Preoperative computed tomography-guided localization for pulmonary nodules: comparison between hook-wire and anchored needle localization.

Introduction: Both hook-wire (HW) and anchored needle (AN) techniques can be used for preoperative computed tomography (CT)-guided localization for pulmonary nodules (PNs). But the outcomes associated with these two materials remain unclear. Aim: To assess the relative safety and efficacy of preoperative CT-guided HW and AN localization for PNs. Material and methods: This was a retrospective analysis of data collected from two institutions. Consecutive patients with PNs between January 2020 and December 2021 who underwent preoperative CT-guided HW or AN localization followed by video-assisted thoracoscopic surgery (VATS) procedures were included in these analyses, which compared the safety and clinical efficiency of these two localization strategies. Results: In total, 98 patients (105 PNs) and 93 patients (107 PNs) underwent CT-guided HW and AN localization procedures, respectively. The HW and AN groups exhibited similar rates of successful PN localization (95.2% vs. 99.1%, p = 0.117), but the dislodgement rate in the HW group was significantly higher than that for the AN group (4.8% vs. 0.0%, p = 0.029). The mean pain score of patients in the HW group was significantly higher than that for the AN group (p = 0.001). HW and AN localization strategies were associated with comparable pneumothorax (21.4% vs. 16.1%, p = 0.349) and pulmonary hemorrhage (29.6% vs. 23.7%, p = 0.354) rates. All patients other than 1 individual in the HW group successfully underwent VATS-guided limited resection. Conclusions: These data suggest that AN represents a safe, well-tolerated, feasible preoperative localization strategy for PNs that may offer value as a replacement for HW localization.

Two exploratory laparotomies within six days: A case of midgut volvulus in an adult with congenital malrotation.

INTRODUCTION: Midgut volvulus in adults based on congenital malrotation, which required emergency surgery, may occur under the stimulation of adverse factors and is rare and easy to be misdiagnosed. PRESENTATION OF CASE: A young male was taken to the emergency room of a local hospital after six hours abdominal pain. Computed tomography (CT) shows intestinal volvulus and exploratory laparotomy was performed. Postoperative CT revealed remission of small intestinal torsion and congenital malrotation of the midgut. The patient vomited frequently within 48 h after the surgery, and was transferred to our hospital for conservative treatment. After 4 days of conservative treatment, the vomiting symptoms were relieved at first, but worsened again after a liquid diet. CT showed complete duodenal obstruction and exploratory laparotomy was performed again. Congenital malrotation was found, which resulted in midgut volvulus and duodenal obstruction due to anomalous fixation of the mesentery. The bowel was placed in normal anatomical position, and the mesentery was sutured to the posterior abdominal wall. The patient was followed up for 24 months with no complaints. DISCUSSION: Due to the rare incidence and atypical pain clinical manifestations, it is difficult for the congenital malrotation in adults to be diagnosed. Midgut volvulus in adults with malrotation is even rarer and requires emergency operation, and may be misdiagnosed. CONCLUSION: Midgut volvulus with midgut malrotation is very rare in adults. Exploratory laparotomy must be careful to reduce misdiagnosis and recurrence of volvulus.

Role of STING in the treatment of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a prevalent form of lung cancer. Patients with advanced NSCLC are currently being treated with various therapies, including traditional radiotherapy, chemotherapy, molecular targeted therapies and immunotherapy. However, a considerable proportion of advance patients who cannot benefit from them. Consequently, it is essential to identify a novel research target that offers an encouraging perspective. The stimulator of interferon genes (STING) has emerged as such a target. At present, it is confirmed that activating STING in NSCLC tumor cells can impede the proliferation and metastasis of dormant tumor cells. This review focuses on the role of STING in NSCLC treatment and the factors influencing its activation. Additionally, it explores the correlation between STING activation and diverse therapy modalities for NSCLC, such as radiotherapy, chemotherapy, molecular targeted therapies and immunotherapy. Furthermore, it proposes the prospect of innovative therapy methods involving nanoparticles, with the aim of using the features of STING to develop more strategies for NSCLC therapy.

Three-dimensional comprehensive evaluation of unilateral alveolar cleft bone grafting with iliac bone and chin bone blocks.

