Association between septic shock and tracheal injury score in intensive care unit patients with invasive ventilation: a prospective single-centre cohort study in China.

OBJECTIVES: There was no evidence regarding the relationship between septic shock and tracheal injury scores. Investigate whether septic shock was independently associated with tracheal injury scores in intensive care unit (ICU) patients with invasive ventilation. DESIGN: Prospective observational cohort study. SETTING: Our study was conducted in a Class III hospital in Hebei province, China. PARTICIPANTS: Patients over 18 years of age admitted to the ICU between 31 May 2020 and 3 May 2022 with a tracheal tube and expected to be on the tube for more than 24 hours. PRIMARY AND SECONDARY OUTCOME MEASURES: Tracheal injuries were evaluated by examining hyperaemia, ischaemia, ulcers and tracheal perforation by fiberoptic bronchoscope. Depending on the number of lesions, the lesions were further classified as moderate, severe or confluent. RESULTS: Among the 97 selected participants, the average age was 56.6±16.5 years, with approximately 64.9% being men. The results of adjusted linear regression showed that septic shock was associated with tracheal injury scores (ß: 2.99; 95% CI 0.70 to 5.29). Subgroup analysis revealed a stronger association with a duration of intubation ≥8 days (p=0.013). CONCLUSION: Patients with septic shock exhibit significantly higher tracheal injury scores compared with those without septic shock, suggesting that septic shock may serve as an independent risk factor for tracheal injury. TRIAL REGISTRATION NUMBER: ChiCTR2000037842, registered 03 September 2020. Retrospectively registered, https://www.chictr.org.cn/edit.aspx?pid=57011&htm=4.

Revision of residual deformities after primary surgery for Wassel-Flatt IV-D thumb duplication using a microsurgical free lateral great toe flap.

We report the application and results of skin defect coverage using the free lateral great toe flap in revision surgery for residual postoperative deformities in Wassel-Flatt type IV-D thumb duplications. This retrospective study included five patients treated between June 2020 and September 2021 to correct angular deformity and repair the secondary skin defect. All the flaps survived. The patients were followed up for 8-12 months and all the reconstructed thumbs had a satisfactory appearance. The results of the Japanese Society for Surgery of the Hand scoring system were excellent in one patient, good in three patients and fair in one patient. The results of the Alignment, Ulnar and Radial stability, Range of motion and Aesthetical aspects (ALURRA) scoring system were good in four patients and moderate in one patient.Level of evidence: IV.

Gold nanorod-chitosan based nanocomposites for photothermal and chemoembolization therapy of breast cancer.

Gold nanorods (AuNR) have received significant attention in tumor thermo-chemotherapy. However, insufficient thermal availability limits the in vivo highly efficient applications of AuNR in photothermal therapy. In this study, we have fabricated N-isopropylacrylamide grafted O-carboxymethyl chitosan nanoparticles (NCMC NPs) with thermo-responsive properties for co-encapsulating AuNR and doxorubicin (DOX), forming AuNR@NCMC/DOX nanocomposites (NCs). As a result of the thermo- and photothermal-responsiveness, AuNR@NCMC/DOX NCs exhibited irreversible aggregation at high temperature and under near-infrared (NIR) irradiation with an increase of size to 3 µm. When AuNR@NCMC/DOX NCs reached tumor sites following intravenous administration, they were located in the tumor vessels under NIR irradiation due to an embolization effect. This response enhanced tumor targeting, on-demand release, and the thermal performance of AuNR@NCMC/DOX NCs. We have observed higher tumor accumulation of DOX and AuNR with subsequent stronger inhibition of tumor growth than that achieved without NIR irradiation. The development of AuNR-based NCs with multiple smart responsivenesses at tumors can provide a promising paradigm for solid tumor treatment via the cooperative effects of photothermal therapy and chemoembolization.

Transverse snuffbox perforator flap for a first-web contracture: an anatomical study and case report.

This cadaveric study describes a dorsal wrist transverse elliptical cutaneous flap, based on radial artery cutaneous perforators in the region of the snuffbox. The flap was then successfully used in a child with thumb hypoplasia and severe first-web contracture.

