Influence of Postoperative Insulin Resistance on Short-Term Outcomes of Radical Gastrectomy for Gastric Cancer: A Microbiome and Metabolome-Based Prospective Cohort Study.

BACKGROUND: Gastrectomy is one of the main treatment modalities for gastric cancer (GC) and induces pathophysiological changes that significantly affect patients' postoperative recovery. In this study, we investigated the relationships between altered insulin resistance (IR), inflammation, and gut microbiota associated with gastrectomy. PATIENTS AND METHODS: This study was a single-center prospective cohort investigation involving 60 patients with GC who underwent gastrectomy between May 2023 and April 2024. Monitoring encompassed IR, inflammation, and nutrition-related markers via blood assays, while gut microbiota analysis employed high-throughput sequencing, and short-chain fatty acids (SCFAs) were examined through targeted metabolomics. The study is registered under the number ChiCTR2300075653. RESULTS: The patients exhibited a significant increase in post-gastrectomy IR markers (P < 0.001), accompanied by elevated inflammation markers (P < 0.001), and also showed decreased nutrition-related indicators (P < 0.001). Notable alterations were observed in the gut microbiota, including reductions in Bifidobacterium and Faecalibacterium, an increase in Streptococcus, and a noteworthy decrease in fecal butyrate. Patients with postoperative IR exhibited poorer inflammation markers (P < 0.05), nutritional indicators (P < 0.05), and postoperative recovery parameters (P < 0.05). Furthermore, significant negative correlations were observed between IR and Bifidobacterium, Faecalibacterium, as well as butyrate. CONCLUSIONS: Patients with GC post-gastrectomy displayed heightened IR, exacerbated inflammation, and compromised nutritional status. Disturbed gut microbiota and reduced fecal butyrate were observed. Gut microbiota and metabolite butyrate production may be predictors of postoperative IR and short-term outcomes in patients with GC.

Clinical and pathogen features of COVID-19-associated infections during an Omicron strain outbreak in Guangzhou, China.

Although the Omicron variant has been associated with greater transmissibility and tropism of the upper respiratory tract, the clinical and pathogenic features of patients infected with the Omicron variant during an outbreak in China have been unclear. Adults with COVID-19 were retrospectively enrolled from seven medical centers in Guangzhou, China, and clinical information and specimens ( BALF, sputum, and throat swabs) from participants were collected. Conventional detection methods, metagenomics next-generation sequencing (mNGS), and other methods were used to detect pathogens in lower respiratory tract samples. From December 2022 to January 2023, we enrolled 836 patients with COVID-19, among which 56.7% patients had severe/critical illness. About 91.4% of patients were infected with the Omicron strain (BA.5.2). The detection rate of possible co-infection pathogens was 53.4% by mNGS, including Klebsiella pneumoniae (16.3%), Aspergillus fumigatus (12.2%), and Pseudomonas aeruginosa (11.8%). The co-infection rate was 19.5%, with common pathogens being Streptococcus pneumoniae (11.5%), Haemophilus influenzae (9.2%), and Adenovirus (6.9%). The superinfection rate was 75.4%, with common pathogens such as Klebsiella pneumoniae (26.1%) and Pseudomonas aeruginosa (19.4%). Klebsiella pneumoniae (27.1%% vs 6.1%, P < 0.001), Aspergillus fumigatus (19.6% vs 5.3%, P = 0.001), Acinetobacter baumannii (18.7% vs 4.4%, P = 0.001), Pseudomonas aeruginosa (16.8% vs 7.0%, P = 0.024), Staphylococcus aureus (14.0% vs 5.3%, P = 0.027), and Streptococcus pneumoniae (0.9% vs 10.5%, P = 0.002) were more common in severe cases. Co-infection and superinfection of bacteria and fungi are common in patients with severe pneumonia associated with Omicron variant infection. Sequencing methods may aid in the diagnosis and differential diagnosis of pathogens. IMPORTANCE: Our study has analyzed the clinical characteristics and pathogen spectrum of the lower respiratory tract associated with co-infection or superinfection in Guangzhou during the outbreak of the Omicron strain, particularly after the relaxation of the epidemic prevention and control strategy in China. This study will likely prompt further research into the specific issue, which will benefit clinical practice.