In this study, we aimed to provide guidance for selecting bone grafting materials in cases of alveolar clefts. Twenty-nine patients with unilateral complete alveolar clefts were categorized into three groups based on the bone grafting material used: Group A (iliac bone block grafts), Group B (iliac cancellous bone grafts), and Group C (chin bone block grafts). Cone-beam computed tomography (CBCT) data were analyzed using Mimics 19.0 software. Results showed that Group A had the highest bone formation rate, with significant differences observed between Groups A and B, as well as between Groups B and C. Group A and Group C had the highest proportion of Type I in volume assessment, while Group B had the highest proportion of Type III, Significant differences were observed in the distribution of volume assessment scores among the three groups. Bone height measurement results indicated that buccal-side measurement points had a higher proportion of Type I bone height than palatal-side measurement points. Bone width measurement results showed that Type I bone width was highest in Group C, while Type IV bone width was highest in Group B. Significant differences were observed in the distribution of implanted bone width among the three groups. Total grafting scores indicated that Types A and D were predominant in Groups A and C, while Group B had the highest proportion of Type D. Significant differences were observed in the distribution of total grafting scores among the three groups. The comprehensive evaluation method provides accurate assessment of alveolar cleft bone grafting outcomes and is applicable in clinical settings. Based on the results, we consider both iliac bone blocks and chin bone blocks as suitable materials for alveolar cleft bone grafting. Grafting material selection should consider preoperative gap volume measured using CBCT, required bone quantity, donor site complications, and overall clinical needs.

A Targeted and Responsive Nanoprodrug Delivery System for Synergistic Glioma Chemotherapy.

Doxorubicin (DOX) is widely used as a chemotherapeutic agent for both hematologic and solid tumors and is a reasonable candidate for glioma treatment. However, its effectiveness is hindered by significant toxicity and drug resistance. Moreover, the presence of the blood-brain barrier (BBB) brings a crucial challenge to glioma therapy. In response, a GSH-responsive and actively targeted nanoprodrug delivery system (cRGD/PSDOX-Cur@NPs) are developed. In this system, a disulfide bond-bridged DOX prodrug (PEG-SS-DOX) is designed to release specifically in the high glutathione (GSH) tumor environment, markedly reducing the cardiotoxicity associated with DOX. To further address DOX resistance, curcumin, serving as a P-glycoprotein (P-gp) inhibitor, effectively increased cellular DOX concentration. Consequently, cRGD/PSDOX-Cur@NPs exhibited synergistic anti-tumor effects in vitro. Furthermore, in vivo experiments validated the superior BBB penetration and brain-targeting abilities of cRGD/PSDOX-Cur@NPs, showcasing the remarkable potential for treating both subcutaneous and orthotopic gliomas. This research underscores that this nanoprodrug delivery system presents a novel approach to inhibiting glioma while addressing resistance and systemic toxicity.

Methionine secreted by tumor-associated pericytes supports cancer stem cells in clear cell renal carcinoma.

Here, we identify a subset of vascular pericytes, defined by expression of platelet-derived growth factor receptor beta (PDGFR-ß) and G-protein-coupled receptor 91 (GPR91), that promote tumorigenesis and tyrosine kinase inhibitors (TKIs) resistance by functioning as the primary methionine source for cancer stem cells (CSCs) in clear cell renal cell carcinoma (ccRCC). Tumor-cell-derived succinate binds to GPR91 on pericyte to activate autophagy for methionine production. CSCs use methionine to create stabilizing N6-methyladenosine in ATPase-family-AAA-domain-containing 2 (ATAD2) mRNA, and the resulting ATAD2 protein complexes with SRY-box transcription factor 9 to assemble super enhancers and thereby dictate its target genes that feature prominently in CSCs. Targeting PDGFR-ß+GPR91+ pericytes with specific GRP91 antagonists reduce intratumoral methionine level, eliminate CSCs, and enhance TKIs sensitivity. These results unraveled the mechanisms by which PDGFR-ß+GPR91+ pericytes provide supportive niche for CSCs and could be used to develop targets for treating ccRCC.

Surface plasma modification of cellulose acetate fiber filter for the adsorption of typical components in smoke components.

