Targeting xCT with sulfasalazine suppresses triple-negative breast cancer growth via inducing autophagy and coordinating cell cycle and proliferation.

There is a substantial unmet need for effective treatment strategies in triple-negative breast cancer (TNBC). Recently, renewed attention has been directed towards targeting glutamine (Gln) metabolism to enhance the efficacy of cancer treatment. Nonetheless, a comprehensive exploration into the mechanistic implications of targeting Gln metabolism in TNBC is lacking. In this study, our objective was to probe the sensitivity of TNBC to alterations in Gln metabolism, using representative TNBC cell lines: MDA-MB-231, MDA-MB-468, and 4T1. Through an integration of bioinformatics, in-vitro, and in-vivo investigations, we demonstrated that sulfasalazine (SAS), like erastin (a known xCT inhibitor), effectively suppressed the expression and transport function of xCT, resulting in a depletion of glutathione levels in MDA-MB-231 and MDA-MB-468 cells. Furthermore, both xCT knockdown and SAS treatment demonstrated the promotion of cellular autophagy. We unveiled a positive correlation between xCT and the autophagy-related molecule p62, their co-expression indicating poor survival outcomes in breast cancer patients. In addition, our research revealed the influence of SAS and xCT on the expression of proteins regulating cell cycle and proliferation. Treatment with SAS or xCT knockdown led to the inhibition of MYC, CDK1, and CD44 expression. Significantly, the combined administration of SAS and rapamycin exhibited a synergistic inhibitory effect on the growth of transplanted breast tumor in mouse models constructed from murine-derived 4T1 cells. Taken together, our findings suggested the potential and clinical relevance of the SAS and rapamycin combination in the treatment of TNBC.

Identification of risk factors and construction of a nomogram predictive model for post-stroke infection in patients with acute ischemic stroke.

BACKGROUND: Post-stroke infection is the most common complication of stroke and poses a huge threat to patients. In addition to prolonging the hospitalization time and increasing the medical burden, post-stroke infection also significantly increases the risk of disease and death. Clarifying the risk factors for post-stroke infection in patients with acute ischemic stroke (AIS) is of great significance. It can guide clinical practice to perform corresponding prevention and control work early, minimizing the risk of stroke-related infections and ensuring favorable disease outcomes. AIM: To explore the risk factors for post-stroke infection in patients with AIS and to construct a nomogram predictive model. METHODS: The clinical data of 206 patients with AIS admitted to our hospital between April 2020 and April 2023 were retrospectively collected. Baseline data and post-stroke infection status of all study subjects were assessed, and the risk factors for post-stroke infection in patients with AIS were analyzed. RESULTS: Totally, 48 patients with AIS developed stroke, with an infection rate of 23.3%. Age, diabetes, disturbance of consciousness, high National Institutes of Health Stroke Scale (NIHSS) score at admission, invasive operation, and chronic obstructive pulmonary disease (COPD) were risk factors for post-stroke infection in patients with AIS (P < 0.05). A nomogram prediction model was constructed with a C-index of 0.891, reflecting the good potential clinical efficacy of the nomogram prediction model. The calibration curve also showed good consistency between the actual observations and nomogram predictions. The area under the receiver operating characteristic curve was 0.891 (95% confidence interval: 0.839-0.942), showing predictive value for post-stroke infection. When the optimal cutoff value was selected, the sensitivity and specificity were 87.5% and 79.7%, respectively. CONCLUSION: Age, diabetes, disturbance of consciousness, NIHSS score at admission, invasive surgery, and COPD are risk factors for post-stroke infection following AIS. The nomogram prediction model established based on these factors exhibits high discrimination and accuracy.

Sodium tanshinone IIA sulfonate protects vascular relaxation in ApoE-knockout mice by inhibiting the SYK-NLRP3 inflammasome-MMP2/9 pathway.

