OBJECTIVE To investigate the targeting effect of folic acid-modified crebanine nanoparticles （FA-Cre@PEG- PLGA NPs， hereinafter referred to as “NPs”） combined with ultrasound irradiation on M109 cells in vitro and in vivo after administration， and explore the anti-tumor mechanism. METHODS CCK-8 assay was used to detect the inhibitory effect of NPs combined with ultrasound irradiation on the proliferation of M109 cells， and the best ultrasound time was selected. Using human lung cancer A549 cells as a control， the targeting of NPs combined with ultrasound irradiation to M109 cells was evaluated by free folic acid blocking assay and cell uptake assay. The effects of NPs combined with ultrasound irradiation on the migration， invasion， apoptosis， cell cycle and reactive oxygen species （ROS） levels of M109 cells were detected by cell scratch test， Transwell chamber test and flow cytometry at 1 h after 958401536@qq.com administration； the changes of mitochondrial membrane potential （MMP） were observed by fluorescence inverted microscope. A mouse subcutaneous tumor model of M109 cells was constructed， and the in vivo tumor targeting of NPs combined with ultrasound irradiation was investigated by small animal in vivo imaging technology. RESULTS NPs combined with ultrasound irradiation could significantly inhibit the proliferation of M109 cells， and the optimal ultrasound time was 1 h after administration. The free folic acid could antagonize the inhibitory effect of NPs on the proliferation of M109 cells， and combined with ultrasound irradiation could partially reverse this antagonism. Compared with A549 cells， the uptake rate of NPs in M109 cells was significantly higher （P＜0.01）， and ultrasound irradiation could promote cellular uptake. NPs combined with ultrasound irradiation could inhibit the migration and invasion of M109 cells and block the cell cycle in the G0/G1 and G2/M phases. Compared with control group， the apoptosis rate of M109 cells and ROS level were increased significantly （P＜0.01）， while the MMP decreased significantly （P＜0.01） in the different concentration （100， 200， 300 μg/mL） groups of M109 cells. Compared with the mice in non-ultrasound group， the fluorescence intensity and tumor-targeting index of the tumor site in the 0 h ultrasound group were significantly enhanced （P＜0.05 or P＜0.01）. CONCLUSIONS NPs combined with ultrasound irradiation have a strong targeting effect on M109 cells in vitro and in vivo， the anti-tumor mechanism includes inhibiting cell migration and invasion， blocking cell cycle， and inducing apoptosis.

Objective: To analyze the characteristics of alcohol poisoning cases among minors receiving pre hospital 120 emergency services in Zhengzhou, providing evidence for regional management strategies of alcohol poisoning among minors. Methods: A retrospective study was conducted on 1 630 alcohol poisoning cases (aged 0-18 years) from Zhengzhou s 120 emergency system during 2017-2019 and 2023. Data on gender, age, occurrence timeframes were analyzed using t-test and χ 2 test for intergroup comparisons. Results: Annual cases were 291 (2017), 353 (2018), 483 (2019), and 503 (2023). Compared with 2017, male alcohol poisoning cases increased by 66.94% while female cases surged 104.35% by 2023. The peak incidence of alcohol poisoning among minors occurred among 16-18 year olds (85.40%), followed by 13-15 year olds (13.74%). Most cases clustered between 21:01-03:00 (60.43%), with male cases peaking at 22:01-23:00 (12.73%) and female cases peaking at 02:01-03:00 ( 11.25 %). Between 00:01-03:00, male cases progressively decreased while female cases increased. Severity distribution showed 355 mild cases (21.78%), 1 035 moderate cases (63.50%), and 240 severe cases (14.72%). Conclusions Zhengzhou region has experienced sustained growth in underage alcohol poisoning cases, predominantly occurring from evening to early morning with moderate severity, female cases demonstrate faster growth rates. Multifaceted regulatory measures should be implemented to strengthen supervision of underage drinking behaviors.