Surface modification of cellulose acetate filter rods with low temperature plasma was performed to explore the retention and adsorption effect of modified filter rods on typical components (CO, H2O, benzene, and formaldehyde) in cigarette smoke. The surface structure and composition of the cellulose acetate filter rods were modified by changing the plasma treatment time. The modified filter rods were characterized by N2 physical adsorption (BET), scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), contact angle of H2O, Fourier transform infrared spectroscopy (FTIR) and in situ DRIFTS. Various functional groups were found on the surface of filter rods with the introduction of plasma modification, which exhibited strong retention performance for water vapor in cigarette smoke at room temperature and significantly enhanced adsorption for harmful substances (CO, benzene, and formaldehyde) in cigarette smoke.

Expanded indications for breast-conserving surgery with oncoplastic approaches compared to conventional approaches: a single-center retrospective comparative cohort study.

Background: Oncoplastic breast-conserving surgery (OPBS) is the evolution of conventional breast-conserving surgery (CBCS); however, data from studies comparing patients who received two surgical procedures are limited. A comparison of differences in terms of the patient characteristics, tumor-nipple distance, volume of resected breast tissue, tumor volume and postoperative breast appearance between patients undergoing OPBS and CBCS was carried out in this study, enhancing the evidence base for OPBS by widening indications and improving patient satisfaction. Methods: From January 2020 to April 2022, the Breast Center of West China Hospital conducted a retrospective comparative study involving 106 patients. Preoperative characteristics of patients were recorded, and the tumor-nipple distance, the volume of resected breast tissue, tumor volume and patient-reported esthetic outcomes measured by the Harris cosmetic scale were compared between patients who underwent OPBS and CBCS. Results: Each group had a median follow-up time of 2 months, ranging from 1 week to 6 months. The tumor-nipple distance was significantly shorter in patients receiving OPBS than in those receiving CBCS (2.98±1.42 vs. 3.85±1.78 cm, P=0.006). The rate of positive margin evaluated by intraoperative frozen section biopsy was significantly lower in OPBS group than in CBCS group (2/43, 4.65% vs. 11/63, 17.46%; P=0.048). The maximum diameter of resected tissue (7.80±2.29 vs. 6.75±1.87 cm, P=0.011) and volume of resected tissue (74.20±42.77 vs. 45.52±30.99 cm3, P<0.001) were significantly larger with OPBS. The tumor size, tumor volume (either clinically measured by ultrasound or pathologically measured), tumor location, and reoperation rate due to positive margins did not differ significantly between groups. Moreover, insignificant differences existed regarding patient satisfaction between two groups (87.30% vs. 81.40%). Conclusions: The OPBS strategy allowed extensive resections and expanded indications with equivalent cosmetic satisfaction and favorable oncological safety.

Therapeutic effectiveness of anlotinib combined with etoposide in extensive-stage small-cell lung cancer: a single-arm, phase II trial.

BACKGROUND: Anlotinib plus chemotherapy as first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC) achieves good efficacy, but there is still room for improvement. This clinical study examined the effectiveness of anlotinib plus etoposide for maintenance therapy in ES-SCLC. METHODS: The current single-arm, prospective phase II study was performed at Jiangsu Cancer Hospital (March 2019 to March 2022). After successful primary etoposide-based therapy, anlotinib was administered at 12 mg/day on days 1 to 14 of 21-day cycles until disease progression or consent withdrawal. All patients also received etoposide at 50 mg/day on days 1 to 14 of 21-day cycles for a maximum of six cycles. Progression-free survival (PFS) constituted the primary study endpoint. Secondary endpoints were overall survival (OS), objective remission rate (ORR), disease control rate (DCR), and safety. In addition, adverse events (AEs) were assessed. RESULTS: Twenty-eight patients were treated. Median PFS and OS were 8.02 (95%CI 5.36-10.67) and 11.04 (95%CI 10.37-11.68) months, respectively. Totally 9 and 18 participants showed a partial response and stable disease, respectively; ORR and DCR were 32.14% and 96.43%, respectively. The commonest all-grade AEs were fatigue (n = 11, 39.28%), hypertension (n = 11, 39.28%), loss of appetite (n = 9, 32.14%), oral mucositis (n = 7, 25.00%) and proteinuria (n = 6, 21.40%). Grade 3-4 AEs included fatigue (n = 4, 14.28%), hypertension (n = 2, 7.14%), hand and foot syndrome (n = 2, 7.14%), oral mucositis (n = 1, 3.57%), hemoptysis (n = 1, 3.57%), proteinuria (n = 1, 3.57%), gingival bleeding (n = 1, 3.57%), and serum creatinine elevation (n = 1, 3.57%). CONCLUSION: Maintenance anlotinib plus etoposide achieves promising PFS and OS in clinical ES-SCLC. REGISTRATION NUMBER: ChiCTR1800019421.

