Tetrodotoxin（TTX）is a potent neurotoxin known for its specific sodium channel blocking effects, widely used in biomedical research. While TTX has been identified in various marine organisms, its true origin remains unclear, and the specific biosynthetic pathways are yet to be elucidated. The reported sources of TTX and the progress in research on TTX biosynthesis were summarized, with a focus on potential microbial sources of TTX, which could provide scientific reference for the production and biosynthesis studies of TTX.

OBJECTIVE To investigate the apoptosis-inducing effect of esculetin （Esc） on acute myeloid leukemia （AML） HL-60 cells by regulating the protein kinase B （AKT）/S-phase kinase-associated protein 2 （SKP2）/MutT homolog 1 （MTH1） pathway. METHODS AML HL-60 cells were randomly divided into control group （routine culture）， Esc low-concentration group （L-Esc group， 25 μmol/L Esc）， Esc medium-concentration group （M-Esc group， 50 μmol/L Esc）， Esc high-concentration group （H-Esc group， 100 μmol/L Esc）， and high-concentration of Esc+ SC79 （AKT agonist） group （100 μmol/L Esc+5 μmol/L SC79）. Cell proliferation in each group was detected by MTT assay and colony formation assay. The level of reactive oxygen species （ROS） in cells was measured by using the CM-H2DCFDA fluorescent probe. Cell apoptosis was analyzed by flow cytometry. Western blot assay was performed to detect the expression levels of apoptosis-related proteins [B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved caspase-3]， AKT/SKP2/MTH1 pathway-related proteins （p-AKT， AKT， SKP2， MTH1）， along with the upstream and downstream proteins of AKT phosphatidylinositol 3-kinase （PI3K）， cyclin-dependent kinase inhibitor 1 （P21） and cyclin-dependent kinase inhibitor 1B （P27）. RESULTS Compared with control group， the cell viability， colony number， and the phosphorylation levels of AKT and PI3K proteins as well as protein expressions of SKP2， MTH1 and Bcl-2 were significantly decreased （P＜0.05）， while ROS level， apoptosis rate， and the expression levels of Bax， cleaved caspase-3， P21 and P27 proteins were significantly increased （P＜0.05）. Moreover， the effects of Esc exhibited concentration-dependence （P＜0.05）. Compared with H-Esc group， above indexes of high-concentration of Esc+ SC79 group were reversed significantly （P＜0.05）. CONCLUSIONS Esc may promote massive ROS production and induce activation of apoptosis in HL-60 cells by inhibiting the AKT/SKP2/MTH1 pathway， thus inhibiting the proliferation of HL-60 cells.

Objective To explore the impact of meteorological factors on the incidence of scarlet fever in Xicheng District of Beijing, and to provide a scientific basis for formulating targeted prevention and control measures. Methods Daily scarlet fever incidence data and corresponding meteorological data from 2010 to 2019 in Xicheng District of Beijing were collected. Using year, month, and day of the week as time-stratified variables, a conditional logistic regression model with a time-stratified case-crossover design was employed to analyze the impact of different meteorological factors on the number of scarlet fever cases in Xicheng District, while controlling for long-term trends, seasonality and other confounding factors. Results From 2010 to 2019, a total of 3,195 cases of scarlet fever were reported in Xicheng District, with an average annual incidence rate of 24.17/100 000. The overall trend showed fluctuating decline, during which three incidence peaks occurred, with the highest incidence rate observed in 2011. No severe or fatal cases were reported. The incidence of scarlet fever exhibited a distinct seasonal bimodal distribution, primarily concentrated between April to June and November to January of the following year. The conditional logistic regression results showed that the average relative humidity and average temperature were positively correlated with scarlet fever cases (β=0.0203, β=0.0613, P＜0.001), while the average vapor pressure was negatively correlated with scarlet fever cases (β=-0.1468, P＜0.001). Increases average relative humidity and average temperature were risk factors for scarlet fever incidence (OR=1.0205，95%CI=1.0150 -1.0261；OR=1.0632，95%CI=1.0379 -1.0891). For every 1.00% increase in average relative humidity, the number of scarlet fever cases increased by 2.05% (1.50% –2.61%). Similarly, for every 1^。C rise in average temperature, the number of cases increased by 6.32% (3.79% – 8.91%). In contrast, an increase in average vapor pressure had a protective effect against scarlet fever (OR=0.8635,95%CI=0.8392-0.8885). For every 1 hPa increase in average vapor pressure, the number of scarlet fever cases decreased by 13.65% (11.15%–16.08%). Conclusion The average relative humidity, average temperature and average vapor pressure are the primary meteorological factors influencing the incidence of scarlet fever in Xicheng District of Beijing, and can be utilized as indicators for the prevention, control, surveillance and early warning of scarlet fever.