Ranking the attribution of high-risk genotypes among women with cervical precancers and cancers: a cross-sectional study in Ningbo, China.

BACKGROUND: The region-specific importance of carcinogenic HPV genotypes is required for optimizing HPV-based screening and promoting appropriate multivalent HPV prophylactic vaccines. This information is lacking for Ningbo, one of the first cities of China's Healthy City Innovation Pilot Program for Cervical Cancer Elimination. Here, we investigated high-risk HPV (HR-HPV) genotype-specific distribution and attribution to biopsy-confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) before mass vaccination in Ningbo, China. METHODS: A total of 1393 eligible CIN2+ archived blocks (including 161 CIN2, 1107 CIN3, and 125 invasive cervical cancers [ICC]) were collected from 2017 to 2020 in Ningbo. HR-HPV DNA was genotyped using the SPF10-DEIA-LiPA25 version 1 detection system and the SureX HPV 25X Genotyping Kit. Genotype-specific attribution to CIN2+ was estimated using a fractional contribution approach. RESULTS: Ranking by the attributable proportions, HPV16 remained the most important genotype in both cervical precancers and cancers, accounting for 36.8% of CIN2, 53.2% of CIN3, and 73.3% of ICC cases. Among cervical precancers, HPV52 (17.3% in CIN2, 12.7% in CIN3) and HPV58 (13.9%, 14.9%) ranked second and third, while HPV33 (8.3%, 7.9%) and HPV31 (6.5%, 4.1%) ranked fourth and fifth, respectively. However, among ICCs, HPV18 (5.7%) accounted for the second highest proportion, followed by HPV33 (5.4%), HPV58 (4.0%), and HPV45 (3.2%). HPV18/45 together accounted for 46.8% of adenocarcinomas, which was slightly lower than that of HPV16 (47.7%). The remaining HR-HPV genotypes (HPV35/39/51/56/59/66/68) combined accounted for only 6.7% of CIN2, 2.9% of CIN3, and 4.2% of ICC. CONCLUSIONS: With Ningbo's strong medical resources, it will be important to continue HPV16/18 control efforts, and could broaden to HPV31/33/45/52/58 for maximum health benefits. However, different strategies should be proposed for other HR-HPV genotypes based on their lower carcinogenic risks.

Unveiling Drimenol: A Phytochemical with Multifaceted Bioactivities.

Drimenol, a phytochemical with a distinct odor is found in edible aromatic plants, such as Polygonum minus (known as kesum in Malaysia) and Drimys winteri. Recently, drimenol has received increasing attention owing to its diverse biological activities. This review offers the first extensive overview of drimenol, covering its sources, bioactivities, and derivatives. Notably, drimenol possesses a wide spectrum of biological activities, including antifungal, antibacterial, anti-insect, antiparasitic, cytotoxic, anticancer, and antioxidant effects. Moreover, some mechanisms of its activities, such as its antifungal effects against human mycoses and anticancer activities, have been investigated. However, there are still several crucial issues in the research on drimenol, such as the lack of experimental understanding of its pharmacokinetics, bioavailability, and toxicity. By synthesizing current research findings, this review aims to present a holistic understanding of drimenol, paving the way for future studies and its potential utilization in diverse fields.

5-Fluorouracil in Combination with Calcium Carbonate Nanoparticles Loaded with Antioxidant Thymoquinone against Colon Cancer: Synergistically Therapeutic Potential and Underlying Molecular Mechanism.

