Objective:To identify strain-specific features of Klebsiella pneumoniae by analyzing metagenomics next generation sequencing (mNGS) data, thereby expanding the downstream applications of mNGS. Methods:The sequences of K.pneumoniae strains were organized from both the self-built database of the long-term multi-center research cohort in China established by the Peking University People′s Hospital from 2009 to 2020 (with 2 345 sequences) and the public databases (with 19 648 sequences). The existing large-scale databases were compressed, and a set of strains representative of clonal groups were screened. A strain genome information library was constructed based on k-mer features, and the most matching representative sequences in the database were searched for the raw mNGS data. The search results of the self-built library and public library were merged and optimized to update the prediction of antimicrobial-resistance characteristics and avoid the impact of uneven data distribution on the results. A total of 314 clinical samples from patients with K.pneumoniae detected by mNGS in the Clinical Microbiology Laboratory of Peking University People′s Hospital from 2022 to 2024 were retrospectively collected, and 101 samples with positive clinical culture results were selected to validate the prediction results. The antimicrobial-resistance phenotypes were verified by clinical antimicrobial susceptibility test results. Whole-genome sequencing was performed on the culture strains of 14 samples randomly selected using random numbers to verify the genotypes. Single nucleotide polymorphism distance analysis was used to verify the occurrence of outbreak events. The χ2 test and Mann-Whitney U test were used for statistical analysis. Results:A representative strain sequence k-mer feature library containing self-built and public sub-libraries was constructed. The library construction required only about 1 hour with <3 GB storage, with a high compression ratio and low update cost. Using k-mer-based analysis, mNGS data achieved precise strain characterization within 4 minutes and and <5 GB memory occupation. There was a significant difference in the antimicrobial-resistance rates to more than half of the antibiotics between the self-built database (90.8%, 2 130/2 345) and the public database (22.7%, 4 457/19 648) ( χ2=4 634.1, P<0.001). After optimizing the search results, the mean category agreement, sensitivity, and specificity of the prediction for eight antibiotics reached 84.8% (323/381), 78.9% (131/166), and 91.2% (196/215), respectively. The target genotypes were successfully detected in 10 out of 12 samples, and two outbreak events (2 samples per event) were successfully identified. Conclusions:An independent analysis process adapted to the needs of identifying the features of K. pneumoniae strains in mNGS data was developed. This process requires minimal computational resources and processing time and can directly achieve the simultaneous analysis of the antimicrobial-resistance phenotypes of K. pneumoniae at the strain level and their corresponding genomic characteristic profiles based on the raw mNGS reads.

As space stations steadily progress into the application and development stage,astronauts will be regularly rotated for space missions,and the impact of the space environment on human health will become an important research topic.Under microgravity,astronauts lose 1%～2%bone mass per month.Astronauts'health phenotype,as well as animal experiments conducted in space,have shown that microgravity leads to significant loss of weight-bearing bone and reduction of ultimate loading in bones.Due to the limited conditions,it is not easy to conduct experiments in space,so various animal models have been used for simulated microgravity experiments to study the mechanisms of bone loss.This review summarizes many studies on osteoporosis under space microgravity and simulated microgravity on the ground,describing different types of bone loss and underlying molecular mechanisms caused by microgravity,as well as the similarities and differences of current conclusions.In addition,this review summarizes the effects of non-bone tissues such as muscles on bone loss under microgravity,and the current measures adopted in the space station to prevent osteoporosis.