Biodegradation of Cholesterol by Enterococcus faecium YY01.

Cholesterol (CHOL) is one of the risk factors causing the blockage of the arterial wall, atherosclerosis, coronary heart disease, and other serious cardiovascular diseases. Here, a promising bacterial strain for biodegrading CHOL was successfully isolated from the gut of healthy individuals and identified as Enterococcus faecium YY01 with an analysis of the 16S rDNA sequence. An initial CHOL of 1.0 g/L was reduced to 0.5 g/L in 5 days, and glucose and beef extract were found to be optimal carbon and nitrogen sources for the rapid growth of YY01, respectively. To gain further insight into the mechanisms underlying CHOL biodegradation, the draft genome of YY01 was sequenced using Illumina HiSeq. Choloylglycine hydrolase, acyltransferase, and alkyl sulfatase was encoded by gene0586, gene1890, and gene2442, which play crucial roles in converting 3α, 7α, 12α-trihydroxy-5ß-choranic acid to choline-CoA and then choline-CoA to bile acid. Notably, choloylglycine hydrolase was closely related to the biosynthesis of both primary and secondary bile acid. The findings of this study provide valuable insights into the metabolism pathway of CHOL biodegradation by YY01 and offer a potential avenue for the development of bacterioactive drugs against hypercholesterolemia.

On-top plasty combined with modified Bilhaut-Cloquet procedure for reconstructing complicated radial polydactyly.

PURPOSE: To present a surgical technique of combining the on-top plasty with modified Bilhaut-Cloquet procedure for reconstructing a rare type of complicated radial polydactyly and evaluate the outcomes. METHODS: Fourteen complicated radial polydactyly in 13 patients were corrected by combining the on-top plasty with modified Bilhaut-Cloquet procedure. Osteotomies were performed as required, and the acral part of the ulnar thumb was transposed onto the proximal part of the radial thumb. The distal parts of the two thumbs were isolated as neurovascular pedicled composite tissue flaps, including part of the distal phalanx and nail bed, and were attached together in an extra-articular way. The tendons were rebalanced, and the nail bed was reconstructed. Objective and subjective outcomes were assessed. RESULTS: The average follow-up time was 32.4 months (6-60 months). All reconstructed thumbs were rated as good in appearance and function. The mean Vancouver Scar Scale score was 1.3 (range 1-2) and the mean Wang-Gao score of the reconstructed thumbnail was 9.4 (range 8-11). The Tada score for the function of the reconstructed thumb was 5.5 (range 5-6). The main active range of motion (ROM) of the interphalangeal joint (IPJ) was 2.1-38.9°. All parents were satisfied with the outcomes. CONCLUSIONS: Because of the diverse manifestations of thumb polydactyly, individualized surgical treatment is recommended, and careful preoperative planning should be made with the principle of combining the best parts of the two thumbs. By combining an on-top plasty with modified Bilhaut-Cloquet procedure, a satisfactory result can be achieved for treating complicated radial polydactyly.

Biodegradation of Gossypol by Aspergillus terreus-YJ01.

Gossypol, generally found in the roots, stems, leaves, and, especially, the seeds of cotton plants, is highly toxic to animals and humans, which inhibits the use of cotton stalks as a feed resource. Here, a promising fungal strain for biodegrading gossypol was successfully isolated from the soil of cotton stalk piles in Xinjiang Province, China, and identified as Aspergillus terreus-YJ01 with the analysis of ITS. Initial gossypol of 250 mg·L-1 could be removed by 97% within 96 h by YJ01, and initial gossypol of 150 mg·L-1 could also be catalyzed by 98% or 99% within 36 h by the intracellular or extracellular crude enzymes of YJ01. Sucrose and sodium nitrate were found to be the optimal carbon and nitrogen sources for the growth of YJ01, and the optimal initial pH and inoculum size for the growth of YJ01 were 6.0 and 1%, respectively. To further elucidate the mechanisms underlying gossypol biodegradation by YJ01, the draft genome of YJ01 was sequenced using Illumina HiSeq, which is 31,566,870 bp in length with a GC content of 52.27% and a total of 9737 genes. Eight genes and enzymes were predicted to be involved in gossypol biodegradation. Among them, phosphoglycerate kinase, citrate synthase, and other enzymes are related to the energy supply process. With sufficient energy, ß-1, 4-endo-xylanase may achieve the purpose of biodegrading gossypol. The findings of this study provide valuable insights into both the basic research and the application of A. terreus-YJ01 in the biodegradation of gossypol in cotton stalks.

