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Importance: The exceedingly high US spending per capita on prescription medications is mediated, at least in part, by the inefficiencies of existing generic pharmaceutical distribution and reimbursement systems; yet, the extent of potential savings and areas for targeted interventions for generic drug prescribers remains underexplored., Objective: We aimed to analyze 2021 Medicare Part D spending on generic drugs in comparison with pricing of a low-cost generic drug program, the Mark Cuban Cost Plus Drug Company (MCCPDC), to gauge the extent of achievable potential savings., Design, Setting, and Participants: In this retrospective, observational study, we performed a systematic analysis of potential Medicare Part D savings when using MCCPDC generic pricing. The 2023 MCCPDC data, as of August 2023, were obtained from the provider's publicly available database. The 2021 Medicare Part D data and prescriber datasets were obtained from the US Centers for Medicare and Medicaid Services., Main Outcomes and Measures: Outcomes included total prescription volume, proportion of drugs with savings, total US dollar Medicare savings, and average weighted price reduction per unit drug. Results were stratified by medical and surgical subspecialties to identify areas for targeted interventions. Subspecialty-wise contribution to total savings versus contribution to total prescription volume was characterized., Results: Total estimated Medicare Part D savings were $8.6 billion using 90-day MCCPDC pricing, with surgical drugs accounting for over $900 million. Nearly 80% of the examined drugs were more price effective through MCCPDC using 90-day supply. Commonly prescribed drugs in cardiology, psychiatry, neurology, transplant surgery, and urology demonstrated the highest estimated absolute savings. The most disproportionate savings relative to prescription volume were observed for drugs in oncology, gynecology, infectious disease, transplant surgery, and colorectal surgery., Conclusions and Relevance: This study underscores the significant potential for Medicare Part D savings through strategies that address the systemic overpayment for generic medications. We identified key areas for reform as well as specific medical and surgical subspecialties where targeted interventions could yield substantial savings., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: With the rapid progress of systematic therapy for hepatocellular carcinoma (HCC), therapeutic strategies combining hepatic arterial infusion chemotherapy (HAIC) with systematic therapy arised increasing concentrations. However, there have been no systematic review comparing HAIC and its combination strategies in the first-line treatment for advanced HCC., Aim: To investigate the efficacy and safety of HAIC and its combination therapies for advanced HCC., Methods: A network meta-analysis was performed by including 9 randomized controlled trails and 35 cohort studies to carry out our study. The outcomes of interest comprised overall survival (OS), progression-free survival (PFS), tumor response and adverse events. Hazard ratios (HR) and odds ratios (OR) with a 95% confidence interval (CI) were calculated and agents were ranked based on their ranking probability., Results: HAIC outperformed Sorafenib (HR = 0.55, 95%CI: 0.42-0.72; HR = 0.51, 95%CI: 0.33-0.78; OR = 2.86, 95%CI: 1.37-5.98; OR = 5.45, 95%CI: 3.57-8.30; OR = 7.15, 95%CI: 4.06-12.58; OR = 2.89, 95%CI: 1.99-4.19; OR = 0.48, 95%CI: 0.25-0.92, respectively) and transarterial chemoembolization (TACE) (HR = 0.50, 95%CI: 0.33-0.75; HR = 0.62, 95%CI: 0.39-0.98; OR = 3.08, 95%CI: 1.36-6.98; OR = 2.07, 95%CI: 1.54-2.80; OR = 3.16, 95%CI: 1.71-5.85; OR = 2.67, 95%CI: 1.59-4.50; OR = 0.16, 95%CI: 0.05-0.54, respectively) in terms of efficacy and safety. HAIC + lenvatinib + ablation, HAIC + ablation, HAIC + anti- programmed cell death 1 (PD-1), and HAIC + radiotherapy had the higher likelihood of providing better OS and PFS outcomes compared to HAIC alone. HAIC + TACE + S-1, HAIC + lenvatinib, HAIC + PD-1, HAIC + TACE, and HAIC + sorafenib had the higher likelihood of providing better partial response and objective response rate outcomes compared to HAIC. HAIC + PD-1, HAIC + TACE + S-1 and HAIC + TACE had the higher likelihood of providing better complete response and disease control rate outcomes compared to HAIC alone., Conclusion: HAIC proved more effective and safer than sorafenib and TACE. Furthermore, combined with other interventions, HAIC showed improved efficacy over HAIC monotherapy according to the treatment ranking analysis., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: The aim of the study was to explore the optimal timing of gonadotropin initiation and the reasonable interval of luteinizing hormone (LH) levels in the gonadotropin-releasing hormone antagonist (GnRH-A) protocol., Methods: A retrospective cohort study was conducted to analyze the data concerning the oocyte retrieval cycles from 1,361 cases with the GnRH-A protocol implemented. The ovarian responses (including AMH, AFC) in these patients were divided into the poor ovarian response group (an antral follicle count [AFC] ≤ 6, n = 394), the normal ovarian response group (an AFC > 6 and < 15, n = 570), and the high ovarian response group (an AFC ≥ 15, n = 397), according to the AFC. The patients were sub-grouped according to LH levels on the protocol initiation day, and the clinical outcomes (including dose of Gn initiation, Gn administration days, GnRH-ant administration days, P levels on the HCG day, E2 levels on the HCG day, LH levels on the HCG day, number of embryos transferred, total fertilization rate, embryo implantation rate(%), proportion of 2PN, proportion of good-quality embryos, endometrial thickness on the hCG injection day(mm), moderate to severe OHSS, AFC on the initiation day, proportion of type A endometrium on the hCG injection day, clinical pregnancy rate, biochemical pregnancy rate, early abortion rate, ectopic pregnancy rate) were compared., Results: On the GnRH-A protocol initiation day, among all patients with different ovarian responses, the body mass index (BMI) in those with an LH ≥ 5 IU/L was lower. The differences in pregnancy outcomes between the LH < 5 IU/L group and the LH ≥ 5 IU/L group were not statistically significant across the different ovarian response groups, but the LH < 5 IU/L group had a higher proportion of good-quality embryos (80.3±24.9 vs. 74.8±26.9, P =0.035) than the LH≥5IU/Lgroup in those with poor ovarian response. The total fertilization rate (82.2±18.1 vs 85.4±15.1, P =0.021) and proportion of two pronuclei (2PN) (69.0±20.9 vs 72.7±19.9, P =0.035) were higher in the LH ≥ 5 IU/L group than the LH<5 IU/L group for those with normal ovarian responses. The embryo implantation rate (41.4±41.3 vs 52.6±43.4, P =0.012) was higher in the LH ≥ 5 IU/L group than in the LH<5 IU/L group in those with high ovarian response. The results of the multivariate logistic analysis showed that the age of the female partner, number of embryos transferred, proportion of good-quality embryos, endometrial thickness on the hCG injection day, and moderate- to-severe ovarian hyperstimulation syndrome (OHSS) were independent factors correlated with the outcome of live births (P < 0.05)., Conclusion: The LH levels on the gonadotropins (Gn) initiation day in the GnRH-A protocol will not affect pregnancy outcomes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Chemokine ligand 14, which has a C-C motif (CCL14), mediates the immunological milieu around tumors. However, its role in the progression of lung adenocarcinoma (LUAD) is still unknown. Our objectives were to study the association between CCL14 and tumor-infiltrating immune cells (TIICs) as well as the predictive significance of CCL14 in LUAD., Methods: The expression of CCL14 in LUAD was examined by using the Oncomine, The Cancer Genome Atlas (TCGA), The University of Alabama at Birmingham CANcer data analysis Portal (UALCAN), and Human Protein Atlas databases. To determine the prognostic significance of CCL14 in LUAD, researchers used the Kaplan‒Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA, version 2). We utilized TIMER and GEPIA2 to investigate the connection between CCL14 and TIICs. Gene set enrichment analysis (GSEA) was used to test for functional enrichment of genes. We used RT‒qPCR to measure CCL14 expression and Cell Counting Kit-8, Transwell, and wound healing assays to investigate the biological role of CCL14., Results: The prognosis of patients with LUAD was worse when CCL14 expression was low. Statistical analysis revealed that CCL14 mRNA expression was significantly greater in lung epithelial cells than in LUAD cell lines in vitro. Enhancing CCL14 expression reduced cell migration, invasion, and proliferation. The results of the immune infiltration research showed that CCL14 and TIICs were positively correlated. Different immune infiltration patterns associated with CCL14 were also shown by TIIC markers. According to GSEA, histone deacetylases, G2/M checkpoints, and Notch signaling pathways were associated with low CCL14 expression., Conclusions: CCL14 is anticipated to emerge as a prognostic marker and therapeutic target for LUAD due to its role in regulating TIICs, suggesting that it may be an antioncogene., (© 2024. The Author(s).)

