Microbiome-host interactions in the pathogenesis of acute exacerbation of chronic obstructive pulmonary disease.

Objective: To explore the underlying mechanisms the airway microbiome contributes to Acute Exacerbation of Chronic Obstructive Pulmonary Disease(AECOPD). Methods: We enrolled 31 AECOPD patients and 26 stable COPD patients, their sputum samples were collected for metagenomic and RNA sequencing, and then subjected to bioinformatic analyses. The expression of host genes was validated by Quantitative Real-time PCR(qPCR) using the same batch of specimens. Results: Our results indicated a higher expression of Rothia mucilaginosa(p=0.015) in the AECOPD group and Haemophilus influenzae(p=0.005) in the COPD group. The Different expressed genes(DEGs) detected were significantly enriched in "type I interferon signaling pathway"(p<0.001, q=0.001) in gene function annotation, and "Cytosolic DNA-sensing pathway"(p=0.002, q=0.024), "Toll-like receptor signaling pathway"(p=0.006, q=0.045), and "TNF signaling pathway"(p=0.006, q=0.045) in KEGG enrichment analysis. qPCR amplification experiment verified that the expression of OASL and IL6 increased significantly in the AECOPD group. Conclusion: Pulmonary bacteria dysbiosis may regulate the pathogenesis of AECOPD through innate immune system pathways like type I interferon signaling pathway and Toll-like receptor signaling pathway.

Are pelvic-abdominal mechanics exercises effective for cesarean delivery rate and postpartum pelvic floor function: A randomized controlled trial.

OBJECTIVES: To examine the effectiveness of pelvic-abdominal mechanics exercise in reducing cesarean section rates and preventing pelvic floor dysfunction in primiparous women. DESIGN: Randomized controlled trial. METHODS: A single-center prospective study was conducted among 200 primiparous participants (aged 18-38 years) who undertook formal card-issuing maternity tests between June 1, 2022, and June 30, 2023. Participants were divided into two groups: exercise (intervention) and control using the random number table method. Participants of the intervention group performed pelvic-abdominal mechanics exercise at least 1 h each time per week for three months. Participants of the control group did not perform any pelvic-abdominal mechanics exercise during pregnancy. This study conducted a comprehensive evaluation from three perspectives, including maternal and neonatal health outcomes during delivery, the recovery status of pelvic floor muscles at 42 days postpartum, and the quality of life during late pregnancy (36-38 weeks) and 42 days postpartum. RESULTS: A significant difference was found in delivery outcomes. The cesarean section rates are significantly higher (p < 0.05) in the control group (36 %) than in the exercise group (19 %). At 42 days postpartum, pelvic floor assessment showed that the exercise group had significantly better results in pelvic floor muscle strength compared to the control group, with statistical significance (p < 0.05). CONCLUSIONS: Pelvic-abdominal mechanics exercise lowers the rate of cesarean section and improves postpartum pelvic floor function.

Treatment of three pediatric AML co-expressing NUP98-NSD1, FLT3-ITD, and WT1.

During the treatment of 89 pediatric patients with Acute Myeloid Leukemia (AML) at the Hematology Department of Kunming Medical University's Children's Hospital from 2020 to 2023, three patients were identified to co-express the NUP98-NSD1, FLT3-ITD, and WT1 gene mutations. The bone marrow of these three patients was screened for high-risk genetic mutations using NGS and qPCR at the time of diagnosis. The treatment was administered following the China Children's Leukemia Group (CCLG)-AML-2019 protocol. All three patients exhibited a fusion of the NUP98 exon 12 with the NSD1 exon 6 and co-expressed the FLT3-ITD and WT1 mutations; two of the patients displayed normal karyotypes, while one presented chromosomal abnormalities. During the induction phase of the CCLG-AML-2019 treatment protocol, the DAH (Daunorubicin, Cytarabine, and Homoharringtonine) and IAH (Idarubicin, Cytarabine, and Homoharringtonine) regimens, in conjunction with targeted drug therapy, did not achieve remission. Subsequently, the patients were shifted to the relapsed/refractory chemotherapy regimen C + HAG (Cladribine, Homoharringtonine, Cytarabine, and G-CSF) for two cycles, which also failed to induce remission. One patient underwent Haploidentical Hematopoietic Stem Cell Transplantation (Haplo-HSCT) and achieved complete molecular remission during a 12-month follow-up period. Regrettably, the other two patients, who did not receive transplantation, passed away. The therapeutic conclusion is that pediatric AML patients with the aforementioned co-expression do not respond to chemotherapy. Non-remission transplantation, supplemented with tailor-made pre- and post-transplant strategies, may enhance treatment outcomes.

Nonpronuclear- and monopronuclear-derived blastocysts do not impair subsequent perinatal and maternal outcomes.

