Bismuth-Containing Quadruple Therapy for Helicobacter pylori Eradication: A Randomized Clinical Trial of 10 and 14 Days.

BACKGROUND: Bismuth-containing quadruple therapy is the first-line treatment for eradicating Helicobacter pylori (H. pylori). The optimal duration for H. pylori eradication using bismuth-containing quadruple therapy remains controversial. Therefore, we aimed to compare the clinical effects of the 10- and 14-day bismuth-containing quadruple treatment regimen to eradicate H. pylori. METHODS: Treatment-naïve patients with H. pylori infection (n = 1300) were enrolled in this multicenter randomized controlled study across five hospitals in China. They were randomized into 10- or 14-day treatment groups to receive bismuth-containing quadruple therapy as follows: vonoprazan 20 mg twice daily; bismuth 220 mg twice daily; amoxicillin 1000 mg twice daily; and either clarithromycin 500 mg twice daily or tetracycline 500 mg four times daily. At least 6 weeks after treatment, we performed a 13C-urea breath test to evaluate H. pylori eradication. RESULTS: The per-protocol eradication rates were 93.22% (564/605) and 93.74% (569/607) (p < 0.001) and the intention-to-treat eradication rates were 88.62% (576/650) and 89.38% (581/650) (p = 0.007) for the 10- and 14-day regimens, respectively. Incidence of adverse effects was lower in patients who received 10- vs. 14 days of treatment (22.59% vs. 28.50%, p = 0.016). We observed no significant differences in the compliance to treatment or the discontinuation of therapy because of severe adverse effects between the groups. CONCLUSION: Compared with the 14-day bismuth-containing quadruple regimens, the 10-day regimen demonstrated a non-inferior efficacy and lower incidence of adverse effects. Therefore, the 10-day regimen is safe and tolerated and could be recommended for H. pylori eradication (NCT05049902).

Preliminary efficacy and safety of YSCH-01 in patients with advanced solid tumors: an investigator-initiated trial.

OBJECTIVE: To evaluate the safety and preliminary efficacy of YSCH-01 (Recombinant L-IFN adenovirus) in subjects with advanced solid tumors. METHODS: In this single-center, open-label, investigator-initiated trial of YSCH-01, 14 patients with advanced solid tumors were enrolled. The study consisted of two distinct phases: (1) the dose escalation phase and (2) the dose expansion phase; with three dose groups in the dose escalation phase based on dose levels (5.0×109 viral particles (VP)/subject, 5.0×1010 VP/subject, and 5.0×1011 VP/subject). Subjects were administered YSCH-01 injection via intratumoral injections. The safety was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events V.5.0, and the efficacy evaluation was performed using Response Evaluation Criteria in Solid Tumor V.1.1. RESULTS: 14 subjects were enrolled in the study, including 9 subjects in the dose escalation phase and 5 subjects in the dose expansion phase. Of the 13 subjects included in the full analysis set, 4 (30.8%) were men and 9 (69.2%) were women. The most common tumor type was lung cancer (38.5%, 5 subjects), followed by breast cancer (23.1%, 3 subjects) and melanoma (23.1%, 3 subjects). During the dose escalation phase, no subject experienced dose-limiting toxicities. The content of recombinant L-IFN adenovirus genome and recombinant L-IFN protein in blood showed no trend of significant intergroup changes. No significant change was observed in interleukin-6 and interferon-gamma. For 11 subjects evaluated for efficacy, the overall response rate with its 95% CI was 27.3% (6.02% to 60.97%) and the disease control rate with its 95% CI was 81.8% (48.22% to 97.72%). The median progression-free survival was 4.97 months, and the median overall survival was 8.62 months. In addition, a tendency of decrease in the sum of the diameters of target lesions was observed. For 13 subjects evaluated for safety, the overall incidence of adverse events (AEs) was 92.3%, the overall incidence of adverse drug reactions (ADRs) was 84.6%, and the overall incidence of >Grade 3 AEs was 7.7%, while no AEs/ADRs leading to death occurred. The most common AEs were fever (69.2%), nausea (30.8%), vomiting (30.8%), and hypophagia (23.1%). CONCLUSIONS: The study shows that YSCH-01 injections were safe and well tolerated and exhibited preliminary efficacy in patients with advanced solid tumors, supporting further investigation to evaluate its efficacy and safety. TRIAL REGISTRATION NUMBER: NCT05180851.

Enhancing Structural Rigidity of Ultrahigh-Ni Oxide Through Al and Nb Dual-Bulk-Doping for High-Voltage Lithium-Ion Batteries.

