Phenylpyruvic acid (PPA) is used as a food and feed additive and has a wide range of applications in the pharmaceutical, chemical and other fields. At present, PPA is mainly produced by chemical synthesis. With the green transformation of the manufacturing industry, biotransformation will be a good alternative for PPA production. The L-amino acid deaminase (PmiLAAD) from Proteus mirabilis has been widely studied for the production of PPA. However, the low yield limits its industrial production. To further enhance the production of PPA and better meet industrial demands, a more efficient synthesis method for PPA was established. In this study, PmiLAAD was heterologously expressed in Escherichia coli. Subsequently, a colorimetric reaction method was established to screen the strains with high PPA production. The semi-rational design of PmiLAAD was carried out, and the obtained triple-site mutant V18 (V437I/S93C/E417A) showed a 35% increase in catalytic activity compared with the wild type. Meanwhile, the effect of N-terminal truncation on the catalytic activity of the V18 mutant was investigated. After the optimization of the whole-cell conditions for the obtained mutant V18-N7, fed-batch conversion was carried out in a 5-L fermenter, and 44.13 g/L of PPA was synthesized with a conversion rate of 88%, which showed certain potential for industrial application. This study lays foundation for the industrial production of phenylpyruvic acid and also offers insights into the biosynthesis of other chemicals.
Escherichia coli/metabolism* ; Proteus mirabilis/genetics* ; Phenylpyruvic Acids/metabolism* ; Protein Engineering/methods* ; Recombinant Proteins/biosynthesis* ; Bacterial Proteins/metabolism*

Sjogren's syndrome (SS) is a common autoimmune disorder that primarily targets exocrine glands, leading to hallmark manifestations of xerostomia and xerophthalmia, with potential progression to multisystem involvement. The rapid advances in omics technologies-including metabolomics, proteomics, and transcriptomics-have yielded substantial insights into SS pathophysiology. This review consolidates current evidence on omics-derived biomarkers in SS. Studies consistently implicate aberrant glucose metabolism, neutrophil-derived enzyme activity, mitochondrial bioenergetic impairment, ferroptosis, and apoptotic pathways as central to SS development. These findings refine our understanding of disease mechanisms and the heterogeneity of therapeutic responses. Hydroxyproline has emerged as a candidate marker for distinguishing SS from IgG4-related disease, whereas distinct cytokine and chemokine signatures may enable earlier diagnosis. Genomic analyses demonstrate a robust association between expression of the rs11797 locus and SS-related lymphomagenesis, and several genes controlling DNA methylation represent promising therapeutic targets. Collectively, these findings lay the groundwork for personalized risk stratification and intervention in SS. The review concludes by summarizing existing progress and outlining priorities for future omics-based investigations.
Humans ; Sjogren's Syndrome/diagnosis* ; Biomarkers/analysis* ; Metabolomics/methods* ; Proteomics/methods* ; Genomics ; Multiomics

Lung cancer, particularly non-small cell lung cancer (NSCLC), is a leading cause of cancer-related mortality worldwide. In recent years, metabolomics has emerged as a key systems biology approach for analyzing small-molecule metabolites in cells, tissues and organisms. It provides new strategies for early diagnosis and metabolic profiling. Additionally, metabolomics plays a crucial role in studying resistance mechanisms in lung cancer. Tumor cell metabolic reprogramming is a key driving factor in the initiation and progression of lung cancer. Metabolomics studies have revealed how lung cancer cells regulate critical pathways such as energy metabolism, lipid metabolism, and amino acid metabolism to adapt to the demands of rapid proliferation and invasive metastasis. This review summarizes the latest advances in metabolomics research in lung cancer, focusing on the characteristics of metabolic reprogramming, the identification of potential metabolic biomarkers, and the prospects of metabolomics in early diagnosis and the elucidation of resistance mechanisms in lung cancer.
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Humans ; Metabolomics/methods* ; Lung Neoplasms/pathology* ; Animals ; Biomarkers, Tumor/metabolism*

