Cytochrome P450 enzymes represent a class of heme-containing protease widely distributed across the biological kingdom. Endowed with a broad substrate scope, diverse catalytic reaction profiles, high regio- and stereoselectivity toward substrates, and mild catalytic conditions, these enzymes stand out as superior biocatalysts with good potential of application. As one of the primary producers of natural products, Streptomyces harbors a wealth of P450 enzymes and natural product biosynthetic gene clusters (BGCs) in its genome, making it a versatile treasure trove for the generation of bioactive small-molecule compounds. This review summarizes the catalytic reactions by Streptomyces-derived P450 enzymes in natural product biosynthesis and delineates the engineering strategies for addressing the practical application challenges of P450 enzymes, aiming to provide some reference and guidance for in-depth research on P450 enzymes and their applications.

Objective: To understand relationship of positive and negative peer events with mental health problems among college students, so as to provide a scientific basis for improving mental health level of college students. Methods: A total of 1 640 freshmen to juniors were randomly selected from two universities in Anhui Province from October to November 2023 by a combination of convenience sampling and cluster random sampling method. The positive and negative peer events, self perceived loneliness and stress levels, anxiety and depression symptoms of students were investigated by using the questionnaire star online. Group comparisons were conducted by using analysis of variance and Chi square test, and multivariate binary Logistic regression and linear regression were used to analyze relationship of positive and negative peer events with mental health problems among college students. Results: About 35.4% of college students reported that they experienced at least one type of negative peer events, and 91.3% reported that they experienced at least one type of positive peer events. After controlling for covariates,multivariate regression analysis found that experiencing 1, ≥2 types of negative peer events were positively correlated with loneliness scores of college students ( β = 1.36,4.04), as well as an increased risk of anxiety symptoms ( OR =2.24,4.33) and depression symptoms ( OR =2.19,4.01); and experiencing ≥2 types of negative peer events was positively correlated with stress scores of college students ( β =1.12)( P <0.05). Experiencing 5-6 and 7 types of positive peer events were negatively correlated with loneliness scores of college students ( β = -1.79, -2.44) and stress ( β =-0.75, -1.12); and experiencing 7 types of positive peer events were associated with a lower risk of anxiety symptoms ( OR =0.74) and depressive symptoms ( OR =0.80) ( P <0.05). The number of negative peer events was positively correlated with loneliness scores ( β =0.80) and stress scores( β =0.24), as well as the risk of anxiety symptoms ( OR =1.30) and depressive symptoms ( OR =1.27) among college students ( P <0.05). The number of positive peer events involved was negatively correlated with loneliness scores( β =-0.39) and stress scores( β =-0.19), as well as the risk of anxiety ( OR =0.92) and depressive symptoms ( OR =0.93) among college students ( P <0.05). The analysis of the moderating effect found that in different groups of positive peer events, reporting 1, ≥2 negative peer events were positively correlated with loneliness scores of college students ( β=1.08- 4.96), as well as an increased risk of anxiety symptoms ( OR =1.79-6.20) and depression symptoms ( OR =1.78-6.77) ( P <0.05); and β and OR coefficients were highest in the group reporting 0-4 types of positive peer events, followed by the group reporting 5-6 types of positive peer events, with lowest coefficients in the group reporting 7 types of positive peer events. Conclusions Negative peer events are positively correlated with psychological problems in college students, and positive peer events are negatively correlated with mental health problems. Positive peer events could alleviate the impact of negative peer events on mental health problems.