Diabetic retinopathy (DR) is a diabetic ocular complication that can lead to poor vision and blindness. This experiment aimed to investigate the ameliorative effect and its mechanism of Panax notoginseng saponins (PNS) eye drops on streptozotocin (STZ)-induced non-proliferative diabetic retinopathy (NPDR) in rats. All experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Shanghai University of Traditional Chinese Medicine (No. PZSHUTCM 211115004). Diabetes mellitus was induced by a single intraperitoneal injection of STZ into rats. Two months later, PNS solution was dropped binocular twice per day at 6 h intervals at dose of 20, 40, and 80 mg·kg^-1 continuously for 1 month. The morphological structure and activation of microglia of the retina were observed by hematoxylin-eosin staining and immunohistochemical assay. The disruption of the blood-retina barrier (BRB) was conducted by the Evans blue dye leakage assay. The number of acellular capillaries in the retina was assessed by digesting and hematoxylin-eosin staining assay. The number of retinal leukocyte adhesion was observed by fluorescein isothiocyanate-coupled concanavalin A lectin labeling assay. The serum expression of inflammatory factors was measured using enzyme-linked immunosorbent assay. Western blot experiments were used to detect the expression of relevant proteins in retinal tissue and transcriptional activation of nuclear factor kappa-B (NF-κB). The results revealed that PNS eye drops significantly increased the thickness of the retina, decreased the number of acellular capillaries, and up-regulated the expression of the tight junction proteins claudin-1 and occludin, thereby alleviating BRB damage. In addition, PNS eye drops were also able to significantly reduce leukocyte adhesion and microglia activation, the expression of inflammatory factors in serum, and the nuclear translocation of retinal p65 proteins, effectively inhibiting the occurrence of retinal inflammation. The above results showed that PNS eye drops played a role in improving NPDR by inhibiting the activation of the NF-κB signaling pathway and reducing inflammation.

ObjectiveHuman Ku70 protein mainly involves the non-homologous end joining (NHEJ) repair of double-stranded DNA breaks (DSB) through its DNA-binding properties, and it is recently reported having an RNA-binding ability. This paper is to explore whether Ku70 has RNA helicase activity and affects miRNA maturation. MethodsRNAs bound to Ku protein were analyzed by RNA immunoprecipitation sequencing (RIP-seq) and bioinfomatic anaylsis. The expression relationship between Ku protein and miRNAs was verified by Western blot (WB) and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assays. Binding ability of Ku protein to the RNAs was tested by biolayer interferometry (BLI) assay. RNA helicase activity of Ku protein was identified with EMSA assay. The effect of Ku70 regulated miR-124 on neuronal differentiation was performed by morphology analysis, WB and immunofluorescence assays with or without Zika virus (ZIKV) infection. ResultsWe revealed that the Ku70 protein had RNA helicase activity and affected miRNA maturation. Deficiency of Ku70 led to the up-regulation of a large number of mature miRNAs, especially neuronal specific miRNAs like miR-124. The knockdown of Ku70 promoted neuronal differentiation in human neural progenitor cells (hNPCs) and SH-SY5Y cells by boosting miR-124 maturation. Importantly, ZIKV infection reduced the expression of Ku70 whereas increased expression of miR-124 in hNPCs, and led to morphologically neuronal differentiation. ConclusionOur study revealed a novel function of Ku70 as an RNA helicase and regulating miRNA maturation. The reduced expression of Ku70 with ZIKV infection increased the expression of miR-124 and led to the premature differentiation of embryonic neural progenitor cells, which might be one of the causes of microcephaly.

Objective To investigate the implementation of surveillance,prevention and control measures for healthcare-associated infection(HAI)in maternal and child healthcare(MCH)institutions,and provide policy evi-dence for optimizing HAI prevention and control in MCH institutions.Methods Stratified sampling was conducted among the MCH institutions at provincial,municipal and county levels in 8 provinces/autonomous regions.A uni-fied questionnaire was designed and the online survey was conducted through"Questionnaire Star".Results The data from 123 MCH institutions were included in the analysis.90.24％of the MCH institutions carried out compre-hensive surveillance on HAI.The ratios of MCH institutions which implemented targeted surveillance on HAI in neonatal intensive care unit(NICU),surgical site infection,multidrug-resistant organisms(MDROs)and HAI in intensive care units(non-NICU excluded)were 89.66％,85.96％,80.77％,and 74.19％,respectively.51.22％MCH institutions adopted information surveillance system on HAI cases.94.31％MCH institutions carried out surveillance on hand hygiene compliance.Over 90％MCH institutions carried out surveillance on environment hy-giene in high-risk departments.71.54％MCH institutions conducted centralized cleaning,disinfection,sterilization and supply for reusable medical instruments in the central sterile supply department(CSSD).Over 90％MCH insti-tutions established three-level pre-examination triage systems.86.18％set up transitional wards.MCH institutions generally adopted a management model with established effective communication,full appointment visits,and sepa-rate visits for special medical groups,such as registered pregnant women,high-risk newborns,healthcare groups,and long-term rehabilitation patients.However,the ratio of institutions conducting on-line follow-up visits was less than 50％.Conclusion MCH institutions have generally carried out comprehensive and targeted surveillance on HAI.Information surveillance need to be facilitated.Hand hygiene and environmental hygiene surveillance has been popularized to a certain extent at all levels of MCH institutions.The cleaning,disinfection,sterilization,and supply processes of reusable medical devices in a few MCH institutions are not standardized.Special medical populations get effective management.On-line healthcare is to be further promoted.