Colon cancer is the third most common cancer worldwide, with high mortality. Adverse side effects and chemoresistance of the first-line chemotherapy 5-fluorouracil (5-FU) have promoted the widespread use of combination therapies. Thymoquinone (TQ) is a natural compound with potent antioxidant activity. Loading antioxidants into nano delivery systems has been a major advance in enhancing their bioavailability to improve clinical application. Hence, this study aimed to prepare the optimal TQ-loaded calcium carbonate nanoparticles (TQ-CaCO3 NPs) and investigate their therapeutic potential and underlying molecular mechanisms of TQ-CaCO3 NPs in combination with 5-FU against colon cancer. Firstly, we developed purely aragonite CaCO3 NPs with a facile mechanical ball-milling method. The pH-sensitive and biocompatible TQ-CaCO3 NPs with sustained release properties were prepared using the optimal synthesized method (a high-speed homogenizer). The in vitro study revealed that the combination of TQ-CaCO3 NPs (15 µM) and 5-FU (7.5 µM) inhibited CT26 cell proliferation and migration, induced cell apoptosis and cell cycle arrest in the G0/G1 phase, and suppressed the CT26 spheroid growth, exhibiting a synergistic effect. Finally, network pharmacology and molecular docking results indicated the potential targets and crucial signaling pathways of TQ-CaCO3 NPs in combination with 5-FU against colon cancer. Therefore, TQ-CaCO3 NPs combined with 5-FU could enhance the anti-colon cancer effects of 5-FU with broader therapeutic targets, warranting further application for colon cancer treatment.

A Bimetallic Nanomodulator to Reverse Immunosuppression via Sonodynamic-Ferroptosis and Lactate Metabolism Modulation.

Triple-negative breast cancer (TNBC) responds poorly to immunotherapy due to insufficient immunogenicity and highly immunosuppressive tumor microenvironment (TME). Herein, an intelligent calcium/cobalt-based nanomodulator (Ca,Co)CO3-LND-TCPP@F127-TA (abbreviated as CCLT@FT) is developed to act as a sonodynamic-ferroptosis inducer and metabolic immunoadjuvant to enhance anti-tumor immunotherapy. More details, simultaneous reactive oxygen species (ROS) generation and glutathione (GSH) depletion can be achieved due to the existence of Co2+/Co3+ redox couple in CCLT@FT. Meanwhile, mitochondrial Ca2+ overload and tetrakis(4-carboxyphenyl) porphyrin (TCPP)-mediated sonodynamic therapy (SDT) further amplify the oxidative stress and promote ferroptosis in tumor cells. More impressively, CCLT@FT can modulate lactate metabolism by doping with cobalt and loading with lonidamine (LND, an inhibitor of MCT4), thereby reversing the high-lactate immunosuppressive TME. Furthermore, the combination with immune checkpoint blockade (ICB) therapy is found to achieve superior anti-tumor immunity, which in turn promotes ferroptosis of tumor cells by downregulating SLC7A11 protein, ultimately creating a "cycle" therapy. Overall, this work demonstrates a novel strategy for enhancing anti-tumor immunotherapy based on a closed-loop enhancement therapeutic route between CCLT@FT inducing ferroptosis/lactate metabolism modulation and ICB therapy, providing an alternative and important reference for effective immunotherapy of TNBC.

Exploring the Therapeutic Potential of 5-Fluorouracil-Loaded Calcium Carbonate Nanoparticles Combined with Natural Compound Thymoquinone for Colon Cancer Treatment.

Given the need for novel and effective therapies for colon cancer, this study aimed to investigate the effects of 5-fluorouracil-loaded calcium carbonate nanoparticles (5FU-CaCO3np) combined with thymoquinone (TQ) against colon cancer. A shaking incubator and a high-speed homogenizer were used to prepare the optimal 5FU-CaCO3np, with characterizations of physicochemical properties, in vitro drug release profile, and biocompatibility. In vitro experiments and molecular docking were employed to evaluate the therapeutic potential of the combination for colon cancer treatment. Study results revealed that 5FU-CaCO3np with a size of approximately 130 nm was synthesized using the high-speed homogenizer. Its favorable biocompatibility, pH sensitivity, and sustained release properties facilitated reduced toxic side effects of 5-FU on NIH3T3 normal cells and enhanced inhibitory effects on CT26 colon cancer cells. The combination of 5FU-CaCO3np (1.875 µM) and TQ (30 µM) showed significantly superior anti-colon cancer effects to 5FU-CaCO3np alone in terms of cell proliferation and migration inhibition, cell apoptosis induction, and spheroid growth suppression in CT26 cells (p < 0.05), with strong interactions between the drugs and targets (E-cadherin, Bcl-2, PCNA, and MMP-2). These results provide evidence for 5FU-CaCO3np as a novel regimen against colon cancer. Combining 5FU-CaCO3np and TQ may offer a new perspective for colon cancer therapy.