Unilateral Tracheobronchial foreign body (TFB) present a common clinical disease, whereas bilateral TFB is a rare and acute condition associated with high mortality rates. This case study discusses a pediatric patient hospitalized due to respiratory distress following accidental ingestion of peanut kernels. A plain chest CT scan revealed obstructive emphysema in the right main bronchus and a foreign body at the opening of the left main bronchus. Surgical removal of the bilateral TFB under extracorporeal circulation resulted in a successful postoperative recovery, leading to discharge on the 9th day. A comprehensive literature search was conducted across databases including PubMed, Web of Science, EMBASE, Cochrane Library, and CNKI, spanning publications from January 2014 to October 2023, utilizing keywords "bronchial foreign body" and "Peanut". After deduplication and relevance screening, 9 pertinent literature sources were included. The objective of this study is to enhance clinical practitioners' understanding of TFB management and improve diagnostic and treatment capabilities through analysis of age of onset, clinical manifestations, diagnosis, and treatment approaches in critically ill pediatric patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Xu, Liu, Zeng, Yan, Hu, Zhang, Guo, Guo and Zhang.)

Medical implants are constantly facing the risk of bacterial infections, especially infections caused by multidrug resistant bacteria. To mitigate this problem, gold nanoparticles with alkyl bromide moieties (Au NPs-Br) on the surfaces were prepared. Xenon light irradiation triggered the plasmon effect of Au NPs-Br to induce free radical graft polymerization of 2-(dimethylamino)ethyl methacrylate (DMAEMA), leading to the formation of poly(DMAEMA) brush-grafted Au NPs (Au NPs- g -PDM). The Au NPs- g -PDM nanocomposites were conjugated with phytic acid (PA) via electrostatic interaction and van der Waals interaction. The as-formed aggregates were deposited on the titanium (Ti) substrates to form the PA/Au NPs- g -PDM (PAP) hybrid coatings through surface adherence of PA and the gravitational effect. Synergistic bactericidal effects of contact-killing caused by the cationic PDM brushes, and local heating generated by the Au NPs under near-infrared irradiation, conferred strong antibacterial effects on the PAP-deposited Ti (Ti-PAP) substrates. The synergistic bactericidal effects reduced the threshold temperature required for the photothermal sterilization, which in turn minimized the secondary damage to the implant site. The Ti-PAP substrates exhibited 97.34% and 99.97% antibacterial and antiadhesive efficacy, respectively, against Staphylococcus aureus ( S. aureus ) and Escherichia coli ( E. coli ), compared to the control under in vitro antimicrobial assays. Furthermore, the as-constructed Ti-PAP surface exhibited a 99.42% reduction in the inoculated S. aureus under in vivo assays. In addition, the PAP coatings exhibited good biocompatibility in the hemolysis and cytotoxicity assays as well as in the subcutaneous implantation of rats.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, pathologically characterized by TDP-43 aggregates. Recent evidence has been indicated that phosphorylated TDP-43 (pTDP-43) is present not only in motor neurons but also in muscle tissues. However, it is unclear whether testing pTDP-43 aggregation in muscle tissue would assist in the diagnosis of ALS. We propose three key questions: (i) Is aggregation of pTDP-43 detectable in routine biopsied muscles? (ii) Can detection of pTDP-43 aggregation discriminate between ALS and non-ALS patients? (iii) Can pTDP-43 aggregation be observed in the early stages of ALS? We conducted a diagnostic study comprising 2 groups: an ALS group in which 18 cases underwent muscle biopsy screened from a registered ALS cohort consisting of 802 patients and a non-ALS control group, in which we randomly selected 54 muscle samples from a biospecimen bank of 684 patients. Among the 18 ALS patients, 3 patients carried pathological GGGGCC repeats in the C9ORF72 gene, 2 patients carried SOD1 mutations, and 7 patients were at an early stage with only one body region clinically affected. The pTDP-43 accumulation could be detected in routine biopsied muscles, including biceps brachii, deltoid, tibialis anterior, and quadriceps. Abnormal aggregation of pTDP-43 was present in 94.4% of ALS patients (17/18) compared to 29.6% of non-ALS controls (16/54; p < 0.001). The pTDP-43 aggregates were mainly close to the sarcolemma. Using a semi-quantified pTDP-43 aggregates score, we applied a cut-off value of 3 as a diagnostic biomarker, resulting in a sensitivity of 94.4% and a specificity of 83.3%. Moreover, we observed that accumulation of pTDP-43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions. Our study provides proof-of-concept for the detection of pTDP-43 accumulation via routine muscle biopsy which may serve as a novel biomarker for diagnosis of ALS., (© 2024 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.)

We conduct a comprehensive theoretical analysis of wurtzite Ga x In 1- x N ternary alloys, focusing on their structural, electronic, elastic, piezoelectric, and dielectric properties through rigorous first-principles calculations. Our investigation systematically explores the influence of varying Ga composition ( x = 0%, 25%, 50%, 75%, 100%) on the alloy properties. Remarkably, we observe a distinctive non-linear correlation between the band gap and Ga concentration, attributable to unique slopes in the absolute positions of the valence band maximum and conduction band minimum with respect to Ga concentration. Our effective band structure analysis reveals the meticulous preservation of Bloch characters near band extrema, minimizing charge carrier scattering. Furthermore, we scrutinize deviations from linear Vegard-like dependence in elastic, piezoelectric, and dielectric constants. Additionally, our calculations encompass various optical properties, including absorption coefficient, reflectivity, refractive index, energy loss function, and extinction coefficient. We analyze their trends with photon energy, providing valuable insights into the optical behavior of Ga x In 1- x N alloys. Our results, in excellent agreement with available experimental data, significantly contribute to a deeper understanding of the alloys' electronic properties. This study offers valuable insights that may illuminate potential applications of Ga x In 1- x N alloys in diverse technological fields., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objective: This research explored the relationship between a patient's nutritional state and inflammatory markers and the prognosis of their non-small cell lung cancer (NSCLC) treatment while receiving a combination of chemotherapy and immunotherapy., Method: This retrospective and single-center analysis included NSCLC patients who received a combination of chemotherapy and immunotherapy at the Department of Oncology at Shanghai Lung Hospital. Patients were categorized based on malnutrition, sarcopenia, sarcopenic obesity, and advanced-lung-cancer-inflammation-index (ALI) scores after collecting nutritional and inflammatory indices. Kaplan-Meier and the Cox models were utilized to analyze survival., Results: There was a significant correlation between malnutrition, sarcopenia, sarcopenic obesity, and low ALI scores with lower overall survival (OS) and progression-free survival (PFS) (p < 0.05). Low ALI score and malnutrition were independent factors influencing patient survival in terms of both OS and PFS (p < 0.01)., Conclusion: The nutritional and inflammatory indices of immunotherapy-treated NSCLC patients substantially affect their prognosis. Assessing these variables could aid in optimizing treatment strategies and improving patient outcomes. Additional research is required to comprehend the intricate relationship between nutrition, inflammation, and cancer progression and to develop individualized therapies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Background: Overexpression of solute carrier family 7 member 8 (SLC7A8) has been shown to relate to the survival time and tumor progression in cancer patients. However, the role of SLC7A8 in lung adenocarcinoma (LUAD) is still obscure., Method: The relationships between SLC7A8 expression in LUAD tissues and clinical values as well as immune infiltration were explored through bioinformatics. The functions and pathways of SLC7A8 in LUAD were investigated using Kyoto Encyclopedia of Genes and Genomes enrichment analysis, Gene Set Enrichment Analysis, Western blotting, and other methods., Results: We found that the expression of SLC7A8 was decreased significantly in LUAD tissues compared with normal tissues, which was related to the dismal survival time and disease progression. Moreover, it carried diagnostic value in LUAD and was a risk factor for dismal prognosis. Receiver operating characteristic curve analysis indicated that the expression level of SLC7A8 carried significant diagnostic value in LUAD. Overexpression of SLC7A8 inhibited the proliferation, invasion, and migration of LUAD cells, likely through a mechanism involving the cell cycle. SLC7A8 expression in LUAD was significantly correlated with the infiltration of immune cells, especially B cells, interstitial dendritic cells, mast cells, CD56 bright cells, natural killer cells, plasmacytoid dendritic cells, T follicular helper cells, T helper 2 and 17 cells, and immune factors., Conclusion: The downregulation of SLC7A8 was related to a dismal prognosis and immune cell infiltration in LUAD. Increasing the expression of SLC7A8 inhibited the growth and migration of LUAD cells, thereby improving the prognosis of patients.