Objective:In order to effectively educate students on tooth defect diseases and restoration techniques, the teaching and research team at the School of Stomatology of Qingdao University developed an integrated course operative dentistry. This course is specifically designed to align with the undergraduate curriculum reform requirements of "Three Early, Two Multiple and One Integration".Methods:The teaching practice of operative dentistry was conducted with the stomatology undergraduates of grade 2020 and 2021. The course group redesigned the curriculum by reorganizing teaching content, rebuilding teaching resources, reconstructing teaching mode, and reshaping the evaluation system. Evaluation of the curriculum design included test scores, satisfaction questionnaires, and teacher self-evaluation. Statistical analysis was performed using SPSS 27.0 software, including independent sample t-tests for numerical variables and Fisher's exact test or Wilcoxon rank sum test for categorical variables. Results:Through the integrated course learning, 92.68% (38/41) of the students of grade 2020 and 97.44% (38/39) of the students of grade 2021 can basically or completely master various dental defect repair schemes and understand the importance of preserving natural tooth. 82.93% (34/41) of the students of grade 2020 and 100.00% (39/39) of the students of grade 2021 could basically or completely master the key points of various dental defect restorations.Conclusions:Through the practice of teaching, it has been confirmed that the integrated course of operative dentistry is beneficial to students' mastering the knowledge and skills of dental defect diseases and their restoration in a more comprehensive way, and is conducive to the cultivation of clinical thinking, hands-on ability and the patient-centered, comprehensive problem-solving thinking, which is in line with the guidance on the innovation and development of medical education.

Objective To explore the symptom clusters in renal transplant recipients and con-struct a concurrent symptom network to identify core symptoms.Methods A total of 343 patients with followed up after renal transplantation were selected as the study subjects.A general information questionnaire and the Chinese version of the Modified Transplant Symptom Occurrence and Symptom Distress Scale were employed to analyze the occurrence of symptoms in patients.In this study,only symptoms with an incidence rate greater than 20％and Spearman correlation coefficient greater than 0.40 between symptom severity and total score were retained.Exploratory factor analysis was used to extract symptom clusters with a factor loading of ≥0.45 as the criterion.The R language was utilized to construct symptom network,based on which core symptoms and bridge symptoms were identified.Results A total of 5 symptom clusters were extracted in this study:the neuro-gastrointestinal symp-tom cluster,the mood-related symptom cluster,the hormone-related symptom cluster,the energy de-ficiency symptom cluster and the vision-related symptom cluster.The core symptoms were anxiety(rs=1.75),mood swings(rs=1.50)and muscle weakness(rs=1.27).The top three symptoms in terms of bridge strength were muscle weakness(rb=0.87),lack of vitality(rb=0.66)and fa-tigue(rb=0.65).Conclusion Multiple symptoms are presented in patients after renal transplanta-tion.Based on the results of symptom network analysis,clinicians can strengthen the assessment of core symptoms and bridge symptoms to develop precise intervention strategies and improve the effectiveness of symptom management.