LACTB suppresses liver cancer progression through regulation of ferroptosis.

Ferroptosis, driven by iron-dependent phospholipid peroxidation, is emerging as an intrinsic cancer defense mechanism. However, the regulatory networks involved in ferroptosis remain largely unknown. Here, we found that serine beta-lactamase-like protein (LACTB) inhibits liver cancer progression by regulating ferroptosis. LACTB is downregulated in liver cancer, and the ectopic expression of LACTB markedly inhibits cell viability, colony formation, and tumour growth. LACTB knockout exerts the opposite effects. Further investigation revealed that LACTB blocks HSPA8 transcription in a p53-dependent manner, resulting in the elevation of NCOA4-mediated ferritinophagy and inhibition of SLC7A11/GSH/GPX4 signalling, thereby triggering ferroptosis and suppressing liver cancer progression. Liver cancer cells with an endogenous mutation of p53 binding site in the HSPA8 promoter exhibited increased resistance to ferroptosis inducers, and the ferroptosis-promoting effect of LACTB was significantly weakened in these mutant cells. Importantly, LACTB is identified as a downstream target of lenvatinib, and adeno-associated virus-mediated overexpression and knockdown of LACTB notably enhance and attenuate the anti-tumour efficacy of lenvatinib in vivo, respectively. Taken together, our study reveals a novel action of LACTB and provides potential therapeutic strategies for enhancing the efficacy of lenvatinib in liver cancer.

Uterine epithelioid trophoblastic tumor with the main manifestation of increased human chorionic gonadotropin: A case report.

BACKGROUND: Epithelioid trophoblastic tumor (ETT) is an extremely rare malignant gestational trophoblastic neoplasm commonly presenting with abnormal vaginal bleeding, abdominal pain, and increased human chorionic gonadotropin (hCG). This study reported a case of uterine ETT with the main manifestation being increased hCG. CASE SUMMARY: A 39-year-old female was referred to the Ningbo Maternal and Child Hospital of China in December 2022, complaining of increased hCG levels for 1 month. Magnetic resonance imaging revealed gestational trophoblastic tumor, and hysteroscopic electrotomy and curettage of intrauterine hyperplasia were performed. The patient was diagnosed with uterine ETT through postoperative pathological examination and immunohistochemical results. Total laparoscopic hysterectomy and bilateral salpingectomy were performed, and hCG levels returned to normal. The patient was without recurrence during the postoperative 3-month follow-up. CONCLUSION: This study reported a case of uterine ETT with the main manifestation being increased hCG, highlighting that ETT should be considered in the presence of abnormal hCG. A total laparoscopic hysterectomy is recommended.

A "Ferroptosis-Amplifier" Hydrogel for Eliminating Refractory Cancer Stem Cells Post-lumpectomy.

The unique "Iron Addiction" feature of cancer stem cells (CSCs) with tumorigenicity and plasticity generally contributes to the tumor recurrence and metastasis after a lumpectomy. Herein, a novel "Ferroptosis Amplification" strategy is developed based on integrating gallic acid-modified FeOOH (GFP) and gallocyanine into Pluronic F-127 (F127) and carboxylated chitosan (CC)-based hydrogel for CSCs eradication. This "Ferroptosis Amplifier" hydrogel is thermally sensitive and achieves rapid gelation at the postsurgical wound in a breast tumor model. Specifically, gallocyanine, as the Dickkopf-1 (DKK1) inhibitor, can decrease the expression of SLC7A11 and GPX4 and synergistically induce ferroptosis of CSCs with GFP. Encouragingly, it is found that this combination suppresses the migratory and invasive capability of cancer cells via the downregulation of matrix metalloproteinase 7 (MMP7). The in vivo results further confirm that this "Ferroptosis Amplification" strategy is efficient in preventing tumor relapse and lung metastasis, manifesting an effective and promising postsurgical treatment for breast cancer.

High-Speed and High-Responsivity Blue Light Photodetector with an InGaN NR/PEDOT:PSS Heterojunction Decorated with Ag NWs.

