Rapid and ultrasensitive detection of pathogen-associated biomarkers is vital for the early diagnosis and therapy of bacterial infections. Herein, we developed a close-packed and ordered Au@AgPt array coupled with a cascade triggering strategy for surface-enhanced Raman scattering (SERS) and colorimetric identification of the Staphylococcus aureus biomarker micrococcal nuclease (MNase) in serum samples. The trimetallic Au@AgPt nanozymes can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) molecules to SERS-enhanced oxidized TMB (oxTMB), accompanied by the color change from colorless to blue. In the presence of S. aureus, the secreted MNase preferentially cut the nucleobase AT-rich regions of DNA sequences on magnetic beads (MBs) to release alkaline phosphatase (ALP), which subsequently mediated the oxTMB reduction for inducing the colorimetric/SERS signal fade away. Using this "on-to-off" triggering strategy, the target S. aureus can be recorded in a wide linear range with a limit of detection of 38 CFU/mL in the colorimetric mode and 6 CFU/mL in the SERS mode. Meanwhile, the MNase-mediated strategy characterized by high specificity and sensitivity successfully discriminated between patients with sepsis (n = 7) and healthy participants (n = 3), as well as monitored the prognostic progression of the disease (n = 2). Overall, benefiting from highly active and dense "hot spot" substrate, MNase-mediated cascade response strategy, and colorimetric/SERS dual-signal output, this methodology will offer a promising avenue for the early diagnosis of S. aureus infection.

BackgroundFear of progression is one of the typical psychological consequences in patients with chronic obstructive pulmonary disease （COPD）. The level of fear of progression is affected by the illness perception status， and the link between social support and fear of progression is acknowledged， whereas the mechanism underlying the three remains unclear due to the lack of empirical research evidence and needs to be further studied. ObjectiveTo explore the mediating role of social support in the relationship between illness perception and fear of progression in COPD patients， and to provide references for effectively alleviating fear in COPD patients. MethodsA total of 435 COPD patients admitted to the Department of Respiratory and Critical Care Medicine， the Affiliated Hospital of Southwest Medical University from March 9 to July 31， 2024 were selected as the study objects. The Chinese version of Fear of Progression Questionnaire-Short Form （FoP-Q-SF）， Chinese version of Brief Illness Perception Questionnaire （BIPQ） and Social Support Rate Scale （SSRS） were used for the evaluation. Pearson's coefficient was calculated to assess the correlation among above scales. Model 4 of the Process macro 3.4.1 for SPSS 25.0 was used to test the mediating effect of social support on the relationship between illness perception and fear of progression， with Bootstrapping used to evaluate the significance of mediating effect. ResultsA total of 412 patients （94.71%） completed this study.BIPQ score was positively correlated with FoP-Q-SF score （r=0.238， P<0.01）， and negatively correlated with SSRS score in COPD patients （r=-0.260， P<0.01）. FoP-Q-SF score was negatively correlated with SSRS score （r=-0.271， P<0.01）. Social support mediated the relationship between illness perception and fear of progression， with an indirect effect value of 0.025 （95% CI： 0.009~0.041）， accounting for 13.02% of the total effect. ConclusionIllness perception can affect the fear of progression in COPD patients both directly and indirectly through social support. ［Funded by Nursing Research Project of Sichuan Province （number， H22010）］