Objective: The roles of MTFR1 in the drug resistance of lung adenocarcinoma (LAC) to cisplatin remain unexplored. In this study, the expression, clinical values and mechanisms of MTFR1 were explored, and the relationship between MTFR1 expression and immune microenvironment was investigated in LAC using bioinformatics analysis, cell experiments, and meta-analysis., Methods: MTFR1 expression and clinical values, and the relationship between MTFR1 expression and immunity were explored, through bioinformatics analysis. The effects of MTFR1 on the growth, migration and cisplatin sensitivity of LAC cells were identified using cell counting kit-8, wound healing and Transwell experiments. Additionally, the mechanisms of drug resistance of LAC cells involving MTFR1 were investigated using western blotting., Results: MTFR1 was elevated in LAC tissues. MTFR1 overexpression was associated with sex, age, primary therapy outcome, smoking, T stage, unfavourable prognosis and diagnostic value and considered an independent risk factor for an unfavourable prognosis in patients with LAC. MTFR1 co-expressed genes involved in the cell cycle, oocyte meiosis, DNA replication and others. Moreover, interfering with MTFR1 expression inhibited the proliferation, migration and invasion of A549 and A549/DDP cells and promoted cell sensitivity to cisplatin, which was related to the inhibition of p-AKT, p-P38 and p-ERK protein expression. MTFR1 overexpression was associated with stromal, immune and estimate scores along with natural killer cells, pDC, iDC and others in LAC., Conclusions: MTFR1 overexpression was related to the unfavourable prognosis, diagnostic value and immunity in LAC. MTFR1 also participated in cell growth and migration and promoted the drug resistance of LAC cells to cisplatin via the p-AKT and p-ERK/P38 signalling pathways.

We investigated root growth of 1-year-old Juglans mandshurica seedlings under different light environments and varying doses of phosphorus fertilizer, to understand the relationship between root resource acquisition strategies and the variations of light and phosphorus availability. There were four shading intensities (full light, 65% full light, 35% full light, and 20% full light) along with three doses of phosphate fertilizer (0 (CK), 200% soil background available phosphorus, and 500% soil background available phosphorus). We measured in root morphology characteristics, architectural characteristics, and mycorrhizal colonization rates of first-order roots. The results showed that average diameter, average root length, and mycorrhizal colonization rates of first-order roots gradually decreased, and the specific root length, specific surface area, branching ratio and branching intensity showed a trend of first increasing and then decreasing with the increases of shading degree. As the phosphorus content decreased, the first-order root diameter gradually became thinner, and the mycorrhizal infection rate gradually increased. Root morphology and architecture of J. mandshurica would undergo adaptive changes under shade, adapting to the shading environment by expanding specific root length, specific surface area, branching ratio and branching intensity. Under phosphorus limitation, root system of J. mandshurica would increase phosphorus absorption through symbiosis with mycorrhizal fungi. When J. mandshurica was artificially regenerate in forest land with a light transmittance of 35%, root morphology and architecture would adapt to the shading environment. The symbiosis between J. mandshurica and mycorrhizal fungi would be enhanced under phosphorus limitation, which could improve phosphorus absorption of roots.

Background: Cerebral venous sinus thrombosis (CVST) is typically associated with a prothrombotic state of the blood, with its causative factors varying widely. Prior research has not reported the simultaneous occurrence of CVST and dural arteriovenous fistulas (DAVFs) as potentially resulting from genetic mutations. In this case report, we introduce a unique occurrence wherein a patient with a heterozygous mutation of the low-density lipoprotein receptor (LDLR) gene presented with CVST in conjunction with DAVFs., Case: Presentation: A male patient, aged 51, sought treatment at our facility due to a consistent decline in cognitive functions accompanied by recurrent headaches. Comprehensive evaluations were administered, including neurological examinations, laboratory tests, magnetic resonance imaging, digital subtraction angiography, and whole exome sequencing. Digital subtraction angiography identified DAVFs in the patient's right sigmoid sinus and an occlusion within the left transverse sinus. The whole exome sequencing of blood samples pinpointed a heterozygous mutation in the LDLR gene (NM&#95;000527:exon12:c.C1747T:p.H583Y). Following the confirmed diagnosis of CVST and DAVFs, the patient underwent anticoagulant therapy combined with endovascular procedures - these comprised embolization of the arteriovenous fistula in the right sigmoid sinus and balloon dilation with stent implantation in the left transverse sinus. A six-month follow-up indicated a significant abatement in the patient's symptoms., Conclusions: This report marks the first documented case of an LDLR gene mutation that could be associated with the onset of CVST and DAVFs. The mutation in the LDLR gene might foster a prothrombotic environment, facilitating the gradual emergence of CVST and the subsequent genesis of DAVFs., (© 2023. The Author(s).)

Owing to the predominance of dopamine (DA) in controlling mental health, planning an innovative method for DA detection with simplicity and high efficacy is conducive to the assessment of neurological disorders. Herein, an efficient fluorogenic tactic has been elaborated for ultrasensitive detection of DA with remarkably enhanced turn-on response. Utilizing a twisted intramolecular charge-transfer (TICT)-suppressing strategy, a highly emissive azocine derivative 11-hydroxy-2,3,6,7,11,12,13,14-octahydro-1 H ,5 H ,10 H -11,14a-methanoazocino[5',4':4,5]furo[2,3- f ]pyrido[3,2,1- ij ]quinolin-10-one ( J-Aza ) is generated via a one-step reaction between DA and 8-hydroxyjulolidine. It is marvelous that J-Aza not only possesses ideal fluorescence quantum yield (Φ F ) as high as 0.956 but also exhibits bathochromic shifted fluorescence (green emissive) and stronger anti-photobleaching capacity superior to traditional azocine-derived 1,2,3,4-tetrahydro-5 H -4,11a-methanobenzofuro[2,3- d ]azocin-5-one ( Aza ) with moderate Φ F , blue fluorescence, and poor photostability. By confining the TICT process, the detection limit to DA can be reduced to 80 pM, which is competitive in contrast to previously reported fluorescence methods. Encouraged by the instant response (within 90 s), wide linear range (0.1-500 nM), great selectivity, and excellent sensitivity, this fluorogenic method has been used for the real-time measurement of DA contents in practical urine samples with satisfactory results. Furthermore, the cerebral DA level in the reserpine-induced depression rat model has also been evaluated by our designed method, demonstrating its potent analytical applicability in the biosensing field.

Background: Postoperative nursing can improve the restlessness and gastrointestinal function of patients with tracheal intubation under general anesthesia in digestive surgery. Wide application of various nursing methods and routine nursing in perioperative nursing of patients with general anesthesia in digestive surgery., Aim: To investigate the impact of early postoperative enteral nutrition nursing based on the enhanced recovery after surgery (ERAS) theory on postoperative agitation and gastrointestinal recovery in patients undergoing general anesthesia that experienced tracheal intubation., Methods: The data of 126 patients with digestive surgery from May 2019 to February 2022 were retrospectively analyzed. According to different nursing methods, they were divided into control group and observation group, with 63 cases in observation group and 63 cases in control group. The patients in the control group had standard perioperative nursing care, whereas those in the observation group got enteral nourishment as soon as possible after surgery in accordance with ERAS theory. Both the rate and quality of gastrointestinal function recovery were compared between the two groups after treatment ended. Postoperative anesthesia-related adverse events were tallied, patients' nutritional statuses were monitored, and the Riker sedation and agitation score (SAS) was used to measure the incidence of agitation., Results: When compared to the control group, the awake duration, spontaneous breathing recovery time, extubation time and postoperative eye-opening time were all considerably shorter ( P < 0.05). There was no significant difference in the recovery time of orientation force between the two groups ( P > 0.05); however, the observation group had a lower SAS score than the control group ( P < 0.05). The recovery time for normal intestinal sounds, the time it took to have the first postoperative exhaust, the time it took to have the first postoperative defecation, and the time it took to have the first postoperative half-fluid feeding were all faster in the observation group than in the control group ( P < 0.05); Fasting blood glucose was lower in the observation group compared to the control group ( P < 0.05), while the albumin and hemoglobin levels were higher on the first and third postoperative days; however, there was no statistically significant difference in the incidence of anesthesia-related adverse reactions between the two groups ( P > 0.05)., Conclusion: The extremely early postoperative enteral nutrition nursing based on ERAS theory can reduce the degree of agitation, improve the quality of recovery, promote the recovery of gastrointestinal function, and improve the nutritional status of patients in the recovery period after tracheal intubation under general anesthesia., Competing Interests: Conflict-of-interest statement: The author declares no competing interests., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: With the advent of the digital economy and the aging population, the demand for diversified health care services and innovative care delivery models has been overwhelming. This trend has accelerated the urgency to implement effective and efficient data exchange and service interoperability, which underpins coordinated care services among tiered health care institutions, improves the quality of oversight of regulators, and provides vast and comprehensive data collection to support clinical medicine and health economics research, thus improving the overall service quality and patient satisfaction. To meet this demand and facilitate the interoperability of IT systems of stakeholders, after years of preparation, Health Level 7 formally introduced, in 2014, the Fast Healthcare Interoperability Resources (FHIR) standard. It has since continued to evolve. FHIR depends on the Implementation Guide (IG) to ensure feasibility and consistency while developing an interoperable health care service. The IG defines rules with associated documentation on how FHIR resources are used to tackle a particular problem. However, a gap remains between IGs and the process of building actual services because IGs are rules without specifying concrete methods, procedures, or tools. Thus, stakeholders may feel it nontrivial to participate in the ecosystem, giving rise to the need for a more actionable practice guideline (PG) for promoting FHIR's fast adoption., Objective: This study aimed to propose a general FHIR PG to facilitate stakeholders in the health care ecosystem to understand FHIR and quickly develop interoperable health care services., Methods: We selected a collection of FHIR-related papers about the latest studies or use cases on designing and building FHIR-based interoperable health care services and tagged each use case as belonging to 1 of the 3 dominant innovation feature groups that are also associated with practice stages, that is, data standardization, data management, and data integration. Next, we reviewed each group's detailed process and key techniques to build respective care services and collate a complete FHIR PG. Finally, as an example, we arbitrarily selected a use case outside the scope of the reviewed papers and mapped it back to the FHIR PG to demonstrate the effectiveness and generalizability of the PG., Results: The FHIR PG includes 2 core elements: one is a practice design that defines the responsibilities of stakeholders and outlines the complete procedure from data to services, and the other is a development architecture for practice design, which lists the available tools for each practice step and provides direct and actionable recommendations., Conclusions: The FHIR PG can bridge the gap between IGs and the process of building actual services by proposing actionable methods, procedures, and tools. It assists stakeholders in identifying participants' roles, managing the scope of responsibilities, and developing relevant modules, thus helping promote FHIR-based interoperable health care services., (©Jingwen Nan, Li-Qun Xu. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 21.08.2023.)