The pursuit of high energy densities propels the design of next-generation nickel-based layered oxide cathodes. The utilization of low-cobalt, ultrahigh-nickel layered oxide cathodes, and the extension of operating voltages promise enhanced energy density. However, stability and safety face challenges associated with nickel content, including structural degradation, lattice oxygen evolution, and thermal instability. In this study, a promising strategy of Al and Nb dual-bulk-doping is presented in high-Ni cathode materials of LiNi0.96Co0.04O2 (NC) to stabilize the bulk structure, suppress oxygen release, and attain superior electrochemical performance at high voltages. The introduction of Al and Nb effectively raises the migration energy of Ni2+ into Li sites and stabilizes lattice oxygen through strengthened Al─O and Nb─O bonds. Furthermore, the substitution of high-valence Nb ions reduces the charge depletion of lattice oxygen and induces an ordered microstructure. The Al and Nb dual-bulk-doping strategy mitigates strain and stress associated with the H2↔H3 phase transition, reducing the generation and propagation of microcracks. The resulting Li(Ni0.96Co0.04)0.985Al0.01Nb0.005O2 (NCAN) cathode exhibits superior cycling stability, with a capacity retention of 77.8% after 300 cycles, even when operating at a high-voltage of 4.4 V, outperforming the NC (48.5%). This work provides a promising perspective for developing high-voltage and high-Ni cathode materials.

A distributed data processing scheme based on Hadoop for synchrotron radiation experiments.

With the development of synchrotron radiation sources and high-frame-rate detectors, the amount of experimental data collected at synchrotron radiation beamlines has increased exponentially. As a result, data processing for synchrotron radiation experiments has entered the era of big data. It is becoming increasingly important for beamlines to have the capability to process large-scale data in parallel to keep up with the rapid growth of data. Currently, there is no set of data processing solutions based on the big data technology framework for beamlines. Apache Hadoop is a widely used distributed system architecture for solving the problem of massive data storage and computation. This paper presents a set of distributed data processing schemes for beamlines with experimental data using Hadoop. The Hadoop Distributed File System is utilized as the distributed file storage system, and Hadoop YARN serves as the resource scheduler for the distributed computing cluster. A distributed data processing pipeline that can carry out massively parallel computation is designed and developed using Hadoop Spark. The entire data processing platform adopts a distributed microservice architecture, which makes the system easy to expand, reduces module coupling and improves reliability.

Analysis of the expression level and predictive value of CLEC16A|miR-654-5p|RARA regulatory axis in the peripheral blood of patients with ischemic stroke based on biosignature analysis.

Introduction: Ischemic stroke (IS) is a cerebrovascular disease that can be disabling and fatal, and there are limitations in the clinical treatment and prognosis of IS. It has been reported that changes in the expression profile of circRNAs have been found during injury in ischemic stroke, and circRNAs play an important role in the IS cascade response. However, the specific mechanisms involved in the pathogenesis of IS are not yet fully understood, and thus in-depth studies are needed. Methods: In this study, one circRNA dataset (GSE161913), one miRNA dataset (GSE60319) and one mRNA dataset (GSE180470) were retrieved from the Gene Expression Omnibus (GEO) database and included, and the datasets were differentially expressed analyzed by GEO2R and easyGEO to get the DEcircRNA, DEmiRNA and DEmRNA, and DEmRNA was enriched using ImageGP, binding sites were predicted in the ENCORI database, respectively, and the competitive endogenous RNA (ceRNA) regulatory network was visualized by the cytoscape software, and then selected by MCC scoring in the cytoHubba plugin Hub genes. In addition, this study conducted a case-control study in which blood samples were collected from stroke patients and healthy medical examiners to validate the core network of ceRNAs constructed by biosignature analysis by real-time fluorescence quantitative qRT-PCR experiments. Results: A total of 233 DEcircRNAs, 132 DEmiRNAs and 72 DEmRNAs were screened by bioinformatics analysis. circRNA-mediated ceRNA regulatory network was constructed, including 148 circRNAs, 43 miRNAs and 44 mRNAs. Finally, CLEC16A|miR-654-5p|RARA competitive endogenous regulatory axis was selected for validation by qRT-PCR, and the validation results were consistent with the bioinformatics analysis. Discussion: In conclusion, the present study establishes a new axis of regulation associated with IS, providing new insights into the pathogenesis of IS.

SGLT2-independent effects of canagliflozin on NHE3 and mitochondrial complex I activity inhibit proximal tubule fluid transport and albumin uptake.