Electrolytic Characteristics of Microhole Array Manufacturing Using Polyacrylamide Electrolyte in 304 Stainless Steel.

Because of the ease with which oxide films form on its surfaces, stainless steel has strong corrosion resistance and excellent processing performance. Electrochemical machining (ECM) is a flexible process that can create microstructures on stainless steel (SS304); however, with traditional masked ECM, the efficiency and accuracy of microstructure machining are low. Proposed here is the use of a non-Newtonian fluid [polyacrylamide (PAM)] as the electrolyte. To date, there have been few papers on the electrochemical dissolution behavior of stainless-steel micromachining with a non-Newtonian fluid as the electrolyte. The aims of the study reported here were to investigate the electrochemical properties of SS304 with PAM and PAM-NaOH as electrolytes, and to explain their electrochemical corrosion mechanisms. The effects of different electrolytes were compared, and the polarization curves of SS304 in PAM and PAM-NaOH electrolyte solutions with different components were analyzed and compared with that in NaNO3 electrolyte. Then, the effects of the main processing parameters (pulse voltage, frequency, and duty ratio) on the machining performance were investigated in detail. A microhole array was obtained with a good quality comprising an average diameter of 330.11 µm, an average depth of 16.13 µm, and a depth-to-diameter ratio of 0.048. Using PAM to process microstructures on stainless-steel surfaces was shown to be feasible, and experiments indicated that the mixed electrolyte (PAM-NaOH) had not only the physical characteristics of a non-Newtonian fluid but also the advantages of a traditional electrolyte to dissolve processing products, and it effectively improved the processing accuracy of masked ECM for SS304.

Analysis of the clinical characteristics of pembrolizumab-induced bullous pemphigoid.

Background: Pembrolizumab, a programmed cell death protein 1 checkpoint inhibitor, is a novel drug used to treat a variety of advanced malignancies. However, it can also result in many immune-related adverse events, with cutaneous toxicities being the most frequent. Regarding pembrolizumab-induced skin adverse reactions, bullous pemphigoid (BP) has the worst effects on quality of life. Recently, there have been more and more reports of BP incidents resulting from pembrolizumab therapy in patients with cancer. This study aimed to define the clinical characteristics, diagnosis and management of pembrolizumab-induced BP and identify potential differences between classical BP and pembrolizumab-induced BP. Methods: Case reports, case series, and case analyses of pembrolizumab-induced BP up to 10 December 2022 were collected for retrospective analysis. Results: Our study included 47 patients (33 males and 14 females) from 40 studies. The median age was 72 years (range 42-86 years). The median time to cutaneous toxicity was 4 months (range 0.7-28 months), and the median time to bullae formation was 7.35 months (range 0.7-32 months). The most common clinical features were tense bullae and blisters (85.11%), pruritus (72.34%), and erythema (63.83%) on the limbs and trunk. In 20 of the 22 cases tested, the serum anti-BP180 autoantibodies were positive. However, in 10 cases (91.90%, 10/11) the circulating autoantibodies of anti-BP230 were negative. 40 patients had skin biopsies and the skin biopsy revealed subepidermal bullae or blister eosinophil infiltration in 75.00% of patients with pembrolizumab-induced BP, 10.00% of patients with lymphocyte infiltration and 20.00% of patients with neutrophil infiltration. There were 20 patients (50%) with eosinophilic infiltration around the superficial dermis vessels, 8 patients (20.00%) with lymphocyte infiltration around the superficial dermis vessels, and 4 patients (10.00%) with neutrophil infiltration around the superficial dermis vessels. Direct immunofluorescence detected linear immunoglobulin G (IgG) IgG and/or complement C3 along the dermo-epidermal junction in 36 patients (94.74%) with BP. IgG positivity was detected by indirect immunofluorescence in 81.82% of patients with BP. All patients were in complete remission (95.65%,44/46) or partial remission (4.35%, 2/46) of BP, whereas 9/46 patients had a relapse or refractory. The majority of patients achieved BP remission after discontinuation of pembrolizumab with a combination of topically and systemically administered steroid treatments, or other medications. The median duration of BP remission was 2 months (range 0.3-15 months). Conclusion: A thorough diagnosis of pembrolizumab-induced BP should be made using clinical signs, biochemical markers, histopathological and immunopathological tests. Pembrolizumab-induced BP had similar clinical characteristics to classic BP. Temporary or permanent discontinuation of pembrolizumab therapy may be required in patients with perbolizumab-induced BP depending on the severity of BP and the response to medication. Pembrolizumab-induced BP may be effectively treated using topical and systemic steroid treatments in combination with other medications (e.g., doxycycline, niacinamide, dapsone, rituximab, intravenous immunoglobulins, dupilumab, cyclophosphamide, methotrexate, mycophenolate mofetil, and infliximab). Clinicians should provide better management to patients with BP receiving pembrolizumab to prevent progression and ensure continuous cancer treatment.