Objective:To explore the related factors and independent risk factors of radiation pneumonitis (RP) in breast cancer patients after radiotherapy, and to guide the optimization of treatment plan for BC and reduce the incidence of RP.Methods:A retrospective analysis was conducted on 770 female breast cancer patients who received postoperative radiotherapy at Deyang People's Hospital between July 2021 and September 2024. The occurrence of RP was observed, and potential clinical and dosimetric factors were analyzed. Continuous variables were assessed using the t-test, categorical variables with the chi-square test, and univariate analysis was used to identify factors associated with RP. Multivariate logistic regression analysis was used to find out the independent risk factors of RP, and receiver operating characteristic (ROC) curves were used to evaluate the predictive value of each factor. Results:Among 770 patients, 46 developed RP (34 grade 1, 12 grade 2). Univariate analysis showed that surgical method, chemotherapy regimen, interval between chemotherapy and radiotherapy, age, planning target volume, and maximum dose of the ipsilateral lung were not associated with RP (all P>0.05). Clinical stage ( χ2=7.84, P=0.020), chest wall + supraclavicular + internal mammary lymph node irradiation ( χ2=104.50, P<0.001), supraclavicular + internal mammary lymph node irradiation ( χ2=8.90, P=0.003), number of chemotherapy cycles ( t=9.88, P<0.001), and ipsilateral lung V 5 Gy( t=16.47, P<0.001), V 10 Gy( t=18.70, P<0.001), V 15 Gy( t=20.23, P<0.001), V 20 Gy( t=23.39, P<0.001), V 25 Gy( t=21.68, P<0.001), V 30 Gy( t=21.67, P<0.001), V 35 Gy( t=20.67, P<0.001), V 40 Gy( t=19.96, P<0.001), V 45 Gy( t=18.59, P<0.001), V 50 Gy( t=11.69, P<0.001), D mean( t=30.76, P<0.001) were significantly correlated with the occurrence of RP. Multivariate analysis revealed that ipsilateral lung V 5 Gy ( OR=1.258, 95% CI: 1.143-1.384, P<0.001), number of chemotherapy cycles ( OR=2.767, 95% CI: 1.781-4.299, P<0.001), and chest wall + supraclavicular + internal mammary lymph node irradiation ( OR=7.926, 95% CI: 2.943-21.349, P<0.001) were independent risk factors for RP. Using V 5 Gy=51.65% as the diagnostic cutoff, the sensitivity and specificity for predicting RP were 0.870 and 0.804, respectively. Taking the number of chemotherapy cycles=6.50 as the cutoff, the sensitivity and specificity of predicting RP were 0.891 and 0.586, respectively. Taking 0.50 as the diagnostic cutoff point, the sensitivity and specificity of chest wall + supraclavicular + internal mammary lymph node irradiation for RP were 0.870 and 0.797, respectively. Conclusions:The number of chemotherapy cycles, ipsilateral lung V 5 Gy, and chest wall + supraclavicular + internal mammary lymph node irradiation are independent risk factors for RP in postoperative female breast cancer patients.

Objective:To evaluate the service capability and operational efficiency of surgical departments in a hospital using data analysis models such as entropy weight TOPSIS and Boston matrix analysis, for references for optimizing medical resource allocation, promoting refined management and sustainable development of the hospital.Methods:The operational data of 24 surgical departments (A~X) in a tertiary public hospital in 2023 from its information system were extracted. The number of doctors, actual number of open beds, and average length of stay etc., were served as evaluation indicators. The TOPSIS and rank sum ratio methods were used to evaluate the medical service capabilities, the data envelopment analysis (DEA) was used to analyze operational efficiency, and Boston matrix analysis was used for departmental classification.Results:In terms of medical service capabilities, the top 5 departments were F, S, K, D, and C ( Ci>0.41), all of which were in the excellent category; The bottom three departments were L, N, and G ( Ci<0.04), all of which were in the poor range. From the perspective of operational efficiency, 8 departments had achieved strong DEA effectiveness, while the remaining 16 departments were non DEA effective, resulting in resource redundancy or insufficient output. According to the Boston Matrix analysis, 8 departments (stars) had strong medical service capabilities and high operational efficiency; 6 departments (cash cows) had poor medical service capabilities but high operational efficiency, and 8 departments (dogs) had poor medical service capabilities and operational efficiency; 2 departments (question marks) had strong medical service capabilities but low operational efficiency. Conclusions:This study comprehensively applied multiple data models to objectively and comprehensively evaluate the service capabilities and operational efficiency of surgical departments. Hospitals could develop corresponding resource allocation optimization strategies based on the Boston matrix classification results, combined with the disease characteristics and business scale configuration of each department.