Beyond glycemic control, SGLT2 inhibitors (SGLT2i) have protective effects on cardiorenal function. Renoprotection has been suggested to involve inhibition of NHE3 leading to reduced ATP-dependent tubular workload and mitochondrial oxygen consumption. NHE3 activity is also important for regulation of endosomal pH, but the effects of SGLT2i on endocytosis are unknown. We used a highly differentiated cell culture model of proximal tubule (PT) cells to determine the direct effects of SGLT2i on Na+-dependent fluid transport and endocytic uptake in this nephron segment. Strikingly, canagliflozin but not empagliflozin reduced fluid transport across cell monolayers, and dramatically inhibited endocytic uptake of albumin. These effects were independent of glucose and occurred at clinically relevant concentrations of drug. Canagliflozin acutely inhibited surface NHE3 activity, consistent with a direct effect, but did not affect endosomal pH or NHE3 phosphorylation. Additionally, canagliflozin rapidly and selectively inhibited mitochondrial complex I activity. Inhibition of mitochondrial complex I by metformin recapitulated the effects of canagliflozin on endocytosis and fluid transport, whereas modulation of downstream effectors AMPK and mTOR did not. Mice given a single dose of canagliflozin excreted twice as much urine over 24 h compared with empagliflozin-treated mice despite similar water intake. We conclude that canagliflozin selectively suppresses Na+-dependent fluid transport and albumin uptake in PT cells via direct inhibition of NHE3 and of mitochondrial function upstream of the AMPK/mTOR axis. These additional targets of canagliflozin contribute significantly to reduced PT Na+-dependent fluid transport in vivo.

Surface-Phosphided Metal Oxide Microspheres as Catalytic Host of Sulfur to Enhance the Performance of Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries are one of the most promising high-energy density secondary batteries due to their high theoretical energy density of 2600 Wh kg-1. However, the sluggish kinetics and severe "shuttle effect" of polysulfides are the well-known barriers that hinder their practical applications. A carefully designed catalytic host of sulfur may be an effective strategy that not only accelerates the conversion of polysulfides but also limit their dissolution to mitigate the "shuttle effect." Herein, in situ surface-phosphided Ni0.96Co0.03Mn0.01O (p-NCMO) oxide microspheres are prepared via gas-phase phosphidation as a catalytic host of sulfur. The as-prepared unique heterostructured microspheres, with enriched surface-coated metal phosphide, exhibit superior synergistic effect of catalytic conversion and absorption of the otherwise soluble intermediate polysulfides. Correspondingly, the sulfur cathode exhibits excellent electrochemical performance, including a high initial discharge capacity (1162 mAh gs-1 at 0.1C), long cycling stability (491 mAh gs-1 after 1000 cycles at 1C), and excellent rate performance (565 mAh gs-1 at 5C). Importantly, the newly prepared sulfur cathode shows a high areal capacity of 4.0 mAh cm-2 and long cycle stability under harsh conditions (high sulfur loading of 5.3 mg cm-2 and lean electrolyte/sulfur ratio of 5.8 µL mg-1). This work proposes an effective strategy to develop the catalytic hosts of sulfur for achieving high-performance Li-S batteries via surface phosphidation.

Diagnostic performance of PIVKA-II in identifying recurrent hepatocellular carcinoma following curative resection: a retrospective cohort study.

Protein induced by vitamin K absence or antagonist II (PIVKA-II) plays a critical role in the diagnosis of hepatocellular carcinoma (HCC), however, studies on its efficacy in diagnosing recurrent HCC were rarely found. A multicenter, retrospective, and observational study was conducted. During the overall follow-up of 5 years, HCC patients who had curative resection were monitored every 3 months in the first year post-surgery and every 6 months thereafter if no recurrence occurred. Tumor markers were collected at the diagnosis of recurrence for those with recurrence and at the last follow-up for those without recurrence. The median serum levels of PIVKA-II and AFP in the recurrence group were significantly higher than those in the non-recurrence group (PIVKA-II: 84.62 vs. 18.76 mAU/ml, p < 0.001; AFP: 4.90 vs. 3.00 ng/ml, p < 0.001) and there is a significant correlation between PIVKA-II and AFP (R = 0.901, p < 0.001). PIVKA-II showed better accuracy than AFP in the diagnosis of overall recurrent HCC (AUC: 0.883 vs. 0.672; p < 0.0001), but also in patients with negative PIVKA-II before curative resection (AUC: 0.878 vs. 0.680, p = 0.001). Clinician should pay more attention to serum PIVKA-II values when following patients after curative HCC resection to detect early recurrence.Clinical trial registration: ChiCTR2300070874.