Scopoletin Reactivates Latent HIV-1 by Inducing NF-κB Expression without Global T Cell Activation.

Reversing HIV-1 latency promotes the killing of infected cells and is essential for cure strategies. However, current latency-reversing agents (LRAs) are not entirely effective and safe in activating latent viruses in patients. In this study, we investigated whether Scopoletin (6-Methoxy-7-hydroxycoumarin), an important coumarin phytoalexin found in plants with multiple pharmacological activities, can reactivate HIV-1 latency and elucidated its underlying mechanism. Using the Jurkat T cell model of HIV-1 latency, we found that Scopoletin can reactivate latent HIV-1 replication with a similar potency to Prostratin and did so in a dose- and time-dependent manner. Moreover, we provide evidence indicating that Scopoletin-induced HIV-1 reactivation involves the nuclear factor kappa B (NF-κB) signaling pathway. Importantly, Scopoletin did not have a stimulatory effect on T lymphocyte receptors or HIV-1 receptors. In conclusion, our study suggests that Scopoletin has the potential to reactivate latent HIV-1 without causing global T-cell activation, making it a promising treatment option for anti-HIV-1 latency strategies.

Purification and Activity of the Second Recombinant Enzyme for Biodegrading Linearized Microcystins by Sphingopyxis sp. USTB-05.

Hepatotoxic microcystins (MCs) are produced and released by the harmful bloom-forming cyanobacteria, which severely threaten drinking water safety and human health due to their high toxicity, widespread distribution, and structural stability. The linearized microcystinase (MlrB) further hydrolyses the poisonous linearized MCs produced by the microcystinase-catalysed MCs to form tetrapeptides. Here, the purification and activity of MlrB were investigated. The results showed that the linearized products generated by 12.5 mg/L MC-LR and MC-RR were removed by purified recombinant MlrB at a protein concentration of 1 mg/L within 30 min. The high catalytic activity of MlrB can be obtained via heterologous expression and affinity purification, which lays the foundation for further studies on the properties and mechanism of MCs biodegradation enzymes.

Enhanced Production of ß-Nicotinamide Mononucleotide with Exogenous Nicotinamide Addition in Saccharomyces boulardii-YS01.

ß-Nicotinamide mononucleotide (NMN), as a key precursor of an essential coenzyme nicotinamide adenine dinucleotide (NAD+), is most recognized for its pathological treatment effects and anti-aging functions. Here, the biosynthesis of NMN from the inexpensive feedstock substrate nicotinamide (Nam) using previously isolated Saccharomyces boulardii-YS01 was investigated. Ultra-high performance liquid chromatography coupled to triple quadrupole tandem mass spectrometry (UPLC-ESI-QqQ-MS/MS) was established for the determination and targeted analysis of NMN, nicotinamide riboside (NR), nicotinic acid (NA), Nam, and NAD+ in YS01 cells. Satisfactory precision and accuracy values were achieved with recoveries above 70% for five analytes. A 5~100 times higher content of NMN in YS01 (0.24~103.40 mg/kg) than in some common foods (0.0~18.8 mg/kg) was found. Combined with genome sequencing and enzyme function annotation, target-acting enzymes, including nudC, ISN1, URH1, PNP, and SIR2, were identified, and the biosynthetic pathway of NMN via Nam was suggested. The initial addition of 3 g/L Nam in the culture medium effectively promoted the generation of NMN, which raised the content of NMN by 39%. This work supplements an alternative resource for NMN production and lays the theoretical foundation for the further construction of NMN transgenic synthesis hosts.