InGaN nanorods possessing larger and wavelength selective absorption by regulating In component based visible light photodetectors (PDs) as one of the key components in the field of visible light communication have received widespread attention. Currently, the weak photoelectric conversion efficiency and slow photoresponse speed of InGaN nanorod (NR) based PDs due to high surface states of InGaN NRs impede the actualization of high-responsivity and high-speed blue light PDs. Here, we have demonstrated high-performance InGaN NR/PEDOT:PSS@Ag nanowire (NW) heterojunction blue light photodetectors utilizing surface passivation and a localized surface plasmon resonance effect. The dark current is significantly reduced by passivating the InGaN NR surface states using PEDOT:PSS. The photoelectric conversion efficiency is significantly increased by increasing light absorption due to the electromagnetic field oscillation of Ag NWs. The responsivity, external quantum efficiency, detectivity, and fall/off time of the InGaN NR/PEDOT:PSS@Ag NW PDs are up to 2.9 A/W, 856%, 6.64 × 1010 Jones, and 439/725 µs, respectively, under 1 V bias and 420 nm illumination. The proposed device design presents a novel approach toward the development of low-cost, high-responsivity, high-speed blue light photodetectors for applications involving visible light communication.

Distinct roles of excitatory and inhibitory neurons in the medial prefrontal cortex in the expression and reconsolidation of methamphetamine-associated memory in male mice.

Methamphetamine, a commonly abused drug, is known for its high relapse rate. The persistence of addictive memories associated with methamphetamine poses a significant challenge in preventing relapse. Memory retrieval and subsequent reconsolidation provide an opportunity to disrupt addictive memories. However, the key node in the brain network involved in methamphetamine-associated memory retrieval has not been clearly defined. In this study, using the conditioned place preference in male mice, whole brain c-FOS mapping and functional connectivity analysis, together with chemogenetic manipulations of neural circuits, we identified the medial prefrontal cortex (mPFC) as a critical hub that integrates inputs from the retrosplenial cortex and the ventral tegmental area to support both the expression and reconsolidation of methamphetamine-associated memory during its retrieval. Surprisingly, with further cell-type specific analysis and manipulation, we also observed that methamphetamine-associated memory retrieval activated inhibitory neurons in the mPFC to facilitate memory reconsolidation, while suppressing excitatory neurons to aid memory expression. These findings provide novel insights into the neural circuits and cellular mechanisms involved in the retrieval process of addictive memories. They suggest that targeting the balance between excitation and inhibition in the mPFC during memory retrieval could be a promising treatment strategy to prevent relapse in methamphetamine addiction.

Probiotic Compounds Enhanced Recovery after Surgery for Patients with Distal Gastric Cancer: A Prospective, Controlled Clinical Trial.

BACKGROUND: Enhanced recovery after surgery (ERAS) for radical distal gastrectomy needs to be improved urgently. We investigated the effects of probiotic compounds (including Lactobacillus plantarum, L. rhamnosus, L. acidophilus, and Bifidobacterium animalis subsp.lactis) on enhance recovery after gastrectomy. METHODS: The patients in this prospective study were divided into probiotic group (PG group, n = 36) and placebo group (CG group, n = 38), taking corresponding capsule according to the protocol during the perioperative period. We compared the trends in perioperative hematologic findings and the postoperative outcomes. Patients' feces were collected for bacterial 16S rRNA sequencing. Patients were followed up at 1 month postoperatively. RESULTS: After the application of probiotics, the patients' postoperative inflammatory response level was reduced, and the trend of postoperative NLR decrease was significantly faster in the patients of the PG group than in the CG group (P = 0.047, partial η2 = 0.054). The trend of postoperative increase in serum albumin concentration in the patients of the PG group was significantly better than that in the CG group (P = 0.016, partial η2 = 0.078). In addition, patients in the PG group met discharge criteria earlier postoperatively and had fewer medical expenses. The quality of life of PG group was improved postoperatively. Postoperative inflammation-related markers, including the ratio of Firmicutes/Bacteroidetes, were increasing in untreated patients. In addition, the postoperative microbial diversity and abundance in the PG group remained stable. CONCLUSIONS: Probiotic compounds can reduce the inflammatory response after gastrectomy and enhance the recovery of the DGC patients by maintaining the stability of the gut microbiota.

