be the most robust among the three models. Based on the results of interaction effects and stratified analysis, the effect of BC exposure on SBP, and the effect of PM2.5 and its five components on PP were greater in female than in males. Compared with elderly hypertensive patients, OM had more significant effects on SBP, DBP and MAP in young and (or) middle-aged hypertensive patients. During the heating season, the effect of PM2.5 and its components on BP was grater compared to the non-heating season. Meanwhile, PM2.5 and its components have a greater influence on BP in patients with hypertension combined with diabetes. Therefore, the findings suggested that both PM2.5 exposure and its components had a significant effect on BP in patients with hypertension. Women and young and middle-aged hypertensive patient were the sensitive population. The implementation of source control and reduction of PM2.5 emission (mainly for SO42-, BC and OM) may be of great significance to control BP level and could reduce the risk of cardiovascular disease in patients with hypertension.

Identification of Cables1 as a critical host factor that promotes ALV-J replication via genome-wide CRISPR/Cas9 gene knockout screening.

Avian leukosis virus subgroup J (ALV-J), a member of the genus Alpharetrovirus, possesses a small genome and exploits a vast array of host factors during its replication cycle. To identify host factors required for ALV-J replication and potentially guide the development of key therapeutic targets for ALV-J prevention, we employed a chicken genome-wide CRISPR/Cas9 knockout library to screen host factors involved in ALV-J infection within DF-1 cells. This screening revealed 42 host factors critical for ALV-J infection. Subsequent knockout assays showed that the absence of the genes encoding cycle-regulatory proteins, namely Cables1, CDK1, and DHFR, significantly inhibited ALV-J replication. Notably, Cables1 knockout cell lines displayed the most pronounced inhibitory effect. Conversely, overexpression assays confirmed that Cables1 significantly promotes ALV-J replication. Immunoprecipitation assays further indicated that Cables1 specifically interacts with the viral protein p15 (viral protease) among all ALV-J proteins, enhancing ALV-J p15 polyubiquitination. Additionally, we identified 26 lysine residues of ALV-J p15 as key sites for ubiquitination, and their replacement with arginine attenuated the replication ability of ALV-J in both in vitro and in vivo assays. This study demonstrates that Cables1 is a critical replication-dependent host factor of ALV-J by enhancing p15 ubiquitination and thereby promoting viral replication. Overall, these findings contribute to a deeper understanding of the ALJ-V replication mechanism and offer a potential target for the prevention and control of ALV-J infection.

Clinical and Computed Tomography Characteristics of Inflammatory Solid Pulmonary Nodules with Morphology Suggesting Malignancy.

RATIONALE AND OBJECTIVES: To investigate the clinical and computed tomography characteristics of inflammatory solid pulmonary nodules (SPNs) with morphology suggesting malignancy, hereinafter referred to as atypical inflammatory SPNs (AI-SPNs). MATERIALS AND METHODS: The CT data of 515 patients with SPNs who underwent surgical resection were retrospectively analyzed. These patients were divided into inflammatory and malignant groups and their clinical and imaging features were compared. Binary logistic regression analysis was performed to identify the independent factors for diagnosing AI-SPNs. An external validation cohort included 133 consecutive patients to test the model's predictive efficiency. RESULTS: Univariate analysis showed that age < 62 years, male sex, maximum spiculation length > 9 mm, polygonal shapes, three-planar ratio > 1.48, Lung window/mediastinal window (L/M) ratio > 1.13, pleural tag type I, satellite lesions, and halo sign were more frequent in AI-SPNs, whereas pleural tag type III, bronchial truncation, and perifocal fibrosis were more common in malignant SPNs (M-SPNs) (all P < 0.05). Binary logistic regression showed age < 62 years, male sex, polygonal shape, three-planar ratio > 1.48, L/M ratio > 1.13, pleural tag type I, satellite lesions, halo sign, and absence of bronchial truncation were independent factors for diagnosing AI-SPNs (AUC, sensitivity, specificity, and accuracy of 0.951, 83.30%, 92.30%, and 87.20%, respectively). In the external validation cohort, the AUC, sensitivity, specificity, and accuracy were 0.969, 90.47%, 90.00%, and 90.23%, respectively. CONCLUSION: AI-SPNs and M-SPNs exhibited different clinical and imaging characteristics. A good understanding of these differences may help reduce diagnostic errors in AI-SPNs and enable to choose an optimal treatment strategy.