Objective:To investigate the efficacy of a domestically developed small esophageal cooling device in implementing targeted temperature management (TTM) after resuscitation and its impact on organ injury using a porcine model of cardiac arrest and resuscitation.Methods:Thirty healthy male domestic white pigs were randomly divided into four groups using a random number table: sham (S group, n=6), normothermia (NT group, n=8), surface cooling (SC group, n=8), and esophageal cooling (EC group, n=8). The S group underwent only surgical preparation, while the other groups were subjected to 12 minutes of ventricular fibrillation followed by 6 minutes of cardiopulmonary resuscitation to establish cardiac arrest. The S and NT groups maintained a core temperature of (37.5±0.5)°C using a surface blanket. In the SC and EC groups, therapeutic hypothermia was induced post-resuscitation via surface blanket or esophageal cooling catheter to achieve a target temperature of 34°C, maintained the target temperature (34±0.5)°C for 6 hours, followed by controlled rewarming at 0.5°C/h to 37°C. Core temperature was continuously monitored for 12 hours post-resuscitation. Hemodynamic parameters, including stroke volume (SV), global ejection fraction (GEF), extravascular lung water index (ELWI), and pulmonary vascular permeability index (PVPI), were assessed using pulse indicator continuous cardiac output (PiCCO) monitoring. Serum levels of cardiac troponin I (cTnI), neuron-specific enolase (NSE), creatinine (Cr), and intestinal fatty acid-binding protein (IFABP) were measured via ELISA at 2, 6, 12, and 24 hours post-resuscitation. Neurological outcomes were evaluated at 24 hours using the neurological deficit score (NDS) and cerebral performance category (CPC). Continuous variables were analyzed using one-way ANOVA. Results:During TTM, the EC group exhibited a faster cooling rate [(1.52±0.18)°C/h vs. (0.94±0.32)°C/h, P<0.05] and shorter time to target temperature [(2.32±0.43) h vs. (3.78±0.82) h, P<0.05] compared to the SC group, with comparable maintenance and rewarming ( P>0.05). Compared to the S group, the NT, SC, and EC groups demonstrated significant post-resuscitation multi-organ injury, characterized by reduced SV and GEF, elevated ELWI and PVPI, and increased serum cTnI, NSE, Cr, IFABP, NDS, and CPC scores (all P<0.05). Relative to the NT group, the SC and EC groups showed improved SV (at 1 h post-resuscitation), GEF (at 1, 2, 4, and 6 h), ELWI (at 12 h), and reduced cTnI and NSE (at 6 h), Cr and IFABP (at 2 h), and NDS and CPC (at 24 h) (all P<0.05). Compared to the SC group, the EC group exhibited lower PVPI (at 12 h), reduced cTnI, Cr, and IFABP (at 2 h), decreased NSE (at 2, 12, and 24 h), and improved NDS (at 24 h) (all P<0.05). Conclusions:In a porcine model of cardiac arrest and resuscitation, the domestic esophageal cooling device facilitated rapid induction, stable maintenance, and controlled rewarming during TTM, outperforming traditional surface cooling. This approach demonstrated superior organ protection, warranting further investigation.

Objective To investigate the correlation between single nucleotide polymorphisms(SNPs)of the EGF gene,including rs11569017(A>T),rs2237051(A>G),rs3733625(C>T),and rs4444903(A>G),and the risk of non-small cell lung cancer(NSCLC)in a Han population of Yunnan.Methods A total of 439 patients with NSCLC and 520 healthy controls were recruited in Yunnan Province between January 2022 and December 2023.Genotyping of four SNP loci in the EGF gene was performed using TaqMan probes,followed by analysis of allele,genotype,genetic model,and haplotype distribution frequencies between NSCLC and control groups.Stratified analyses were further conducted based on NSCLC pathological types and clinical stages.Results The rs2237051 locus showed significant differences in allele(P=0.011)and genotype(P=0.042)frequencies between the squamous cell carcinoma(SCC)group and the control group.The frequency of the A allele was lower in the SCC group than in the control group(OR=0.71,95%CI 0.54～1.85),but there was no difference after Bonferroni correction(P>0.0125).Under the log-additive model,the rs2237051-2G/G+A/G genotype was associated with an increased risk of SCC(P=0.01;OR=1.42,95%CI 1.08～1.86).However,the association lost statistical significance after Bonferroni correction(P>0.0125).The haplotype rs11569017-rs2237051-rs3733625-rs4444903 has no difference between the two groups(P>0.0125).The stratified analysis revealed no significant associations between the genetic loci and different disease stages(P>0.0125).Conclusion In the Yunnan Han population,the individuals carrying the rs2237051-A allele of the EGF gene have a significantly lower risk of squamous lung cancer,but further functional experiments are needed to verify the protective mechanism.