Under the background of the Healthy China Strategy, public hospitals urgently need to break through the limitations of the traditional medical mode, build a precise and continuous medical service system to meet the growing personalized health needs of the people. In 2022, a tertiary public hospital launched a multidisciplinary whole course management service practice. By integrating multidisciplinary medical and health resources, clarifying service targets and contents, forming a whole course management service team, constructing a supporting information platform, linking full process services, creating standardized service processes, and providing patients with comprehensive, full process, professional, and accurate full cycle intervention management and care. The hospital covered diseases in stages, ensuring continuous medical for patients after leaving the hospital, improving their medical experience, and supporting the high-quality development of the hospital. As of June 2024, the hospital′s multidisciplinary whole course management services had covered 25 departments and 41 disease, and 43 management teams have been established. A total of 7 453 patients signed up for the whole course service. This practice achieved good results, could provide references for the implementation of whole course management services led by public hospitals.

Objective:To compare the clinical outcomes of immediate breast reconstruction using latissimus dorsi flap with implant versus mesh with implant based on BREAST-Q evaluation.Methods:From the clinical database of the First Affiliated Hospital of Nanjing Medical University, the patients who underwent immediate breast reconstruction after total mastectomy from January 2020 to December 2023 were selected as the research subjects. All breast reconstruction surgeries were performed by the same surgeon. Patients were divided into two groups according to surgical methods: the latissimus dorsi muscle flap combined with implant immediate breast reconstruction group (LD group) and the mesh combined with implant immediate breast reconstruction group (mesh group). Patients were followed up in outpatient clinics or by telephone one year after surgery. The BREAST-Q was used to evaluate the surgical outcomes of both groups from four dimensions: psychosocial well-being, sexual well-being, chest-physical well-being, and breast satisfaction. The score range for each dimension was 0-100, with higher scores indicating greater patient satisfaction with quality of life and surgical outcomes. Statistical analysis was performed using SPSS 22.0 software. Normally distributed measurement data were expressed as Mean ± SD, and comparisons between the two groups were performed using independent sample t-test. Count data were expressed as number of cases and percentages, and comparisons between groups were performed using chi-square test or Fisher’s exact test. P<0.05 was considered statistically significant. Results:A total of 123 patients were included, with 59 patients in the LD group and 64 patients in the mesh group. In the LD group, the mean age was (37.7±7.0) years, body mass index (BMI) was (22.6±2.6) kg/m 2, and clinical tumor staging showed 2, 22, 30, and 5 cases for stages 0, Ⅰ, Ⅱ, and Ⅲ, respectively. In the mesh group, the mean age was (39.1±7.0) years, BMI was (22.6±2.8) kg/m 2, and clinical tumor staging showed 1, 25, 38, and 0 cases for stages 0, Ⅰ, Ⅱ, and Ⅲ, respectively. There were no statistically significant differences between the two groups in baseline characteristics including age, BMI, and clinical tumor staging (all P>0.05). One year after surgery, the BREAST-Q result showed no statistically significant differences between the LD group and mesh group in psychosocial well-being [(83.0±19.8) points vs. (80.8±19.3) points] and sexual well-being [(62.1±30.4) points vs. (65.8±25.6) points] (all P>0.05). However, the LD group had lower chest-physical well-being scores than the mesh group [(40.6±9.7) points vs. (45.1±9.6) points, P<0.05], while breast satisfaction scores were higher in the LD group than in the mesh group [(68.0±17.8) points vs. (59.8±12.6) points, P<0.01]. Conclusion:Immediate breast reconstruction by both latissimus dorsi flap with implant and mesh with implant can improve patients’ psychosocial and sexual well-being by enhancing breast appearance. However, LD technique provides better breast satisfaction, while the mesh technique offers advantages in physical well-being of the chest wall and upper body. Surgeons should select the most appropriate breast reconstruction technique based on patients’ anatomical conditions, treatment history, and individual needs to optimize postoperative quality of life and satisfaction.

