ObjectiveTo investigate the effect of mitochondrial calcium uniporter （MCU） on the cytoskeleton of pancreatic ductal epithelial cells in a mouse model of acute pancreatitis （AP） induced by caerulein （CAE）， to analyze the role of MCU in the development of AP， and to provide a theoretical basis for clinical treatment. MethodsIn the in vivo experiment， wild-type male C57BL6/J mice， aged 4 weeks， were randomly divided into control group and AP group， with 6 mice in each group. The mice in the AP group were given intraperitoneal injection of CAE to establish a model of AP， and those in the control group were given intraperitoneal injection of an equal volume of normal saline. Serum and pancreatic tissue samples were collected after 24 hours of modeling. HE staining was used to observe pancreatic histopathological changes； Western Blot was used to measure the expression levels of MCU， glutathione peroxidase 4 （GPX4）， and acyl-CoA synthetase long chain family member 4 （ASCL4）； kits were used to measure the serum level of amylase. In the in vitro experiment， the human pancreatic ductal epithelial cell line HPDE6-C7 was co-cultured with CAE for 24 hours to establish an in vitro AP model， and the cells were divided into control group， CAE group， RR （an MCU activity inhibitor） group， CAE+RR group， Fer-1 （an ferroptosis inhibitor） group， CAE+Fer-1 group， Erastin （an ferroptosis inducer） group， and CAE+Erastin group. CCK-8 assay was used to observe the influence of different agents on cell viability； Western Blot was used to measure the expression levels of MCU， GPX4， and ASCL4； immunofluorescence assay was used to measure reactive oxygen species （ROS）， actin cytoskeleton， and monolayer permeability； kits were used to measure the concentrations of malondialdehyde （MDA）， glutathione （GSH）， Fe²⁺， and total iron. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for comparison between two groups. ResultsIn the in vivo experiment， compared with the control group， the AP group had significant increases in pancreatic histopathological score， the serum level of amylase， and the expression levels of MCU and ASCL4， as well as a significant reduction in the expression of GPX4 （all P<0.05）. In the in vitro experiment， compared with the control group， the CAE group had significant increases in the expression levels of MCU and ASCL4， a significant reduction in the expression of GPX4， and significant increases in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability， as well as a significant reduction in the concentration of GSH （all P<0.05）， with the presence of actin cytoskeleton disruption. Compared with the CAE group， the CAE+RR group had a significant increase in the expression level of GPX4， a significant reduction in the expression level of ASCL4， and significant reductions in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability and a significant increase in the concentration of GSH （all P<0.05）， with alleviation of actin cytoskeleton disruption. Compared with the CAE group， the CAE+Fer-1 group had significant reductions in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability and a significant increase in the concentration of GSH （all P<0.05）， with alleviation of actin cytoskeleton disruption. Compared with the CAE group， the CAE+Erastin group had significant increases in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability and a significant reduction in the concentration of GSH （all P<0.05）， with aggravation of actin cytoskeleton disruption. ConclusionDuring the onset of AP， MCU mediates oxidative stress-induced ferroptosis and leads to the disruption of the pancreatic ductal epithelial barrier， which may be one of the possible pathogeneses of AP.

ObjectiveTo describe the disposal process of the first imported case of Zika virus disease in Shanghai, and to provide a reference for the prevention and control of imported infectious diseases in the future. MethodsA retrospective review was conducted of the process by which epidemiological investigation, etiological testing, and case management were performed by the Shanghai municipal-and district-level Centers for Disease Control and Prevention (CDC) after one imported case of Zika virus disease was identified by Shanghai Customs. ResultsOn April 8th, 2025, customs authority at a certain airport in Shanghai identified a febrile inbound case (case A, female, 40 years old). An antecubital venous blood specimen was obtained and analyzed by nucleic acid testing for various vector-borne pathogens, by which Zika virus nucleic acid was found to be positive. On 9 April, the district CDC collected antecubital venous blood specimens again from Case A and her three accompanying travelers (B, C, and D), and nucleic acid testing was conducted for multiple mosquito-borne infectious diseases. Case A again tested positive for Zika virus nucleic acid, while Traveler D (male, aged 6 years) tested positive for dengue virus nucleic acid. The other two travelers tested negative. Case A and Traveler D were subsequently transferred to a designated district hospital for isolation and treatment. After discharge, both cases left China and returned to their overseas residence. ConclusionCase A was the first imported case of Zika virus disease in Shanghai. For cases with a history of living in endemic areas of multiple infectious diseases such as dengue virus, Zika virus and chikungunya virus, it is necessary to carry out rapid testing of multiple pathogens simultaneously to prevent missed diagnosis or misdiagnosis.