BACKGROUND: Hyperlipidemia damages vascular wall and serves as a foundation for diseases such as atherosclerosis, hypertension and stiffness. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is implicated in vascular dysfunction associated with hyperlipidemia-induced vascular injury. Sodium tanshinone IIA sulfonate (STS), a well-established cardiovascular protective drug with recognized anti-inflammatory, antioxidant, and vasodilatory properties, is yet to be thoroughly investigated for its impact on vascular relaxant imbalance induced by hyperlipidemia. METHODS: In this study, we treated ApoE-knockout (ApoE-/-) mouse with STS and assessed the activation of the NLRP3 inflammasome, expression of MMP2/9, integrity of elastic fibers, and vascular constriction and relaxation. RESULTS: Our findings reveal that STS intervention effectively preserves elastic fibers, significantly restores aortic relaxation function in ApoE-/- mice, and reduces their excessive constriction. Furthermore, STS inhibits the phosphorylation of spleen tyrosine kinase (SYK), suppresses NLRP3 inflammasome activation, and reduces MMP2/9 expression. CONCLUSIONS: These results demonstrate that STS protects vascular relaxation against hyperlipidemia-induced damage through modulation of the SYK-NLRP3 inflammasome-MMP2/9 pathway. This research provides novel insights into the mechanisms underlying vascular relaxation impairment in a hyperlipidemic environment and uncovers a unique mechanism by which STS preserves vascular relaxation, offering valuable foundational research evidence for its clinical application in promoting vascular health.

Nicotinamide riboside restores nicotinamide adenine dinucleotide levels and alleviates brain injury by inhibiting oxidative stress and neuroinflammation in a mouse model of intracerebral hemorrhage.

Hemorrhagic stroke is a global health problem owing to its high morbidity and mortality rates. Nicotinamide riboside is an important precursor of nicotinamide adenine dinucleotide characterized by a high bioavailability, safety profile, and robust effects on many cellular signaling processes. This study aimed to investigate the protective effects of nicotinamide riboside against collagenase-induced hemorrhagic stroke and its underlying mechanisms of action. An intracerebral hemorrhage model was constructed by stereotactically injecting collagenase into the right striatum of adult male Institute for Cancer Research mice. After 30 minutes, nicotinamide riboside was administered via the tail vein. The mice were sacrificed at different time points for assessments. Nicotinamide riboside reduced collagenase-induced hemorrhagic area, significantly reduced cerebral water content and histopathological damage, promoted neurological function recovery, and suppressed reactive oxygen species production and neuroinflammation. Nicotinamide riboside exerts neuroprotective effects against collagenase-induced intracerebral hemorrhage by inhibiting neuroinflammation and oxidative stress.

Zinc attenuates monocrotaline-induced pulmonary hypertension in rats through upregulation of A20.

Pulmonary hypertension (PH) is characterized by excessive proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs), in which inflammatory signaling caused by activation of the NF-κB pathway plays an important role. A20 is an important negative regulator of the NF-κB pathway, and zinc promotes the expression of A20 and exerts a protective effect against various diseases (e.g. COVID19) by inhibiting the inflammatory signaling. The role of A20 and intracellular zinc signaling in PH has been explored, but the extracellular zinc signaling is not well understood, and whether zinc has protective effects on PH is still elusive. Using inductively coupled plasma mass spectrometry (ICP-MS), we studied the alteration of trace elements during the progression of monocrotaline (MCT)-induced PH and found that serum zinc concentration was decreased with the onset of PH accompanied by abnormalities of other three elements, including copper, chromium, and magnesium. Zinc chloride injection with the dosage of 5 mg/kg intraperitoneally partially corrected this abnormality and inhibited the progression of PH. Zinc supplementation induced the expression of A20 in lung tissue and reduce the inflammatory responses. In vitro, zinc supplementation time-dependently upregulated the expression of A20 in PASMCs, therefore correcting the excessive proliferation and migration of cells caused by hypoxia. Using genetically encoded-FRET based zinc probe, we found that these effects of zinc ions are not achieved by entering cells, but most likely by activating cell surface zinc receptor (ZnR/GPR39). These results provide the first evidence of the effectiveness of zinc supplementation in the treatment of PH.