Dynamic Metal-Phenolic Coordination Complexes for Versatile Surface Nanopatterning.

We report a general nanopatterning strategy that takes advantage of the dynamic coordination bonds between polyphenols and metal ions (e.g., Fe3+ and Cu2+) to create structures on surfaces with a range of properties. With this methodology, under acidic conditions, 29 metal-phenolic complex-based precursors composed of different polyphenols and metal ions are patterned using scanning probe and large-area cantilever free nanolithography techniques, resulting in a library of deposited metal-phenolic nanopatterns. Significantly, post-treatment of the patterns under basic conditions (i.e., ammonia vapor) triggers a change in coordination state and results in the in situ generation of more stable networks firmly attached to the underlying substrates. The methodology provides control over feature size, shape, and composition, almost regardless of substrate (e.g., Si, Au, and silicon nitride). Under reducing conditions (i.e., H2) at elevated temperatures (180-600 °C), the patterned features have been used as nanoreactors to synthesize individual metal nanoparticles. At room temperature, the ammonia-treated features can reduce Ag+ to form metal nanostructures and be modified with peptides, proteins, and thiolated DNA via Michael addition and/or Schiff base reaction. The generality of this technique should make it useful for a wide variety of researchers interested in modifying surfaces for catalytic, chemical and biological sensing, and template-directed assembly purposes.

[Experimental Study on the Characteristic Changes of the Immunological Microenvironment at the Maternal-Fetal Interface in IVF-ET Pregnancy].

Objective: To investigate the characteristic functional changes of the decidual natural killer (NK) cells and γδ T cells, two immunocytes in the decidua, at the maternal-fetal interface in in vitro fertilization-embryo transfer (IVF-ET) pregnancy. Methods: Decidual samples were collected from 12 women of natural pregnancy (NP) and 32 women of IVF-ET pregnancy, who were enrolled in the NP group and the IVF-ET group, respectively. Then part of the decidual samples were paraffin-embedded for HE staining and immunofluorescence staining, while the rest of the samples were digested and Percoll was used for isolating decidual immunocytes (DICs) by gradient centrifugation. Flow cytometry was used to determine the cell counts of decidual NK cells and γδ T cells and the expression levels of their surface activation markers, CD69 and NKG2D in the NP and the IVF-ET groups. In addition, the expression levels of IFN-γ, TNF-α, IL-17A, and IL-10, the intracellular cytokines, and granzyme B, perforin, and granulysin, the cytolytic granules, were measured. The characteristic changes in the relevant immunological indicators were compared and analyzed. Results: HE staining of the tissue specimens showed that the typical structure of decidua was observed, and that lymphocytes were enriched in the decidua. Immunofluorescence staining showed that the percentage of decidual NK (dNK) cells in nucleated cells of the IVF-ET group was significantly lower than that of the NP group ( P<0.05). Flow cytometry analysis of DICs showed that, compared with those of the NP group, the percentage of dNK cells of the IVF-ET group was decreased ( P<0.05) and the expression levels of IL-10 and perforin were significantly decreased in the IVF-ET group ( P<0.05). However, there was no significant difference in the decidual γδ T (dγδT) cell count between the two groups. The expression of IL-10, IL-17A, and perforin was downregulated in the IVF-ET group ( P<0.05). There was no significant difference in the expression of IFN-γ, TNF-α, granzyme B, and granulysin, the cellular function indicators ( P>0.05). Conclusion: The dNK cell count and the secretion of some intracellular cytokines of dNK and dγδT cells of women of IVF-ET pregnancy decreased to some degree, which suggests that certain changes may have taken place in the immunological microenvironment at the maternal-fetal interface. The specific effect of these changes on pregnancy outcomes needs further investigation.