[Guidelines for construction of traditional Chinese medicine pharmacovigilance system in medical institutions].

The group standard Guidelines for construction of traditional Chinese medicine(TCM) pharmacovigilance system in medical institutions, managed by Chinese Association of Chinese Medicine and led by the Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences and Dongfang Hospital of Beijing University of Chinese Medicine, was announced on National Group Standard Information Platform on January 16, 2024, with the standard number T/CACM 1563. 2-2024. According to EU pharmacovigilance regulations and the second-level guidance principles of International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use(ICH), the unique characteristics of TCM were fully considered, and the relevant systems and procedures for constructing TCM pharmacovigilance systems in medical institutions were clearly defined. This included establishing TCM pharmacovigilance information platforms, arranging staff, formulating various regulations, and monitoring adverse reactions of TCM(including TCM decoction pieces, granules, Chinese patent medicines, in-hospital preparations, and pre-marketed Chinese patent medicines). It aimed to develop a TCM pharmacovigilance system in medical institutions that was tailored to the characteristics of TCM. The system could be appropriately adjusted according to the scope of practice and actual circumstances of medical institutions at different levels. This will enhance the implementation of TCM pharmacovigilance work and safeguard medication safety. The group standard underwent multiple rounds of consultations with internal and external experts and has ultimately evolved into a guiding document applicable to medical institutions and related entities engaged in pharmacovigilance activities.

Effects of lower-limb active resistance exercise on mobility, physical function, knee strength and pain intensity in patients with total knee arthroplasty: a systematic review and meta-analysis.

BACKGROUND: Total knee arthroplasty (TKA) successfully alleviates pain from knee osteoarthritis, but muscle strength and function are reduced for a long period postoperatively. Postoperative active resistance exercise may play a relevant role. PURPOSE: To systematically evaluate effects of lower-limb active resistance exercise (ARE) on mobility, physical function, muscle strength and pain intensity in patients with TKA. METHODS: A search was conducted in PubMed, EMBASE, and Cochrane Library databases from inception to September 2023. Only randomized controlled trials (RCTs) that compared the effects of ARE and no intervention or other rehabilitation program without PRE were included. The outcome variables were mobility (Maximal walking speed [MWS]/6-Minute Walk Test[6MWT]), physical function (Stair Climb Test [SCT]/Timed Up and Go [TUG]), knee extension/ flexion power(KEP/KFP), joint range of motion (ROM) and pain. Standardized Mean Differences (SMD) or Mean Differences (MD) and 95% confidence intervals (CI) were calculated and combined in meta-analyses. The Cochrane Collaboration's Handbook were used for the methodological quality assessments. GRADE was used to assess the quality of evidence. The meta-analysis was performed using the RevMan 5.4 software. RESULTS: A total of 14 randomized controlled trials, involving 880 patients, were finally included. The lower-limb ARE exhibited significantly greater improvement in MWS (MD 0.13, 95%CI 0.08-0.18, P < 0.00001), TUG(MD -0.92, 95%CI -1.55- -0.28, P = 0.005), KEP (SMD 0.58, 95%CI 0.20-0.96, P = 0.003), KFP (SMD 0.38, 95%CI 0.13-0.63, P = 0.003), ROM-flexion (MD 2.74, 95%CI 1.82-3.67, P < 0.00001) and VAS (MD - 4.65, 95% CI - 7.86- -1.44, p = 0.005) compared to conventional exercise(CE) immediately post-intervention. However, there were no statistically significant differences between both groups in regard to 6MWT (MD 7.98, 95%CI -4.60-20.56, P = 0.21), SCT (MD -0.79, 95%CI -1.69-0.10, P = 0.08) and ROM-extension (MD -0.60, 95%CI -1.23-0.03, P = 0.06). CONCLUSIONS: According to the results of meta-analysis, patients undergoing TKA who receive the lower extremity ARE show better clinical effects in terms of pain relief, strength recovery and knee ROM. Simultaneously, it may be beneficial to improve mobility and physical function of patients after TKA.