Objective: To create a prediction model for stroke risk among middle-aged and elderly populations, so as to provide a basis for early identification of high-risk population for stroke. Methods: From October to December 2023, residents aged ≥45 years in Chongchuan District, Nantong City, Jiangsu Province were selected using a multi-stage stratified random sampling method. The demographic information, life behavior, and chronic disease data were collected through a questionnaire survey. The standardized prevalence of stroke was calculated using data from the seventh National Population Census. The subjects were randomly divided into the training set and the internal validation set according to the ratio of 8∶2. The basic demographic information, life behavior, and chronic diseases of residents aged ≥45 years in Rugao City were collected from July to August 2023 as the external validation set. Predictive factors were selected using multivariable logistic regression model, and a nomogram for stroke among residents aged ≥45 years was established. The prediction effect was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC), calibration curve, and Hosmer-Lemeshow goodness of fit test. Results: A total of 6 290 residents aged ≥45 years were included, including 2 975 males (47.30%) and 3 315 females (52.70%). The average age was (61.90±10.20) years. The prevalence of stroke was 3.80%, and the standardized prevalence was 3.36%. The multivariable logistic regression showed that age, smoking, hypertension, and hyperlipidemia were predictors of stroke risk among residents aged ≥45 years, and the prediction model was ln[p/(1-p)]=-4.619+0.046×age+0.383×smoking+0.887×hypertension+0.678×hyperlipidemia. The AUC values of the training set, internal validation set, and external validation set were 0.748, 0.755, and 0.738, respectively. The consistency indexes were 0.748, 0.755, and 0.738, respectively. The Hosmer-Lemeshow goodness of fit test showed a good fitting effect (P>0.05). Conclusion The prediction model based on age, smoking, hypertension, and hyperlipidemia has good discrimination and calibration, and can be used to predict the risk of stroke among middle-aged and elderly populations aged ≥45 years.

Signal detection is a critical task in drug safety regulation. However, it inevitably generates irrelevant or false signals, posing challenges for resource allocation by marketing authorization holders. To reasonably assess these signals, different countries have established various principles for prioritizing the evaluation of risk signals. This study systematically compares these principles and finds that the U.S. Food and Drug Administration(FDA) focuses on practical issues, such as identifying drug confusion or drug interactions. However, China's Good Pharmacovigilance Practices and the European Medicines Agency(EMA) emphasize a comprehensive evaluation framework. The Council for International Organizations of Medical Sciences(CIOMS) emphasizes the consistency of multiple data sources, highlighting the reliability of signal evaluation. China practices a multidisciplinary approach combining traditional Chinese and western medicine, and the risk signals related to traditional Chinese medicine(TCM) have unique characteristics, including complex components, cumulative toxicity, specific theoretical foundations, and drug interactions. The different priorities in risk signal evaluation principles across countries suggest that China should strengthen clinical trial research, emphasize corroboration with evidence of multiple sources, and pay particular attention to the risks of drug interactions in the TCM regulatory science. Establishing the risk signal prioritization principles that align with the characteristics of TCM enables more precise and efficient scientific regulation of TCM.
Humans ; Medicine, Chinese Traditional/standards* ; China ; Drugs, Chinese Herbal/adverse effects* ; United States ; United States Food and Drug Administration

Objective To explore the effectiveness of an integrated laparoscopic simulation training course (best essential surgical technique training, BEST) in enhancing laparoscopic peritoneal suturing techniques in surgical residents.Methods As an integrated two-stage program, the BEST course applied basic laparoscopic training system with simple molds in phase Ⅰ training, and then adopted advanced laparoscopic training system, 3D Laparoscope and ex-vivo animal models in phase Ⅱ training. The laparoscopic suturing techniques were practiced in phase Ⅱ training. From August 2021 to July 2024, surgical residents in the second year of the national standardized training program were divided into pilot and control groups based on whether they had undergone the BEST course. Two cases of laparoscopic peritoneal suture were performed by the surgical residents under supervision in the department of gastrointestinal surgery. The operative time, quality of suture, and independent completion rate were compared between the two groups.Results A total of 33 surgical residents (19 in pilot group and 14 in control group) were included in this study, and a total of 66 cases of laparoscopic peritoneal suture were performed (38 in pilot group and 28 in control group). The operative time was significantly shorter in pilot group than that in control group (15.7 min vs. 17.5 min, P=0.025). The quality of suture was significantly better in pilot group compared to control group (P=0.023). In pilot group, all peritoneal sutures were performed by residents independently, whereas in control group, 3 cases (10.7%) were assisted by the supervisor, and the independent completion rate was different significantly (P=0.039).Conclusions The BEST course can help improve surgical residents′ laparoscopic peritoneal suturing techniques and could be promoted in the national standardized training program for surgical residents.