Objective To observe the characteristic symptoms in breast cancer-bearing mice and the beneficial effect of ginger-processed Jiangxiangru polysaccharides on traditional Chinese medical symptoms.Methods Thirty-eight mice were used for modeling and divided into normal,model,positive,and low-,medium-,and high-dose ginger-processed Jiangxiangru polysaccharide groups.Mice in the normal group were not inoculated with tumors and mice in the normal and model groups received physiological saline intragastrically.Mice in the positive group received celecoxib solution intragastrically,and mice in the low-,medium-,and high-dose groups received the same dose but different concentrations of ginger-processed Jiangxiangru polysaccharide solution intragastrically.Changes in body weight and tumor size were recorded after 4 weeks of continuous administration.Symptoms were observed at the end of the experiment.RGB values in photographs of the tongues,tails,and claws from mice in each group were analyzed and recorded.The degrees of blood deficiency,yin deficiency,and tumor phlegm stasis were calculated based on the method of quantitative dialectical diagnosis.The tumors were isolated and weighed,and the tumor volume and inhibition rate were calculated to determine the beneficial effect of ginger-processed Jiangxiangru polysaccharides on traditional Chinese medical symptoms.Results Mice in the breast cancer model group showed signs of blood deficiency,yin deficiency,and phlegm stasis.Tumor size was significantly reduced in mice in the ginger-processed Jiangxiangru polysaccharide groups.Ginger-processed Jiangxiangru polysaccharides inhibited tumor growth and improved blood deficiency,yin deficiency,and tumor phlegm stasis in breast cancer-bearing mice,with the best result in the high-dose group.Conclusions Ginger-processed Jiangxiangru polysaccharides can improve the symptoms of blood deficiency,yin deficiency,and tumor phlegm stasis in breast cancer-bearing mice,especially at high doses.

Xeroderma pigmentosum(XP)is a rare autosomal recessive disorder related to XP gene variation,often causing secondary malignant tumors.This article reports a case of a young child with secondary squamous cell carcinoma of the lower lip caused by xero-derma pigmentosum.Through a review of relevant literature,the clinical characteristics,pathogenesis,clinical pathological manifesta-tions,and prognosis of XP are discussed.

Objective:Currently, there is a lack of targeted training programs for resident physicians in cardiopulmonary resuscitation (CPR) in China. This study aims to establish a stratified training indicator system for resident physicians in CPR that is in line with the medical realities in China.Methods:Expert consultation questionnaires were designed through literature review, group discussions, and surveys. Two rounds of expert consultation were conducted using the modified Delphi method to develop the stratified training indicator system for resident physicians in CPR. Statistical analysis was performed using SPSS 26.0 software and Kendall's coefficient of concordance was used to assess the consistency of expert opinions.Results:A total of 15 experts participated in two rounds of questionnaire consultation, with a positive coefficient of 100.00% and an authority coefficient of 0.91, indicating high expert engagement and authority, thus ensuring the credibility of the results. The coefficient of variation for expert ratings in the first round of questionnaire consultation ranged from 0 to 0.40, with a concordance coefficient of 0.22 ( P<0.001). In the second round of questionnaire consultation, the coefficient of variation for expert ratings ranged from 0 to 0.24, with a concordance coefficient of 0.25 ( P<0.001). The Kendall's coefficient of concordance for expert opinions showed statistically significant differences in both rounds of questionnaire consultation, indicating consensus among experts and reliable results. This system consisted of 6 primary indicators and 32 secondary indicators. Conclusions:Based on the modified Delphi method, this study established a stratified training indicator system for resident physicians in CPR. In the future, based on the research findings, CPR training programs adapted to the medical realities in China will be developed and promoted to validate their scientific and practical value.

Objective To sort out the management system of clinical trial drugs in our hospital,and analyze the construction and practical experience of the information system in the whole process management of clinical trial drugs,and to further improve the efficiency and quality of clinical trials.Methods Based on the original management of clinical trial drugs,an information system in line with the situation of our hospital was applied to manage the whole process of clinical trial drugs.Results Compared with the traditional management,the information system can automatically record the data of inbound and outbound storage,distribution,retrieval and return of trial drugs in real time,pre-review the prescriptions and randomized documents of clinical trial drugs,and realise paperless office.Conclusions The information system can ensure the safety,accuracy and traceability of the data of drugs used in clinical trial.The system can also save resources,improve the efficiency and quality of clinical trial management.