Engineering the Intestinal Lymphatic Transport of Oral Nanoparticles to Educate Macrophages for Cancer Combined Immunotherapy.

The effectiveness of the commonly used therapy is low for treating triple-negative breast cancer (TNBC). Macrophages, accounting for up to 50% of the TNBC tumor mass, are involved in innate and adaptive immunity, which can serve as an effective weapon against TNBC via combined immunotherapy. Here, we engineered mannose and glycocholic acid-modified trimethyl chitosan (MTG) nanoparticles (NPs) encapsulating signal regulatory protein α (SIRPα) siRNA (siSIRPα, a macrophage checkpoint inhibitor) and mucin 1 (MUC1) pDNA (pMUC1, a therapeutic pDNA vaccine) (MTG/siSIRPα/pMUC1 NPs) for in situ educating macrophages via an oral route to exert the cooperative antitumor effects of siSIRPα and pMUC1. Orally delivered MTG-based NPs accumulated in the macrophages in lymph nodes and tumor tissues via the intestinal lymphatic transport pathway, leading to strong cellular immunity responses. Following the transfection of orally administered MTG/siSIRPα/pMUC1 NPs within the same macrophages, siSIRPα strengthened the pMUC1 vaccine-induced systemic cellular immunity, while pMUC1 enhanced siSIRPα-mediated macrophage phagocytosis, M1-phenotype polarization, and tumor microenvironment (TME) remodeling at the tumor sites, thereby inhibiting the growth and metastasis of TNBC. The simultaneous achievements of the mutual promotion of innate and adaptive immunity in the local TME and in the whole body suggested that MTG/siSIRPα/pMUC1 NPs would provide a promising paradigm for the combined immunotherapy of TNBC via oral delivery of genes.

Cellulose nanocrystal as an enhancing core for antitumor polymeric micelles to overcome biological barriers.

Polymeric micelles are extensively studied nanocarriers to improve the solubility, blood circulation, biodistribution, and adverse effects of chemotherapeutic drugs. However, the antitumor efficacy of polymeric micelles is often restricted due to multiple biological barriers, including blood fluid shear stress (FSS) and limited tumor penetration in vivo. Herein, cellulose nanocrystal (CNC) as a green material with rigidity and rod-shaped structure is developed to be an enhancing core for polymeric micelles to overcome these biological barriers. Doxorubicin (DOX) loaded methoxy poly (ethylene glycol)-block-poly (D, L-lactic acid) (mPEG-PLA, PP) ligated CNC nanoparticles (PPC/DOX NPs) are fabricated via one-pot synthesis. In comparison to the self-assembled DOX loaded mPEG-PLA micelles (PP/DOX NPs), PPC/DOX NPs exhibit remarkable improvements in FSS resistance, cellular internalization, blood circulation, tumor penetration, and antitumor efficacy owing to the unique rigidity and rod-shaped structure of CNC core. Moreover, PPC/DOX NPs present various advantages beyond DOX·HCl and CNC/DOX NPs. The superiority of PPC/DOX NPs in antitumor efficacy reveals the effectiveness of adopting CNC as the enhancing core for polymeric micelles, suggesting that CNC is a promising biomaterial in advancing nanomedicine.

Comparative Genomic Analysis of Sphingomonas morindae sp. NBD5 and Sphingopyxis sp. USTB-05 for Producing Macular Pigment.