As a microbial therapy method, fecal microbiota transplantation (FMT) has attracted the attention of researchers in recent years. As one of the most direct and effective methods to improve gut microbiota, FMT achieves therapeutic benefits by transplanting functional gut microbiota from healthy human feces into the intestines of patients to reconstruct new gut microbiota. FMT has been proven to be an effective treatment for gastrointestinal diseases such as Clostridium difficile infection, irritable bowel syndrome, and inflammatory bowel disease. In addition, the clinical and basic research of FMT outside the gastrointestinal system is also emerging. It is worth noting that there is bidirectional communication between the gut microbial community and the central nervous system (CNS) through the gut-brain axis. Some gut bacteria can synthesize and release neurotransmitters such as glutamate, gamma-aminobutyric acid (GABA) and dopamine. Imbalanced gut microbiota may interfere with the normal levels of these neurotransmitters, thereby affecting brain function. Gut microbiota can also produce metabolites that may cross the blood-brain barrier and affect CNS function. FMT may affect the occurrence and development of CNS and its related diseases by reshaping the gut microbiota of patients through a variety of pathways such as nerves, immunity, and metabolites. This article introduces the development of FMT and the research status of FMT in China, and reviews the basic and clinical research of FMT in neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease), neurotraumatic diseases (spinal cord injury, traumatic brain injury) and stroke from the characteristics of three types of nervous system diseases, the characteristics of intestinal flora, and the therapeutic effect and mechanism of fecal microbiota transplantation, summarize the common mechanism of fecal microbiota transplantation in the treatment of CNS diseases and the therapeutic targets. We found that the common mechanisms of FMT in the treatment of nervous system diseases may include the following 3 categories through summary and analysis. (1) Gut microbiota metabolites, such as SCFAs, TMAO and LPS. (2) Inflammatory factors and immune inflammatory pathways such as TLR-MyD88 and NF-κB. (3) Neurotransmitter 5-HT. In the process of reviewing the studies, we found the following problems. (1) In basic researches on the relationship between FMT and CNS diseases, there are relatively few studies involving the autonomic nervous system pathway. (2) Clinical trial studies have shown that FMT improves the severity of patients’ symptoms and may be a promising treatment for a variety of neurological diseases. (3) The improvement of clinical efficacy is closely related to the choice of donor, especially emphasizing that FMT from healthy and young donors may be the key to the improvement of neurological diseases. However, there are common challenges in current research on FMT, such as the scientific and rigorous design of FMT clinical trials, including whether antibiotics are used before transplantation or different antibiotics are used, as well as different FMT processes, different donors, different functional analysis methods of gut microbiota, and the duration of FMT effect. Besides, the safety of FMT should be better elucidated, especially weighing the relationship between the therapeutic benefits and potential risks of FMT carefully. It is worth mentioning that the clinical development of FMT even exceeds its basic research. Science and TIME rated FMT as one of the top 10 breakthroughs in the field of biomedicine in 2013. FMT therapy has great potential in the treatment of nervous system diseases, is expected to open up a new situation in the medical field, and may become an innovative weapon in the medical field.