Gegen Qinlian decoction inhibited M1 macrophage polarization and ulcerative colitis progression through regulating histone lactylation.

Ulcerative colitis (UC) is a persistent inflammatory condition affecting the bowels. Gegen Qinlian decoction (GQD) has been widely used in the therapy of gastrointestinal diseases. We investigated the protective impacts and mechanism of GQD against UC. To establish the UC model, dextran sulfate sodium (DSS) was utilized. The disease activity index (DAI), colon length and colonic pathology were assessed to examine the impacts of GQD on UC. The level of pan-lysine lactylation (Pan kla) and specific sites were detected using western blot. Then, the inflammatory factors and the oxidative stress parameters were measured via the corresponding kits, respectively. Our findings demonstrated that GQD suppressed the lactate generation and LDH activity. The western blot revealed that GQD inhibited the expression of Pan kla and specific sites of H3K18la, H3K23la, H4K8la, and H4K12la. Furthermore, the suppressive effects on inflammation and oxidative stress caused by GQD were counteracted upon the exogenous lactate. GQD suppressed the phenotypic differentiation of M1 macrophages by reducing the expression of M1 markers, which was also reversed by exogenous lactate. In conclusion, GQD effectively suppressed UC progression through histone lactylation. Our results broadened the theoretical basis for the clinical use of GQD.

Hybrid teaching after COVID-19: advantages, challenges and optimization strategies.

BACKGROUND: In the post-pandemic era of higher education, hybrid teaching has emerged as a prevalent approach and is anticipated to persist as a defining trend in the future teaching reforms worldwide. However, despite its widespread adoption, certain limitations have become apparent. The objective of this study is to identify the genuine factors that impact students' performance, explore strategies that teachers can employ to enhance their teaching effectiveness and enhance students' academic self-efficacy. METHODS: The study was performed among undergraduate medical students enrolled in Physiology course at Harbin Medical University in 2020 and 2022. Since 2020, influenced by the COVID-19 pandemic, a hybrid teaching method based on an established offline teaching model called BOPPPS was implemented. A questionnaire was performed in both 2020 and 2022 to evaluate students' satisfaction and efficiency of our hybrid teaching. A comparison was also carried out on the final examination scores of students majoring in Pharmacy and Clinical Pharmacy across the years 2020 to 2022. RESULTS: The final examination scores of students in 2022 were significantly lower than those in 2020 and 2021 both in Pharmacy and Clinical Pharmacy majors. There was also a decrease of the score in students of Clinical Pharmacy in 2021 compared to 2020. The questionnaire indicated that over half (52.0%) of the students in 2022 preferred offline teaching method, in contrast to 39.1% in 2020. There were obvious changes in students from 2020 to 2022 about the disadvantages of hybrid teaching, the improvement of students' learning ability and the duration of students' autonomous learning. Through cross statistical analysis, online learning styles, learning ability improvement and students' learning burden have been identified as the primary factors influencing their preference for future teaching method. CONCLUSIONS: Hybrid teaching is still a necessary trend in the future teaching reform base on its multiple advantages. However, in order to improve the teaching outcomes and foster students' participation and learning initiatives, it is imperative to undertake additional reforms in the future teaching process.

The effect of fasting plasma glucose on in-hospital mortality after acute myocardial infarction in patients with and without diabetes: findings from a prospective, nationwide, and multicenter registry.