Sphingomonas morindae sp. NBD5, which we previously identified and tested, is a new bacterial strain for producing lutein. Here, based on the next-generation sequencing technology, we analyzed high throughput genomic sequences and compared related functional genes of Sphingomonas morindae sp. NBD5 and Sphingopyxis sp. USTB-05. The genome of Sphingomonas morindae sp. NBD5 has two sets of chromosomes, which is 4,239,716 bp and harbors 3882 protein coding genes. There are 59 protein-coding genes related to the macular pigment (MP) biosynthesis, of which four genes (ackA, pgm, gpmI and pckA) are unique. These genes, pckG, porB, meh, and fldA, are unique in Sphingopyxis sp. USTB-05. The analysis of Sphingomonas morindae sp. NBD5 and Sphingopyxis sp. USTB-05 genomes gives an insight into the new pathway for MP production. These genes for the transformation of glucose to MP were also found in Sphingomonas morindae sp. NBD5 and Sphingopyxis sp. USTB-05. This study expands the understanding of the pathway for complete biosynthesis of MP by Sphingomonas morindae sp. NBD5 and Sphingopyxis sp. USTB-05.

Intraoperative Observation of the Proper Digital Nerves in Wassel-Flatt Type â £ Radial Polydactyly.

PURPOSE: The aim of the study was to present the intraoperative findings of the relevant digital nerves of the duplicated thumbs in an excision and reconstruction procedure for the Wassel-Flatt type Ⅳ radial polydactyly. METHODS: The study was conducted on patients with Wassel-Flatt type IV radial polydactyly who underwent excision and reconstruction between 2018 and 2021 at our institution. The ulnar digital nerve of the radial thumb and the radial digital nerve of the ulnar thumb were identified and traced intraoperatively. The level of the bifurcation of the nerves and abnormal findings were documented. RESULTS: A total of 123 hands in 119 patients were included in this study. In 114 hands, the bifurcation of the nerves was located within 1 cm of the metacarpophalangeal flexion crease. The radial digital nerve to the ulnar thumb was abnormally compressed in deep fascial tissue in 7 of these 114 hands. In 5 hands, the level of bifurcation was more than 1 cm proximal to the crease. No radial digital nerve to the ulnar thumb was identified in the remaining 4 hands. CONCLUSIONS: Although rare, abnormal nerve compression of the digital nerve may exist in duplicated thumbs of Wassel-Flatt type IV radial polydactyly. CLINICAL RELEVANCE: In an excision and reconstruction procedure, we suggest that the bifurcation of the nerves should be identified before the nerve to the radial thumb is excised to avoid injuring the nerve to the main ulnar thumb.

The use of the ratio of C-reactive protein to albumin for the diagnosis of pediatric septic arthritis.

Purpose: This study aimed to investigate the relationship between the ratio of c-reactive protein to albumin (CAR) and pediatric septic arthritis (PSA). Methods: Clinical and laboratory data were collected. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive ability of CAR in identifying PSA. Multivariable logistic regression analyses was performed to calculate adjusted odds ratio (OR) with 95% confidence interval (CI). Results: We included 305 patients with PSA (CAR ≤ 0.447, 182 patients; CAR > 0.447, 123 patients) between September 2013 and November 2022. ROC analysis showed that CAR performed best in diagnosing PSA, with an area under curve (AUC) value of 0.828. After adjusted for potential confounders, we found that high CAR was associated with PSA (OR = 6.85, 95% CI: 2.30-20.40, p = 0.001). In sensitivity analyses, subgroups analyses, and propensity score matching, the results remain stable. Conclusions: The CAR (>0.447) at admission was an independent risk factor for PSA. It is worthy to further investigate this association.

Neutralization of five SARS-CoV-2 variants of concern by convalescent and BBIBP-CorV vaccinee serum.

The prevalence of SARS-CoV-2 variants of concern (VOCs) is still escalating throughout the world. However, the level of neutralization of the inactivated viral vaccine recipients' sera and convalescent sera against all VOCs, including B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta), and B.1.1.529 (Omicron) remains to be lack of comparative analysis. Therefore, we constructed pseudoviruses of five VOCs using a lentiviral-based system and analyzed their viral infectivity and neutralization resistance to convalescent and BBIBP-CorV vaccinee serum at different times. Our results show that, compared with the wild-type strain (WT), five VOC pseudoviruses showed higher infection, of which B.1.617.2 and B.1.1.529 variant pseudoviruses exhibited higher infection rates than wild-type or other VOC strains, respectively. Sera from 10 vaccinated individuals at the 1, 3 and 5-month post second dose or from 10 convalescent at 14 and 200 days after discharge retained neutralizing activity against all strains but exhibited decreased neutralization activity significantly against the five VOC variant pseudoviruses over time compared to WT. Notably, 100% (30/30) of the vaccinee serum samples showed more than a 2.5-fold reduction in neutralizing activity against B.1.1.529, and 90% (18/20) of the convalescent serum samples showed more than 2.5-fold reduction in neutralization against B.1.1.529. These findings demonstrate the reduced protection against the VOCs in vaccinated and convalescent individuals over time, indicating that it is necessary to have a booster shot and develop new vaccines capable of eliciting broad neutralization antibodies.