OBJECTIVE To analyze the distribution and drug resistance of pathogenic bacteria in hospital-associat-ed infections for patients after renal transplantation,and to provide a reference for the rational selection of antibac-terial drugs for anti-infective treatment in such patients.METHODS Clinical data were collected from 89 hospital-ized patients who underwent renal transplantation and developed hospital-associated infection at Beidaihe Rehabili-tation and Recuperation Center(formerly known as 281 Hospital)from 2017 to 2021.The pathogenic bacteria de-tected in different types of hospital-associated infections and the drug resistance of the main pathogenic bacteria were analyzed.RESULTS A total of 89 pathogenic bacterial strains were isolated from the 89 patients with hospi-tal-associated infection,including 74 gram-negative bacterial strains(83.15％)and 15 gram-positive bacterial strains(16.85％).The predominant pathogenic bacterial strains were Klebsiella pneumoniae,Escherichia coli and Pseudomonas aeruginosa.Respiratory tract infection was the most common.E.coli showed severe drug re-sistance,with high drug resistance rates to various antibacterial drugs(complete drug resistance to piperacillin and ampicillin).K.pneumoniae was generally drug resistant to ampicillin.Enterobacter cloacae showed high sensitivi-ty to carbapenems,amikacin and enzyme inhibitor combinations.P.aeruginosa had low drug resistance rates to imipenem and meropenem.Staphylococcus aureus was completely drug resistant to antibacterial drugs such as penicillin,erythromycin and gentamicin,and no drug-resistant strains to vancomycin and linezolid were found.CONCLUSIONS The gram-negative bacteria are dominant among the bacteria isolated from the renal trans-planted patients with postoperative hospital-associated infections,with a high detection rate of E.coli and a severe drug resistance situation.Therefore,it is necessary to strengthen the monitoring of drug resistance in renal trans-plant recipients and make rational choices of antibacterial drugs.

Objective:To construct a continuity of care plan for adolescent fixed orthodontic patients based on the theory of timing, and provide systematic and standardized nursing interventions for adolescent fixed orthodontic patients.Methods:Guided by the theory of timing, preliminary plan items were formulated through literature review and questionnaire survey. Using the Delphi method, 15 experts were consulted for two rounds to determine the continuity of care plan for adolescent fixed orthodontic patients from October to December, 2023.Results:The effective response rates of the two rounds of questionnaires were 15/15, respectively. The expert authority levels were 0.93 and 0.94, and the Kendall harmony coefficients were 0.28 and 0.38, respectively. The differences were statistically significant (both P<0.001). The final established plan included 5 primary indicators, 23 secondary indicators, and 47 tertiary indicators. Conclusions:The continuity of care plan for adolescent fixed orthodontic patients based on the timing theory is reliable and scientific, and can meet the continuity of care needs of patients at different stages, providing reliable clinical basis for carrying out continuity of care.

OBJECTIVE To analyze the distribution and drug resistance of pathogenic bacteria in hospital-associat-ed infections for patients after renal transplantation,and to provide a reference for the rational selection of antibac-terial drugs for anti-infective treatment in such patients.METHODS Clinical data were collected from 89 hospital-ized patients who underwent renal transplantation and developed hospital-associated infection at Beidaihe Rehabili-tation and Recuperation Center(formerly known as 281 Hospital)from 2017 to 2021.The pathogenic bacteria de-tected in different types of hospital-associated infections and the drug resistance of the main pathogenic bacteria were analyzed.RESULTS A total of 89 pathogenic bacterial strains were isolated from the 89 patients with hospi-tal-associated infection,including 74 gram-negative bacterial strains(83.15％)and 15 gram-positive bacterial strains(16.85％).The predominant pathogenic bacterial strains were Klebsiella pneumoniae,Escherichia coli and Pseudomonas aeruginosa.Respiratory tract infection was the most common.E.coli showed severe drug re-sistance,with high drug resistance rates to various antibacterial drugs(complete drug resistance to piperacillin and ampicillin).K.pneumoniae was generally drug resistant to ampicillin.Enterobacter cloacae showed high sensitivi-ty to carbapenems,amikacin and enzyme inhibitor combinations.P.aeruginosa had low drug resistance rates to imipenem and meropenem.Staphylococcus aureus was completely drug resistant to antibacterial drugs such as penicillin,erythromycin and gentamicin,and no drug-resistant strains to vancomycin and linezolid were found.CONCLUSIONS The gram-negative bacteria are dominant among the bacteria isolated from the renal trans-planted patients with postoperative hospital-associated infections,with a high detection rate of E.coli and a severe drug resistance situation.Therefore,it is necessary to strengthen the monitoring of drug resistance in renal trans-plant recipients and make rational choices of antibacterial drugs.