CONTEXT: The routine clinical practice is to prioritize the transfer of blastocysts derived from 2PN embryos if they are available. For women who only have blastocysts resulting from 0PN and 1PN embryos, whether to transfer these embryos or discard them has been an ongoing debate over the years. OBJECTIVE: To investigate the perinatal and obstetric outcomes following the transfer of vitrified-warmed single blastocysts derived from 0PN and 1PN zygotes. DESIGN: Retrospective cohort study. SETTING: University-affiliated IVF center. PATIENT(S): This study included singletons born to women who had undergone 0PN and 1PN vitrified-warmed single blastocyst transfers, compared to those resulting from 2PN vitrified-warmed single blastocyst transfers from 2012 to 2020. INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): Perinatal and obstetric outcomes. RESULT(S): A total of 7,284 women were included in the final analysis. Of these, 386, 316, and 6582 cycles resulted from 0PN-, 1PN-, and 2PN-derived blastocysts transfer, respectively. The rates of clinical pregnancy, miscarriage, and live birth were similar across the study cohorts in both unadjusted and adjusted analyses. When comparing the 0PN and 2PN groups, no differences were found in birth outcomes after adjusting for confounders. Similarly, maternal complications and mode of delivery were comparable between these two study cohorts. Birth parameters were also similar between the 1PN and 2PN blastocyst groups, except for more male births in the 1PN cohort. Furthermore, a comparison between the 1PN and 2PN groups did not reveal any significant differences in maternal outcomes. CONCLUSION: The current study showed that the transfer of 0PN and 1PN blastocysts did not compromise reproductive outcomes or increase maternal and perinatal complications. This information is valuable for clinicians to counsel couples effectively and guide them in making informed decisions.

Determining Whether an Individual is 18 Years or Older Based on the Third Molar Root Pulp Visibility in East China.

OBJECTIVES: To investigate the age-related changes of the mandibular third molar root pulp visibility in individuals in East China, and to explore the feasibility of applying this method to determine whether an individual is 18 years or older. METHODS: A total of 1 280 oral panoramic images were collected from the 15-30 years old East China population, and the mandibular third molar root pulp visibility in all oral panoramic images was evaluated using OLZE 0-3 four-stage method, and the age distribution of the samples at each stage was analyzed using descriptive statistics. RESULTS: Stages 0, 1, 2 and 3 first appeared in 16.88, 19.18, 21.91 and 25.44 years for males and in 17.47, 20.91, 22.01 and 26.01 years for females. In all samples, individuals at stages 1 to 3 were over 18 years old. CONCLUSIONS: It is feasible to determine whether an individual in East China is 18 years or older based on the mandibular third molar root pulp visibility on oral panoramic images.

The impact of adverse pregnancy events in the initial cycle on subsequent pregnancy outcomes.

CONTEXT: Evidence is accumulating on the impact of previous adverse pregnancy events on future fertility in natural conceptions. However, there is limited knowledge on whether an ectopic pregnancy (EP) or miscarriage after an initial in vitro fertilization (IVF) cycle affects the subsequent outcomes. OBJECTIVE: To investigate the effect of first IVF outcomes: miscarriage, EP, and no pregnancy, on the second cycle outcomes based on a freeze-all strategy. DESIGN: Retrospective cohort study. SETTING: University-affiliated IVF center. PATIENT(S): This study involved 16,479 women who had undergone 2 complete frozen embryo transfers (FET) and were classified into 3 groups based on first FET outcomes. INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): Live birth rate (LBR). RESULT(S): After correcting for confounders, the LBR after the second FET was similar between women who suffered an EP and those who had no pregnancies in their first FET cycles (adjusted OR (aOR), 1.03; 95% confidence interval (CI), 0.83-1.28). However, women who experienced a miscarriage versus those with no prior pregnancy in the first FET had significantly higher LBR in their second cycles (aOR, 1.33; 95% CI, 1.20-1.48). The LBR after the second FET was comparable between the previous EP and miscarriage groups (aOR, 1.24; 95% CI, 0.98-1.58). Similar results were found in the propensity score matching models, supporting the robustness of the main findings. CONCLUSION: Women who had a miscarriage in the first FET cycle had a higher chance of achieving live births in the subsequent treatment cycle when compared to those who had no pregnancy in the initial cycle. Furthermore, it was found that an EP resulting from the first treatment cycle did not negatively impact reproductive outcomes in the next FET cycles.

A pharmacovigilance study of FDA adverse events for sugammadex.