Objective:To analyze the clinical characteristics and outcomes of Haemophilus influenzae (Hi) meningitis in children. Methods:This is a retrospective case series study. This study included 34 Hi meningitis patients who admitted to Beijing Children′s Hospital, Capital Medical University, from January 1, 2010, to December 31, 2023. Data on clinical presentations, laboratory tests, hearing assessment and outcomes at discharge were collected. Patients were divided into 2 groups according to the outcome at discharge: favorable outcome group and unfavorable outcome group. Mann-Whitney U test and Fisher exact test was used to estimate the risk factors for an unfavorable outcome at discharge. Results:Thirty-four patients were enrolled. There were 16 males and 18 females. The age at onset ranged from 3 months to 12 years. Fever (34 patients (100%)), convulsions (17 patients (50%)), and coma (21 patients (62%)) were the common clinical presentations. Twenty-four patients (71%) developed complications. There were 15 patients (44%) needed treatment in the intensive care unit, 5 patients (15%) received intubation, and 4 patients (12%) had developed shock. The favorable outcome group included 23 patients, and the unfavorable outcome group included 11 patients. Female, patients with limb movement disability, dystonia, ventriculomegaly or hydrocephalus, and a concentration of glucose in the initial cerebrospinal fluid lower than 1 mmol/L were risk factors of unfavorable outcome at discharge (all P<0.05). Among the 23 patients (68%) in favorable outcomes group, 13 patients (57%) had data available on their long-term follow-up results, including 12 patients with favorable long-term outcomes and 1 patient with unfavorable long-term outcome. Among the 11 patients (32%) in unfavorable outcomegroup, 1 patient died, the other 10 patients (91%) had data available on their long-term outcomes. Eight patients had unfavorable long-term outcomes and 2 patients with favorable long-term outcomes. Patients who had unfavorable outcomes at discharge were at a greater risk of experiencing unfavorable long-term outcomes ( P=0.001). Conclusions:It is common for patients with Hi meningitis to have intracranial complications or develop into critical conditions. Patients who have limb movement disability, dystonia, ventriculomegaly or hydrocephalus, and who exhibit a concentration of glucose in the initial cerebrospinal fluid lower than 1 mmol/L tend to have unfavorable outcomes; they need to be assessed for sequelae.

Weissella viridescens(W.viridescens)was used as the trained immunity inducer.We mo-nitored the protective efficacy against lethal infection of Candida albicans.After W.viridescens training,inflammatory mediator level was measured by NO assay kit upon re-stimulation,and the bacterial killing ability of peritoneal macrophages(PMs)was detected by counting CFU after Staphylococcus aureus(S.aureus)infection.The expression proteins in the classical signaling pathway of trained immunity were detected.Meanwhile,the PMs were pretreated with the corre-sponding inhibitors for the corroborative mechanism.The results showed that W.viridescens could induce trained immunity.The survival rate of Galleria mellonella treated with W.viridescens was still as high as 70％at 48 h,which protected against lethal infection of Candida albicans.W.viri-descens-trained PMs presented immune-enhancing activity,producing more inflammatory mediator(NO)after LPS stimulation and accelerating the clearance of S.aureus.To our delight,the high ex-pression levels of AKT/mTOR/HIF1α were observed under W.viridescens training.Moreover,in-hibiting the AKT/mTOR/HIF1α signaling with inhibitors dampened the trained response to LPS after W.viridescens training.Altogether,these results suggested that W.viridescens induces trained immunity through the AKT-mTOR-HIF-1α pathway to enhance the pro-inflammatory and anti-in-fective capacities of host cells.