Objective: Non-invasive methods for hemoglobin (Hb) monitoring can provide additional and relatively precise information between invasive measurements of Hb to help doctors' decision-making. We aimed to develop a new method for Hb monitoring based on mask R-CNN and MobileNetV3 with eye images as input., Methods: Surgical patients from our center were enrolled. After image acquisition and pre-processing, the eye images, the manually selected palpebral conjunctiva, and features extracted, respectively, from the two kinds of images were used as inputs. A combination of feature engineering and regression, solely MobileNetV3, and a combination of mask R-CNN and MobileNetV3 were applied for model development. The model's performance was evaluated using metrics such as R 2 , explained variance score (EVS), and mean absolute error (MAE)., Results: A total of 1,065 original images were analyzed. The model's performance based on the combination of mask R-CNN and MobileNetV3 using the eye images achieved an R 2 , EVS, and MAE of 0.503 (95% CI, 0.499-0.507), 0.518 (95% CI, 0.515-0.522) and 1.6 g/dL (95% CI, 1.6-1.6 g/dL), which was similar to that based on MobileNetV3 using the manually selected palpebral conjunctiva images (R 2 : 0.509, EVS:0.516, MAE:1.6 g/dL)., Conclusion: We developed a new and automatic method for Hb monitoring to help medical staffs' decision-making with high efficiency, especially in cases of disaster rescue, casualty transport, and so on., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hu, Li, Shu, Song, Liang, Sun, Wu, Li, Tan, Yang, Yang, Xu, Chen and Yi.)

Objective: To investigate the safety and efficacy of the two-channel dilatation procedure for subcutaneous tunneling in the lower abdomen during pelvic lymph node dissection for penile cancer., Methods: A retrospective analysis was conducted on the clinical data of 6 patients treated from January 2020 to December 2022 using the dual-channel expansion technique for penile cancer lymph node dissection., Results: All 6 cases ( 12 sides) successfully underwent prophylactic inguinal lymph node dissection. The average laparoscopic dissection time was ( 82.50 ± 12.08) minutes per side, with an average blood loss of （28.33 ± 10.95） ml. The number of lymph nodes dissected was （11.16 ± 1.02） for the superficial group and ( 0.67 ± 0.74 ) for the deep group. Postoperative pathology was negative in all cases. The average postoperative hospital stay was （7.33 ± 1.60 ） days, with a catheter removal time of （12.00 ± 2.06）days. Postoperative complications included abnormal skin sensations in 5 sides, lower limb edema in 3 sides, lymphedema in 3 sides, and cellulitis in 1 side. During a follow-up period of （20.60 ± 12.51）months, there were no instances of tumor recurrence or metastasis in the inguinal region among the patients., Conclusion: The dual-channel expansion technique for inguinal lymph node dissection via a subcutaneous tunnel is a safe and feasible treatment for penile cancer. It has a low complication rate, allows for thorough dissection of inguinal lymph nodes, and offers advantages in terms of surgical time.

Transcriptional adaptor 3 (TADA3/ADA3) is a conserved transcriptional co-activator and is dysregulated in many aggressive tumors. However, the role of TADA3 in non-small cell lung cancer (NSCLC) remains unknown. It was previously demonstrated that TADA3 expression correlates with poor prognosis in patients with NSCLC. In the present study, the expression and function of TADA3 were investigated in cells in vitro and in vivo. TADA3 expression was evaluated in clinical specimens and cell lines using reverse transcription-quantitative PCR and western blot analysis. The TADA3 protein level was significantly higher in human NSCLC specimens compared with matched normal tissues. In human NSCLC cell lines, short hairpin RNA-mediated silencing of TADA3 suppressed their proliferative, migratory and invasive abilities in vitro, and delayed G1 to S phase progression through the cell cycle. Consistent with this, TADA3 silencing increased expression of the epithelial marker E-cadherin and reduced expression of the mesenchymal markers, N-cadherin, Vimentin, Snail, and Slug. To verify the effect of TADA3 on tumor formation and growth in vivo, a mouse tumor xenograft model was established. TADA3 silencing slowed the growth of NSCLC tumor xenografts in nude mice, and excised tumors showed a similarly altered pattern of epithelial-mesenchymal transition (EMT) marker expression. The present results demonstrated the significance of TADA3 in regulating the growth and metastasis of NSCLC and may provide a theoretical basis for early diagnosis and targeted therapy of NSCLC.

Sequencing technology is the most commonly used technology in molecular biology research and an essential pillar for the development and applications of molecular biology. Since 1977, when the first generation of sequencing technology opened the door to interpreting the genetic code, sequencing technology has been developing for three generations. It has applications in all aspects of life and scientific research, such as disease diagnosis, drug target discovery, pathological research, species protection, and SARS-CoV-2 detection. However, the first- and second-generation sequencing technology relied on fluorescence detection systems and DNA polymerization enzyme systems, which increased the cost of sequencing technology and limited its scope of applications. The third-generation sequencing technology performs PCR-free and single-molecule sequencing, but it still depends on the fluorescence detection device. To break through these limitations, researchers have made arduous efforts to develop a new advanced portable sequencing technology represented by nanopore sequencing. Nanopore technology has the advantages of small size and convenient portability, independent of biochemical reagents, and direct reading using physical methods. This paper reviews the research and development process of nanopore sequencing technology (NST) from the laboratory to commercially viable tools; discusses the main types of nanopore sequencing technologies and their various applications in solving a wide range of real-world problems. In addition, the paper collates the analysis tools necessary for performing different processing tasks in nanopore sequencing. Finally, we highlight the challenges of NST and its future research and application directions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Sun, Wang, Liu, Bai, Chen, Liu, Qiao, Chen, Yuan, Sha, Zhang, Xu and Li.)

Objective: Despite the increasing number of genes associated with Charcot-Marie-Tooth (CMT) disease, many patients currently still lack appropriate genetic diagnosis for this disease. Autosomal dominant mutations in aminoacyl-tRNA synthetases (ARSs) have been implicated in CMT. Here, we describe causal missense mutations in the gene encoding seryl-tRNA synthetase 1 (SerRS) for 3 families affected with CMT., Methods: Whole-exome sequencing was performed in 16 patients and 14 unaffected members of 3 unrelated families. The functional impact of the genetic variants identified was investigated using bioinformatic prediction tools and confirmed using cellular and biochemical assays., Results: Combined linkage analysis for the 3 families revealed significant linkage (Zmax LOD = 6.9) between the genomic co-ordinates on chromosome 1: 108681600-110300504. Within the linkage region, heterozygous SerRS missense variants segregated with the clinical phenotype in the 3 families. The mutant SerRS proteins exhibited reduced aminoacylation activity and abnormal SerRS dimerization, which suggests the impairment of total protein synthesis and induction of eIF2α phosphorylation., Interpretation: Our findings suggest the heterozygous SerRS variants identified represent a novel cause for autosomal dominant CMT. Mutant SerRS proteins are known to impact various molecular and cellular functions. Our findings provide significant advances on the current understanding of the molecular mechanisms associated with ARS-related CMT. ANN NEUROL 2023;93:244-256., (© 2022 American Neurological Association.)