BACKGROUND: Sugammadex, a selective steroidal neuromuscular blocking agent reversal agent, is increasingly employed for the rapid restoration of neuromuscular function. This study aimed to conduct a comprehensive evaluation of sugammadex's safety profile. METHODS: Adverse events (AEs) related to sugammadex reported in the FDA Adverse Event Reporting System (FAERS) database from January 2009 to September 2023 were extracted. Disproportionality analysis with four measures: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) were employed to detect significant AEs. We also inspected for unexpected AEs absent from the sugammadex FDA approval documentation and categorized AEs based on the latest version (26.1) of 'Important Medical Event Terms List (IME list)' developed by the EudraVigilance Expert Working Group. RESULTS: A total of 1452 reports were linked to sugammadex. At the preferred terms (PTs) levels, 98 sugammadex-related AEs were identified, including "anaphylactic reaction", "bradycardia", "bronchospasm" and "cardiac arrest". Among them, 37 representing unexpected events were absent from official FDA labeling, and 50 AEs were recognized as IME warranting observation. Notably, 19 PTs denoted serious AEs were absent from labeling yet needing IME surveillance, including: "Kounis syndrome", "angioedema", "pulseless electrical activity" and "laryngeal edema". CONCLUSION: The study identified unexpected and potentially life-threatening AEs associated with sugammadex, a valuable agent for rapidly reversing neuromuscular blockade. Clinicians are advised to be mindful of these potential risks, particularly in patients with allergies or existing cardiovascular or respiratory conditions.

Application of Free Flaps in Reconstruction of Head and Neck Soft Tissue Defects With Bone Exposure.

BACKGROUND: Reconstruction of head and neck soft tissue defects with bone exposure is both challenging and technically demanding for plastic surgeon. Objectives in head and neck soft tissue defects with bone exposure reconstruction are consistent restoration of functionality while also improving appearance. This study retrospectively analyzed the results of head and neck reconstructions using various types of free flaps over the past 4 years. METHODS: A retrospective analysis was conducted from June 2019 to June 2023 on 12 patients treated at our hospital for head and neck soft tissue defects with bone exposure due to various causes. These included 4 cases of trauma from car accidents, 1 burn case, and 7 postoperative malignant tumor removals. The defect sizes ranged from 4 × 6 to 15 × 45 cm. Different free flaps were used for repair based on the defect, including 6 anterolateral thigh flaps, 3 forearm flaps, 2 latissimus dorsi flaps, and 1 dorsalis pedis flap. Flaps were designed and harvested to match the defect size and transplanted via anastomosed vessels. RESULTS: All 12 flaps survived successfully. One patient required flap thinning surgery postoperatively. All patients were followed up for over 3 months, showing good color and texture of the transplanted flaps, satisfactory healing, and significant aesthetic improvement. Donor sites showed significant scarring without functional impairment. CONCLUSION: Free flap repair for head and neck soft tissue defects with bone exposure is feasible and yields good results.

Assembly of core-shell Fe3O4 @CD-MOFs derived hollow magnetic microcubes for efficient extraction of hazardous substances: Plausible mechanisms for selective adsorption.

Hazardous heavy metals and organic substances removal is of great significance for ensuring the safety of aquatic-ecosystem, yet the highly effective and selective extraction always remains challenging. To address this problem, magnetic hollow microcubes were fabricated through thermal carbonization of Fe3O4-COOH@ Î³-CD-MOFs, and core-shell structured precursors were in-situ greenly constructed on a large scale via microwave-assisted self-assembly strategy. As noted, the development of secondary crystallization was utilized to achieve uniform dispersion of cores within MOFs frameworks and thus improved magnetic and adsorption ability of composites. Acquired magnetic Fe3O4 @HC not only can harvest excellent extraction of heavy metals (Cd, Pb, and Cu of 129.87, 151.05, and 106.98 mg·g-1) but also exhibit highly selective adsorption ability for cationic organics (separation efficiency higher than 95.0 %). Impressively, Fe3O4 @HC achieved outstanding adsorption (60-80 %) of Cd in realistic mussel cooking broth with no obvious loss in amino acid. Characterizations better offer mechanistic insight into the enhanced selectivity of positively charged pollutants can be attributed to synergistic effect of ions exchange and electrostatic interaction of abundant oxygen-containing functional groups. Our study provides a feasible route by rationally developing core-shell structured composites to promote the practical applications of sustainable water treatment and value-added utilization of processing by-products.

Preparation of PLCL/ECM nerve conduits by electrostatic spinning technique and evaluationin vitroandin vivo.