Recent advances in pharmaceutical cocrystals of theophylline.

Currently, cocrystallization is a promising strategy for tailoring the physicochemical properties of active pharmaceutical ingredients. Theophylline, an alkaloid and the most primary metabolite of caffeine, is a readily available compound found in tea and coffee. It functions primarily as a bronchodilator and respiratory stimulant, making it a mainstay treatment for lung diseases like asthma. Theophylline's additional potential benefits, including anti-inflammatory and anticancer properties, and its possible role in neurological disorders, have garnered significant research interest. Cocrystal formation presents a viable approach to improve the physicochemical properties of theophylline and potentially mitigate its toxic effects. This review comprehensively explores several successful studies that utilized cocrystallization to favorably alter the physicochemical properties of theophylline or its CCF. Notably, cocrystals can not only enhance the solubility and bioavailability of theophylline but also exhibit synergistic effects with other APIs. The review further delves into the hydrogen bonding sites within the theophylline structure and the hydrogen bonding networks observed in cocrystal structures.

Identification and expression analysis of bZIP transcription factors in Setaria italica in response to dehydration stress.

Among the largest transcription factor families in plants, bZIPs are crucial for various developmental and physiological processes, particularly abiotic stress resistance. Setaria italica has become a model for understanding stress resistance mechanisms. In this study, we identified 90 bZIP transcription factors in the Setaria italica genome. SibZIPs were classified into 13 groups based on references to Arabidopsis bZIPs. Members in the same group shared similar motifs and gene structure pattern. In addition, gene duplication analysis indenfied 37 pairs of segmental duplicated genes and none tandem duplicated genes in S. italica suggesting segmental duplication contributed to the expansion of the S. italica bZIP gene family. Moreover, the number of SibZIPs genes (39) exhibiting higher expression in roots was significantly more than that in other organs. Twelve SibZIP genes were upregulated in response to dehydration stress. In conclusion, our study advances the current understanding of SibZIP genes and provide a number of candidates for functional analysis of drought tolerance in S. italica.

cNPAS2 induced ß cell dysfunction by regulating KANK1 expression in type 2 diabetes.

BACKGROUND: Diabetes mellitus type 2 (T2DM) is formed by defective insulin secretion with the addition of peripheral tissue resistance of insulin action. It has been affecting over 400 million people all over the world. AIM: To explore the pathogenesis of T2DM and to develop and implement new prevention and treatment strategies for T2DM. METHODS: Receiver operating characteristic (ROC) curve analysis was used to conduct diagnostic markers. The expression level of genes was determined by reverse transcription-PCR as well as Western blot. Cell proliferation assays were performed by cell counting kit-8 (CCK-8) tests. At last, T2DM mice underwent Roux-en-Y gastric bypass surgery. RESULTS: We found that NPAS2 was significantly up-regulated in islet ß cell apoptosis of T2DM. The ROC curve revealed that NPAS2 was capable of accurately diagnosing T2DM. NPAS2 overexpression did increase the level of KANK1. In addition, the CCK-8 test revealed knocking down NPAS2 and KANK1 increased the proliferation of MIN6 cells. At last, we found that gastric bypass may treat type 2 diabetes by down-regulating NPAS2 and KANK1. CONCLUSION: This study demonstrated that NPAS2 induced ß cell dysfunction by regulating KANK1 expression in type 2 diabetes, and it may be an underlying therapy target of T2DM.

[Treatment of New Daily Persistent Headache With Esketamine: Report of One Case].

New daily persistent headache (NDPH) is a kind of persistent headache that patients can identify the exact date of the sudden onset.It is one of the rare primary headaches difficult to be cured and may lead to disability,seriously affecting the daily life and work.The exact pathogenesis of NDPH remains unclear,which makes the treatment difficult.Here we report a case of refractory NDPH treated by intravenous injection of esketamine at a sub-anesthetic dose.

Syndecan-1 inhibition promotes antitumor immune response and facilitates the efficacy of anti-PD1 checkpoint immunotherapy.