Objective:To construct an artificial intelligence (AI)-based automatic grading model for neurological severity at acute phase of patients with traumatic cervical spinal cord injury (TCSCI) and evaluate its efficacy.Methods:A retrospective cohort study was conducted to analyze the clinical data of 315 patients with TCSCI admitted to the Second Affiliated Hospital of Naval Medical University from January 2019 to December 2023, including 243 males and 72 females, aged 30-75 years [(57.6±7.0)years]. Injured segments involved C 1-C 4 in 143 patients and C 5-C 8 in 172. According to the American Spinal Injury Association (ASIA) scale, the injuries were classified as Grade A in 15 patients, Grade B in 53, Grade C in 74, and Grade D in 173. The patients were randomly divided into training group ( n=252) and test group ( n=63) with a ratio of 8∶2. The patients′ sensory and motor functions were assessed according to the ASIA scale within 48 hours after injury. The cervical spine MRI instance segmentation model was used to extract injury severity features of TCSCI patients in sagittal T2-weighted images. The grading model consisted of a two-layer cascade network. The first layer involved gradient boosting, Gaussian naive bayes, K-nearest neighbors, decision tree, random forest and support vector machine classifier. In the training group, the 6 machine learning models were trained separately. In the second layer, the performance of the six models was optimized to obtain the corresponding optimal grading models, so as to match the models with the best grading performance for each feature. In the test group, the performance of each model was evaluated by calculating accuracy, recall, precision, average precision, and F1 score. Results:A total of 138 clinical and imaging features were included to construct an automatic grading model for neurological severity of TCSCI patients at acute phase, comprising 132 clinical neurological features (including 56 light touch sensory scores, 56 pinprick sensory scores, and 20 key muscle scores) and 6 MRI imaging features. In the test group, the accuracy, recall, precision, average precision and F1 score of the six models, including gradient boosting, Gaussian naive bayes, K-nearest neighbors, decision tree, random forest and support vector machine classifier in the first layer of the automatic grading model for neurological severity at acute phase of TCSCI patients, in the overall grading of light touch, pinprick sensory and key muscle motor function were all above 0.86. In terms of the overall light touch function grading performance, the models with the highest accuracy, recall, precision, average precision, and F1 score were K-nearest neighbors (0.90), gradient boosting (0.99), Gaussian naive bayes (0.98), random forest (0.96), and gradient boosting (0.96), respectively. In terms of the overall pinprick sensory function grading performance, the models with the highest accuracy, recall, precision, average precision, and F1 score were gradient boosting (0.98), Gaussian naive bayes (0.98), gradient boosting (0.99), decision tree (0.99), and gradient boosting (0.95), respectively. In terms of the overall key muscle motor function grading performance, the models with the highest accuracy, recall, precision, average precision, and F1 score were K-nearest neighbors (0.97), gradient boosting and support vector machine classifier (0.97), decision tree (0.95), random forest (0.95), and support vector machine classifier (0.96), respectively. In terms of sensory function, gradient boosting had the highest number of superior performances in the overall light touch and pinprick sensory function grading. In terms of motor function, the support vector machine classifier had the highest number of superior performances in the overall key muscle motor function grading.Conclusion:The automatic grading model for neurological severity at acute phase of patients with TCSCI that is constructed based on machine learning models and two-layer cascade networks can achieve the optimization of the grading performance of each feature and exhibit a strong grading ability for the sensory and motor function severity.