Nomogram for prediction of hearing rehabilitation outcome in children with congenital sensorineural hearing loss after cochlear implantation.

Background: Reliable predictors for rehabilitation outcomes in patients with congenital sensorineural hearing loss (CSNHL) after cochlear implantation (CI) are lacking. The purchase of this study was to develop a nomogram based on clinical characteristics and neuroimaging features to predict the outcome in children with CSNHL after CI. Methods: Children with CSNHL prior to CI surgery and children with normal hearing were enrolled into the study. Clinical data, high resolution computed tomography (HRCT) for ototemporal bone, conventional brain MRI for structural analysis and brain resting-state fMRI (rs-fMRI) for the power spectrum assessment were assessed. A nomogram combining both clinical and imaging data was constructed using multivariate logistic regression analysis. Model performance was evaluated and validated using bootstrap resampling. Results: The final cohort consisted of 72 children with CSNHL (41 children with poor outcome and 31 children with good outcome) and 32 healthy controls. The white matter lesion from structural assessment and six power spectrum parameters from rs-fMRI, including Power4, Power13, Power14, Power19, Power23 and Power25 were used to build the nomogram. The area under the receiver operating characteristic (ROC) curve of the nomogram obtained using the bootstrapping method was 0.812 (95 % CI = 0.772-0.836). The calibration curve showed no statistical difference between the predicted value and the actual value, indicating a robust performance of the nomogram. The clinical decision analysis curve showed a high clinical value of this model. Conclusions: The nomogram constructed with clinical data, and neuroimaging features encompassing ototemporal bone measurements, white matter lesion values from structural brain MRI and power spectrum data from rs-fMRI showed a robust performance in predicting outcome of hearing rehabilitation in children with CSNHL after CI.

Chrysin Inhibits TAMs-Mediated Autophagy Activation via CDK1/ULK1 Pathway and Reverses TAMs-Mediated Growth-Promoting Effects in Non-Small Cell Lung Cancer.

The natural flavonoid compound chrysin has promising anti-tumor effects. In this study, we aimed to investigate the mechanism by which chrysin inhibits the growth of non-small cell lung cancer (NSCLC). Through in vitro cell culture and animal models, we explored the impact of chrysin on the growth of NSCLC cells and the pro-cancer effects of tumor-associated macrophages (TAMs) and their mechanisms. We observed that M2-TAMs significantly promoted the growth and migration of NSCLC cells, while also markedly activating the autophagy level of these cells. Chrysin displayed a significant inhibitory effect on the growth of NSCLC cells, and it could also suppress the pro-cancer effects of M2-TAMs and inhibit their mediated autophagy. Furthermore, combining network pharmacology, we found that chrysin inhibited TAMs-mediated autophagy activation in NSCLC cells through the regulation of the CDK1/ULK1 signaling pathway, rather than the classical mTOR/ULK1 signaling pathway. Our study reveals a novel mechanism by which chrysin inhibits TAMs-mediated autophagy activation in NSCLC cells through the regulation of the CDK1/ULK1 pathway, thereby suppressing NSCLC growth. This discovery not only provides new therapeutic strategies for NSCLC but also opens up new avenues for further research on chrysin.

A retrospective cohort study to observe the efficacy and safety of Endoscopic Submucosal Dissection (ESD) with adjuvant radiotherapy for T1a-MM/T1b-SM Esophageal Squamous Cell Carcinoma (ESCC).