Objective. Artificial nerve scaffolds composed of polymers have attracted great attention as an alternative for autologous nerve grafts recently. Due to their poor bioactivity, satisfactory nerve repair could not be achieved. To solve this problem, we introduced extracellular matrix (ECM) to optimize the materials.Approach.In this study, the ECM extracted from porcine nerves was mixed with Poly(L-Lactide-co-ϵ-caprolactone) (PLCL), and the innovative PLCL/ECM nerve repair conduits were prepared by electrostatic spinning technology. The novel conduits were characterized by scanning electron microscopy (SEM), tensile properties, and suture retention strength test for micromorphology and mechanical strength. The biosafety and biocompatibility of PLCL/ECM nerve conduits were evaluated by cytotoxicity assay with Mouse fibroblast cells and cell adhesion assay with RSC 96 cells, and the effects of PLCL/ECM nerve conduits on the gene expression in Schwann cells was analyzed by real-time polymerase chain reaction (RT-PCR). Moreover, a 10 mm rat (Male Wistar rat) sciatic defect was bridged with a PLCL/ECM nerve conduit, and nerve regeneration was evaluated by walking track, mid-shank circumference, electrophysiology, and histomorphology analyses.Main results.The results showed that PLCL/ECM conduits have similar microstructure and mechanical strength compared with PLCL conduits. The cytotoxicity assay demonstrates better biosafety and biocompatibility of PLCL/ECM nerve conduits. And the cell adhesion assay further verifies that the addition of ECM is more beneficial to cell adhesion and proliferation. RT-PCR showed that the PLCL/ECM nerve conduit was more favorable to the gene expression of functional proteins of Schwann cells. Thein vivoresults indicated that PLCL/ECM nerve conduits possess excellent biocompatibility and exhibit a superior capacity to promote peripheral nerve repair.Significance.The addition of ECM significantly improved the biocompatibility and bioactivity of PLCL, while the PLCL/ECM nerve conduit gained the appropriate mechanical strength from PLCL, which has great potential for clinical repair of peripheral nerve injuries.

Bioenzyme-nanoenzyme-chromogen all-in-one test strip for convenient and sensitive detection of malathion in water environment.

The presence of pesticide residues in aquatic environments poses a significant threat to both aquatic ecosystems and human health. The presence of these residues can result in significant harm to aquatic ecosystems and can negatively impact the health of aquatic organisms. Consequently, this issue requires urgent attention and effective measures to mitigate its impact. However, developing sensitive and rapid detection methods remains a challenge. In this study, an all-in-one test strip, which integrated bioenzymes, nanoenzymes, and a chromogen, was developed in combination with an enzyme labeling instrument for a highly sensitive and convenient sensing of malathion residues. The oxidase activity of heme chloride (Hemin) in the strip can catalyze the oxidation of H2O2 and 3,3',5,5'-tetramethylbenzidine (TMB) to produce a blue-colored oxide. Simultaneously, the alkaline phosphatase (ALP) present in the strip can break down l-ascorbic acid-2-phosphate to produce ascorbic acid (AA). This AA then acts to reduce the oxidized form of TMB, turning it into a colorless substance and leading to the disappearance of its fluorescent signal. In the presence of a pesticide, the activity of ALP is inhibited and formation of AA is blocked, thereby preventing the reduction of oxidized TMB and producing a colored signal. According to this principle, the integrated test strip detected the target pesticide with high performance as per the optical density value determined via an enzyme marker. The detection limit of the test strip was 0.209 ng/mL with good sensitivity. The method was used for detecting malathion in actual river water samples, and the recoveries were in the range of 93.53 %-96.87 %. The newly devised technique effectively identified malathion in samples of natural water. This research has introduced a novel approach for the precise and convenient surveillance of pesticide remnants. Additionally, these discoveries could inspire the advancement of proficient multi-enzyme detection systems.

Enhancing neuroinduction activity of PLCL-based nerve conduits through native epineurium integration.

Autologous nerve grafts have been considered the gold standard for peripheral nerve grafts. However, due to drawbacks such as functional loss in the donor area and a shortage of donor sources, nerve conduits are increasingly being considered as an alternative approach. Polymer materials have been widely studied as nerve repair materials due to their excellent processing performance. However, their limited biocompatibility has restricted further clinical applications. The epineurium is a natural extra-neural wrapping structure. After undergoing decellularization, the epineurium not only reduces immune rejection but also retains certain bioactive components. In this study, decellularized epineurium (DEP) derived from the sciatic nerve of mammals was prepared, and a bilayer nerve conduit was created by electrospinning a poly (l-lactide-co-ε-caprolactone) (PLCL) membrane layer onto the outer surface of the DEP. Components of the DEP were examined; the physical properties and biosafety of the bilayer nerve conduit were evaluated; and the functionality of the nerve conduit was evaluated in rats. The results demonstrate that the developed bilayer nerve conduit exhibits excellent biocompatibility and mechanical properties. Furthermore, this bilayer nerve conduit shows significantly superior therapeutic effects for sciatic nerve defects in rats compared to the pure PLCL nerve conduit. In conclusion, this research provides a novel strategy for the design of nerve regeneration materials and holds promising potential for further clinical translation.