Objective:To systematically evaluate and synthesize qualitative studies on the journey experiences and needs of patients with cancer-associated venous thromboembolism (CAT) , providing reference for developing full-course intervention strategies oriented to CAT prevention and management needs.Methods:Literature was retrieved from PubMed, Web of Science, Embase, Cochrane Library, CINAHL, China National Knowledge Infrastructure, Wanfang Data, and VIP regarding qualitative studies on CAT patients' prevention and management journey experiences and needs, from database inception to June 30, 2024. The quality of included literature was assessed using the 2024 version of the Joanna Briggs Institute (JBI) Qualitative Research Quality Appraisal Criteria. Findings were synthesized using a Meta-synthesis approach.Results:A total of 13 studies were included, from which 104 themes were extracted and categorized into 12 new categories, ultimately integrated into three synthesized findings: tasks change as the journey progresses; emotions gradually shift from negative to positive; pain points are key areas to improve the journey experience.Conclusions:CAT patients experience varying journey-related experiences and needs. Healthcare providers should identify key management content at each stage to meet patients' multidimensional and diverse prevention and management needs, constructing individualized management plans oriented to CAT journey requirements.

Objective To analyze the infection status and subtype distribution characteristics of human papillomavirus(HPV)patients in Dongguan area from 2017 to 2023,as well as the relationship between the subtype distribution of HPV-positive patients and their cervical histopathology.Methods A total of 21 316 patients who underwent HPV genotyping in Dongguan Maternal and Maternal and Child Health Hospital of Dongguan from 2017 to 2023 were selected as the research subjects.Cervical exfoliated cells were collected from females,and specimens from lesion sites were collected from males.The 23 types of HPV genotyping were performed on the exfoliated cell specimens of the patients by PCR-reverse dot hybridization.Statistically analyze the annual prevalence of HPV subtypes from 2017 to 2023,the viral infection status of patients of dif-ferent genders and age groups,as well as the relationship between the subtype distribution of HPV-positive patients and their cervical histopathology.Results The overall detection rate of HPV was 31.5％(6 719/21 316).The annual prevalence of HPV showed a significant downward trend from 2017 to 2023(P＜0.001),and HPV types 52,16,58,53,and 51 were the most common.Female infections were mainly high-risk HPV types 52,16,58,53 and 51.Male infections were mainly low-risk HPV types 6 and 43 and high-risk HPV types 52,51 and 68.People under the age of 25 and those aged 55-＜65 were high-risk groups for infection,with detection rates of 46.6％(668/1 432)and 42.3％(473/1 117),respectively.There was a statistically significant difference in the overall detection rate among different age groups(P＜0.001).The HPV16 type increased significantly with the progression of cervical lesions from 15.0％(80/545)in patients with cervical intraepi-thelial neoplasia(CIN)Ⅰ to 36.3％(198/545)in patients with CIN Ⅱ-Ⅲ,and the difference was statistically significant(P＜0.001).HPV16 is the main infectious subtype of CIN Ⅱ-Ⅲ.Conclusion The detection rate of HPV in Dongguan area shows a downward trend from 2017 to 2023,and it is age and gender-specific.HPV 16 is closely related to high-grade CIN in HPV genotyping.

Objective:To systematically evaluate and synthesize qualitative studies on the journey experiences and needs of patients with cancer-associated venous thromboembolism (CAT) , providing reference for developing full-course intervention strategies oriented to CAT prevention and management needs.Methods:Literature was retrieved from PubMed, Web of Science, Embase, Cochrane Library, CINAHL, China National Knowledge Infrastructure, Wanfang Data, and VIP regarding qualitative studies on CAT patients' prevention and management journey experiences and needs, from database inception to June 30, 2024. The quality of included literature was assessed using the 2024 version of the Joanna Briggs Institute (JBI) Qualitative Research Quality Appraisal Criteria. Findings were synthesized using a Meta-synthesis approach.Results:A total of 13 studies were included, from which 104 themes were extracted and categorized into 12 new categories, ultimately integrated into three synthesized findings: tasks change as the journey progresses; emotions gradually shift from negative to positive; pain points are key areas to improve the journey experience.Conclusions:CAT patients experience varying journey-related experiences and needs. Healthcare providers should identify key management content at each stage to meet patients' multidimensional and diverse prevention and management needs, constructing individualized management plans oriented to CAT journey requirements.