A meta-analysis for prevalence of infectious laryngotracheitis in chickens in mainland China in 1981-2022.

BACKGROUND: Infectious laryngotracheitis (ILT) is a highly infectious upper respiratory tract disease of chickens caused by infectious laryngotracheitis virus or Gallid herpesvirus 1 (GaHV-1). ILT is an important respiratory disease of chickens and annually causes significant economic losses in the chicken industry. Although numerous relevant studies have been published, the overall prevalence of ILT infection among chicken in mainland China is still unknown, and associated risk factors need to be evaluated to establish preventive measures. RESULTS: The present study reviewed the literature on the prevalence of ILT in chickens in China as of December 20, 2022, retrieved from six databases-CNKI, Wanfang, VIP, PubMed, Web of Science, and ScienceDirect-were used to retrieve relevant studies published between January 1, 1981 and December 20, 2022. The literature quality of studies was assessed, and 20 studies with a total of 108,587 samples were included in the meta-analysis. Results of the meta-analysis showed that the overall prevalence of ILT was 10% (95% confidence interval: 8 -12%) through the random-effects model, which showed high heterogeneity, I2 = 99.4%. Further subgroup analyses showed that the prevalence of ILT decreased over time; furthermore, the prevalence in Northwest China was slightly lower than that in North China and South China, and the prevalence estimated using the diagnostic technique AGP was higher than that reported using other diagnostic techniques. CONCLUSIONS: ILT is prevalent to some extent in mainland China. Given that the ILT attenuated live vaccine has a certain level of virulence and the prevalence differences between regions, we recommend controlling breeding density, improving immunization programs and continuously monitoring viruses and to prevent ILT prevailing in mainland China.

Ferroptosis Mediates Pulmonary Fibrosis: Implications for the Effect of Astragalus and Panax notoginseng Decoction.

Objective: To investigate the mechanism through which Astragalus and Panax notoginseng decoction (APD) facilitates the treatment of ferroptosis-mediated pulmonary fibrosis. Materials and Methods: First, the electromedical measurement systems were used to measure respiratory function in mice; the lungs were then collected for histological staining. Potential pharmacologic targets were predicted via network pharmacology. Finally, tests including immunohistochemistry, reverse transcription-quantitative polymerase chain reaction, and western blotting were used to evaluate the relative expression levels of collagen, transforming growth factor ß, α-smooth muscle actin, hydroxyproline, and ferroptosis-related genes (GPX4, SLC7A11, ACSL4, and PTGS2) and candidates involved in the mediation of pathways associated with ferroptosis (Hif-1α and EGFR). Results: APD prevented the occurrence of restrictive ventilation dysfunction induced by ferroptosis. Extracellular matrix and collagen fiber deposition were significantly reduced when the APD group compared with the model group; furthermore, ferroptosis was attenuated, expression of PTGS2 and ACSL4 increased, and expression of GPX4 and SLC7A11 decreased. In the APD group, the candidates related to the mediation of ferroptosis (Hif-1α and EGFR) decreased compared with the model group. Discussion and Conclusions. APD may ameliorate restrictive ventilatory dysfunction through the inhibition of ferroptosis. This was achieved through the attenuation of collagen deposition and inflammatory recruitment in pulmonary fibrosis. The underlying mechanisms might involve Hif-1α and EGFR.

Association of acylcarnitines with maternal cardiometabolic risk factors is defined by chain length: the S-PRESTO study.

CONTEXT: Due to the essential role of carnitine as an intermediary in amino acid, carbohydrate and lipid metabolism, a detailed characterization of circulating and urinary carnitine concentrations will aid in elucidating the molecular basis of impaired maternal metabolic flexibility and facilitating timely intervention for expectant mothers. OBJECTIVE: To investigate the association of maternal plasma and urinary free carnitine and acylcarnitines with cardiometabolic risk factors. METHODS: LC-MS/MS-based quantification of free carnitine and acylcarnitines (C2-C18) was performed on 765 plasma and 702 urine samples collected at preconception, 26-28 weeks' pregnancy, and three months postpartum in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) cohort study. RESULTS: Plasma concentrations of free carnitine and acylcarnitines decreased coupled with increased renal clearance in pregnancy compared to preconception and postpartum. Renal clearance of carnitine increased with an increase in pre-pregnancy body mass index (ppBMI) and gestational weight gain. Plasma short-chain acylcarnitines were positively associated with ppBMI, irrespective of the physiological state, while medium- and long-chain acylcarnitines were negatively associated with ppBMI at preconception and postpartum but showed a positive association in pregnancy. Similarly, plasma short-chain acylcarnitines were positively associated with HOMA-IR whereas medium- and long-chain acylcarnitines were negatively associated with HOMA-IR at preconception and in pregnancy. Mothers who developed gestational diabetes mellitus during pregnancy had ∼10% higher plasma propionylcarnitine concentration and ∼18% higher urine tiglylcarnitine concentration compared to mothers with normal glucose metabolism at preconception. CONCLUSIONS: This study provides the metabolic and physiological basis of maternal carnitine homeostasis, which can be used in assessment of maternal cardiometabolic health at preconception to improve pregnancy outcomes.