Objective This study aimed to compare the current Essen rabies post-exposure immunization schedule(0-3-7-14-28)in China and the simple 4-dose schedule(0-3-7-14)newly recommended by the World Health Organization in terms of their safety,efficacy,and protection. Methods Mice were vaccinated according to different immunization schedules,and blood was collected for detection of rabies virus neutralizing antibodies(RVNAs)on days 14,21,28,35,and 120 after the first immunization.Additionally,different groups of mice were injected with lethal doses of the CVS-11 virus on day 0,subjected to different rabies immunization schedules,and assessed for morbidity and death status.In a clinical trial,185 rabies-exposed individuals were selected for post-exposure vaccination according to the Essen schedule,and blood was collected for RVNAs detection on days 28 and 42 after the first immunization. Results A statistically significant difference in RVNAs between mice in the Essen and 0-3-7-14 schedule groups was observed on the 35th day(P<0.05).The groups 0-3-7-14,0-3-7-21,and 0-3-7-28 showed no statistically significant difference(P>0.05)in RVNAs levels at any time point.The post-exposure immune protective test showed that the survival rate of mice in the control group was 20%,whereas that in the immunization groups was 40%.In the clinical trial,the RVNAs positive conversion rates on days 28(14 days after 4 doses)and 42(14 days after 5 doses)were both 100%,and no significant difference in RVNAs levels was observed(P>0.05). Conclusion The simple 4-dose schedule can produce sufficient RVNAs levels,with no significant effect of a delayed fourth vaccine dose(14-28 d)on the immunization potential.

Objective:To compare the efficacy of conventional open ankle fusion and three dimensional(3D) printed guide plate assisted arthroscopic ankle fusion.Methods:A retrospective cohort study was performed on 256 patients with advanced traumatic ankle arthritis, who were admitted to the Department of Orthopaedics, Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from May 2018 to February 2023 and underwent ankle fusion procedures. The study cohort comprised 119 males and 137 females, with an age of (59.6±9.5) years (range: 37 to 83 years). Among them, 175 cases underwent internal fixation with plates and screws (58 cases through the combined medial and lateral approach, and 117 cases through the simple lateral approach), 48 cases underwent internal fixation with screws through the anterior approach (conventional open group), and 33 cases underwent minimally invasive arthroscopic ankle fusion assisted by 3D printed guide plate (3D printed guide plate arthroscopy group). Propensity score matching was employed to achieve a 1∶1 match(caliper value=0.02) between the baseline characteristics of patients in the 3D printed guide plate arthroscopy group and the conventional open group. Perioperative and follow-up data between the two groups were compared using the t-test, Mann-Whitney U test, Wilcoxon signed rank test, χ2 test or corrected χ2 test as appropriate. Results:Matching was successfully achieved with 20 cases in both the 3D printed guide plate arthroscopy group and the conventional open group, and there were no statistically significant differences in baseline characteristics between the two groups (all P>0.05). The operation time in the 3D printed guide plate arthroscopy group was significantly longer than that in the conventional open group ((88.9±5.6) minutes vs. (77.9±11.7) minutes; t=-2.392, P=0.022), while the frequency of intraoperative fluoroscopies ((1.7±0.8) times vs. (5.2±1.2) times; t=10.604, P<0.01) and length of hospitalization ((5.5±0.9) days vs. (6.4±1.5) days; t=2.480, P=0.018) were significantly lower in the 3D printed guide plate arthroscopy group compared to the conventional open group. The fusion rate was 95.0% (19/20) in the 3D printed guide plate arthroscopy group and 85.0% (17/20) in the conventional open group, with no statistically significant difference between the two groups ( χ2=0.278, P=0.598). The fusion time was (12.1±2.0) weeks in the conventional open group and (11.1±1.7) weeks in the 3D printed guide plate arthroscopy group, with no statistically significant difference between the two groups ( t=1.607, P=0.116). At the final follow-up, the American Orthopedic Foot and Ankle Society ankle hindfoot scale was (72.6±5.5)points in the 3D printed guide plate arthroscopy group and (70.5±5.8)points in the conventional open group, with no statistically significant difference between the two groups ( t=-1.003, P=0.322). The pain visual analogue score of the 3D printed guide plate arthroscopy group was ( M(IQR)) 1.50 (1.00) points, lower than that of the conventional open group by 3.00 (1.00) points, with statistically significant differences ( Z=-3.937, P<0.01). There was no significant difference in complication rate between the conventional open group and the 3D printed guide plate arthroscopy group (25.0%(5/20) vs. 5.0%(1/20), χ2=1.765， P=0.184). Conclusion:3D printed guide plate assisted arthroscopic ankle fusion exhibited several advantages, including reduced frequency of fluoroscopies, alleviation of postoperative pain, and decreased complications and length of hospitalization.