Objective:To investigate the effects of enriched environments on behavioral development at toddler period of preterm who had experienced early repeated operative pain.Methods:A cross-sectional study was conducted. A total of 80 high-risk preterm children of 2 years of age, who had experienced repeated pain stimuli in the neonatal intensive care unit (NICU), were enrolled as preterm group from the High-risk Children Clinic of Children′s Hospital of Nanjing Medical University from October 2016 to March 2021. Furthermore, 39 full-term healthy children, aged 2 years, who were undergoing routine check-ups during the same period, were selected as the full-term group. The preterm group was further divided into preterm intervention group and preterm non-intervention group based on the implementation of enriched environment interventions. Data of neonatal characteristics from 3 groups were collected. Growth and development indicators at the age of 2 years were measured. Neuropsychological development evaluated by Gesell developmental scale. Behavioral development evaluated by child behavior check list. The salivary cortisol levels in response to novelty (baseline, task, end) were collected. The family environment, including maternal parenting pressure, were evaluated through a survey questionnaire. One-way ANOVA and least significant difference (LSD) tests were used to compare physical development, maternal parenting stress, Gesell neuropsychological development, and behavioral problems among the 3 groups. A repeated-ANOVA and LSD tests were employed to compare the patterns of salivary cortisol secretion. Pearson correlation analysis was used to explore the influencing factors related to neuropsychological and behavioral development and cortisol level.Results:There were 44 cases in the preterm intervention group (17 males, gestational age of (31.3±2.8) weeks), and 36 in the preterm non-intervention group (29 males, gestational age of (32.5±2.6) weeks). The full-term group consisted of 39 children (23 males, gestational age of (39.3±2.1) weeks). At 2 years of age, the height, weight, and head circumference of the preterm intervention group and non-intervention group were all lower than those of the full-term group (all P<0.05).The Gesell developmental schedule showed that the preterm non-intervention group scored all lower in gross motor, fine motor, adaptive, language and personal-social domains compared to the full-term group (91±7 vs. 97±6, 88±9 vs. 94±6, 89±8 vs. 99±8, 84±10 vs. 100±15, 89±7 vs. 95±6), with statistical significance (all P<0.01). The preterm intervention group scored all higher than the preterm non-intervention group in gross motor, fine motor, adaptive and language domains (all P<0.05), with no significant difference compared to the full-term group (all P>0.05). The number of needle painful procedures during hospitalization in NICU of the non-intervention group was negatively correlated to the adaptive development quotient ( r=-0.48, P<0.05). Furthermore, the preterm non-intervention group exhibited higher scores in social withdrawal, depression, somatic complaints, aggression, and destructive behaviors compare to the full-term group and preterm intervention group ( F=8.07, 5.67, 7.72, 7.90, 7.06; all P<0.05); while the preterm intervention group showed no significant difference compared to full-term group (all P>0.05). Behavioral problems (social withdrawal and depression) in the preterm non-intervention group were positively correlated with maternal parenting stress ( r=0.66, 0.50; both P<0.05). In response to novel visual stimuli and cognitive challenges, the preterm non-intervention group had significantly higher salivary cortisol levels compared to the full-term group ( P=0.006), which were negatively correlated with the frequency of early painful procedures ( r=-0.83, -0.80; both P<0.01). There was no significant difference in cortisol secretion pattern between the intervention group and the full-term group ( P=0.772). Conclusion:Enriched environmental interventions can improve neuropsychological development, decrease behavioral problems, and down-regulate consistent high cortisol response to task in preterm infants who have experienced repeated procedural pain in the NICU by the age of 2 years.

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.
Animals ; Coronavirus Papain-Like Proteases/antagonists & inhibitors* ; Cricetinae ; Humans ; Mice ; Pandemics ; SARS-CoV-2/enzymology* ; COVID-19 Drug Treatment

Genome-scale metabolomics analysis is increasingly used for pathway and function dis-covery in the post-genomics era.The great potential offered by developed mass spectrometry(MS)-based technologies has been hindered,since only a small portion of detected metabolites were iden-tifiable so far.To address the critical issue of low identification coverage in metabolomics,we adopted a deep metabolomics analysis strategy by integrating advanced algorithms and expanded reference databases.The experimental reference spectra and in silico reference spectra were adopted to facilitate the structural annotation.To further characterize the structure of metabolites,two approaches were incorporated into our strategy,i.e.,structural motif search combined with neutral loss scanning and metabolite association network.Untargeted metabolomics analysis was performed on 150 rice cultivars using ultra-performance liquid chromatography coupled with quadrupole-Orbitrap MS.Consequently,a total of 1939 out of 4491 metabolite features in the MS/MS spectral tag(MS2T)library were annotated,representing an extension of annotation coverage by an order of magnitude in rice.The differential accumulation patterns of flavonoids between indica and japon-ica cultivars were revealed,especially O-sulfated flavonoids.A series of closely-related flavonolignans were characterized,adding further evidence for the crucial role of tricin-oligolignols in lignification.Our study provides an important protocol for exploring phytochemical diversity in other plant species.