[The Optimal Storage Condition and Storage Time of Umbilical Cord Blood from Collection to Preparation].

OBJECTIVE: To explore the optimal storage condition and time of umbilical cord blood from collection to preparation. METHODS: Collect cord blood samples from 30 healthy newborns, with each new born's umbilical cord blood was divided into two parts on average. One part was stored in cold storage (4 ℃) and the other was stored at room temperature (20-24 ℃). Samples were taken at 24, 36, 48, 60 and 72 h, respectively, total nucleated cells (TNC) count and TNC viability was analyzed. Flow cytometry was used to detect the ratio of viable CD34+ cells to viable CD45+ cells and viability of CD34+ cells, and colony-forming unit-granulocyte-macrophage (CFU-GM) count was performed by hematopoietic progenitor cell colony culture. The change trend of each index over time was observed, and the differences in each index was compared between cold storage and room temperature storage under the same storage time. RESULTS: The TNC count (r 4 ℃=-0.9588， r 20-24 ℃=-0.9790), TNC viability (r 4 ℃=-0.9941， r 20-24 ℃=-0.9970), CD34+ cells viability (r 4 ℃=-0.9932， r 20-24 ℃=-0.9828) of cord blood stored in cold storage (4 ℃) and room temperature storage (20-24 ℃) showed a consistent downward trend with the prolongation of storage time. The percentage of viable CD34+ cells (r 4 ℃=0.9169， r 20-24 ℃=0.7470) and CFU-GM count (r 4 ℃=-0.2537， r 20-24 ℃=-0.8098) did not show consistent trends. When the storage time was the same, the TNC count, TNC viability, CD34+ cells viability and CFU-GM count of cord blood stored in cold storage were higher than those stored at room temperature. Under the same storage time (24, 36, 48, 60 or 72 h), TNC viability in room temperature storage was significantly lower than that in cold storage (P <0.001), but TNC count, percentage of viable CD34+ cells and CFU-GM count were not significantly different between room temperature storage and cold storage. When stored at room temperature for 24 h and 36 h, the viability of CD34+ cells was significantly lower than that in cold storage (P <0.001, P <0.01), when the storage time for 48, 60 and 72 h, there was no significant difference in the CD34+ cells viability between room temperature storage and cold storage. CONCLUSION: It is recommended that cord blood be stored in cold storage (4 ℃) from collection to preparation, and processed as soon as possible.

Exploration of decision aids to support advance care planning: A scoping review.

BACKGROUND: Advance care planning is a process through which people communicate their goals and preferences for future medical care. Due to the complexity of the decision-making process, decision aids can assist individuals in balancing potential benefits and risks of treatment options. OBJECTIVE: While decision aids have the potential to better promote advance care planning, their characteristics, content and application effectiveness are unclear and lack systematic review. Therefore, we aimed to explore these three aspects and establish a foundation for future research. DESIGN: Scoping review. METHODS: This scoping review adheres to the framework proposed by Arksey and O'Malley and the PRISMA-ScR list. Six English-language databases were systematically searched from the time of construction until 1 December 2023. Two researchers conducted the article screening and data extraction, and the extracted data was presented in written tables and narrative summaries. RESULTS: Of the 1479 titles and abstracts, 20 studies fulfilled the inclusion criteria. Types of decision aids were employed, mainly websites and videos. Decision aid's primary components center around 11 areas, such as furnishing information, exploring treatment and care preferences. The main manifestations were a significant increase in knowledge and improved recognition of patients' target value preferences. Among the aids, websites and videos for advance care planning have relatively high content acceptability and decision-making process satisfaction, but their feasibility has yet to be tested. CONCLUSIONS: Decision aids were varied, with content focused on describing key information and exploring treatment and care preferences. Regarding application effects, the aids successfully facilitated the advance care planning process and improved the quality of participants' decisions. Overall, decision aids are efficient in improving the decision-making process for implementing advance care planning in cancer and geriatric populations. In the future, personalised decision aids should be developed based on continuous optimization of tools' quality and promoted for clinical application. REPORTING METHOD: The paper has adhered to the EQUATOR guidelines and referenced the PRISMAg-ScR checklist. NO PATIENT OR PUBLIC CONTRIBUTION: This is a review without patient and public contribution. REGISTRATION: https://doi.org/10.17605/OSF.IO/YPHKF, Open Science DOI: 10.17605/OSF.IO/YPHKF.