Objective:To investigate the alterations in the topological properties of gray matter and white matter dynamic and static functional brain networks in patients with major depressive disorder (MDD) and bipolar depression (BDD) using graph theory analysis, and to evaluate the potential of their combination as biomarkers for differential diagnosis between unipolar and bipolar depression.Methods:From March 2021 to April 2024, inpatients were recruited from the Department of Psychosomatic Medicine, Zhongda Hospital, Southeast University, including 132 patients with MDD, 84 patients with BDD, and 91 healthy controls (HCs). Resting-state structural and functional MRI data were collected, and dynamic and static functional brain networks of gray matter and white matter were constructed. Graph theory analysis was applied to calculate global and nodal network properties, differences in topological attributes among the three groups were compared by One-way analysis of covariance, and Turkey′s post hoc test was used for further pairwise comparison. The network topology attribute indicators with statistically significant inter-group differences were selected using the Least Absolute Shrinkage and Selection Operator regression (LASSO) for feature classification. The diagnostic performance of combined gray and white matter network features for distinguishing MDD from BDD was assessed using receiver operating characteristic (ROC) curves and a random forest model.Results:In the analysis of the static gray matter functional network, both MDD and BDD patients showed abnormal local topological properties. Compared with HCs, the MDD group exhibited abnormal betweenness centrality (BC) in the left inferior frontal gyrus, left precuneus, left ventromedial occipital cortex, right ventromedial occipital cortex, and right anterior thalamus ( t=-3.95-3.62, all P<0.05). The degree centrality (DC) of the left and right anterior thalamus was also abnormal in the MDD group ( t=3.78,4.14, both P<0.001), as was the nodal efficiency (Ne) of the left precuneus and bilateral anterior thalamus ( t=2.37, 3.61, 3.82, all P<0.05). Compared with HCs, the BDD group showed abnormalities in DC and Ne of the left precuneus ( t=-2.76, P=0.014; t=-3.01, P=0.007). In the analysis of the dynamic white matter functional network, both MDD and BDD patients demonstrated abnormal temporal variability of local topological properties. Compared with HCs, the MDD and BDD groups showed reduced BC temporal variability in the left superior corona radiata ( t=-2.39, P=0.047; t=-4.28, P<0.001), and there were significant differences in DC temporal variability in the right posterior limb of the internal capsule and lentiform nucleus ( t=2.65, P=0.021; t=3.49, P=0.001) in MDD group compared with HCs and BBD. The differential diagnosis model combining gray and white matter dynamic and static network topological features achieved an area under the ROC curve of 0.80. Conclusion:Both MDD and BDD exhibit altered topological properties in static gray matter functional networks and dynamic white matter functional networks. The combination of these features may aid in the differential diagnosis of MDD and BDD.

BACKGROUND:Postoperative adjuvant chemotherapy is a common method for the treatment of gastric cancer,but the curative effect of chemotherapy in different patients varies considerably.A new pre-clinical treatment model is needed to guide personalized drug therapy for patients with gastric cancer.OBJECTIVE:To construct organoid model based on gastric cancer tissue and investigate its application in personalized drug screening.METHODS:The tissue samples of 20 patients with gastric cancer were collected,digested and decomposed,mixed with matrix glue,and cultured with organoid medium containing epidermal growth factor and fibroblast growth factor 10.Hematoxylin-eosin staining and immunohistochemical method were used to verify the homogeneity of pathological morphology and immune molecular markers of gastric cancer organoids and original tumor tissues.The feasibility of the established gastric cancer organoid model for drug screening was evaluated through drug sensitivity screening of six drugs including carboplatin,irinotecan,fluorouracil,oxaliplatin,paclitaxel,and epirubicin.RESULTS AND CONCLUSION:Fourteen organoids of gastric cancer cases were successfully cultured.There were individual differences in morphology and growth characteristics of organoids.All organoids could be stably passed through,froze and resuscitated.Gastric cancer organoids retained the same morphological features and immunomolecular expression as primary tumor tissues.Six organoids showed different drug sensitivities to six chemotherapy drugs,which initially confirmed the feasibility of gastric cancer organoids as a drug screening model in vitro.