Objective:To construct a continuity of care plan for adolescent fixed orthodontic patients based on the theory of timing, and provide systematic and standardized nursing interventions for adolescent fixed orthodontic patients.Methods:Guided by the theory of timing, preliminary plan items were formulated through literature review and questionnaire survey. Using the Delphi method, 15 experts were consulted for two rounds to determine the continuity of care plan for adolescent fixed orthodontic patients from October to December, 2023.Results:The effective response rates of the two rounds of questionnaires were 15/15, respectively. The expert authority levels were 0.93 and 0.94, and the Kendall harmony coefficients were 0.28 and 0.38, respectively. The differences were statistically significant (both P<0.001). The final established plan included 5 primary indicators, 23 secondary indicators, and 47 tertiary indicators. Conclusions:The continuity of care plan for adolescent fixed orthodontic patients based on the timing theory is reliable and scientific, and can meet the continuity of care needs of patients at different stages, providing reliable clinical basis for carrying out continuity of care.

To create flexible and high-quality pediatric continuing education opportunities, the Children's Hospital of Zhejiang University School of Medicine has developed an online teaching system based on the medical consortium information system, mobile application, and website, which includes "5G+" digital classroom for case teaching, hierarchical diagnosis and treatment tracking, mobile courses, and live interactive lectures about difficult medical cases as support extensions of offline training. From 2020 to 2023, over 9 000 people participated in online activities. The results of questionnaire survey, theoretical examination, and semi-structured interview showed that the members of the medical consortium were satisfied with the training content and effect of the online medical continuing education model; medical personnel's theoretical levels were improved after training; the interviewees believed that online training was flexible and convenient with regard to time, location, and space, with positive impact for improving clinical ability and personal development. However, the online form cannot yet replace the traditional refresher training completely. In the future, we will establish a unified evaluation and assessment mechanism, form a standardized management system, and introduce advanced technologies, so as to encourage enthusiastic and effective participation, and promote the rational and efficient use of medical education resources.

Objective:To investigate the effects of remimazolam on hemodynamics during the induction of general anesthesia and postoperative cognitive function in patients undergoing cardiac valve replacement surgery.Methods:A randomized controlled study was conducted involving 80 patients who underwent heart valve replacement surgery at Yan'an University Affiliated Hospital from January 2020 to December 2023. The patients were randomly assigned to either a control group or an observation group, with 40 patients in each group. The control group received routine general anesthesia, while the observation group received additional remimazolam during the routine anesthesia process. Hemodynamic parameters were compared between the two groups at different time points: heart rate and mean arterial pressure were recorded before anesthesia induction (T1), at the beginning of anesthesia induction (T2), 5 minutes after anesthesia induction (T3), at the time of tracheal intubation (T4), and 5 minutes after tracheal intubation (T5). The level of anesthesia during induction was compared between the two groups. Cognitive function in both groups was evaluated before and immediately after surgery. Additionally, the incidence of anesthesia-related adverse events during the perioperative period was compared between the two groups.Results:At T4 and T5, the heart rates in the observation group were (79.23 ± 10.22) beats/min and (78.54 ± 9.94) beats/min, respectively, and the mean arterial pressures were (115.64 ± 21.04) mmHg (1 mmHg = 0.133 kPa) and (108.61 ± 17.99) mmHg. Both values were significantly lower than those in the control group [heart rate: (84.51 ± 10.35) beats/min, (84.31 ± 10.08) beats/min, mean arterial pressure: (130.06 ± 19.25) mmHg, (121.62 ± 18.61) mmHg, t = 2.30, 2.58, 3.20, 3.18, all P < 0.05]. The time taken for the EEG bi-frequency index to drop below 60 and the EEG bi-frequency index before tracheal intubation in the observation group were both significantly lower than those in the control group ( t = 3.03, 3.14, both P < 0.05). Immediately after surgery, the Mini-Mental State Examination (MMSE) score in the control group showed a significant decrease ( t = 6.43, P < 0.05), while the MMSE score in the observation group did not change significantly ( t = 0.60, P > 0.05). Moreover, the immediate postoperative MMSE score in the observation group [(26.98 ± 2.97) points] was significantly higher than that in the control group [(23.15 ± 2.78) points, t = -5.95, P < 0.05]. There was no statistically significant difference in the incidence of anesthesia-related adverse events between the two groups (χ2 = 0.66, P > 0.05). Conclusion:Remimazolam can maintain hemodynamic stability during the induction of anesthesia in patients undergoing cardiac valve replacement surgery, facilitate the rapid attainment of satisfactory sedation, and reduce immediate postoperative cognitive dysfunction. Furthermore, the use of remimazolam in conjunction with routine general anesthesia does not significantly increase anesthesia-related risks, demonstrating a high level of safety.

