ObjectiveTo investigate and manage an imported dengue fever (DF) outbreak in Shanghai in 2024, to summarize the experience and lessons learned from the on-site management, and to provide a reference basis for future prevention and control of DF. MethodsEpidemiological investigation and case search were carried out for an imported DF outbreak in Shanghai, 2024. Real-time fluorescence polymerase chain reaction (RT-PCR) was used to detect dengue virus nucleic acid in the serum samples from cases. Meanwhile, emergency vector surveillance and mosquito control measures were carried out in the affected areas, and the effectiveness of the management was evaluated. ResultsAccording to the epidemiological investigation, it was confirmed that this epidemic was a family cluster of imported DF, with both cases infected in Thailand and developed symptoms successively after returning to Shanghai. Laboratory testing identified the pathogens as dengue virus serotype-3 (DENV-3). In the core and precautionary area, ultra-low-volume space spraying and residual spraying were combined to kill adult mosquitoes, and at the same time, comprehensive cleaning and elimination of mosquito breeding sites was carried out. After 2 weeks, the Breteau Index (BI) in the core area decreased from 20 to 5, and the mosquito net trap index decreased from 2 mosquitoes (net·hour)^-1 to 0.67 mosquitoes (net·hour)^-1. Continuous implementation of mosquito control measures kept the BI and net trap index below the safety thresholds [BI<5 and mosquito net trap index <2 mosquitoes (net·hour)^-1] both in the core and precautionary area. ConclusionEarly diagnosis and isolation of patients, combined with rapid suppression of the density of vector Aedes mosquitoes, are the key measures to prevent the transmission of imported DF cases.

Objective To explore the clinical factors influencing complete response in patients with locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (nCRT). Methods Clinical data of LARC patients treated in the Department of Radiation Oncology at Beijing Shijitan Hospital between January 2013 and December 2024 were retrospectively collected. All patients received nCRT, after which surgery or a watch-and-wait approach was adopted based on treatment response. Univariable and multivariable logistic regression analyses were performed to identify prognostic factors influencing complete response. A clinical prediction model was constructed based on the multivariable analysis results, and its predictive performance was evaluated using the receiver operating characteristic curve. Results A total of 113 eligible patients were included. After nCRT, 19 patients (16.8%) achieved complete response, including 3 with clinical complete response and 16 with pathological complete response. Univariable analysis indicated that pretreatment clinical N stage, extramural venous invasion, carcinoembryonic antigen level, and neoadjuvant treatment regimen were associated with complete response after nCRT (P<0.05). Multivariable logistic regression analysis identified pretreatment extramural venous invasion, carcinoembryonic antigen level, and neoadjuvant treatment regimen as independent influencing factors for complete response (P<0.05). A prediction model incorporating these independent factors yielded an area under the receiver operating characteristic curve of 0.813 (95% confidence interval: 0.713-0.913), with a sensitivity of 89.5% and a specificity of 60.6%, demonstrating good predictive performance. Conclusion Pretreatment extramural venous invasion, carcinoembryonic antigen level, and neoadjuvant treatment regimen are independent factors influencing complete response after nCRT in LARC patients. The prediction model combining these factors may assist in evaluating treatment efficacy following nCRT in LARC patients.