[A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020]. / 2019­2020å¹´160ä¾‹å„¿ç«¥è‚ºç‚Žé“¾çƒèŒè„‘è†œç‚Žä¸´åºŠæµè¡Œç— å­¦å¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To investigate the clinical characteristics and prognosis of pneumococcal meningitis (PM), and drug sensitivity of Streptococcus pneumoniae (SP) isolates in Chinese children. METHODS: A retrospective analysis was conducted on clinical information, laboratory data, and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country. RESULTS: Among the 160 children with PM, there were 103 males and 57 females. The age ranged from 15 days to 15 years, with 109 cases (68.1%) aged 3 months to under 3 years. SP strains were isolated from 95 cases (59.4%) in cerebrospinal fluid cultures and from 57 cases (35.6%) in blood cultures. The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87) and 27% (21/78), respectively. Fifty-five cases (34.4%) had one or more risk factors for purulent meningitis, 113 cases (70.6%) had one or more extra-cranial infectious foci, and 18 cases (11.3%) had underlying diseases. The most common clinical symptoms were fever (147 cases, 91.9%), followed by lethargy (98 cases, 61.3%) and vomiting (61 cases, 38.1%). Sixty-nine cases (43.1%) experienced intracranial complications during hospitalization, with subdural effusion and/or empyema being the most common complication [43 cases (26.9%)], followed by hydrocephalus in 24 cases (15.0%), brain abscess in 23 cases (14.4%), and cerebral hemorrhage in 8 cases (5.0%). Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old, with rates of 91% (39/43) and 83% (20/24), respectively. SP strains exhibited complete sensitivity to vancomycin (100%, 75/75), linezolid (100%, 56/56), and meropenem (100%, 6/6). High sensitivity rates were also observed for levofloxacin (81%, 22/27), moxifloxacin (82%, 14/17), rifampicin (96%, 25/26), and chloramphenicol (91%, 21/23). However, low sensitivity rates were found for penicillin (16%, 11/68) and clindamycin (6%, 1/17), and SP strains were completely resistant to erythromycin (100%, 31/31). The rates of discharge with cure and improvement were 22.5% (36/160) and 66.2% (106/160), respectively, while 18 cases (11.3%) had adverse outcomes. CONCLUSIONS: Pediatric PM is more common in children aged 3 months to under 3 years. Intracranial complications are more frequently observed in children under 1 year old. Fever is the most common clinical manifestation of PM, and subdural effusion/emphysema and hydrocephalus are the most frequent complications. Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates. Adverse outcomes can be noted in more than 10% of PM cases. SP strains are high sensitivity to vancomycin, linezolid, meropenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.

[Intervention effect of narrative therapy on non-suicidal self-injury in adolescents with depressive disorder: a prospective randomized controlled study]. / å™äº‹æ²»ç–—å¯¹é’å°‘å¹´æŠ‘éƒç—‡æ‚£è€ éžè‡ªæ€æ€§è‡ªä¼¤çš„å¹²é¢„æ•ˆæžœï¼šä¸€é¡¹å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To study the intervention effect of narrative therapy on non-suicidal self-injury (NSSI), as well as anxiety and depression symptoms in adolescents with depressive disorder. METHODS: Sixty adolescents with depressive disorder and NSSI were randomly assigned to either the intervention group or the control group using coin flipping. The control group received conventional psychological support, while the intervention group received individual narrative therapy in addition to the conventional psychological support (twice a week, 60 minutes per session, for a total of 3 weeks). Assessment of treatment efficacy was conducted using the Adolescent Self-Harm Questionnaire, Children's Depression Inventory, and Children's Anxiety and Mood Scale before the intervention, at the end of the intervention, and one month after the intervention for both groups. RESULTS: A total of 26 adolescents in the intervention group and 29 adolescents in the control group completed the entire study. At the end of the intervention and one month after the intervention, the intervention group showed a significant reduction in the NSSI frequency score, NSSI level, anxiety score, and depression score compared to before the intervention (P<0.017). Moreover, at the end of the intervention and one month after the intervention, the intervention group exhibited significantly lower NSSI frequency score, NSSI severity score, NSSI level, anxiety score and depression score compared to the control group (P<0.05). CONCLUSIONS: Narrative therapy is effective in reducing NSSI frequency and alleviating NSSI severity, as well as anxiety and depression symptoms in adolescents with depressive disorder.