Background A large amount of iron deposition in the brain can cause neuronal damage by inducing oxidative stress, neuroinflammation, and abnormal mitochondrial function. In addition, iron deposition is also reported to be closely related to the pathogenesis of Alzheimer's disease (AD). The neurofibrillary tangles aggregated by tau hyperphosphorylation are one of the important pathological features of AD. Objective To investigate potential effect of exogenous trivalent iron ions on neuronal activity in human neuroblastoma (SH-SY5Y) cells and tau hyperphosphorylation and aggregation. Methods SH-SY5Y cells were treated with ferric chloride (FeCl₃) at four concentrations (10, 100, 200, and 400 mg·L⁻¹). Cell survival rate was then detected by CCK8 assay. Intracellular iron content was determined prussian blue (Perl's) by iron staining after 24 h exposure to FeCl₃ at 10 or 200 mg·L⁻¹. Transfection of tau-P301L plasmid was conducted to construct an AD-like cell model for tau overexpression. The differences in the expression of the phosphorylated tau (p-tau) protein in SH-SY5Y cells and SH-SY5Y cells with tau overexpression were detected by Western blotting after 24 h exposure to FeCl₃ at 10 and 200 mg·L⁻¹. After dilution with phosphate buffered saline (PBS), FeCl₃, human tauR3, and FeCl₃ + tauR3 were incubated at 37℃, and the fluorescence intensity reflecting tau aggregation level was measured by thioflavin T(ThT) method at 12, 24, 36, 48, 60, 72, 84, and 96 h, respectively. Meanwhile, after 96 h coincubation of FeCl₃ and tauR3, the fibers formed by tau aggregation were observed under a transmission electron microscope (TEM). Results After 24 h of FeCl₃ exposure, the cell survival rate of SH-SY5Y cells among all groups was statistically different (F=8.63, P<0.01). The cell survival rates in the 200 and 400 mg·L⁻¹ groups were 80.1% and 68.7% of the control group, respectively (P<0.05). Compared with the control group, the nuclei of the 200 mg·L⁻¹ FeCl₃ group were mainly yellowish-brown after iron staining and the positive cell rate was up-regulated by 12.9% (P<0.01). After 24 h of FeCl₃ exposure , the p-tau (Ser396) protein expression was statistically different among all groups (F=11.6, P<0.01). Compared with the control group, the p-tau protein expression level of SH-SY5Y cells in the 200 mg·L⁻¹ group was up-regulated by 72.7% (P<0.01). After FeCl₃-treated SH-SY5Y cells with tau overexpression for 24 h, the p-tau (Ser396) protein expression was statistically different among all groups (F=27.8, P<0.01). Compared with the tau group, the p-tau (Ser396) protein expression level of SH-SY5Y cells in the tau + 200 mg·L⁻¹ group was up-regulated by 44.6% (P<0.05). Compared with the tauR3 group, the fluorescence intensities in the 84 and 96 h tauR3 + FeCl₃ groups were up-regulated by 49.9% and 53.7% (P<0.01) respectively. After 96 h of coincubation, compared with the tauR3 group, FeCl₃ + tauR3 aggravated tau aggregation and formed fiber deposition under TEM. Conclusion Exogenous trivalent iron ions may inhibit SH-SY5Y cell viability, promote the phosphorylation of tau in SH-SY5Y cells transfected with tau-P301L plasmid, and aggravate tauR3 aggregation and fiber production.