Objective:To explore the effect of combining intermittent θ pulse stimulation (iTBS) of the cerebellum with lower extremity exoskeleton robot support on the balance and walking function of stroke survivors.Methods:Seventy-five stroke survivors complicated with lower extremity dysfunction were divided into an iTBS group, an exoskeleton group and a combined group, each of 25, according to a random number table. In addition to conventional rehabilitation training, the iTBS group was given cerebellar iTBS combined with traditional walking training, the exoskeleton group received sham cerebellar iTBS combined with walking training assisted by a lower extremity exoskeleton robot. The combined group received both therapies. The schedule was once a day, 5 days a week for 3 weeks. Before and after the treatment, the 10-metre walking test (10MWT), the Berg Balance Scale (BBS) and the Fugl-Meyer lower extremity assessment (FMA-LE) were used to evaluate the subjects′ walking ability, balance and lower extremity motor ability. Gait and neuro-electrophysiological tests were also conducted in all three groups.Results:After the treatment, a significant improvement was observed in the 10MWT times, BBS scores, FMA-LE scores, stride frequency and stride speed of all three groups compared with before the treatment. On average, the results of the exoskeleton and combined groups were significantly better than those of the iTBS group, and those of the combined group were significantly better than among the exoskeleton group. Almost everyone′s MEP latency and amplitude had improved significantly compared with before the treatment, but the improvements in the exoskeleton group tended to be superior to those in the iTBS group ( P≤0.05). The latency in the combined group averaged (21.25±1.70)ms, and the amplitude averaged (184.17±6.54)μV, both significantly better than the exoskeleton group′s averages. Conclusions:Cerebellum iTBS combined with lower extremity exoskeleton walker training can significantly improve the motor functioning, balance and walking ability of stroke survivors.

Objective:To explore the effect of combining repeated peripheral (rPMS) and central transcranial magnetic stimulation (rTMS) in treating upper limb motor dysfunction after a stroke.Methods:Seventy-eight patients with upper limb motor dysfunction after a stroke were randomly divided into a control group, an rTMS group and a combined magnetic stimulation group, each of 26. All three groups underwent routine rehabilitation, while the rTMS group was repeatedly given low frequency transcranial magnetic stimulation of the M1 region on the unaffected side, and the combined group also received repeated peripheral magnetic stimulation at Erb′s point on the affected upper limb. There was one treatment session a day, 5 days a week for 3 weeks. Before and after the treatment, everyone′s upper limb motor function was quantified using the Fugl-Meyer upper extremity assessment (FMA-UE) and the Wolf motor function test (WMFT). Skill in the activities of daily living was quantified in terms of a Barthel index (BI). Motor recovery of the upper limbs and hands was assessed using Brunnstrom staging. The latency and amplitude of the motor evoked potentials (MEPs) in the subjects′ affected abductor pollicis brevis muscles were also recorded before and after the treatment. Pearson correlation coefficients quantified the correlation between the changes in FMA-UE scores and MEP amplitudes before and after the treatment in the three groups.Results:There were no significant differences among the three groups before the treatment. Afterward, however, the average FMA-UE, WMFT and BI scores, as well as the upper limb and hand Brunnstrom stages and the average MEP latencies and amplitudes of all the three groups had improved significantly. The combined group′s average results were then significantly better than the other two groups′ averages, except for the upper limb Brunnstrom stages. The increases in MEP amplitude were positively correlated with the increases in FMA-UE scores among the rTMS and the combined group, but there was no significant correlation between them in the control group.Conclusions:The combined application of rPMS and contralateral low frequency rTMS can effectively relieve motor dysfunction in the upper limbs in the early stages after a stroke.

Objective:To evaluate the immunogenicity and immune persistence of human rabies vaccine (Vero cell) in healthy people aged 10-17 years and compare it with a group of adults aged 18-60 years.Methods:This study was conducted between July 2021 and November 2022 with Shangyu district and Shengzhou city of Shaoxing city, Zhejiang Province selected as the research sites. Zagreb regimen (2-1-1 schedule) and Essen regimen (1-1-1-1-1 schedule) were used for rabies vaccine administration. Serum samples were collected at different time points before and after immunization to compare the differences in seropositivity rates and geometric mean concentrations (GMC) between the 10-17 age group and the 18-60 age group.Results:A total of 1 200 healthy participants aged 10-60 were included, with 157 individuals (13.1%) in the 10-17 age group and 1 043 individuals (86.9%) in the 18-60 age group. Both groups displayed a nearly 100% seropositivity rate at 3, 6 and 12 months, and the participants in the same age group had similar antibody levels. The GMC of antibodies gradually increased after vaccination and peaked on 14 d. The 10-17 age group showed higher GMC of antibodies than the 18-60 age group at 14 d after the first dose (Zagreb regimen: 81.85 IU/ml vs 63.15 IU/ml, t=2.411, P=0.018; Essen regimen: 86.61 IU/ml vs 69.24 IU/ml, t=3.906, P<0.001). Similar differences were observed in the GMC of antibodies at 14 d and 3 months after the full vaccination course, but these differences gradually decreased and disappeared at 6 and 12 months after vaccination. Conclusions:Human rabies vaccine (Vero cell) has lasting immune protection in all participants within one year after vaccination, with no significant differences between the two vaccination regimens. Participants aged 10-17 have higher antibody levels compared to adults aged 18-60, but there is no significant difference in immune persistence between the two age groups.