BACKGROUND AND AIM: The clinical outcome of endoscopy submucosal dissection with subsequent radiotherapy for esophageal squamous cell carcinoma remain unclear. In this study we aim to investigate the efficacy and safety of endoscopic submucosal dissection with adjuvant radiotherapy in the treatment of superficial esophageal squamous cell carcinoma involving the muscularis mucosae (T1a-MM) or the submucosa < 200 µm (T1b-SM1). METHODS: We analyzed 20 patients with pathologically confirmed T1a-MM or T1b-SM1 esophageal squamous cell carcinoma treated by endoscopic submucosal dissection from 2016 to 2020 in Lihuili Hospital, 9 patients received adjuvant radiotherapy (RT group) and 11 patients received did not (non-RT group). RESULTS: All 20 patients underwent en bloc resection, and both the vertical and horizontal margins were negative. There was no recurrence or lymph node metastasis in the RT group, and no serious complications or death were observed. In the non-RT group, 2 patients had local recurrence and 1 had distant metastasis. None of the 20 patients died of esophageal carcinoma. CONCLUSIONS: Adjuvant radiotherapy following endoscopic submucosal dissection may be a safe and effective method for the treatment of T1a-MM/T1b-SM1 superficial esophageal squamous cell carcinoma.

Neuroimaging features of primary central nervous system post-transplantation lymphoproliferative disorder following hematopoietic stem cell transplant in patients with ß-thalassemia: a case series and review of literature.

PURPOSE: Primary central nervous system post-transplantation lymphoproliferative disorder (PCNS-PTLD) is a rare but serious complication of hematopoietic stem cell transplantation (HSCT) in patients with severe ß-thalassemia. This study aimed to assess the clinical presentation, pathological characteristics, neuroimaging findings, and treatment strategies in patients with ß-thalassemia who developed PCNS-PTLD and to compare a case series from our transplant center to reported cases from literature. METHODS: We retrospectively reviewed our hospital database and identified four cases of pathologically confirmed PCNS-PTLD without a history of systemic PTLD in patients with severe ß-thalassemia after HSCT. We also performed a relevant literature review on PCNS-PTLD. RESULTS: The median time from transplantation to diagnosis of PCNS-PTLD was 5.5 months. Intracerebral lesions were usually multiple involving both supratentorial and infratentorial regions with homogeneous or rim enhancement. All patients had pathologically confirmed PCNS-PTLD with three patients having diffuse large B-cell lymphoma and the fourth patient having plasmacytic hyperplasia. There was low response to treatment with a median survival of 83 days. CONCLUSION: PCNS-PTLD should be considered in the differential diagnosis of patients with ß-thalassemia who had an intracranial lesion on neuroimaging after HSCT. CRITICAL RELEVANCE STATEMENT: This case series with a comprehensive review of neuroimaging and clinical characteristics of children with primary central nervous system post-transplantation lymphoproliferative disorder should advance our understanding and improve management of this rare yet severe complication following transplant for ß-thalassemia. KEY POINTS: • We assessed clinical presentation, treatment strategies, and neuroimaging characteristics of PCNS-PTLD in patients with ß-thalassemia after transplantation. • Patients with ß-thalassemia may have post-transplantation lymphoproliferative disorder presenting as brain lesions on neuroimaging. • Neuroimaging findings of the brain lesions are helpful for prompt diagnosis and proper management.

Enhancing Water Resistance in Foam Cement through MTES-Based Aerogel Impregnation.

The propensity of foamed concrete to absorb water results in a consequential degradation of its performance attributes. Addressing this issue, the integration of aerogels presents a viable solution; however, their direct incorporation has been observed to compromise mechanical properties, attributable to the effects of the interface transition zone. This study explores the incorporation of MTES-based aerogels into foamed cement via an impregnation technique, examining variations in water-cement ratios. A comprehensive analysis was conducted, evaluating the influences of MTES-based aerogels on the thermal conductivity, compressive strength, density, chemical composition, and microstructure of the resultant composites across different water-cement ratios. Our findings elucidate that an increment in the water-cement ratio engenders a gradual regularization of the pore structure in foamed concrete, culminating in augmented porosity and diminished density. Notably, aerogel-enhanced foamed concrete (AEFC) exhibited a significant reduction in water absorption, quantified at 86% lower than its conventional foamed concrete (FC) counterpart. Furthermore, the softening coefficient of AEFC was observed to surpass 0.75, with peak values reaching approximately 0.9. These results substantiate that the impregnation of MTES-based aerogels into cementitious materials not only circumvents the decline in strength but also bolsters their hydrophobicity and water resistance, indirectly enhancing the serviceability and longevity of foamed concrete. In light of these findings, the impregnation method manifests promising potential for broadening the applications of aerogels in cement-based materials.