Objective: To understand the mosquito infestation status in schools in Jing an District of Shanghai from 2019 to 2025, so as to provide a basis for mosquito control work in schools. Methods: Four schools of each school type (colleges and secondary specialized schools, primary and secondary schools, nurseries and kindergartens) were respectively selected from Jing an District as the survey sites by combination of stratified sampling and convenience sampling. Mosquito breeding sites surveys (including small stagnant water and medium and large static water) and adult mosquito monitoring were carried out in schools every August, from 2019 to 2025. The breeding sites surveys were investigated by visual inspection and spoon trapping methods, and the adult mosquito monitoring was investigated by the human baited trapping. Chi square test was used for inter group comparison. Results: A total of 970 small stagnant water were surveyed from 2019 to 2025, with the positive rate of 17.01% for mosquito breeding. The highest positive rate was in colleges and secondary specialized schools (25.07%). The top three positive breeding sites for mosquito were unused containers(27.46%), waste tires (16.67%), and bonsai and aquatic plants (16.52%). There were statistically significant differences in the positive rates for mosquito breeding among different years, school types and waterlogging types ( χ 2=122.70, 28.48 , 24.80, all P <0.01). A total of 640 medium and large static water were surveyed, and the positive rate for mosquito breeding was 7.34%. There was a statistically significant difference for the positive rate among different years ( χ 2= 50.23 , P <0.01). The highest positive rate for mosquito breeding was in colleges and secondary specialized schools (9.63%), and there was no statistically significant difference for the positive rate among different school types ( χ 2=4.41, P =0.11). From 2019 to 2025, a total of 390 mosquitoes were captured in the time period from 16:30 to 17:00, all of which were Aedes albopictus; the adult mosquito density in colleges and secondary specialized schools was the highest, being 2.38 mosquitoes/(0.5 h ·person). A total of 210 mosquitoes were captured in the time period from 19:00 to 19:30 during 2019-2025, among which Aedes albopictus accounted for 74.76% and Culex pipiens pallens accounted for 25.24%. The adult mosquito density in colleges and secondary specialized schools was the highest, being 1.15 mosquitoes/(0.5 h ·person). In colleges and secondary specialized schools, the area with the largest number of captured mosquitoes was around the teaching buildings and libraries(44.78%). In primary and secondary schools, as well as nurseries and kindergartens, the area with the largest number of captured mosquitoes was around the school gates and playgrounds( 49.44% , 53.60%), the difference in mosquito distribution in different regions among different types of schools was statistically significant ( χ 2=111.39, P <0.01). Conclusions The mosquito density in Jing an District schools is generally higher during summer. It is recommended that the school strengthen the management of mosquito breeding sites and the control of adult mosquitoes before the start of autumn semester, so as to prevent insect infestation of mosquitoes.

OBJECTIVE To construct a prediction model for tacrolimus trough concentration based on population pharmacokinetics （PPK） information and machine learning， evaluate its predictive performance in clinical therapeutic drug monitoring （TDM） data， and provide evidence-based support for individualized dose adjustment of tacrolimus after renal transplantation. METHODS A retrospective cohort study design was adopted， and consecutive TDM records of kidney transplant recipients treated in the First Affiliated Hospital of University of Science and Technology of China （Anhui Provincial Hospital） from January to June 2025 were included to construct the final analysis set. Based on 29 input variables including previous TDM concentration， previous concentration/dose （ C / D ） ratio， and individual predicted exposure （IPRE）， 13 commonly used regression algorithm models and 1 weighted ensemble model were systematically compared. The dataset was split into training set and test set in an 80∶20 ratio by patient. Five-fold cross-validation based on patient grouping was performed on the training set， and the model performance was evaluated on the obtained evaluation points using the coefficient of determination （ R 2 ）， mean absolute error （MAE）， root mean square error （RMSE）， Pearson correlation coefficient （Corr） and ±20%/±30% accuracy. The SHapley Additive exPlanations （SHAP） method was used for model interpretability analysis to identify core predictive features. RESULTS A total of 809 consecutive TDM records from 83 kidney transplant recipients were included， with 66 cases in the training set and 17 cases in the test set. The SVR model showed the best performance， with R 2 of 0.649 8， MAE of 1.126 0 ng/mL， RMSE of 1.478 6 ng/mL， Corr of 0.819 1， ±20% accuracy of 59.68%， and ±30% accuracy of 79.03%. The Weighted Ensemble model and Extra Trees model ranked second and third， respectively. SHAP interpretability analysis showed that the top 6 features contributing to the prediction were IPRE， previous TDM concentration， previous C/D ratio， dose-normalized concentration， hematocrit （HCT）， and concentration-dose coefficient （ θ cd ）， among which IPRE was the core predictive feature （SHAP mean value 0.915 4）. CONCLUSIONS The machine learning model incorporating PPK information demonstrates good predictive ability for tacrolimus concentration in the current TDM cohort. SVR is the optimal model， IPRE is the core predictive feature of the model， and a few core PK-derived features （IPRE， dose-normalized concentration， θ cd ） together with clinical features （previous TDM concentration， HCT， etc.） constitute the main information sources for model prediction.