Dental caries is a major disease that seriously endangers human oral health. Dental plaque biofilm composed of many microorganisms is the primary factor of dental caries. Inhibiting biofilm formation has become the focus of research on the prevention and treatment of dental caries. Streptococcus mutans and Candida albicans, as common pathogenic bacteria in the oral cavity, are closely related to the occurrence of dental caries. The interaction between the two can lead to the rapid onset of dental caries. In recent years, many studies have found that Candida albicans promotes the occurrence of caries by interacting with Streptococcus mutans, including physical adhesion, promoting the production of exopolysaccharides (EPS), reducing the pH of the microecological environment, forming a highly cariogenic acidic environment, and secreting quorum sensing molecules to trigger quorum sensing. As a communication mechanism between microorganisms, the quorum sensing system mainly includes three main types: autoinducing peptide (AIP) system, autoinducer-2 (AI-2) system, and Acyl-homoserine lactone (AHL) system. At present, quorum sensing has been shown to promote the occurrence of diseases by activating the expression of microbial pathogenicity-related genes, promoting EPS synthesis and biofilm formation. The CSP-ComDE and ComRS quorum sensing systems of Streptococcus mutans allow the bacteria to survive and cause disease in extreme environments that are unfavorable for survival, while the quorum sensing system of Candida albicans is mainly mediated by farnesol, which has a negative regulatory effect on the yeast-hyphae transformation of Candida albicans. Studying the quorum sensing phenomenon of the two bacteria is helpful to understand the etiology of caries. In recent years, many studies have reported the use of quorum sensing inhibitors in anti-microbial applications. The study of microbial quorum sensing systems and inhibitors will help the prevention and treatment of caries. With the increasing interest in biofilm-related research, and a new method for in-depth study of the biofilm formation process and quorum sensing behavior using microfluidic and chip laboratory technology is proposed. The author summarizes the cariogenic effects, the quorum sensing system and quorum sensing inhibitors of Streptococcus mutans and Candida albicans.

Weissella viridescens(W.viridescens)was used as the trained immunity inducer.We mo-nitored the protective efficacy against lethal infection of Candida albicans.After W.viridescens training,inflammatory mediator level was measured by NO assay kit upon re-stimulation,and the bacterial killing ability of peritoneal macrophages(PMs)was detected by counting CFU after Staphylococcus aureus(S.aureus)infection.The expression proteins in the classical signaling pathway of trained immunity were detected.Meanwhile,the PMs were pretreated with the corre-sponding inhibitors for the corroborative mechanism.The results showed that W.viridescens could induce trained immunity.The survival rate of Galleria mellonella treated with W.viridescens was still as high as 70％at 48 h,which protected against lethal infection of Candida albicans.W.viri-descens-trained PMs presented immune-enhancing activity,producing more inflammatory mediator(NO)after LPS stimulation and accelerating the clearance of S.aureus.To our delight,the high ex-pression levels of AKT/mTOR/HIF1α were observed under W.viridescens training.Moreover,in-hibiting the AKT/mTOR/HIF1α signaling with inhibitors dampened the trained response to LPS after W.viridescens training.Altogether,these results suggested that W.viridescens induces trained immunity through the AKT-mTOR-HIF-1α pathway to enhance the pro-inflammatory and anti-in-fective capacities of host cells.