HtrAs are essential for the survival of the haloarchaeon Natrinema gari J7-2 in response to heat, high salinity, and toxic substances.

Bacterial and eukaryotic HtrAs can act as an extracytoplasmic protein quality control (PQC) system to help cells survive in stress conditions, but the functions of archaeal HtrAs remain unknown. Particularly, haloarchaea route most secretory proteins to the Tat pathway, enabling them to fold properly in well-controlled cytoplasm with cytosolic PQC systems before secretion. It is unclear whether HtrAs are required for haloarchaeal survival and stress response. The haloarchaeon Natrinema gari J7-2 encodes three Tat signal peptide-bearing HtrAs (NgHtrA, NgHtrB, and NgHtrC), and the signal peptides of NgHtrA and NgHtrC contain a lipobox. Here, the in vitro analysis reveals that the three HtrAs show different profiles of temperature-, salinity-, and metal ion-dependent proteolytic activities and could exhibit chaperone-like activities to prevent the aggregation of reduced lysozyme when their proteolytic activities are inhibited at low temperatures or the active site is disrupted. The gene deletion and complementation assays reveal that NgHtrA and NgHtrC are essential for the survival of strain J7-2 at elevated temperature and/or high salinity and contribute to the resistance of this haloarchaeon to zinc and inhibitory substances generated from tryptone. Mutational analysis shows that the lipobox mediates membrane anchoring of NgHtrA or NgHtrC, and both the membrane-anchored and free extracellular forms of the two enzymes are involved in the stress resistance of strain J7-2, depending on the stress conditions. Deletion of the gene encoding NgHtrB in strain J7-2 causes no obvious growth defect, but NgHtrB can functionally substitute for NgHtrA or NgHtrC under some conditions.IMPORTANCEHtrA-mediated protein quality control plays an important role in the removal of aberrant proteins in the extracytoplasmic space of living cells, and the action mechanisms of HtrAs have been extensively studied in bacteria and eukaryotes; however, information about the function of archaeal HtrAs is scarce. Our results demonstrate that three HtrAs of the haloarchaeon Natrinema gari J7-2 possess both proteolytic and chaperone-like activities, confirming that the bifunctional nature of HtrAs is conserved across all three domains of life. Moreover, we found that NgHtrA and NgHtrC are essential for the survival of strain J7-2 under stress conditions, while NgHtrB can serve as a substitute for the other two HtrAs under certain circumstances. This study provides the first biochemical and genetic evidence of the importance of HtrAs for the survival of haloarchaea in response to stresses.

Effects of different fractions of inspired oxygen on gas embolization during hysteroscopic surgery: A double-blind, randomized, controlled trial.

OBJECTIVE: Gas embolism is a common complication of hysteroscopic surgery that causes serious concern among gynecologists and anesthesiologists due to the potential risk to patients. The factors influencing gas embolism in hysteroscopic surgery have been extensively studied. However, the effect of the oxygen concentration inhaled by patients on gas embolism during hysteroscopic surgery remains elusive. Therefore, we designed a double-blind, randomized, controlled trial to determine whether different inhaled oxygen concentrations influence the occurrence of gas embolism during hysteroscopic surgery. METHODS: This trial enrolled 162 adult patients undergoing elective hysteroscopic surgery who were randomly divided into three groups with inspired oxygen fractions of 30%, 50%, and 100%. Transthoracic echocardiography (four-chamber view) was used to evaluate whether gas embolism occurred. Before the start of surgery, the four-chamber view was continuously monitored. RESULTS: The number of gas embolisms in the 30%, 50%, and 100% groups was 36 (69.2%), 30 (55.6%), and 24 (44.4%), respectively. The incidence of gas embolism gradually decreased with increasing inhaled oxygen concentration (P = 0.031). CONCLUSION: In hysteroscopic surgery, a higher oxygen concentration inhaled by patients may reduce the incidence of gas embolism, indicating that a higher inhaled oxygen concentration, especially 100%, could be recommended for patients during hysteroscopic surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry (https://www.chictr.org.cn/showproj.html?proj=53779, Registration number: ChiCTR2000033202).