BACKGROUND:Postoperative adjuvant chemotherapy is a common method for the treatment of gastric cancer,but the curative effect of chemotherapy in different patients varies considerably.A new pre-clinical treatment model is needed to guide personalized drug therapy for patients with gastric cancer.OBJECTIVE:To construct organoid model based on gastric cancer tissue and investigate its application in personalized drug screening.METHODS:The tissue samples of 20 patients with gastric cancer were collected,digested and decomposed,mixed with matrix glue,and cultured with organoid medium containing epidermal growth factor and fibroblast growth factor 10.Hematoxylin-eosin staining and immunohistochemical method were used to verify the homogeneity of pathological morphology and immune molecular markers of gastric cancer organoids and original tumor tissues.The feasibility of the established gastric cancer organoid model for drug screening was evaluated through drug sensitivity screening of six drugs including carboplatin,irinotecan,fluorouracil,oxaliplatin,paclitaxel,and epirubicin.RESULTS AND CONCLUSION:Fourteen organoids of gastric cancer cases were successfully cultured.There were individual differences in morphology and growth characteristics of organoids.All organoids could be stably passed through,froze and resuscitated.Gastric cancer organoids retained the same morphological features and immunomolecular expression as primary tumor tissues.Six organoids showed different drug sensitivities to six chemotherapy drugs,which initially confirmed the feasibility of gastric cancer organoids as a drug screening model in vitro.

Objective:To compare the clinical outcomes of immediate breast reconstruction using latissimus dorsi flap with implant versus mesh with implant based on BREAST-Q evaluation.Methods:From the clinical database of the First Affiliated Hospital of Nanjing Medical University, the patients who underwent immediate breast reconstruction after total mastectomy from January 2020 to December 2023 were selected as the research subjects. All breast reconstruction surgeries were performed by the same surgeon. Patients were divided into two groups according to surgical methods: the latissimus dorsi muscle flap combined with implant immediate breast reconstruction group (LD group) and the mesh combined with implant immediate breast reconstruction group (mesh group). Patients were followed up in outpatient clinics or by telephone one year after surgery. The BREAST-Q was used to evaluate the surgical outcomes of both groups from four dimensions: psychosocial well-being, sexual well-being, chest-physical well-being, and breast satisfaction. The score range for each dimension was 0-100, with higher scores indicating greater patient satisfaction with quality of life and surgical outcomes. Statistical analysis was performed using SPSS 22.0 software. Normally distributed measurement data were expressed as Mean ± SD, and comparisons between the two groups were performed using independent sample t-test. Count data were expressed as number of cases and percentages, and comparisons between groups were performed using chi-square test or Fisher’s exact test. P<0.05 was considered statistically significant. Results:A total of 123 patients were included, with 59 patients in the LD group and 64 patients in the mesh group. In the LD group, the mean age was (37.7±7.0) years, body mass index (BMI) was (22.6±2.6) kg/m 2, and clinical tumor staging showed 2, 22, 30, and 5 cases for stages 0, Ⅰ, Ⅱ, and Ⅲ, respectively. In the mesh group, the mean age was (39.1±7.0) years, BMI was (22.6±2.8) kg/m 2, and clinical tumor staging showed 1, 25, 38, and 0 cases for stages 0, Ⅰ, Ⅱ, and Ⅲ, respectively. There were no statistically significant differences between the two groups in baseline characteristics including age, BMI, and clinical tumor staging (all P>0.05). One year after surgery, the BREAST-Q result showed no statistically significant differences between the LD group and mesh group in psychosocial well-being [(83.0±19.8) points vs. (80.8±19.3) points] and sexual well-being [(62.1±30.4) points vs. (65.8±25.6) points] (all P>0.05). However, the LD group had lower chest-physical well-being scores than the mesh group [(40.6±9.7) points vs. (45.1±9.6) points, P<0.05], while breast satisfaction scores were higher in the LD group than in the mesh group [(68.0±17.8) points vs. (59.8±12.6) points, P<0.01]. Conclusion:Immediate breast reconstruction by both latissimus dorsi flap with implant and mesh with implant can improve patients’ psychosocial and sexual well-being by enhancing breast appearance. However, LD technique provides better breast satisfaction, while the mesh technique offers advantages in physical well-being of the chest wall and upper body. Surgeons should select the most appropriate breast reconstruction technique based on patients’ anatomical conditions, treatment history, and individual needs to optimize postoperative quality of life and satisfaction.