Multi-omics provide insights into the regulation of DNA methylation in pear fruit metabolism.

BACKGROUND: Extensive research has been conducted on fruit development in crops, but the metabolic regulatory networks underlying perennial fruit trees remain poorly understood. To address this knowledge gap, we conduct a comprehensive analysis of the metabolome, proteome, transcriptome, DNA methylome, and small RNAome profiles of pear fruit flesh at 11 developing stages, spanning from fruitlet to ripening. Here, we systematically investigate the metabolic landscape and regulatory network involved. RESULTS: We generate an association database consisting of 439 metabolites and 14,399 genes to elucidate the gene regulatory network of pear flesh metabolism. Interestingly, we detect increased DNA methylation in the promoters of most genes within the database during pear flesh development. Application of a DNA methylation inhibitor to the developing fruit represses chlorophyll degradation in the pericarp and promotes xanthophyll, ß-carotene, and abscisic acid (ABA) accumulation in the flesh. We find the gradual increase in ABA production during pear flesh development is correlated with the expression of several carotenoid pathway genes and multiple transcription factors. Of these transcription factors, the zinc finger protein PbZFP1 is identified as a positive mediator of ABA biosynthesis in pear flesh. Most ABA pathway genes and transcription factors are modified by DNA methylation in the promoters, although some are induced by the DNA methylation inhibitor. These results suggest that DNA methylation inhibits ABA accumulation, which may delay fruit ripening. CONCLUSION: Our findings provide insights into epigenetic regulation of metabolic regulatory networks during pear flesh development, particularly with regard to DNA methylation.

One-Step Construction of 1,3,4-Oxadiazoles with Anticancer Activity from Tertiary Amines via a Sequential Copper(I)-Catalyzed Oxidative Ugi/aza-Wittig Reaction.

An unparalleled copper(I)-catalyzed synthesis of 1,3,4-oxadiazoles from tertiary amines in one step has been described. The one-pot reactions involving (N-isocyanimine)triphenylphosphorane, tertiary amines, and carboxylic acids resulted in the formation of 1,3,4-oxadiazoles in moderate to good yields through a consecutive oxidative Ugi/aza-Wittig reaction, enabling the direct functionalization of sp3 C-H bonds adjacent to the nitrogen atom. This method offered several notable advantages, including ligands-free, exceptional productivity and a high functional group tolerance. The preliminary biological evaluation demonstrated that compound 4f inhibited hepatoma cells efficiently, suggesting potentially broad applications of the approach for synthesis and medicinal chemistry.

Safety of an inactivated COVID-19 vaccine (CoronaVac) in children aged 7-14 years in Taizhou, China.

Our study aimed to evaluate the safety of CoronaVac, an inactivated vaccine made by Sinovac, in children aged 7-14. We conducted a parent-administered online survey to monitor adverse reactions after vaccinating children in Taizhou, China, from February 15, 2021, to January 19, 2022. 767 parents completed the survey after receiving a questionnaire via WeChat. Overall, 15.3 % (117/767) of children experienced adverse effects after the first dose, and 12.2 % (88/724) after the second. Muscle pain was the most common adverse reaction post-first dose (10.0 %), while localized pain or itching at the injection site was most common after the second dose (7.6 %). In conclusion, the vaccine has a low incidence of side effects. The mild to moderate, transient, and common nature of these effects further boosts parents' confidence in vaccinating their children.

Esmolol increases the fecal abundance of Lactobacillus in a rat model of sepsis.