The neutralization of B.1.617.1 and B.1.1.529 sera from convalescent patients and BBIBP-CorV vaccines.

The SARS-CoV-2 variants B.1.617.1 (Kappa) contain multiple mutations in the spike protein. However, the effect of B.1.617.1 lineage-related mutants on viral infectivity and inactivated-virus vaccine efficacy remains to be defined. We therefore constructed 12 B.1.617.1-related pseudoviruses and systematically studied the effects of mutations on virus infectivity and neutralization resistance to convalescent and inactivated virus vaccine sera. Our results show that the B.1.617.1 variant exhibited both higher infectivity and neutralization resistance in sera at 1 or 3 months after vaccination of 28 individuals and at 14 and 200 days after discharge of 15 convalescents. Notably, 89% of vaccines and 100% of the convalescent serum samples showed more than 2.5-fold reduction in neutralization against one single mutation: E484Q. Besides, we found a significant decrease in neutralizing activity in convalescent patients and BBIBP-CorV vaccines for B.1.1.529. These findings demonstrate that inactivated-virus vaccination or convalescent sera showed reduced, but still significant, neutralization against the B.1.617.1 variant.

Dexamethasone promotes osteoblast apoptosis through the Chk2/p53 signaling pathway.

BACKGROUND: Glucocorticoids (GCs) are widely used to treat inflammatory or autoimmune diseases. However, several studies have reported that the use of GCs can lead to numerous complications, the most serious of which are osteoporosis and osteonecrosis of the femoral head (ONFH). Osteoblast apoptosis has been identified as an important event in the development of GC-induced osteoporosis and ONFH. However, the mechanisms underlying the regulation of these processes have not yet been explored. OBJECTIVES: To observe the effect of dexamethasone (Dex) on the apoptosis of osteoblasts and explore its mechanism, as well as provide a new therapeutic idea for GC­induced osteoporosis and ONFH. MATERIAL AND METHODS: Cell proliferation and apoptosis of MC3T3-E1 cells after Dex treatment were determined using the CellTiter-Glo® Luminescent Cell Viability Assay kit and Annexin V-FITC/PI Double Staining Apoptosis Detection Kit, respectively. The expression of caspase-3/cleaved caspase-3 and poly(ADP-ribose) polymerase (PARP)/cleaved PARP in MC3T3-E1 cells after Dex treatment was determined with western blotting. The expression of p53 and checkpoint kinase 2 (Chk2) in MC3T3-E1 cells after Dex treatment was analyzed using western blotting and polymerase chain reaction (PCR). The effects of p53 knockdown and Chk2 knockdown on Dex-induced apoptosis of MC3T3-E1 cells were also characterized. RESULTS: Dexamethasone remarkably inhibited cell growth and induced the apoptosis of MC3T3-E1 cells. We also observed that Dex induced osteoblast apoptosis by promoting p53 expression. The regulatory effect of Dex on p53 expression is mediated by the upregulation of Chk2, which interacted with p53 and inhibited p53 degradation. The knockdown of p53 alleviated Dex-induced MC3T3-E1 cell apoptosis by decreasing the expression of cleaved caspase-3 and cleaved PARP. CONCLUSIONS: We demonstrated that Dex increased Chk2 protein expression, which stabilized the protein expression of p53, and in turn promoted osteoblast apoptosis.