Objective:To compare the efficacy of conventional open ankle fusion and three dimensional(3D) printed guide plate assisted arthroscopic ankle fusion.Methods:A retrospective cohort study was performed on 256 patients with advanced traumatic ankle arthritis, who were admitted to the Department of Orthopaedics, Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from May 2018 to February 2023 and underwent ankle fusion procedures. The study cohort comprised 119 males and 137 females, with an age of (59.6±9.5) years (range: 37 to 83 years). Among them, 175 cases underwent internal fixation with plates and screws (58 cases through the combined medial and lateral approach, and 117 cases through the simple lateral approach), 48 cases underwent internal fixation with screws through the anterior approach (conventional open group), and 33 cases underwent minimally invasive arthroscopic ankle fusion assisted by 3D printed guide plate (3D printed guide plate arthroscopy group). Propensity score matching was employed to achieve a 1∶1 match(caliper value=0.02) between the baseline characteristics of patients in the 3D printed guide plate arthroscopy group and the conventional open group. Perioperative and follow-up data between the two groups were compared using the t-test, Mann-Whitney U test, Wilcoxon signed rank test, χ2 test or corrected χ2 test as appropriate. Results:Matching was successfully achieved with 20 cases in both the 3D printed guide plate arthroscopy group and the conventional open group, and there were no statistically significant differences in baseline characteristics between the two groups (all P>0.05). The operation time in the 3D printed guide plate arthroscopy group was significantly longer than that in the conventional open group ((88.9±5.6) minutes vs. (77.9±11.7) minutes; t=-2.392, P=0.022), while the frequency of intraoperative fluoroscopies ((1.7±0.8) times vs. (5.2±1.2) times; t=10.604, P<0.01) and length of hospitalization ((5.5±0.9) days vs. (6.4±1.5) days; t=2.480, P=0.018) were significantly lower in the 3D printed guide plate arthroscopy group compared to the conventional open group. The fusion rate was 95.0% (19/20) in the 3D printed guide plate arthroscopy group and 85.0% (17/20) in the conventional open group, with no statistically significant difference between the two groups ( χ2=0.278, P=0.598). The fusion time was (12.1±2.0) weeks in the conventional open group and (11.1±1.7) weeks in the 3D printed guide plate arthroscopy group, with no statistically significant difference between the two groups ( t=1.607, P=0.116). At the final follow-up, the American Orthopedic Foot and Ankle Society ankle hindfoot scale was (72.6±5.5)points in the 3D printed guide plate arthroscopy group and (70.5±5.8)points in the conventional open group, with no statistically significant difference between the two groups ( t=-1.003, P=0.322). The pain visual analogue score of the 3D printed guide plate arthroscopy group was ( M(IQR)) 1.50 (1.00) points, lower than that of the conventional open group by 3.00 (1.00) points, with statistically significant differences ( Z=-3.937, P<0.01). There was no significant difference in complication rate between the conventional open group and the 3D printed guide plate arthroscopy group (25.0%(5/20) vs. 5.0%(1/20), χ2=1.765， P=0.184). Conclusion:3D printed guide plate assisted arthroscopic ankle fusion exhibited several advantages, including reduced frequency of fluoroscopies, alleviation of postoperative pain, and decreased complications and length of hospitalization.