BACKGROUND: Disorders of the gut microbiome could be responsible for the progression of multiple organ dysfunction syndrome. In this study, we examined the effect of esmolol on the gut microbiome in a rat model of sepsis induced by cecal ligation and puncture (CLP). METHODS: The animals (n = 32) were randomly divided into 3 groups: Sham group (sham operation + normal saline treatment, n = 8), CLP group (cecal ligation and puncture + normal saline treatment, n = 12), and CLP + ESM group (cecal ligation and puncture + esmolol treatment, n = 12). After 24 h, feces in the colon were collected for 16S rRNA gene sequencing and nitric oxide analysis. In addition, colon was removed for immunohistochemical staining of inducible nitric oxide synthase (iNOS). RESULTS: Four rats in the CLP group and two rats in the CLP + ESM group died. The abundance of Lactobacillus in the CLP + ESM group was higher than CLP group (P = 0.048). In the linear discriminant analysis effect size analysis, Norank f Muribaculaceae, Escherichia-Shigella and Lactobacillus were the predominant bacteria in the Sham group, CLP group and CLP + ESM group, respectively. The iNOS expression in colonocytes stained by brown in the CLP group were much more than Sham group (P = 0.001). Compared to CLP group, the iNOS expression in colonocytes reduced after esmolol treatment (P = 0.013). The concentration of nitric oxide in colon feces was different in Sham group, CLP group and CLP + ESM group (1.31 ± 0.15µmmol/l vs. 1.98 ± 0.27µmmol/l vs. 1.51 ± 0.14µmmol/l, P = 0.001). In addition, the concentration of nitric oxide in CLP group was higher than Sham group (P = 0.001) or CLP + ESM group (P = 0.001). CONCLUSIONS: Esmolol increased the fecal abundance of Lactobacillus in a rat model of sepsis. Moreover, esmolol reduced the iNOS expression of colonocytes and the nitric oxide concentration of colon feces.

[Determination of three new herbicide residues in soil, sediment and water by liquid chromatography-tandem mass spectrometry].

Herbicides play an important role in preventing and controlling weeds and harmful plants and are increasingly used in agriculture, forestry, landscaping, and other fields. However, the effective utilization rate of herbicides is only 20%-30%, and most herbicides enter the atmosphere, soil, sediment, and water environments through drift, leaching, and runoff after field application. Herbicide residues in the environment pose potential risks to ecological safety and human health. Therefore, establishing analytical methods to determine herbicide residues in environmental samples is of great importance. In this study, an analytical method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) in positive electrospray ionization mode (ESI+) was developed for the determination of isoxaflutole, metazachlor, and saflufenacil residues in soil, sediment, and water. The instrumental detection parameters, including electrospray ionization mode, mobile phase, and chromatographic column, were optimized. The mobile phases were methanol (A) and 0.1% formic acid aqueous solution (B). Gradient elution was performed as follows: 0-1.0 min, 60%A; 1.0-2.0 min, 60%A-90%A; 2.0-3.0 min, 90%A; 3.0-4.0 min, 90%A-60%A; 4.0-5.0 min, 60%A. The samples were salted after extraction with acetonitrile and cleaned using a C18 solid-phase extraction column. Different solid-phase extraction columns and leaching conditions were investigated during sample pretreatment. Working curves in the neat solvent and matrix were constructed by plotting the measured peak areas as a function of the concentrations of the analytes in the neat solvent and matrix. Good linearities were found for isoxaflutole, metazachlor, and saflufenacil in the solvent and matrix-matched standards in the range of 0.0005-0.02 mg/L, with r≥0.9961. The matrix effects of the three herbicides in soil, sediment, and water ranged from -10.1% to 16.5%. The limits of detection (LODs, S/N=3) for isoxaflutole, metazachlor, and saflufenacil were 0.05, 0.01, and 0.02 µg/kg, respectively. The limits of quantification (LOQs, S/N=10) for isoxaflutole, metazachlor, and saflufenacil were 0.2, 0.05, and 0.05 µg/kg, respectively. The herbicides were applied to soil, sediment, and water at spiked levels of 0.005, 0.1, and 2.0 mg/kg, respectively. The average recoveries for isoxaflutole, metazachlor, and saflufenacil in soil, sediment, and water were in the ranges of 77.2%-101.9%, 77.9%-105.1%, and 80.8%-107.1%, respectively. The RSDs for isoxaflutole, metazachlor, and saflufenacil were in the ranges of 1.4%-12.8%, 1.2%-7.7%, and 1.5%-11.5%, respectively. The established method was used to analyze actual samples collected from four different sites in Zhejiang Province (Xiaoshan, Taizhou, Dongyang, and Yuhang) and one site in Heilongjiang (Jiamusi). The proposed method is simple, rapid, accurate, stable, and highly practical. It can be used to detect isoxaflutole, metazachlor, and saflufenacil residues in soil, sediment, and water and provides a reference for monitoring the residual pollution and environmental behavior of herbicides.