Identification of potential biomarkers and immune infiltration characteristics in recurrent implantation failure using bioinformatics analysis.

Introduction: Recurrent implantation failure (RIF) is a frustrating challenge because the cause is unknown. The current study aims to identify differentially expressed genes (DEGs) in the endometrium on the basis of immune cell infiltration characteristics between RIF patients and healthy controls, as well as to investigate potential prognostic markers in RIF. Methods: GSE103465, and GSE111974 datasets from the Gene Expression Omnibus database were obtained to screen DEGs between RIF and control groups. Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes Pathway analysis, Gene Set Enrichment Analysis, and Protein-protein interactions analysis were performed to investigate potential biological functions and signaling pathways. CIBERSORT was used to describe the level of immune infiltration in RIF, and flow cytometry was used to confirm the top two most abundant immune cells detected. Results: 122 downregulated and 66 upregulated DEGs were obtained between RIF and control groups. Six immune-related hub genes were discovered, which were involved in Wnt/-catenin signaling and Notch signaling as a result of our research. The ROC curves revealed that three of the six identified genes (AKT1, PSMB8, and PSMD10) had potential diagnostic values for RIF. Finally, we used cMap analysis to identify potential therapeutic or induced compounds for RIF, among which fulvestrant (estrogen receptor antagonist), bisindolylmaleimide-ix (CDK and PKC inhibitor), and JNK-9L (JNK inhibitor) were thought to influence the pathogenic process of RIF. Furthermore, our findings revealed the level of immune infiltration in RIF by highlighting three signaling pathways (Wnt/-catenin signaling, Notch signaling, and immune response) and three potential diagnostic DEGs (AKT1, PSMB8, and PSMD10). Conclusion: Importantly, our findings may contribute to the scientific basis for several potential therapeutic agents to improve endometrial receptivity.

RANKL up-regulated by progesterone aggravates lipopolysaccharide-induced acute lung injury during pregnancy.

Acute lung injury (ALI) is a common acute respiratory disease with high morbidity and mortality rate in pregnant women. Receptor activator of NF-κB ligand (TNFSF11, also known as RANKL) exerts either pro-inflammatory or anti-inflammatory effects on the immune response. LPS administration reduced the survival time (n = 10, p < 0.01), increased wet/dry ratio (n = 10, p < 0.001) and lung injury score (n = 10, p < 0.001), the elevated proportions of plasmacytoid dendritic cells (pDCs) (n = 10, p < 0.0001), tissue-resident DCs (resDCs) (n = 10, p < 0.0001), macrophages (n = 10, p < 0.0001), and neutrophils (n = 10, p < 0.0001), and the expressions of costimulatory molecules and inflammation cytokines (n = 10, p < 0.05) in lungs of pregnant mice, compared with non-pregnant mice. In vitro, progesterone up-regulated the expression of RANKL (n > 6, p < 0.05) on pulmonary fibroblasts. The results of cytokine arrays showed that the cytokines associated with inflammatory response and leukocyte differentiation were decreased in pulmonary fibroblasts after treatment with anti-RANKL neutralizing antibody, compared with control pulmonary fibroblasts. More notably, we found that Tnfsf11-/- pregnant mice had longer survival durations (n = 10, p < 0.01), lower lung injury scores (n = 10, p < 0.05), and lower immune cell infiltration (n = 10, p < 0.05). These data imply that the RANKL/RANK axis plays an essential role in LPS-induced ALI during pregnancy possibly through a variety of pathways.