To characterize human antibodies against low-calcium response V(LcrV)antigen of Yersinia pestis,the mono-clonal antibodies were screened and assayed.Antibody gene was derived from peripheral blood mononuclear cells of the vaccin-ees immunized by plague subunit vaccine in phase Ⅱb clinical trial.Human ScFv antibody library was constructed by phage dis-play.After panning library by using recombinant LcrV antigen,antibody variable genes were sequenced and converted into IgG1 format to evaluate its binding specificity and relevant parameters.An anti-plague human ScFv antibody library was estab-lished contained 7.54× 108 independent clones.After panning by LcrV antigen,3 human antibodies named as RV-B4,RV-D1 and RV-E8,respectively,were identified.Using indirect enzyme-linked immunosorbent assay(ELISA)and Western blot(WB),the specific bindings of the mAbs to LcrV antigen were confirmed.The dissociation constant(KD)of them to LcrV is 2.1 nmol/L,1.24 nmol/L and 42 nmol/L,respectively.Minor protective efficacy was found among 3 human antibodies in Y.pestis 141-infected mice.Three anti-LcrV monoclonal antibodies generated from immunized vaccinees were binding specific antibod-ies and could not block plague infection in mice.These antibodies are the potential candidate reagents for basic research of plague immunity and the application of plague diagnosis.

Objective:To analyze the association between the pre-pregnancy oral microbiota of women and fetal overgrowth, and the possible mechanisms involved.Methods:A nested case-control study design based on a pre-pregnancy cohort was used to select 51 mothers who delivered macrosomia and/or large-for-gestational-age (LGA) infants from the population recruited at the Maternal and Child Health Care Hospital of Jiading District in Shanghai from October 2016 to December 2021 as the case group. A control group was formed by selecting 204 mothers who delivered infants with normal birth weight and appropriate for gestational age during the same period, in a 1:4 ratio. The LGA subgroup consisted of 48 mothers who delivered LGA infants from the total population, and a corresponding control group of 192 was randomly selected from the remaining mothers who delivered non-LGA infants in a 1∶4 ratio for the LGA subgroup analysis. The 16S rRNA gene sequencing technique was utilized to detect pre-pregnancy saliva samples to compare the characteristics of the oral microbiota, differential microorganisms, and differential functional pathways between groups. Nonparametric Wilcoxon rank-sum tests, two independent samples t-tests, or Chi-square (or Fisher's exact) tests were used for statistical analysis. Factor analysis was conducted on the pre-pregnancy diet data of women, and the primary dietary pattern of each study subject was identified based on the highest score of the dietary pattern factors. For microbiota count data, α and β diversity indices were calculated using R and QIIME2 software, and the corresponding microbiota functional count data were acquired through PICRUSt2. Results:(1) General data: There was no significant difference in the time interval from pre-pregnancy sampling to pregnancy and from sampling to delivery between the two groups. In the case group, there were three cases of macrosomia and 48 cases (94.1%) of LGA. The corresponding control group for the LGA subgroup consisted of 192 cases. There were no significant differences in dietary patterns between the case group and the control group. (2) α diversity analysis: The species richness index of the case group was lower than that of the control group [(367.27±84.57) vs. (408.71±93.08), multivariate analysis, P=0.009], while no significant differences were found between the two groups in the Shannon and Simpson indices; the species richness index of the LGA subgroup was also lower than that of the corresponding control group [(371.04±83.92) vs. (408.04±94.21), multivariate analysis, P=0.033], with no significant differences in the Shannon and Simpson indices. (3) β diversity analysis: There was a statistically significant difference in the unweighted UniFrac distance of the oral microbiota between the case group and the control group ( R2=0.006, F=1.479, P=0.048). No significant differences were found in the β diversity indices of the oral microbiota between the LGA subgroup and the corresponding control group. (4) Differential microbiota analysis: There were 14 differential microbiotas from phylum to genus between the case group and the control group. At the genus level, members of the G1 genus of the Streptococcaceae were enriched in the case group, while the Lautropia, Dialister, Leptotrichia, and Rothia were enriched in the control group. In the LGA subgroup and its corresponding control group, there were 14 differential microbiota from phylum to genus; at the genus level, Leptotrichia, Rothia, G6 genus of the Saccharibacteria, and Selenomonas were enriched in the control group (all LDA value>2, and all P<0.05). (5) Differential functional analysis: In the case group, metabolic pathways such as nicotinate degradation [log 2 fold change ( FC)=3.510, q=0.005], de novo synthesis of pyrimidine nucleotides (log 2FC=0.078, q=0.005), and L-tyrosine degradation pathway (log 2FC=0.710, q=0.034) were enriched in the oral microbiota of women. In the LGA subgroup, compared to the corresponding control group, metabolic pathways related to nicotinate degradation were enriched in the oral microbiota (log 2FC=3.660, q=0.012). Conclusions:There are differences in the structure of the pre-pregnancy oral microbiota of mothers with overgrown fetuses compared to those with normally grown fetuses, and mothers of normally grown fetuses show higher diversity in their pre-pregnancy oral microbiota. The enrichment of certain pathogenic bacteria and the reduction of symbiotic bacteria in the pre-pregnancy oral microbiota are associated with fetal overgrowth, and this association may be mediated by functional pathways such as nicotinate degradation.