Introduction: Perioperative critical events will affect the quality of medical services and threaten the safety of patients. Using scientific methods to evaluate the perioperative risk of critical illness is of great significance for improving the quality of medical services and ensuring the safety of patients., Method: At present, the traditional scoring system is mainly used to predict the score of critical illness, which is mainly dependent on the judgment of doctors. The result is affected by doctors' knowledge and experience, and the accuracy is difficult to guarantee and has a serious lag. Besides, the statistical prediction method based on pure data type do not make use of the patient's diagnostic text information and cannot identify comprehensive risk factor. Therefore, this paper combines the text features extracted by deep neural network with the pure numerical type features extracted by XGBOOST to propose a deep neural decision gradient boosting model. Supervised learning was used to train the risk prediction model to analyze the occurrence of critical illness during the perioperative period for early warning., Results: We evaluated the proposed methods based on the real data of critical illness patients in one hospital from 2014 to 2018. The results showed that the critical disease risk prediction model based on multiple modes had faster convergence rate and better performance than the risk prediction model based on text data and pure data type., Discussion: Based on the machine learning method and multi-modal data of patients, this paper built a prediction model for critical adverse events in patients, so that the risk of critical events can be predicted for any patient directly based on the preoperative and intraoperative characteristic data. At present, this work only classifies and predicts the occurrence of critical illness during or after operation based on the preoperative examination data of patients, but does not discuss the specific time when the patient was critical illness, which is also the direction of our future work., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Xu and Yi.)

Background: Lungs were initially thought to be sterile. However, with the development of sequencing technologies, various commensal microorganisms, especially bacteria, have been observed in the lungs of healthy humans. Several studies have also linked lung microbes to infectious lung diseases. However, few databases have focused on the metagenomics of lungs to provide microbial compositions and corresponding metadata information. Such a database would be handy for researching and treating lung diseases., Methods: To provide researchers with a preliminary understanding of lung microbes and their research methods, the LDMD collated nearly 10,000 studies in the literature covering over 30 diseases, gathered basic information such as the sources of lung microbe samples, sequencing methods, and processing software, as well as analyzed the metagenomic sequencing characteristics of lung microbes. Besides, the LDMD also contained data collected in our laboratory., Results: In this study, we established the Lung Disease Microorganisms Database (LDMD), a comprehensive database of microbes involved in lung disease. The LDMD offered sequence analysis capabilities, allowing users to upload their sequencing results, align them with the data collated in the database, and visually analyze the results., Conclusion: In conclusion, the LDMD possesses various functionalities that provide a convenient and comprehensive resource to study the lung metagenome and treat lung diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xu, Yang, Liang, Chen, Sun, Zhang, Liu, Qiao and Li.)

Graphite anodes are well established for commercial use in lithium-ion battery systems. However, the limited capacity of graphite limits the further development of lithium-ion batteries. Hard carbon obtained from biomass is a highly promising anode material, with the advantage of enriched microcrystalline structure characteristics for better lithium storage. Tannin, a secondary product of metabolism during plant growth, has a rich source on earth. But the mechanism of hard carbon obtained from its derivation in lithium-ion batteries has been little studied. This paper successfully applied the hard carbon obtained from tannin as anode and illustrated the relationship between its structure and lithium storage performance. Meanwhile, to further enhance the performance, graphene oxide is skillfully compounded. The contact with the electrolyte and the charge transfer capability are effectively enhanced, then the capacity of PVP-HC is 255.5 mAh g -1 after 200 cycles at a current density of 400 mA g -1 , with a capacity retention rate of 91.25%. The present work lays the foundation and opens up ideas for the application of biomass-derived hard carbon in lithium anodes.

Introduction: There are few analyses of the 15 red blood group system antigen coding genes found in the Yunnan Yi nationality. This has caused many poteintial dangers relating to clinical blood transfusion. In this report, the coding genes and distribution of 15 blood group antigens system in the Yi nationality were tested and compared with those of Han nationality and other ethnic minorities., Methods: The samples came from the healthy subjects in the first people's Hospital of Qujing, Yunnan Province. Two hundred and three Yunnan Yi and 197 Han nationality individuals were included. Thirty-three blood group antigens with a low frequency from the 15 blood group systems of Yunnan Yi blood donors were genotyped and analyzed by PCR-SSP. Sanger sequencing was used to detect A4GALT from the Yunnan Yi nationality. The χ 2 test was used to analyze observed and expected values of gene distribution to verify conformation to the Hardy-Weinberg equilibrium law. Fisher's exact test was used to analyze gene frequency distribution, and the statistical significance was set at p  < 0.05., Results: The ABO blood group examination results for the Yi nationality and the local Han nationality in Qujing City, Yunnan Province, showed the majority were type A and type O, while the least prevalent was type AB. RhD+ accounts for more than 98% of the Yi and Han populations. There was a significant difference in ABO blood group antigen distribution between these two nationalities ( p  < 0.05), but there was no significant difference in the composition ratio of D antigen in the Rh blood group system ( p  > 0.05). Compared with Tibetan (Tibet), Zhuang (Nanning), and Dong (Guangxi), the gene distribution frequencies of Rh blood group system phenotype CC were significantly lower in the Yunnan Yi nationality ( p  < 0.05). There were significant differences in six erythrocyte phenotypic antigens in the Yi nationality in Yunnan compared with Han nationality, such as LW(a-b-), JK(a-b+), MMSs, Di(a-b+), Wr(a-b-), and Kp(a-b+) ( p  < 0.05). There were gene phenotypes with a low frequency in the four rare blood group systems: LW, MNS, Wright, and Colton. Several different mutation types occurred in the P1PK blood group system's A4GALT gene., Conclusion: Yunnan Yi nationality has a unique genetic background. There are some significantly different distributions of blood group system genes with a low frequency in different regions and groups in China. Multiple mutations in the A4GALT gene of the P1PK blood group system may be related to their environment and ethnic evolution., Competing Interests: The authors have no conflicts of interest to declare. All authors have read and approved the final version of the manuscript. They had full access to all of the data in this study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis. Kun‐hua He affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; No important aspects of the study have been omitted; Any discrepancies from the study as planned have been explained., (© 2022 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Solid-state nanopore sequencing has shown impressive performances in several research scenarios but is still challenging, mainly due to the ultrafast speed of DNA translocation and significant noises embedded in raw signals. Hence, event detection, aiming to locate precisely these translocation events, is the fundamental step of data analysis. However, existing event detection methods use either a user-defined global threshold or an adaptive threshold determined by the data, assuming the baseline current to be stable over time. These disadvantages limit their applications in real-world application scenarios, especially considering that the results of different methods are often inconsistent. In this study, we develop an automated adaptive method called AutoNanopore, for fast and accurate event detection in current traces. The method consists of three consecutive steps: current trace segmentation, current amplitude outlier identification by straightforward statistical analyses, and event characterization. Then we propose ideas/metrics on how to quantitatively evaluate the performance of an event detection method, followed by comparing the performance of AutoNanopore against two state-of-the-art methods, OpenNanopore and EventPro. Finally, we examine if one method can detect the overlapping events detected by the other two, demonstrating that AutoNanopore has the highest coverage ratio. Moreover, AutoNanopore also performs well in detecting challenging events: e.g., those with significantly varying baselines., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Objective: To explore the pathological characteristics of three mice models of temporomandibular joint degenerative joint disease (TMJDJD), including osteoarthritis and osteoarthrosis, and to provide references for animal experimental study regarding the pathological mechanism of osteoarthritis and osteoarthrosis. Methods: A total of 54 8-week-old male C57BL/6 mice were selected to construct three TMJDJD animal models, including bilateral temporomandibular joint (TMJ) Freund's complete adjuvant (FCA) injection model, bilateral TMJ monosodium iodoacetate (MIA) injection model, and right TMJ discectomy model. FCA injection model (15 mice) was divided into saline injection group, FCA injection group-1 week, FCA injection group-2 week, FCA injection group-4 week and FCA injection group-6 week, 3 mice were used at each time point, with a total of 6 TMJs on both sides. MIA injection model (15 mice) was separated into saline injection group, MIA injection group-1 week, MIA injection group-2 week, MIA injection group-4 week and MIA injection group-6 week, 3 mice were used at each time point, with a total of 6 TMJs on both sides. TMJ discectomy model (24 mice) was split into control group, discectomy group-2 week group, discectomy group-4 week and discectomy group-6 week, six mice were used at each time point, with a total of six right TMJs. General pictures of the bilateral joints area of mice were collected 1 day after drug injection, and stereoscopic images of condylar tissues were collected 4 weeks after microsurgery for discectomy. Mouse TMJ tissue sections from each time point were stained with HE and toluidine blue, respectively, synovial tissues were scored for synovial inflammation, and the percentage of proteoglycan in condylar cartilage was quantitatively analyzed. Results: One day after intra-articular FCA or MIA injection, the width of bilateral TMJ were significantly increased in FCA injection groups [(24.60±0.46) mm] compared with the saline injection group [(21.63±0.52) mm] ( t =4.25, P <0.013), the width of bilateral TMJ in MIA injection groups [(24.50±0.62) mm] were also significantly higher than that in saline injection group [(21.40±0.52) mm] ( t =3.82, P =0.019). The synovitis scores in FCA injection groups 1, 2, 4, 6 weeks after FCA injection were significantly higher than that of the saline injection group ( F =18.09, P <0.001), with the proteoglycan of condylar cartilage increased firstly and then decreased compared with the saline injection group ( F =21.59, P <0.001). Condylar cartilage proteoglycan loss in different degrees were observed 1, 2, 4 and 6 weeks after MIA injection ( F =13.59, P <0.001), and synovitis scores were increased at different degrees compared with saline injection group ( F =14.79, P <0.001). The morphology of condylar cartilage in discectomy groups mice were severely damaged, synovial tissues showed dense connective tissue lesions at 2, 4 and 6 weeks postoperatively, condylar cartilage tissues showed a time-dependent loss of proteoglycan compared with the control group ( F =40.62, P <0.001). Conclusions: Intra-articular FCA injection establishes a mouse model of TMJ osteoarthritis with severe synovial inflammation. Intra-articular MIA injection constructs a mouse model of typical TMJ osteoarthritis. Discectomy establishes a mouse TMJ osteoarthrosis model with severe condylar cartilage destruction.