Objective To investigate the mechanism by which mycobacterial antigen 85B (Ag85B) inhibits autophagy and promotes apoptosis in Hodgkin lymphoma (HL) cells. Methods The clinical data and pathological tissue slides were retrospectively collected from 80 HL children and 30 children with reactive lymphadenopathy (control group) treated at the First Affiliated Hospital of Xinjiang Medical University. Immunohistochemical analysis was performed to assess the expression of microtubule-associated protein 1 light chain 3 (LC3),sequestosome 1 (P62/SQSTM1),and Beclin-1 in the pathological tissues of HL and control groups. Human Hodgkin lymphoma cells (HDLM-2) were divided into the HDLM-2 group and the HDLM-2+Ag85B groups (with Ag85B concentrations of 0.5,1,2,and 4 μg/mL). The CCK8 method was used to measure HDLM-2 cell proliferation;qRT-PCR was employed to detect the expression of LC3,P62,Beclin-1,Akt,and mTOR mRNA in cells. An apoptosis kit was used to detect cell apoptosis. Results The positive expression of LC3 and Beclin-1 in the HL group were higher than those in the control group (P<0.05),while the positive expression of P62 was lower than that in the control group (P<0.05). In stages Ⅲ-Ⅳ compared to stages Ⅰ-Ⅱ,the positive expression of LC3 and Beclin-1 increased,while the positive expression of P62 decreased (P<0.05). Cell experiment results showed that the HDLM-2+Ag85B group had suppressed cell proliferation compared to the HDLM-2 group,with decreased mRNA expression of LC3 and Beclin-1,and increased mRNA expression of P62,PI3K,Akt,and mTOR,leading to increased cell apoptosis. Notably,when Ag85B was at a concentration of 2 μg/mL,it had the strongest effect on HDLM-2 cells after 24 hours (P<0.05). Conclusions Autophagy is enhanced in children with HL and increases with disease stage. Ag85B can inhibit the proliferation and autophagy of HL tumor cells and promote apoptosis,possibly related to the activation of the PI3K/Akt/mTOR pathway.

Objective:To explore the plasma metabolomic characteristics of children with transfusion-dependent thalassemia(TDT),and reveal the changes of metabolic pattern in children with TDT.Methods:23 children with TDT who received regular blood transfusion in Ganzhou Women and Children's Health Care Hospital in 2021 were selected,and 11 healthy children who underwent physical examination during the same period were selected as the control group.The routine indexes between children with TDT and the control group were compared,and then the metabolic composition of plasma samples from children with TDT and the control group was detected by liquid chromatography-mass spectrometry.An OPLS-DA model was established to perform differential analysis on the detected metabolites,and the differential metabolic pathways between the two groups were analyzed based on the differential metabolites.Results:The results of routine testing showed that the indexes of ferritin,bilirubin,total bile acid,glucose and triglycerides in children with TDT were significantly higher than those in healthy controls,while hemoglobin and total cholesterol were significantly lower(all P＜0.05).However there was no significant difference in lactate dehydrogenase between the two groups(P＞0.05).Compared with the control group,190 differential metabolites(VIP＞1)were identified in TDT children.Among them,168 compounds such as arginine,proline and glycocholic acid were significantly increased,while the other 22 compounds such as myristic acid,eleostearic acid,palmitic acid and linoleic acid were significantly decreased.The metabolic pathway analysis showed that the metabolic impact of TDT on children mainly focused on the upregulation of amino acid metabolism and downregulation of lipid metabolism.Conclusion:The amino acid and lipid metabolism in children with TDT were significantly changed compared with the healthy control group.This finding is helpful to optimize the treatment choice for children with TDT,and provides a new idea for clinical treatment.