Objective To analyze the value of contrast-enhanced ultrasound (CEUS) quantitative parameters in identifying benign and malignant ovarian tumors so as to provide reference for ultrasound diagnosis of ovarian cancer. Methods A total of 116 patients with ovarian tumors admitted to the hospital between February 2021 and February 2024 were enrolled. All patients underwent CEUS examination. Pathological fingdings served as the gold standard to evaluate the diagnostic performance of CEUS quantitative parameters. Results Pathological examination identified 74 benign and 42 malignant ovarian tumors. No significant differences were observed between the two groups in terms of initial enhancement time, enhancement intensity or regression rate (P>0.05). The time to peak was significantly longer in patients with benign tumors than in those with malignant tumors (P<0.05). Whereas peak intensity and enhancement rate were significantly lower in the benign goup (P<0.05). ROC curves analysis showed that when using a single parameter for diagnosis, enhancement rate yielded the largest area under the curve (AUC) of 0.977. Its sensitivity and specificity were 95.24% and 98.65%. The combination of parameters achieved an even larger AUC of 0.998, with a sensitivity of 97.62% and a specificity of 98.65%. Conclusion The combination of CEUS quantitative (time to peak, peak intensity and enhancement rate) demonstrates good diagnostic value for benign and malignant ovarian tumors and improves diagnostic sensitivity.

Objective:To investigate the application value of intraoperative electrocochleography（ECochG） monitoring technique and insertion techniques in cochlear implant（CI） and analyze its relationship with postoperative residual hearing（RH） preservation. Methods:Thirty-one patients（35 ears） who received CI in our hospital from June 2022 to July 2024 were enrolled. The Advanced Bionics Active Insertion Monitoring（AIM） system was used for real-time ECochG monitoring during surgery. Intraoperative cochlear microphonics （CM） waveform changes were recorded and analyzed in relation to postoperative RH preservation. Results:①ECochG recordings were successfully obtained in 34 of 35 ears （97.1%）. ②According to Harris classification, there were 7 ears（20.6%） of Type A（rising）, 7 ears（20.6%） of Type C（declining）, 8 ears（23.5%） of Type CC（fluctuating）, and 12 ears（35.3%） of Type D（no response）. ③The total CM amplitude decrease was significantly moderately correlated with postoperative low-mid frequency hearing loss（r=0.67, P=0.017）. The total CM amplitude decrease was significantly moderately correlated with postoperative low frequency hearing loss（r=0.65, P=0.023）. ④For the mean amplitude variation, the Amax was 30.70 μV, the Amin was 8.64 μV, and the Aend was 18.27 μV. ⑤Sixteen cases completed postoperative follow-up, with an average low-mid frequency（125-1 000 Hz） residual hearing loss of 15.25 dB HL and a RH preservation rate of 87.5%. Conclusion:Intraoperative ECochG monitoring can effectively predict postoperative residual hearing changes, effectively guide surgical manipulation, and improve residual hearing preservation rate.
Humans ; Cochlear Implantation/methods* ; Audiometry, Evoked Response ; Cochlear Implants ; Male ; Female ; Adult ; Middle Aged ; Monitoring, Intraoperative ; Adolescent ; Young Adult ; Minimally Invasive Surgical Procedures ; Child ; Aged ; Postoperative Period

Tumor metastasis is the leading cause of high mortality in most cancers, and numerous studies have demonstrated that the malignant crosstalk of multiple components in the tumor microenvironment (TME) together promotes tumor metastasis. Cancer-associated fibroblasts (CAFs) are the major stromal cells and crosstalk centers in the TME of various kinds of tumors, such as breast cancer, pancreatic cancer, and prostate cancer. Recently, the CAF-induced pro-tumor metastatic TME has gained wide attention, being considered as one of the effective targets for tumor therapy. With in-depth research, CAFs have been found to promote tumor metastasis through multiple mechanisms, such as inducing epithelial-mesenchymal transition in tumor cells, remodeling the extracellular matrix, protecting circulating tumor cells, and facilitating the formation of a pre-metastatic niche. To enhance the anti-tumor metastasis effect, therapeutic strategies designed by combining nano-drug delivery systems with CAF modulation are undoubtedly a desirable choice, as evidenced by the research over the past decades. Herein, we introduce the physiological properties of CAFs, detail the possible mechanisms whereby CAFs promote tumor metastasis, categorize CAFs-based nano-drug delivery strategies according to their anti-metastasis functions and discuss the current challenges, possible solutions, as well as the future directions in order to provide a theoretical basis and reference for the utilization of CAFs-based nano-drug delivery strategies to promote tumor metastasis therapy.