[Clinical value of renal artery resistance index and urinary angiotensinogen in early diagnosis of acute kidney injury in patients with sepsis].

OBJECTIVE: To investigate the value of renal artery resistance index (RRI) and urinary angiotensinogen (UAGT) in the early diagnosis of acute kidney injury (AKI) in patients with sepsis. METHODS: A prospective study was conducted. Seventy-eight patients with sepsis admitted to the department of critical care medicine of General Hospital of Ningxia Medical University from January to September 2021 were enrolled. Patients were observed for the development of AKI within 1 week. General data [gender, age, body mass index (BMI), major infection sites and critical illness related scores], laboratory indicators [mean arterial pressure (MAP), central venous pressure (CVP), procalcitonin (PCT), arterial blood lactic acid (Lac), etc.], duration of mechanical ventilation and length of intensive care unit (ICU) stay were recorded. After hemodynamic stabilization of the patients, renal ultrasound was performed to measure the RRI within 24 hours after ICU admission. Urine samples were taken immediately after diagnosis, and the level of UAGT was detected by enzyme-linked immunosorbent assay (ELISA). The above parameters were compared between the two groups. Multivariate Logistic regression was used to analyze the risk factors of AKI in patients with sepsis. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of related indicators for AKI in sepsis. RESULTS: A total of 78 patients were finally enrolled, of which 45 developed AKI and 33 did not. Compared with the non-AKI group, the rates of vasoactive drugs use, 28-day mortality, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation II (APACHE II) score, PCT, Lac, RRI and UAGT were significantly higher in the AKI group [rates of vasoactive drugs use: 68.9% vs. 39.4%, 28-day mortality: 48.9% vs. 24.2%, SOFA score: 12.0 (10.5, 14.0) vs. 8.0 (7.0, 10.0), APACHE II score: 22.0 (18.0, 27.5) vs. 16.0 (15.0, 18.5), PCT (µg/L): 12.5±2.6 vs. 10.9±2.8, Lac (mmol/L): 2.6 (1.9, 3.4) vs. 1.9 (1.3, 2.6), RRI: 0.74±0.03 vs. 0.72±0.02, UAGT (µg/L): 75.16±19.99 vs. 46.28±20.75, all P < 0.05], the duration of mechanical ventilation and the length of ICU stay were significantly prolonged [duration of mechanical ventilation (days): 8.0 (7.0, 12.0) vs. 5.0 (4.0, 6.0), length of ICU stay (days): 14.0 (10.0, 16.0) vs. 9.0 (8.0, 11.5), both P < 0.01], and MAP was significantly lowered [mmHg (1 mmHg ≈ 0.133 kPa): 68.5±11.2 vs. 74.2±12.8, P < 0.05]. There was no significant difference in other parameters between the two groups. Multivariate Logistic regression analysis showed that SOFA score [odds ratio (OR) = 2.088, 95% confidence interval (95%CI) was 1.322-3.299], APACHE II score (OR = 1.447, 95%CI was 1.134-1.845), RRI (OR = 1.432, 95%CI was 1.103-1.859), and UAGT (OR = 1.077, 95%CI was 1.035-1.121) were independent risk factors for sepsis complicated with AKI (all P < 0.01). ROC curve analysis showed that SOFA score, APACHE II score, RRI and UAGT had certain predictive value for AKI in septic patients, the area under the ROC curve (AUC) were 0.814 (95%CI was 0.716-0.912), 0.804 (95%CI was 0.708-0.901), 0.789 (95%CI was 0.690-0.888), and 0.840 (95%CI was 0.747-0.934), respectively, and the AUC of RRI combined with UAGT was 0.912 (95%CI was 0.849-0.974), which was better than the above single index (all P < 0.05). CONCLUSIONS: RRI combined with UAGT has a high early predictive value for septic AKI.

Single-cell transcriptome profiling of the human endometrium of patients with recurrent implantation failure.