Tumor cell-originated events prevent efficient antitumor immune response and limit the application of anti-PD1 checkpoint immunotherapy. We show that syndecan-1 (SDC1) has a critical role in the regulation of T cell-mediated control of tumor growth. SDC1 inhibition increases the permeation of CD8+ T cells into tumors and triggers CD8+ T cell-mediated control of tumor growth, accompanied by increased proportions of progenitor-exhausted and effector-like CD8+ T cells. SDC1 deficiency alters multiple signaling events in tumor cells, including enhanced IFN-γ-STAT1 signaling, and augments antigen presentation and sensitivity to T cell-mediated cytotoxicity. Combinatory inhibition of SDC1 markedly potentiates the therapeutic effects of anti-PD1 in inhibiting tumor growth. Consistently, the findings are supported by the data from human tumors showing that SDC1 expression negatively correlates with T cell presence in tumor tissues and the response to immune checkpoint blockade therapy. Our findings suggest that SDC1 inhibits antitumor immunity, and that targeting SDC1 may promote anti-PD1 response for cancer treatment.

Chain mediating effect of gratitude and meaning in life between nurses' psychological response and emergency capability-a multicenter cross-sectional study.

BACKGROUND: Clinical nurses face high-pressure situations requiring rapid decision-making and skilled intervention, impacting their psychological responses and emergency capabilities. Understanding the relationships between psychological factors like gratitude and meaning in life is crucial for improving nurses' performance in emergencies. This study explores the mediating role of gratitude and meaning in life in the impact of psychological responses on clinical nurses' emergency capabilities, aiming to enhance their effectiveness in such situations. METHODS: This study is a multi-center cross-sectional survey. A questionnaire survey was conducted among 1833 clinical nurses in five tertiary hospitals in Anhui Province, China including general information questionnaire, nurses' emergency capability scale, Meaning in life scale, Gratitude scale and Psychological response questionnaire. According to the results of the questionnaire survey, a chain mediating model was constructed and tested. RESULTS: The total score of emergency capability of 1833 clinical nurses was (71.65 ± 10.77), the total score of meaning in life was (50.67 ± 9.04), the total score of gratitude was (30.96 ± 3.57), and the total score of psychological response was 13.00 (6.00, 20.00). The emergency capability of subjects was positively correlated with the meaning in life, the total score of gratitude scale and the scores of each dimension of the two scales, and negatively correlated with the total score of psychological response scale and each dimension of this scale (all P < 0.05). The total effect coefficient, direct effect coefficient and indirect effect coefficient of psychological response on nurses' emergency capability are - 0.230, -0.110 and - 0.120 respectively, that is, the indirect effect accounts for 52.17% of the total effect. Among the indirect effects, the specific mediating effects of gratitude and meaning in life account for 22.50% and 62.50% respectively, and the chain mediating effects of gratitude and meaning in life account for 15.00%. CONCLUSION: Gratitude and meaning in life have multiple mediating roles in the mechanism of psychological response that affecting clinical nurses' emergency capability. Therefore, it is very important to pay attention to dynamically evaluating the psychological response level of clinical nurses, and strive to improve their gratitude and meaning in life, so as to further enhance their emergency response ability.

Serum tumor markers: potential indicators for occult lymph node metastasis in clinical T1 - 2N0M0 small cell lung cancer patients.

In their letter-to-the-editor entitled "Letter to the Editor: Incidence rate of occult lymph node metastasis in clinical T1 - 2N0M0 small cell lung cancer patients and radiomic prediction based on contrast-enhanced CT imaging: a multicenter study", Prof. Chen et al. provided insightful comments and suggestions on our original study. We appreciate the authors' feedback and have conducted a preliminary exploration of the predictive value of serum tumor markers (TMs) for occult lymph node metastasis (OLM) in clinical T1 - 2N0M0 (cT1 - 2N0M0) small cell lung cancer (SCLC) patients. The results indicate that neuron-specific enolase (NSE), carbohydrate antigen 125 (CA125), and squamous cell carcinoma antigen (SCC) have potential predictive value for detecting OLM in cT1 - 2N0M0 SCLC patients. Additionally, further exploration and confirmation through prospective, large-scale studies with robust external validation are needed.