OBJECTIVES: To evaluate the predictive value of fasting plasma glucose (FPG) for in-hospital mortality in patients with acute myocardial infarction (AMI) with different glucose metabolism status. METHODS: We selected 5,308 participants with AMI from the prospective, nationwide, multicenter CAMI registry, of which 2,081 were diabetic and 3,227 were nondiabetic. Patients were divided into high FPG and low FPG groups according to the optimal cutoff values of FPG to predict in-hospital mortality for diabetic and nondiabetic cohorts, respectively. The primary endpoint was in-hospital mortality. RESULTS: Overall, 94 diabetic patients (4.5%) and 131 nondiabetic patients (4.1%) died during hospitalization, and the optimal FPG thresholds for predicting in-hospital death of the two cohorts were 13.2 mmol/L and 6.4 mmol/L, respectively. Compared with individuals who had low FPG, those with high FPG were significantly associated with higher in-hospital mortality in diabetic cohort (10.1% vs. 2.8%; odds ratio [OR] = 3.862, 95% confidence interval [CI]: 2.542-5.869) and nondiabetic cohort (7.4% vs. 1.7%; HR = 4.542, 95%CI: 3.041-6.782). After adjusting the potential confounders, this significant association was not changed. Furthermore, FPG as a continuous variable was positively associated with in-hospital mortality in single-variable and multivariable models regardless of diabetic status. Adding FPG to the original model showed a significant improvement in C-statistic and net reclassification in diabetic and nondiabetic cohorts. CONCLUSIONS: This large-scale registry indicated that there is a strong positive association between FPG and in-hospital mortality in AMI patients with and without diabetes. FPG might be useful to stratify patients with AMI.

Effect of Acupuncture on Neurogenic Claudication Among Patients With Degenerative Lumbar Spinal Stenosis : A Randomized Clinical Trial.

BACKGROUND: Acupuncture may improve degenerative lumbar spinal stenosis (DLSS), but evidence is insufficient. OBJECTIVE: To investigate the effect of acupuncture for DLSS. DESIGN: Multicenter randomized clinical trial. (ClinicalTrials.gov: NCT03784729). SETTING: 5 hospitals in China. PARTICIPANTS: Patients with DLSS and predominantly neurogenic claudication pain symptoms. INTERVENTION: 18 sessions of acupuncture or sham acupuncture (SA) over 6 weeks, with 24-week follow-up after treatment. MEASUREMENTS: The primary outcome was change from baseline in the modified Roland-Morris Disability Questionnaire ([RMDQ] score range, 0 to 24; minimal clinically important difference [MCID], 2 to 3). Secondary outcomes were the proportion of participants achieving minimal (30% reduction from baseline) and substantial (50% reduction from baseline) clinically meaningful improvement per the modified RMDQ. RESULTS: A total of 196 participants (98 in each group) were enrolled. The mean modified RMDQ score was 12.6 (95% CI, 11.8 to 13.4) in the acupuncture group and 12.7 (CI, 12.0 to 13.3) in the SA group at baseline, and decreased to 8.1 (CI, 7.1 to 9.1) and 9.5 (CI, 8.6 to 10.4) at 6 weeks, with an adjusted difference in mean change of -1.3 (CI, -2.6 to -0.03; P = 0.044), indicating a 43.3% greater improvement compared with SA. The between-group difference in the proportion of participants achieving minimal and substantial clinically meaningful improvement was 16.0% (CI, 1.6% to 30.4%) and 12.6% (CI, -1.0% to 26.2%) at 6 weeks. Three cases of treatment-related adverse events were reported in the acupuncture group, and 3 were reported in the SA group. All events were mild and transient. LIMITATION: The SA could produce physiologic effects. CONCLUSION: Acupuncture may relieve pain-specific disability among patients with DLSS and predominantly neurogenic claudication pain symptoms, although the difference with SA did not reach MCID. The effects may last 24 weeks after 6-week treatment. PRIMARY FUNDING SOURCE: 2019 National Administration of Traditional Chinese Medicine "Project of building evidence-based practice capacity for TCM-Project BEBPC-TCM" (NO. 2019XZZX-ZJ).