The limitations of antifungal drugs and severe drug resistance make the treatment of invasive fungal infections (IFIs) a great challenge. Itraconazole (ITZ), as a clinical first-line drug, has a wide range of antifungal activity, but it is still limited by adverse reactions such as liver and kidney toxicity, headache and abdominal pain due to its poor water solubility and easy to cause drug accumulation by injection. In this study, the amphiphilic polymer gallic acid-chitosan-cinnamaldehyde (GA-CS-CN) was prepared by amide reaction and Schiff-base reaction. The drug-loaded nanoparticles (GA-CS-CN/ITZ) were prepared by ultrasonic method. The properties of nanoparticles formulations and its in vitro antifungal activity were investigated in the study. Studies have shown that GA-CS-CN/ITZ is spherical, homogeneous and stable, and has good biological safety. The average particle size was 239.57 ± 31.37 nm, ITZ encapsulation efficiency was (93.41 ± 1.12)%, and the cumulative drug release was (62.25 ± 1.88)% at 48 h in vitro. The antifungal activity results of Candida albicans ATCC 10231 (C. albicans) showed that it had the optimal antifungal effect and could significantly enhance the antifungal activity of free drugs. GA-CS-CN/ITZ prepared in this study has excellent biological safety and anti-C. albicans performance, which provides a new choice for the treatment of C. albicans infection and has good application potential in the treatment of this fungal infection.

OBJECTIVE To explore the effect of changing lifestyle diet in the treatment of laryngeal reflux disease(LRPD).METHODS A total of 92 patients with LRPD who received outpatient treatment in the Second Affiliated Hospital of Fujian Medical University from January 2022 to June 2023 were selected as the study control,divided into control group(46 cases)and treatment group(46 cases).The control group was treated with conventional acid suppression and gastric motogenic therapy.The treatment group was treated on the basis of the control group with giving guidance on lifestyle and diet.The changes of reflux symptom index scale(RSI)and reflux sign score scale(RFS)and the clinical efficacy of the two groups were compared 8 weeks and 12 weeks after treatment.RESULTS RSI total score was improved 8 weeks after treatment compared with before treatment in both RSI control group and treatment group(P＜0.05).The total RSI score of 12 weeks after treatment was improved compared with that of 8 weeks after treatment in both control and treatment groups(P＜0.05).The total RFS score at 8 weeks after treatment was improved in both control group and treatment group compared with before treatment(P＜0.05).Compared with 8 weeks after treatment,the total RFS score in both control group and treatment group was improved(P＜0.05).After 8 weeks of treatment,the total effective rate of the control group(60.9%)was compared with that of the treatment group(71.7%),and there was no significant difference between the two groups(χ2=1.335,P=0.513).After 12 weeks of treatment,the total effective rate of the control group(73.9%)was compared with the total effective rate of the treatment group(91.3%),and the difference between the two groups was statistically significant(χ2=6.226,P=0.044).CONCLUSION The change of lifestyle and diet should become an important part of the treatment of LRPD.By adjusting the unhealthy lifestyle and diet,the symptoms of patients can be significantly reduced and better clinical efficacy can be obtained.