Introduction: Despite great advances in assisted reproductive technology (ART), recurrent implantation failure (RIF) cannot be effectively avoided. Notably, cellular characteristics and communication that regulate endometrial receptivity and differentiation, and its disorders in RIF at window of implantation (WOI) remain rudimentary. Objectives: In this study, we profiled the endometrial cells present at the WOI timing in RIF patients and healthy controls using single-cell RNA sequencing (scRNA-seq) and provided a detailed molecular and cellular map of a healthy and RIF endometrium at the WOI. Method: In the current study, the endometrium from RIF patient (n = 6; age range, 32 - 35 years) and control (Ctrl) (n = 3; age range, 29 - 35 years) groups were studied at a single-cell resolution. single-cell RNA-seq and analysis were performed on the endometrium of patients with RIF and Ctrl. Immunofluorescence, flow cytometry assays, and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to verify cellular identity and function. Results: We profiled the transcriptomes of 60222 primary human endometrial cells isolated from control and RIF patients at a single-cell resolution. We discovered dramatic differential expression of endometrial receptivity-related genes in four major endometrial fibroblast-like cells from RIF patients compared to the control endometrium. We observed that CD49a+CXCR4+NK cells were diminished in proportion with RIF. The decrease in subset of CD63highPGRhigh endometrial epithelial cells with high levels of progesterone receptor, autophagy and exosomes should contribute to the decrease in subset of NK cells. Additionally, we characterized aberrant molecular and cellular characteristics and endometrial cell-cell communication disorders in RIF patients. Conclusion: Our study provides deeper insights into endometrial microenvironment disorder of RIF that are potentially applicable to improving the etiological diagnosis and therapeutics of unexplained RIF.

Primary implant stability based on alternative site preparation techniques: A systematic review and meta-analysis.

AIM: To evaluate the effect of special implant site preparation methods in improving primary implant stability in low-density bone. MATERIAL AND METHODS: This meta-analysis included studies published in English and Mandarin Chinese up to March 31, 2022 from MEDLINE/PubMed, Embase, Scopus, and Wanfang databases. The primary stability of five site preparation methods were measured using implant stability quotient. The random-effects model was chosen for data analysis. Grading of recommendations assessment, development, and evaluation assessment was adopted as a collective grading of the overall body of evidence. RESULTS: 12 of the 17 studies included in the meta-analysis were randomized control trials. Three studies investigated osseodensification drilling (OD), eight studies examined osteotome technique (OT), five studies explored piezosurgery (PS), and four studies were conducted on under-drilling (UD). Meta-analysis showed a statistically significant increase in primary stability for the OD (mean difference [MD], 10.25; 95% CI: 4.97-15.52; p < 0.001), OT (MD, 6.34; 95% CI: 2.26-10.42; p = 0.002), and UD (MD, 11.43; 95% CI: 5.17-17.68; p < 0.001) groups when compared to the conventional drilling group, while the PS group did not (MD, 1.50; 95% CI: -2.54-5.54; p = 0.47). CONCLUSION: Significantly higher primary implant stability was shown in the OD, UD, and OT groups compared to the conventional drilling group. PS displayed the least favorable primary stability and when compared to conventional drilling, was not statistically significant.

Sound induces analgesia through corticothalamic circuits.

Sound-including music and noise-can relieve pain in humans, but the underlying neural mechanisms remain unknown. We discovered that analgesic effects of sound depended on a low (5-decibel) signal-to-noise ratio (SNR) relative to ambient noise in mice. Viral tracing, microendoscopic calcium imaging, and multitetrode recordings in freely moving mice showed that low-SNR sounds inhibited glutamatergic inputs from the auditory cortex (ACxGlu) to the thalamic posterior (PO) and ventral posterior (VP) nuclei. Optogenetic or chemogenetic inhibition of the ACxGlu→PO and ACxGlu→VP circuits mimicked the low-SNR sound-induced analgesia in inflamed hindpaws and forepaws, respectively. Artificial activation of these two circuits abolished the sound-induced analgesia. Our study reveals the corticothalamic circuits underlying sound-promoted analgesia by deciphering the role of the auditory system in pain processing.