Adjustable nanoarchitectonics of N-doping Yolk-Shell carbon spheres via "Pyrolysis-Capture" method for High-Performance supercapacitor.

The energy storage capacity of porous carbon materials is closely tied to their surface structure and chemical properties. However, developing an innovative and straightforward approach to synthesize yolk-shell carbon spheres (YCs) remains a great challenge till date. Herein, we prepared a series of porous nitrogen-doped yolk-shell carbon spheres (NYCs) via a "pyrolysis-capture" method. This method involves coating the resorcinol-formaldehyde (RF) resin sphere with a layer of compact silica shell induced by 2-methylimidazole (ME) catalysis to produce a confined nano-space. Based on the confined effect of compact silica shell, volatile gases emitted from the RF resin and ME during pyrolysis can not only diffuse into the pores of the RF resin but can also be captured to form an outer carbon shell. This results in the tunable structures of NYCs materials. As the pyrolysis temperature rises, the shell thickness of NYCs reduces, the pore size expands, the roughness increases, and the N/O content of surface elements is enhanced. Notably, as an electrode material used forsupercapacitors,the optimized NYCs-800 exhibits excellent performance with a capacitance of 301.2F g-1 at the current density of 1 A/g and outstanding cycling life stability of 96.1% after 10,000 cycles. These results signify that controlling the surface structure and chemical properties of NYCs materials is an effective approach for constructing advanced energy storage materials.

Several major herb pairs containing Coptidis rhizoma: a review of key traditional uses, constituents and compatibility effects.

Herb compatibility is the soul of traditional Chinese Medicine prescriptions. Coptidis rhizoma (CR) (Coptis chinensis Franch., Coptis deltoidea C.Y.Cheng et Hsiao, or Coptis teeta Wall.; family Ranunculaceae), is a well-known herb. The bitter and cold nature of CR can irritate the spleen and stomach, and certain ingredients in CR may trigger allergic reactions. Herb combinations can help alleviate the side effects caused by CR. Through data analysis and literature research, there are many herbs combined with CR have a high frequency, but only a few are currently used as formulae in clinical practice. The results showed that these six herb pairs are usually widely studied or used as prescriptions in the clinic. This paper describes the six herb pairs from the key traditional uses, changes in bioactive constituents, and compatibility effects, especially with Euodiae fructus (family Rutaceae), Scutellariae radix (family Lamiaceae), Magnoliae Officinalis cortex (family Magnoliaceae), Glycyrrhizae radix et rhizoma (family Fabaceae), Ginseng radix et rhizoma (family Araliaceae), and Aucklandiae radix (family Asteraceae), and found that herbs are more effective when used in combination. Therefore, it is feasible to establish some methods to study herb pairs comprehensively from different perspectives. This paper aims to provide the latest and most comprehensive information on the six herb pairs and summarize the pattern of CR compatibility effects. It aims to attract more attention, and further experimental studies will be conducted to investigate and evaluate the effects of herb pairs containing CR. These data can also provide valuable references for researchers and also provide more possibilities for future applications in clinical practice and new drug development.

DNA-terminus-dependent transcription by T7 RNA polymerase and its C-helix mutants.

The remarkable success of messenger RNA (mRNA)-based vaccines has underscored their potential as a novel biotechnology platform for vaccine development and therapeutic protein delivery. However, the single-subunit RNA polymerase from bacteriophage T7 widely used for in vitro transcription is well known to generate double-stranded RNA (dsRNA) by-products that strongly stimulate the mammalian innate immune response. The dsRNA was reported to be originated from self-templated RNA extension or promoter-independent transcription. Here, we identified that the primary source of the full-length dsRNA during in vitro transcription is the DNA-terminus-initiated transcription by T7 RNA polymerase. Guanosines or cytosines at the end of DNA templates enhance the DNA-terminus-initiated transcription. Moreover, we found that aromatic residues located at position 47 in the C-helix lead to a significant reduction in the production of full-length dsRNA. As a result, the mRNA synthesized using the T7 RNA polymerase G47W mutant exhibits higher expression efficiency and lower immunogenicity compared to the mRNA produced using the wild-type T7 RNA polymerase.