Objective To compare the epidemic characteristics of seasonal influenza in Xicheng District, Beijing, between 2018-2019 and 2023-2024. Methods The present study was a cross-sectional study. The influenza cases and etiological surveillance data of Xicheng District, Beijing in 2018-2019 and 2023-2024, respectively, were analyzed to study the differences in the incidence rate of influenza cases in different ages, regions, occupations, and etiological detection results during the four years. Results There were significant differences in the incidence rates of influenza (χ²=37 038.65，P＜0.05) and the interval between visits (Z=468.692, P < 0.05) in 2018, 2019, 2023 and 2024. There were statistically significant differences in the incidence rates of influenza among different age groups, streets, and occupations during the four years (Z=75.646, 209.276, 72.132, 361.176, 43.570, all P < 0.05). Compared with 2018-2019, the growth rate of influenza in Xicheng District, Beijing in 2023-2024 was the highest in the 15-24 year-old group, Tianqiao Street, and housework and unemployed people. The difference in the interval between influenza visits among people of different age groups during these 4 years was statistically significant (P < 0.05). The growth rate of the interval between influenza visits in Xicheng District, Beijing in 2023-2024 was the highest in the 15-24 year-old group, while it showed a decrease in the 0-4 year-old group. The etiology in 2018-2019 was mainly H1N1 and H3N2 subtypes, and in 2023-2024 it was mainly H3N2 subtype and influenza B, and the peak values of H1N1, H3N2 subtype and influenza B in 2023-2024 were all higher than those in 2018-2019. Conclusion During the epidemic period, non-medical interventions have changed the transmission mode, seasonal peak and subtype distribution of influenza virus. As the epidemic has eased, the pattern of influenza has gradually rebounded.

Background: Cerebral hypoxia-ischemia impairs brain development in extremely preterm infants and is associated with poor neurological outcomes. Near-infrared spectroscopy (NIRS) is a noninvasive continuous monitoring method for regional cerebral oxygen saturation (rcSO2).Purpose: This study evaluated the clinical feasibility and neurological impact of a neurocritical care bundle that incorporates prolonged multidisciplinary hemodynamic monitoring and a stepwise management algorithm. Methods: Preterm infants with a gestational age (GA) ≤28 weeks or birth weight (BW) ≤1,000 g were prospectively enrolled in a bundle group subjected to NIRS for rcSO2, electrical cardiometry for cardiac output, and daily brain and cardiac echography during the first 72 hours of life. Monitoring was repeated weekly in the first month and then monthly until discharge or the term-equivalent age (TEA) was reached. We implemented a stepwise management algorithm for treating cerebral hypoxia. The primary outcome was a composite of mortality and adverse neurological events (structural abnormalities or electroencephalogram-confirmed seizures) before discharge. The secondary outcomes were the physiological pattern of rcSO2 within the initial 72 hours and up to discharge or TEA. Results: Thirty preterm infants (GA, 27.1±2.0 weeks; BW, 830±225 g) were enrolled in the bundle group. The mean time-averaged rcSO2 (66.8%±10.3%) was not associated with GA or BW. However, postnatal age appeared to influence physiological rcSO2 changes, given that rcSO2 values were higher during the initial 72 hours than at subsequent intervals. Seven infants (23.3%) had poor outcomes and significantly lower time-averaged rcSO2 (51.1% [50.0%–65.2%] vs. 71.8% [67.1%–73.1%], P=0.002). Multivariate regression indicated that a lower rcSO2 was an independent risk factor, and a 65% threshold showed an optimal predictive value for poor outcomes. Conclusion The neurocritical care bundle helped identify preterm infants at risk of cerebral hypoxia, and lower rcSO2 was an independent risk factor for composite mortality and adverse neurological outcomes.