OBJECTIVES: To investigate the role of the calcium/calmodulin (CaM)-mediated activation of calcineurin (CN)-nuclear factor of activated T cells (NFAT) signaling pathway in mediating the regulatory effect of hyperforin (HY) on stress-induced depression-like disorder (DP) in mice. METHODS: C57BL/6J mice were randomly divided into control group, DP model group, and hyperforin treatment group (n=15). Behavioral changes of the mice were assessed using open field test (OFT), sucrose preference test (SPT), tail suspension test (TST), light/dark box test (LDB), and novel object suppression test (NSFT). Immunohistochemistry was used to detect tyrosine hydroxylase (TH) expression in the CA1 region of the hippocampus, and serum serotonin (5-HT) and norepinephrine (NA) levels were detected with ELISA. Western blotting was used to analyze the expressions of TNF-α, IL-1β, IL-2, and CN-NFAT pathway proteins. In cultured BV-2 microglial cells with lipopolysaccharide (LPS) stimulation, the effects of hyperforin and CN inhibitor (CNIS) on expressions of ionized calcium-binding adapter molecule 1 (IBA-1), 5-HT, NA, inflammatory cytokines and CN-NFAT pathway proteins were examined using immunofluorescence assay, ELISA or Western blotting. RESULTS: Compared with the control mice, the mice in DP group showed significantly reduced activity in OFT, decreased sucrose consumption in SPT, reduced shuttle crossing in LDB, and lowered food intake in NSFT with significantly increased immobility in TST. The mice with DP showed significantly decreased TH-positive neurons, lowered 5-HT and NA levels, and increased expressions of TNF-α, IL-1β, IL-2 and CaM-CN-NFAT pathway proteins. In cultured BV-2 cells, LPS stimulation strongly increased cellular IBA-1 expression, decreased the levels of neurotransmitters (5-HT and NA), and increased the levels of inflammatory cytokines and CN-NFAT signaling, and these changes were effectively reversed by treatment with hyperforin or CNIS. CONCLUSIONS Hyperforin improves stress-induced depression-like behaviors in mice and activated BV-2 cells by targeting the CN-NFAT signaling pathway.
Animals ; Mice, Inbred C57BL ; Mice ; Microglia/drug effects* ; Depression/etiology* ; Perylene/pharmacology* ; Calcineurin/metabolism* ; NFATC Transcription Factors/metabolism* ; Calcium Signaling/drug effects* ; Stress, Psychological ; Phloroglucinol/pharmacology* ; Signal Transduction ; Male ; Behavior, Animal/drug effects* ; Terpenes

As a biocatalyst, laccase has been widely studied and applied in the papermaking industry. However, the low catalytic efficiency and poor stability of natural laccase limit its application in the pulping process. To develop the laccase with high activity and strong tolerance, we carried out directed evolution for modification of the laccase derived from Bacillus pumilus and screened out the mutants F282L/F306L and Q275P from the random mutant library by high-throughput screening. The specific activities of F282L/F306L and Q275P were 280.87 U/mg and 453.94 U/mg, respectively, which were 1.42 times and 2.30 times that of the wild-type laccase. Q275P demonstrated significantly improved thermal stability, with the relative activity 20% higher than that of the wild-type laccase after incubation at 40 ℃, 50 ℃, and 70 ℃ for 4 h. F282L/F306L and Q275P showed greater tolerance to metal ions and organic solvents than the wild-type laccase. The K_m value of the wild-type laccase was 374.97 μmo/L, and those of F282L/F306L and Q275P were reduced to 318.96 μmo/L and 360.71 μmo/L, respectively, which suggested that the substrate affinity of laccase was improved after mutation. The k_cat values of F282L/F306L and Q275P for the substrate ABTS were 574.00 s^-1 and 898.03 s^-1, respectively, which were 1.1 times and 1.7 times that of the wild-type laccase, indicating the improved catalytic efficiency. Q275P demonstrated better performance than the wild-type laccase in pulping, as manifested by the reduction of 0.82 in the Kappa number and the increases of 2.00% ISO, 7.8%, and 7.2% in whiteness, tensile index, and breaking length, respectively. This work lays a foundation for improving the adaptation of laccase to the environment of the papermaking industry.
Laccase/chemistry* ; Directed Molecular Evolution ; Enzyme Stability ; Bacillus pumilus/genetics* ; Mutation ; Biocatalysis ; Catalysis