Effects of edge disorder on the stability of quantum oscillations in two-dimensional coupled systems.

This paper utilizes the theory of quantum diffusion to analyze the electron probability and spreading width of a wavepacket on each layer in a two-dimensional (2D) coupled system with edge disorder, aiming to clarify the effects of edge disorder on the stability of the electron periodic oscillations in 2D coupled systems. Using coupled 2D square lattices with edge disorder as an example, we show that, the electron probability and wavepacket spreading width exhibit periodic oscillations and damped oscillations, respectively, before and after the wavepacket reaches the boundary. Furthermore, these electron oscillations exhibit strong resistance against disorder perturbation with a longer decay time in the regime of large disorder, due to the combined influences of ordered and disordered site energies in the central and edge regions. Finally, we numerically verified the universality of the results through bilayer graphene, demonstrating that this anomalous quantum oscillatory behavior is independent of lattice geometry. Our findings are helpful in designing relevant quantum devices and understanding the influence of edge disorder on the stability of electron periodic oscillations in 2D coupled systems.

A classical epithelial state drives acute resistance to KRAS inhibition in pancreas cancer.

Intra-tumoral heterogeneity in pancreatic ductal adenocarcinoma (PDAC) is characterized by a balance between basal and classical epithelial cancer cell states, with basal dominance associating with chemoresistance and a dismal prognosis. Targeting oncogenic KRAS, the primary driver of pancreatic cancer, shows early promise in clinical trials but efficacy is limited by acquired resistance. Using genetically engineered mouse models and patient-derived xenografts, we find that basal PDAC cells are highly sensitive to KRAS inhibitors. Employing fluorescent and bioluminescent reporter systems, we longitudinally track cell-state dynamics in vivo and reveal a rapid, KRAS inhibitor-induced enrichment of the classical state. Lineage-tracing identifies these enriched classical PDAC cells to be a reservoir for disease relapse. Genetic ablation of the classical cell-state is synergistic with KRAS inhibition, providing a pre-clinical proof-of-concept for this therapeutic strategy. Our findings motivate combining classical-state directed therapies with KRAS inhibitors to deepen responses and counteract resistance in pancreatic cancer.

Clinical efficacy of Osteoking in knee osteoarthritis therapy: a prospective, multicenter, non-randomized controlled study in China.

Background: Osteoking has been extensively used for the treatment of knee osteoarthritis (KOA). However, it is lack of high-quality evidence on the clinical efficacy of Osteoking against KOA and the comparison with that of nonsteroidal anti-inflammatory drugs (NSAIDs). Aims: To evaluate the efficacy and safety of Osteoking in treating KOA. Methods: In the current study, a total of 501 subjects were recruited from 20 medical centers, and were divided into the Osteoking treatment group (n = 428) and the NSAIDs treatment group (n = 73). The Propensity Score Matching method was used to balance baseline data of different groups. Then, the therapeutic effects of Osteoking and NSAIDs against KOA were evaluated using VAS score, WOMAC score, EQ-5D-3L and EQ-VAS, while the safety of the two treatment were both assessed based on dry mouth, dizziness, diarrhea, etc. Results: After 8 weeks of treatment, the Osteoking group was compared with the NSAIDs group, the VAS score [2.00 (1.00, 3.00) vs. 3.00 (2.00, 4.00)], WOMAC pain score [10.00 (8.00, 13.00) vs. 11.00 (8.00, 16.00) ], WOMAC physical function score [32.00 (23.00, 39.00) vs. 39.07 ± 16.45], WOMAC total score [44.00 (31.00, 55.00) vs. 53.31 ± 22.47) ], EQ-5D-3L score [0.91 (0.73, 0.91) vs. 0.73 (0.63, 0.83) ] and EQ-VAS score [80.00 (79.00, 90.00) vs. 80.00 (70.00, 84.00) ] were improved by the treatment of Osteoking for 8 weeks more effectively than that by the treatment of NSAIDs. After 8 weeks of treatment with Osteoking, the VAS scores of KOA patients with the treatment of Osteoking for 8 weeks were reduced from 6.00 (5.00, 7.00) to 2.00 (1.00, 3.00) (p < 0.05), which was better than those with the treatment of NSAIDs starting from 2 weeks during this clinical observation. Importantly, further subgroup analysis revealed that the treatment of Osteoking was more suitable for alleviating various clinical symptoms of KOA patients over 65 years old, with female, KL II-III grade and VAS 4-7 scores, while the clinical efficacy of NSAIDs was better in KOA patients under 65 years old and with VAS 8-10 scores. Of note, there were no differences in adverse events and adverse reactions between the treatment groups of the two drugs. Conclusion: Osteoking may exert a satisfying efficacy in relieving joint pain and improving life quality of KOA patients without any adverse reactions, especially for patients with KL II-III grades and VAS 4-7 scores. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=55387, Identifier ChiCTR2000034475.