Objective To explore the clinical efficacy of single-branch intraoperative stent combined with modified bilateral cerebral perfusion in type A aortic dissection. Methods A retrospective analysis was conducted on the clinical data of patients who underwent surgery for type A aortic dissection at the First Affiliated Hospital of Anhui Medical University from January 2021 to May 2024. Patients were divided into a test group (single branch stent+modified bilateral cerebral perfusion) and a control group (traditional surgical method, straight stent+unilateral cerebral perfusion) according to the surgical method. Propensity score matching analysis was used to match the two groups of patients with a ratio of 1:1, and the perioperative data and clinical efficacy after matching were compared. Results A total of 14 patients were included in the test group, including 13 males and 1 female, with an average age of (46.6±16.4) years. There were 56 patients in the control group, including 38 males and 18 females, with an average age of (52.1±11.7) years. After propensity score matching, 14 patients were included in each group. Compared with the control group, the ventilator support time [(27.4±24.3) h vs. (93.4±88.0) h, P=0.018], length of stay in the intensive care unit [(2.8±1.8) d vs. (8.7±6.5) d, P=0.009], and postoperative awakening time [(5.4±2.2) h vs. (8.8±4.8) h, P=0.047] in the test group were shorter than those in the control group, with statistically significant differences. There was no statistical difference in neurological complications between the two groups (P=1.000). Conclusion Single-branch intraoperative stent combined with modified bilateral cerebral perfusion can effectively shorten ventilator support time, length of stay in the intensive care unit, and postoperative awakening time, and is safe and effective for the treatment of type A aortic dissection, which is worth further promotion.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Objective To explore the correlation and lag effect between meteorological factors and the incidence of scarlet fever in Xicheng District, Beijing, and to provide a theoretical basis for the surveillance, early warning，and scientific prevention and control of scarlet fever. Methods Based on the daily scarlet fever incidence data and concurrent meteorological data in Xicheng District, Beijing from 2010 to 2019, the distributed lag non-linear model (DLNM) was used to analyze the impact of meteorological factors on the incidence of scarlet fever. Results The risk of scarlet fever was the highest when the daily average temperature was 34.2℃ with a lag of 0 days (RR=1.175, 95% CI:1.006-1.372). The risk was the second highest when the daily average temperature was 2.2℃ with a lag of 12 days (RR=1.123, 95% CI:1.044 -1.209). The cumulative relative risk of scarlet fever was statistically significant when the daily average temperature ranged from 27.2℃ to 34.2℃, with the highest cumulative relative risk at 34.2℃ (RR=1.906, 95%CI:1.215-2.989). When the daily average relative humidity was 19.5% with a lag of 6 days, the risk of scarlet fever incidence was the highest (RR=1.022, 95% CI: 1.005-1.040). The cumulative relative risk was statistically significant when the daily average relative humidity ranged from 24.7% to 40.2%, with the highest cumulative relative risk at 27.3% (RR=1.170, 95% CI: 1.020-1.343). The risk of scarlet fever was the highest when the daily average vapor pressure was 1.2 hPa with a lag of 5 days (RR=1.029, 95%CI:1.008-1.050). The cumulative relative risk of scarlet fever was statistically significant when the daily average vapor pressure was 1.2-7.4 hPa, and the highest cumulative risk was when the daily average vapor pressure was 1.2 hPa (RR=1.362, 95% CI:1.022-1.815). Conclusion There is a nonlinear relationship between meteorological factors and the incidence of scarlet fever in Xicheng District, Beijing, with a certain lag effect. Daily average temperature (27.2-34.2℃), daily average relative humidity (28.6~36.3%) and daily average vapor pressure (1.2-7.4 hPa) increase the risk of scarlet fever. These factors can be used as indicators for the prevention, control, surveillance, and early warning of scarlet fever.