Objective To study the effects of painful procedures during neonatal period on rats' hippocampal gene expression in later life.Method A total of 28 newborn male rats were randomly assigned into two equal groups.From day1 (P1) to day7(P7) after birth,rats in the pain group received four times of needle acupuncture at the foot everyday,simulating the infants' experience in the NICU.Rats in control group were touched at the same side of the foot with a cotton swab.Transcriptome sequencing of the hippocampus of the two groups were examined on day 8 (P8) and day 21 (P21).The gene expression profiles were established and the differentially expressed genes were screened for functional analysis.Quantitative Real-time polymerase chain reaction (qRT-PCR) was used to confirm these differentially expressed genes (GABRB1,GRIN2A,IL1 RAPL1) related to pain-stimulated response or brain cognition,and one of the key genes was further verified using Western blotting.Result The sequencing results showed that there were only 6 differentially expressed genes in hippocampal tissues of rats on P8 in the two groups.Howerer,the number increased to 53 on P21 and 85.0％ of these genes were down-regulated (45/53).Gene Ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the differentially expressed genes were mainly expressed on the cell membrane,voltage-gated ion channels,synapses,neurotransmitter receptors,immune responses,etc.The qRT-PCR and Western-blot results of key genes were consistent with the transcriptome sequencing.Conclusion Pain stimuli at an early stage after birth may trigger differentially expression of voltage-gated ion channel proteins,neurotransmitter receptors,and some key genes such as GABRB1 on hippocampal synaptic cell membranes in rats.These phenomenon may provide initial explanation for the molecular mechanism of early pain stimuli on neonatal brain development.

Objective To evaluate left ventricular systolic and diastolic functions of patients with coronary slow flow (CSF) according to left ventricular myocardial systolic/diastolic performances (MSP/MDP) by using two-dimensional speckle tracking echocardiography (STE).Methods Fifty patients with CSF diagnosed with coronary angiography (CSF group) and 45 patients without CSF (control group) underwent STE.Left ventricular systolic longitudinal,radial and circumferential peak strain and early-diastolic peak strain rate were measured,and left ventricular MSP and MDP were calculated,then the results were statistically analyzed between the 2 groups.Results Compared with control group,left ventricular systolic longitudinal,radial and circumferential peak strain and early-diastolic peak strain rate,MSP and MDP reduced in CSF group (all P＜0.05).The mean thrombolysis in myocardial infarction (TIMI) frame count (TFC) of coronary artery was negatively correlated with MDP (r=-0.23,P=0.04),and the number of affected coronary arteries was negatively correlated with MDP (r=-0.31,P=0.03).There was significant difference of MDP among patients with different numbers of affected coronary arteries and control group (all P＜0.05),and MDP in affected 2 and 3 coronary arteries patients were lower than those of the control group (all P＜ 0.05).Conclusion Left ventricular systolic and diastolic functions is impaired in patients with CSF.The mean TFC and the number of affected coronary arteries are negatively correlated with left ventricular diastolic function.Left ventricular MSP and MDP are comprehensive parameters in evaluating systolic and diastolic functions.

A 68-year-old female patient with rheumatic heart disease and auricular fibrillation received warfarin (10.5 mg per week, totally 6 weeks;then 12 mg per week, totally 3 weeks).The international nomalized ratio (INR) was monitored regularly.Her INR was steady and reached the standard during the medication.She took Zhisou Lixiao Wan 12 g daily by herself because of cough on the 10th week.Four days later she found multiple ecchymosis at her front of right leg and the INR was 6.46.Warfarin was withdrawn while Zhisou Lixiao Wan was continued.Three days later, the ecchymosis was absorbed obviously and the INR decreased to 2.96.Zhisou Lixiao Wan was stopped and warfarin was taken by 12 mg weekly.Five days later, her INR was 2.24 and the ecchymosis disappeared completely.

A 74-year-old female patient received oral carbamazepine 0. 1g thrice daily because of epilepsy after acute ischemic stroke. On the third day, the patient suddenly presented drowsiness which gradually aggravated to a state of mild coma within 30 minutes. The electrocardiogram showed that sick sinus syndrome and junctional rhythm with a heart rate of 34 beats per minute. The patient was diagnosed as Adams-Stokes syndrome which may be induced by carbamazepine. She was given an intravenous injection of atropine sulfate 0. 5 mg immediately. Then atropine sulfate 1 mg in 5% glucose injection 500 ml was slowly given by intravenous drip. Two hours later, the patient regained consciousness. The electrocardiogram showed restoration of sinus rhythm with a heart rate of 48 beats per minute. Carbamazepine was withdrawn and disturbance of consciousness did not recur.