Alterations in physico-chemical properties, microstructure, sensory characteristics, and volatile compounds of red pepper (Capsicum annuum var. conoides) during various thermal drying durations.

Red pepper (Capsicum annuum var. conoides) is commonly used for dried pepper production in China, and the drying process, particularly the during duration, profoundly affects its quality. The findings indicate that prolonged exposure to high temperatures during thermal drying results in significant darkening, an evident decrease in red and yellow tones, and gradual transformation of the pepper's microscopic structure from granular to compact, along with 88% reduction in moisture content and 81% decrease in thickness. The capsaicinoid content increased, resulting in a 4.3-fold increase in spiciness after drying compared to that of fresh pepper. The pepper aroma shifts from fruity, choking, and grassy to herb, dry wood, and smoky. Compounds such as 2-Acetylfuran, furfural, 2-methylfuran, 1-methylpyrrole, 2-methylpyrazine, and 2,5-dimethylpyrazine exhibited positive correlations with drying time, whereas ethyl 2-methylpropanoate, ethyl butanoate, ethyl 2-methylbutanoate, ethyl hexanoate, and 3-methylbutyl butanoate showed negative correlations, indicating their potential as markers for monitoring thermal drying processes.

Analysis of BK Virus Infection in Children After Hematopoietic Cell Transplantation: A Retrospective Single-Center Study.