High-performance lithium ion batteries (LIBs) juggling high reversible capacity, excellent rate capability and ultralong cycle stability are urgently needed for all electronic devices. Here we report employing a vesicle-like porous N-doped carbon material (abbr. N/C-900) as a highly active anode for LIBs to balance high capacity, high rate and long life. The N/C-900 material was fabricated by pyrolysis of a designed crystal MOF LCU-104, which exhibits a graceful two-fold interpenetrating structural feature of N-rich nanocages {Zn 6 (dttz) 4 } linked through an N-donor ligand bpp (H 3 dttz = 4,5-di(1 H -tetrazol-5-yl)-2 H -1,2,3-triazole, bpp = 1,3-bis(4-pyridyl)propane). The features of LCU-104 combine high N content (35.1%), interpenetration, and explosive characteristics, which endow the derived N/C material with optimized N-doping for tuning its chemical and electronic structure, a suitably thicker wall to enhance its stability, and a vesicle-like structure to improve its porosity. As an anode material for LIBs, N/C-900 delivers a highly reversible capacity of ca. 734 mA h g -1 at a large current density of 1 A g -1 until the 2000th cycle, revealing its ultralong cycle stability and excellent rate capability. The unique structure and preferential interaction between abundant pyridinic N active sites and Li atoms are responsible for the improved excellent lithium storage capacity and durability performances of the anode according to analysis of the results of computational modeling.

Esophageal cancer (ESCA) is one of the common malignant tumors. The roles and signaling mechanisms of spindle apparatus coiled-coil protein 1 (SPDL1) in ESCA progression have not been reported previously. Therefore, the expression levels and potential clinical roles of SPDL1 were investigated using data from multiple databases and tissue samples of 53 ESCA patients who underwent 18F-FDG positron emission tomography (PET)/computed tomography (CT) before therapy. The signaling mechanisms of SPDL1 involved in ESCA progression were investigated via bioinformatics analysis. The effects of SPDL1 on the growth and migration of ESCA cells were investigated using CCK-8, Edu, and transwell assays. SPDL1 was upregulated in ESCA tissues. Increased SPDL1 expression was associated with age, grade, drinking history, cancer stage, lymph node metastasis, TP53 mutation, and poor prognosis in patients with ESCA. SPDL1 overexpression was significantly correlated with SUVmax, SUVmean, and TLG of PET/CT. SPDL1 silencing inhibited cell proliferation, migration, and invasion. SPDL1 was significantly enriched in cell cycle, spliceosome, DNA replication, and other processes. The hub genes of a constructed protein-protein interaction network included CDK1, BUB1, CCNB1, BUB1B, CCNA2, CDC20, MAD2L1, AURKB, NDC80, and PLK1, which were related to SPDL1 expression. The findings of this study suggest that SPDL1 may serve as a biomarker of ESCA prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Guo, Yang, Zeng, Xu, Zhang, Liu, Guo and Zhang.)

Three new lanostane triterpenoids, designated as 6-hydroxyl schiglausin A ( 1 ), 29-hydroxyl schiglausin D ( 2 ), and 6-hydroxyl schiglausin G ( 3 ), were isolated from the ethanol extract of the stems of Schisandra viridis . Structural elucidation of all the compounds were performed by spectral methods such as 1D and 2D ( 1 H - 1 H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. The isolated compounds were tested in vitro for cytotoxic activities. As a result, compound 1 exhibited cytotoxic activities for all six tested human lung cancer cell lines with IC 50 values less than 10 μM.

Background: Amyotrophic lateral sclerosis (ALS) is an incurable and fatal neurodegenerative disease; most ALS patients die within 3 to 5 years after symptom onset, usually as a consequence of respiratory failure. In the present study, we aim to screen the survival-related pulmonary function parameters, and to explore the predictive value of peak expiratory flow (PEF) in disease severity and prognosis in patients with ALS., Methods: The discovery cohort included 202 ALS patients, and the demographic and clinical characteristics of eligible patients were collected and pulmonary function tests were performed using MS-PFT spirometer. In the validation cohort, 62 newly diagnosed ALS patients performed the pulmonary function test by MS-PFT spirometer and household peak flow meter (KOKA) simultaneously., Results: Among 12 pulmonary function parameters, FVC, FEV1, PEF, MEF75%, and MVV were identified to be independent predictive factors for survival. PEF was highly correlated with FVC (r = 0.797), MVV (r = 0.877), FEV1 (r = 0.847), and MEF75% (r = 0.963). Besides, the values of PEF were positively associated with disease severity (ALSFRS-R score, r s  = 0.539, P < 0.0001), and negatively associated with progression rate (ΔALSFRS-R, r s  = -0.316, P < 0.0001). Finally, we also confirmed that the values of KOKA-measured PEF were highly correlated with the ones measured using MS-PFT spirometer (r = 0.9644, p < 0.0001)., Conclusions: Our work emphasizes the critical role of PFTs in predicting prognosis of ALS patients. PEF is an easily available pulmonary function index, which is also a promising indicator in predicting disease severity and survival for ALS patients., (© 2022. The Author(s).)

Background: Chronic obstructive pulmonary disease (COPD) is a universal respiratory disease resulting from the complex interactions between genes and environmental conditions. The process of COPD is deteriorated by repeated episodes of exacerbations, which are the primary reason for COPD-related morbidity and mortality. Bacterial pathogens are commonly identified in patients' respiratory tracts both in the stable state and during acute exacerbations, with significant changes in the prevalence of airway bacteria occurring during acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Therefore, the changes in microbial composition and host inflammatory responses will be necessary to investigate the mechanistic link between the airway microbiome and chronic pulmonary inflammation in COPD patients., Methods: We performed metatranscriptomic and metagenomic sequencing on sputum samples for twelve AECOPD patients before treatment and for four of them stable COPD (stabilization of AECOPD patients after treatment). Sequencing reads were classified by Kraken2, and the host gene expression was analyzed by Hisat2 and HTseq. The correlation between genes was obtained by the Spearman correlation coefficient. Mann-Whitney U -test was applied to identify microbes that exhibit significantly different distribution in two groups., Results: At the phyla level, the top 5 dominant phyla were Firmicutes , Actinobacteria , Proteobacteria , Bacteroidetes , and Fusobacteria . The proportion of dominant gates in metagenomic data was similar in metatranscriptomic data. There were significant differences in the abundance of specific microorganisms at the class level between the two methods. No significant difference between AECOPD and stable COPD was found. However, the different expression levels of 5 host genes were significantly increased in stable COPD and were involved in immune response and inflammatory pathways, which were associated with macrophages., Conclusion: Our study may provide a clue to investigate the mechanism of COPD and potential biomarkers in clinical diagnosis and treatment., Competing Interests: YO and YN were employed by company Vision Medicals. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Zhang, Zhang, Ouyang, Sun, Liu, Qaio, Xu, Niu and Li.)

High-β&#95;{θe} (a ratio of the electron thermal pressure to the poloidal magnetic pressure) steady-state long-pulse plasmas with steep central electron temperature gradient are achieved in the Experimental Advanced Superconducting Tokamak. An intrinsic current is observed to be modulated by turbulence driven by the electron temperature gradient. This turbulent current is generated in the countercurrent direction and can reach a maximum ratio of 25% of the bootstrap current. Gyrokinetic simulations and experimental observations indicate that the turbulence is the electron temperature gradient mode (ETG). The dominant mechanism for the turbulent current generation is due to the divergence of ETG-driven residual flux of current. Good agreement has been found between experiments and theory for the critical value of the electron temperature gradient triggering ETG and for the level of the turbulent current. The maximum values of turbulent current and electron temperature gradient lead to the destabilization of an m/n=1/1 kink mode, which by counteraction reduces the turbulence level (m and n are the poloidal and toroidal mode number, respectively). These observations suggest that the self-regulation system including turbulence, turbulent current, and kink mode is a contributing mechanism for sustaining the steady-state long-pulse high-β&#95;{θe} regime.