Objective:To observe the efficacy and safety of polatuzumab vedotin(pola)combined with chemotherapy in the treatment of relapsed and refractory diffuse large B-cell lymphoma(R/R DLBCL).Methods:A total of 23 patients with R/R DLBCL treated at the First Affiliated Hospital of Zhejiang University and its Liangzhu Branch from April 2023 to March 2024 were retrospectively collected.All patients were treated with pola combined with chemotherapy regimens such as BR,R-GDP,R-CHOP,or other regimens.Results:All 23 patients were evaluable for efficacy,with 10 achieving complete response(CR),7 partial response(PR),3 stable disease(SD),and 3 progressive disease(PD).The most common adverse events included myelosuppression,fever,and pulmonary infection.No severe adverse events resulted in drug withdrawal.Conclusion:Pola combined with chemotherapy demonstrates promising efficacy and a favorable safety profile in the treatment of R/R DLBCL.

Objective:To explore effect of information management mode of full lifecycle for medical equipment on the basis of Service-Oriented Architecture(SOA)on the information management for information management of full lifecycle in hospital.Methods:An information management mode of full lifecycle for medical equipment was adopted to conduct information management for full lifecycle of medical equipment,so as to solve a series of problems included perception for the situation of equipment,and early warning for fault,and so on.A total of 100 medical equipment in clinical use at The First Rongjun Youfu Hospital of Shandong Province from February 2023 to February 2024 were selected for the study.In them,50 equipment were managed under a continuous improvement mode,while the other 50 equipment were managed by using a SOA-based information management mode of full lifecycle(information management mode).The score of management quality for equipment,management standardization and operational quality of the two kinds of management modes were compared.A self-designed satisfaction questionnaire of using and managing equipment was used to survey the satisfactions of medical engineers,operators of equipment,and staffs of equipment department in using and managing equipment,who involved in usage and management for equipment.Results:Under the information management mode,the scores for usage of equipment,the return efficiency,safety performance,maintenance quality,cleaning quality,and overall evaluation were respectively(22.98±2.11),(23.69±1.65),(22.74±1.36),(23.65±1.54),and(93.01±4.65),all of which were significantly higher than those of the continuous improvement mode,with statistically significant differences(t=6.672,11.428,9.256,12.976,13.182,P<0.05).The standardizations of usage operation of equipment,cleaning and disinfection,safety monitoring,and quality control of adopting information management mode were higher than those of adopting continuous improvement mode(x2=13.709,11.679,11.284,15.120,P<0.05).The failure rates of surgical equipment,therapeutic equipment,diagnostic equipment,dialysis equipment,and emergency equipment of adopting information management mode were all lower than those of adopting continuous improvement mode,with statistically significant differences(x2=16.872,13.878,17.156,11.679,12.805,P<0.05).Satisfaction scores of medical engineers,operators for equipment,and staffs of equipment department of adopting information management mode were significantly higher than those of adopting the continuous improvement mode,with statistically significant differences(t=16.872,13.878,17.156,P<0.05).Conclusion:The application of a SOA-based information management mode of full lifecycle for medical equipment in management for medical equipment can enhance management level for equipment,and improve operational quality of equipment,and enhance safety and utilization efficient of using equipment.