BACKGROUND: BK virus (BKV) is one of the most common causes of hemorrhagic cystitis (HC) in children undergoing hematopoietic stem cell transplantation (HSCT). Viruses can be found in urine and serum of immunocompromised patients. OBJECTIVE: This study aimed to evaluate the incidence, clinical course, and risk factors for BKV infection in children undergoing HSCT. METHODS: Retrospectively analyzed children who underwent HSCT at Beijing Children's Hospital, Capital Medical University from June 2020 to June 2022. Data related to the clinical manifestations, engraftment, and prognosis were extracted from medical records. Patients were divided into the case group and the control group, according to the BKV infection or not after HSCT. RESULTS: A total of 149 patients were enrolled in this study, and 61 (40.9%) patients developed BKV infection after HSCT. Among the 61 patients, BKV load was detected in all patients in urine samples and 22 patients in blood samples. The median value of BKV DNA copies in urine and plasma were 9.50×107 (5.37×102 to 6.84×109) copies/mL and 2.97×103 (9.96×102 to 3.58×108) copies/mL, respectively. The median time from beginning of the conditioning regimen to BKV infection was 23 (0 to 273) days, and the first positive time of urinary BKV was earlier than that of blood (13.5 d [0.0 to 123.0 d] vs. 30.5 d [7.0 to 165.0 d], P=0.003). Among the patients with BKV infection, 36 (59.0%) patients met the diagnosis of hemorrhagic cystitis (HC), and the incidence was higher than that in the control group (P<0.001). Similarly, 15 (24.6%) patients developed renal function damage in the case group and the proportion was higher than that in the control group. The median follow-up was 5.67 (0.03 to 24.90) months, and there was no significant difference in 1-year overall survival rate between the case group and the control group (84.2%±5.7% vs. 95.3%±2.3%, P=0.688), but the incidence of TA-TMA/VOD (31.1%) and diffuse alveolar hemorrhage (9.8%) in the case group was higher than that in the control group (P=0.002 and 0.038, respectively). Multivariate analysis showed that age above 5 years old (OR=9.039, 95% CI: 3.561-24.333, P<0.001) and use of MMF (OR=2.708, 95% CI: 1.041-7.044, P<0.05) were independent risk factors for BKV infection after HSCT. CONCLUSION: Among children after HSCT, the incidence of BKV infection was high and BKV infection was associated with an increased incidence of TA-TMA/VOD and diffuse alveolar hemorrhage. Patients older than 5 years of age at the time of HSCT and treated with MMF were more likely to develop BKV infection.

[Basic research in sepsis: advances and challenges].

Although the understanding of sepsis has evolved from "sepsis 1.0" to "sepsis 3.0", and the consensus on clinical management of sepsis has been continuously updated, the incidence rate and mortality of sepsis remain high. Therefore, in-depth investigation of the pathogenesis and related influencing factors of sepsis is of great significance for revealing the nature of sepsis and improving the clinical outcome of sepsis patients. This review will focus on the key issues in the basic research of sepsis, and summarize the recent advances and challenges in this field, mainly including genetic polymorphism, microorganisms, high-mobility group box 1 (HMGB1), endothelial dysfunction, immunotherapy, and biomarkers, aiming to provide new insights for the diagnosis and treatment of sepsis.

Contribution of inwardly rectifying potassium channel 4.1 in orofacial neuropathic pain: Regulation of pannexin 3 via the reactive oxygen species-activated P38 MAPK signal pathway.

The involvement of inwardly rectifying potassium channel 4.1 (Kir4.1) in neuropathic pain has been established. However, there is limited understanding of the downstream mechanism through which Kir4.1 contributes to orofacial neuropathic pain. The objective of this study was to examine the regulation of Kir4.1 on the expression of pannexin 3 (Panx3) in the trigeminal ganglion (TG) and the underlying mechanism in the context of orofacial neuropathic pain caused by chronic constriction injury of the infraorbital nerve (CCI-ION). The study observed a significant increase in Panx3 expression in the TG of mice with CCI-ION. Inhibition of Panx3 in the TG of CCI-ION mice resulted in alleviation of orofacial mechanical allodynia. Furthermore, conditional knockdown (CKD) of Kir4.1 in the TG of both male and female mice led to mechanical allodynia and upregulation of Panx3 expression. Conversely, overexpression of Kir4.1 decreased Panx3 levels in the TG and relieved mechanical allodynia in CCI-ION mice. In addition, silencing Kir4.1 in satellite glial cells (SGCs) decreased Panx3 expression and increased the phosphorylation of P38 MAPK. Moreover, silencing Kir4.1 in SGCs increased the levels of reactive oxygen species (ROS). The elevated phosphorylation of P38 MAPK resulting from Kir4.1 silencing was inhibited by using a superoxide scavenger known as the tempol. Silencing Panx3 in the TG in vivo attenuated the mechanical allodynia caused by Kir4.1 CKD. In conclusion, these findings suggest that the reduction of Kir4.1 promotes the expression of Panx3 by activating the ROS-P38 MAPK signalling pathway, thus contributing to the development of orofacial neuropathic pain.