Importance: A rapid nutritional transition has caused greater childhood obesity prevalence in many countries, but the repertoire of effective preventive interventions remains limited., Objective: To determine the effectiveness of a novel multifaceted intervention for obesity prevention in primary school children., Design, Setting, and Participants: A cluster randomized clinical trial was conducted during a single school year (from September 11, 2018, to June 30, 2019) across 3 socioeconomically distinct regions in China according to a prespecified trial protocol. Twenty-four schools were randomly allocated (1:1) to the intervention or the control group, with 1392 eligible children aged 8 to 10 years participating. Data from the intent-to-treat population were analyzed from October 1 to December 31, 2019., Interventions: A multifaceted intervention targeted both children (promoting healthy diet and physical activity) and their environment (engaging schools and families to support children's behavioral changes). The intervention was novel in its strengthening of family involvement with the assistance of a smartphone app. The control schools engaged in their usual practices., Main Outcomes and Measures: The primary outcome was the change in body mass index (BMI; calculated as weight in kilograms divided by height in square meters) from baseline to the end of the trial. Secondary outcomes included changes in adiposity outcomes (eg, BMI z score, prevalence of obesity), blood pressure, physical activity and dietary behaviors, obesity-related knowledge, and physical fitness. Generalized linear mixed models were used in the analyses., Results: Among the 1392 participants (mean [SD] age, 9.6 [0.4] years; 717 boys [51.5%]; mean [SD] BMI, 18.6 [3.7]), 1362 (97.8%) with follow-up data were included in the analyses. From baseline to the end of the trial, the mean BMI decreased in the intervention group, whereas it increased in the control group; the mean between-group difference in BMI change was -0.46 (95% CI, -0.67 to -0.25; P < .001), which showed no evidence of difference across different regions, sexes, maternal education levels, and primary caregivers (parents vs nonparents). The prevalence of obesity decreased by 27.0% of the baseline figure (a relative decrease) in the intervention group, compared with 5.6% in the control group. The intervention also improved other adiposity outcomes, dietary, sedentary, and physical activity behaviors, and obesity-related knowledge, but it did not change moderate- to vigorous-intensity physical activity, physical fitness, or blood pressure. No adverse events were observed during the intervention., Conclusions and Relevance: The multifaceted intervention effectively reduced the mean BMI and obesity prevalence in primary school children across socioeconomically distinct regions in China, suggesting its potential for national scaling., Trial Registration: ClinicalTrials.gov Identifier: NCT03665857.

Background: Breast cancer is the most common cause of cancer-related death among women, and prognosis is especially poor for patients with triple-negative breast cancer (TNBC); therefore, there is an urgent need for new effective therapies. Recent studies have demonstrated that the uracil auxotroph Toxoplasma gondii vaccine displays anti-tumor effects. Here, we examined the immunotherapy effects of an attenuated uracil auxotroph strain of T. gondii against 4T1 murine breast cancer., Methods: We constructed a uracil auxotroph T. gondii RH strain via orotidine 5'-monophosphate decarboxylase gene deletion (RH-Δompdc) with CRISPR/Cas9 technology. The strain's virulence in the T. gondii-infected mice was determined in vitro and in vivo by parasite replication assay, plaque assay, parasite burden detection in mice peritoneal fluids and survival analysis. The immunomodulation ability of the strain was evaluated by cytokine detection. Its anti-tumor effect was evaluated after its in situ inoculation into 4T1 tumors in a mouse model; the tumor volume was measured, and the 4T1 lung metastasis was detected by hematoxylin and eosin and Ki67 antibody staining, and the cytokine levels were measured by an enzyme-linked immunosorbent assay., Results: The RH-Δompdc strain proliferated normally when supplemented with uracil, but it was unable to propagate without the addition of uracil and in vivo, which suggested that it was avirulent to the hosts. This mutant showed vaccine characteristics that could induce intense immune responses both in vitro and in vivo by significantly boosting the expression of inflammatory cytokines. Inoculation of RH-Δompdc in situ into the 4T1 tumor inhibited tumor growth, reduced lung metastasis, promoted the survival of the tumor-bearing mice and increased the secretion of Th1 cytokines, including interleukin-12 (IL-12) and interferon-γ (INF-δ), in both the serum and tumor microenvironment (TME)., Conclusion: Inoculation of the uracil auxotroph RH-Δompdc directly into the 4T1 tumor stimulated anti-infection and anti-tumor immunity in mice, and resulted in inhibition of tumor growth and metastasis, promotion of the survival of the tumor-bearing mice and increased secretion of IL-12 and IFN-γ in both the serum and TME. Our findings suggest that the immunomodulation caused by RH-Δompdc could be a potential anti-tumor strategy., (© 2021. The Author(s).)

Infection associated with multidrug-resistant (MDR) bacteria has become a serious threat to public health, and there is an urgent demand of developing new antibiotics that offer combinatorial therapy to effectively combat MDR. Herein, a multifunctional two-dimensional nanoantibiotic was facilely designed and established on the basis of the covalent conjugation of CO-releasing molecule (CORM-401) and electrostatic adsorption of hyaluronic acid (HA) onto single-layered graphene quantum dots (SGQDs) to assemble SGQDs-CORM@HA nanosheets, abbreviated as SCH. Upon the enrichment of as-prepared nanoantibiotics in the community of targeted microbe, bacterial-secreted hyaluronidase (HAase) would cleave HA on SCH, and the sharp edges as well as the reactive sites on SGQDs-CORM nanosheets were exposed for cascade activation of synergistic antibacterial effects. Specifically, ultrathin SGQDs-CORM nanosheets can penetrate into bacterial cells deemed as the unique "nanoknife" effect. Under white light irradiation, SGQDs-CORM nanosheets can act as a high-efficient photosensitizer to generate cytotoxic singlet oxygen ( 1 O 2 ), as a well-recognized reactive oxygen species (ROS), to produce high oxidative stress and damage bacteria. As a complementary to photodynamic therapy (PDT), the accumulation of local ROS further triggered the release of CO to hinder the bacterial growth via causing plasma membrane damage and inducing metabolic disorders. Such synergistic treatment regimen arising from cascade-activated "nanoknife" effect and photodynamic/CO gas therapy, was devoted to outstanding on-demand antibacterial performance both in vitro and in vivo. Fascinatingly, the nanoplatform showed good biocompatibility toward both normal somatic cells and non-targeted bacteria. The remarkable antibacterial capability and admirable biocompatibility endow SCH with great potential to fight against MDR pathogens for in-coming clinical translations., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: It remains under subject of debate regarding the optimal route of luteal support for hormone replacement therapy- frozen embryo transfer (HRT-FET) cycles. We compared efficacy of vaginal progesterone gel combined with oral dydrogesterone and intramuscular progesterone for HRT-FET lutein support., Methods: This is a retrospective observational study. After matching for propensity score of getting vaginal + oral treatment, a total of 208 FET cycles in the vaginal progesterone combined with oral dydrogesterone and 624 cycles in the intramuscular progesterone group were enrolled. Pregnancy outcomes and neonatal outcomes including chemical pregnancy rate, clinical pregnancy rate, implantation rate, spontaneous abortion rate, live birth rate, gestational weeks, pre-term delivery, birth weight, and congenital anomalies rate were compared., Results: No significant differences were observed in patient characteristics such as age, duration of infertility, type of infertility, or hormone level after matching. Chemical pregnancy rate (68.3 % versus 70.5 %), clinical pregnancy rate (64.9 % versus 64.4 %), implantation rate (52.3 % versus 50.2 %), spontaneous abortion rate (21.5 % versus 18.4 %), and live birth rate (49.0 % versus 51.3 %) were similar in both group without statistically significant difference. No significant differences in neonatal outcomes were observed between the two groups., Conclusion: We observed similar pregnancy outcomes in both vaginal progesterone gel combined with oral dydrogesterone and intramuscular progesterone protocol. Vaginal progesterone gel combined with oral dydrogesterone can be substituted for intramuscular progesterone given that vaginal plus oral use has good safety and is more convenient and may be associated with less side effect caused by intramuscular injection., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

With the rapid development and advancement in orthodontic and orthopedic technologies, the demand for biomedical-grade titanium (Ti) alloys is growing. The Ti-based implants are susceptible to bacterial infections, leading to poor healing and osteointegration, resulting in implant failure or repeated surgical intervention. Silk sericin (SS) is hydrophilic, biocompatible, and biodegradable and could induce a low immunological response in vivo . As a result, it would be intriguing to investigate the use of hydrophilic SS in surface modification. In this work, the tyrosine moiety in SS was oxidized by tyrosinase (or polyphenol oxidase) to the 3,4-dihydroxyphenylalanine (DOPA) form, generating the catechol moiety-containing SS (SSC). Inspired by the adhesion of mussel foot proteins, the SSC coatings could be directly deposited onto multiple surfaces in SS and tyrosinase mixed stock solutions to create active surfaces with catechol groups. Further, the SSC-coated Ti surfaces were hybridized with silver nanoparticles (Ag NPs) via in situ silver ion (Ag + ) reduction. The antibacterial properties of the Ag NPs/SS-coated Ti surfaces are demonstrated, and they can prevent bacterial cell adhesion as well as early-stage biofilm formation. In addition, the developed Ag NPs/SSC-coated Ti surfaces exhibited a negligible level of cytotoxicity in L929 mouse fibroblast cells.

Objective: To understand the characteristics of the HIV-1 molecular networks in injected drug users (IDUs) in Guangzhou from 2008 to 2017, and provide reference for the prevention and control of AIDS in this population. Methods: The serum samples of newly diagnosed HIV-1 positive IDUs in Guangzhou from 2008 to 2017 were collected, HIV-1 RNA was extracted for pol gene amplification and sequencing. The molecular cluster in the phylogenetic tree was identified by Cluster Picker 1.2.3 for cluster analysis. TN93 model in HyPhy2.2.4 was used to calculate the gene distance between the cluster sequences. Software Cytoscape3.8.2 was used to visualize the molecular network, and χ 2 test or exact probability method was used for cluster analysis and centrality analysis. Results: A total of 586 sequences were successfully amplified (73.9%, 586/793), and 80 molecular clusters were produced, with a clustering rate of 46.6% (273/586). In molecular clusters, the proportions of the strains from IDUs in Han ethnic group (48.4%, 260/537), IDUs who were local residents in Guangdong (52.7%, 146/277) and IDUs whose strain sequence subtype was CRF55&#95;01B (93.3%, 14/15) were higher. In the molecular network, the degree range was 1-7, and nodes with degree ≥3 accounted for 12.8% (24/187), which was associated with another 81 nodes in the molecular network (43.3%, 81/187). The centrality analysis showed that the proportions of housework/unemployed with high degree centrality (19.0%, 19/100), high intermediary (22.0%, 22/100), and high proximity centrality (32.0%, 32/100) were higher in IDUs infected with HIV-1. Conclusion: The risk of HIV-1 clustering in IDUs in Guangzhou was high, suggesting that IDUs who were from both Guangdong and Guangxi and were house workers or unemployed should be viewed as the key targets, and precise intervention should be implemented to reduce the HIV-1 infection rate in this population.

Little is known about the transcriptomic plasticity and adaptive mechanisms of circulating tumor cells (CTCs) during hematogeneous dissemination. Here we interrogate the transcriptome of 113 single CTCs from 4 different vascular sites, including hepatic vein (HV), peripheral artery (PA), peripheral vein (PV) and portal vein (PoV) using single-cell full-length RNA sequencing in hepatocellular carcinoma (HCC) patients. We reveal that the transcriptional dynamics of CTCs were associated with stress response, cell cycle and immune-evasion signaling during hematogeneous transportation. Besides, we identify chemokine CCL5 as an important mediator for CTC immune evasion. Mechanistically, overexpression of CCL5 in CTCs is transcriptionally regulated by p38-MAX signaling, which recruites regulatory T cells (Tregs) to facilitate immune escape and metastatic seeding of CTCs. Collectively, our results reveal a previously unappreciated spatial heterogeneity and an immune-escape mechanism of CTC, which may aid in designing new anti-metastasis therapeutic strategies in HCC.

Background: Managing noncommunicable diseases through primary healthcare has been identified as the key strategy to achieve universal health coverage but is challenging in most low- and middle-income countries. Stroke is the leading cause of death and disability in rural China. This study aims to determine whether a primary care-based integrated mobile health intervention (SINEMA intervention) could improve stroke management in rural China., Methods and Findings: Based on extensive barrier analyses, contextual research, and feasibility studies, we conducted a community-based, two-arm cluster-randomized controlled trial with blinded outcome assessment in Hebei Province, rural Northern China including 1,299 stroke patients (mean age: 65.7 [SD:8.2], 42.6% females, 71.2% received education below primary school) recruited from 50 villages between June 23 and July 21, 2017. Villages were randomly assigned (1:1) to either the intervention or control arm (usual care). In the intervention arm, village doctors who were government-sponsored primary healthcare providers received training, conducted monthly follow-up visits supported by an Android-based mobile application, and received performance-based payments. Participants received monthly doctor visits and automatically dispatched daily voice messages. The primary outcome was the 12-month change in systolic blood pressure (BP). Secondary outcomes were predefined, including diastolic BP, health-related quality of life, physical activity level, self-reported medication adherence (antiplatelet, statin, and antihypertensive), and performance in "timed up and go" test. Analyses were conducted in the intention-to-treat framework at the individual level with clusters and stratified design accounted for by following the prepublished statistical analysis plan. All villages completed the 12-month follow-up, and 611 (intervention) and 615 (control) patients were successfully followed (3.4% lost to follow-up among survivors). The program was implemented with high fidelity, and the annual program delivery cost per capita was US$24.3. There was a significant reduction in systolic BP in the intervention as compared with the control group with an adjusted mean difference: -2.8 mm Hg (95% CI -4.8, -0.9; p = 0.005). The intervention was significantly associated with improvements in 6 out of 7 secondary outcomes in diastolic BP reduction (p < 0.001), health-related quality of life (p = 0.008), physical activity level (p < 0.001), adherence in statin (p = 0.003) and antihypertensive medicines (p = 0.039), and performance in "timed up and go" test (p = 0.022). We observed reductions in all exploratory outcomes, including stroke recurrence (4.4% versus 9.3%; risk ratio [RR] = 0.46, 95% CI 0.32, 0.66; risk difference [RD] = 4.9 percentage points [pp]), hospitalization (4.4% versus 9.3%; RR = 0.45, 95% CI 0.32, 0.62; RD = 4.9 pp), disability (20.9% versus 30.2%; RR = 0.65, 95% CI 0.53, 0.79; RD = 9.3 pp), and death (1.8% versus 3.1%; RR = 0.52, 95% CI 0.28, 0.96; RD = 1.3 pp). Limitations include the relatively short study duration of only 1 year and the generalizability of our findings beyond the study setting., Conclusions: In this study, a primary care-based mobile health intervention integrating provider-centered and patient-facing technology was effective in reducing BP and improving stroke secondary prevention in a resource-limited rural setting in China., Trial Registration: ClinicalTrials.gov NCT03185858., Competing Interests: The authors have declared that no competing interests exist.

Titanium (Ti) and its alloys are primarily explored to produce biomedical implants owing to their improved mechanical stability, corrosion resistance, low density, and good biocompatibility. Despite, Ti substrate surfaces are easily contaminated by plasma proteins and bacteria. Herein, a simple one-step process for the simultaneous deposition of a polyphenol tannic acid (TA) and four-armed poly(ethylene glycol) (PEG 10k -4-OH) on the Ti substrate (Ti-TA/PEG) surface was described. Additionally, a two-step process has been employed to fabricate the Ti-TA-PEG surface via successive deposition of TA and PEG 10k -4-OH for comparison. The resultant Ti-TA/PEG surface prepared by simultaneous deposition of TA and PEG 10k -4-OH exhibits higher coating thickness and better surface coverage than the Ti-TA-PEG surface. The Ti-TA/PEG and Ti-TA-PEG surfaces could actively inhibit the non-specific adsorption of proteins, suppress the bacterial and platelet adhesion, and prevents biofilm formation. Moreover, the Ti-TA/PEG surface displays a better antifouling performance than the Ti-TA-PEG surface. Thus, the present study demonstrates a simple and convenient approach for constructing polymeric coating with good anti-adhesive properties on the Ti substrate surface., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The prevalence of human brucellosis in Qinghai Province of China has been increasing rapidly, with confirmed cases distributed across 31 counties. However, the epidemiology of brucellosis transmission has not been fully elucidated. To characterize the infecting strains isolated from humans, multiple-locus variable-number tandem repeats analysis (MLVA) and whole-genome single-nucleotide polymorphism (SNP)-based approaches were employed., Methods: Strains were isolated from two males blood cultures that were confirmed Brucella melitensis positive following biotyping and MLVA. Genomic DNA was extracted from these two strains, and whole-genome sequencing was performed. Next, SNP-based phylogenetic analysis was performed to compare the two strains to 94 B. melitensis strains (complete genome and draft genome) retrieved from online databases., Results: The two Brucella isolates were identified as B. melitensis biovar 3 (QH2019001 and QH2019005) following conventional biotyping and were found to have differences in their variable number tandem repeats (VNTRs) using MLVA-16. Phylogenetic examination assigned the 96 strains to five genotype groups, with QH2019001 and QH2019005 assigned to the same group, but different subgroups. Moreover, the QH2019005 strain was assigned to a new subgenotype, IIj, within genotype II. These findings were then combined to determine the geographic origin of the two Brucella strains., Conclusions: Utilizing a whole-genome SNP-based approach enabled differences between the two B. melitensis strains to be more clearly resolved, and facilitated the elucidation of their different evolutionary histories. This approach also revealed that QH2019005 is a member of a new subgenotype (IIj) with an ancient origin in the eastern Mediterranean Sea.