Objective To explore the adverse event signals of children using macrolide drugs （azithromycin, clarithromycin, and erythromycin）, and provide reference for rational medicine use in clinical practice. Methods Data from children under 12 years old were extracted from the US FAERS database spanning from the first quarter of 2004 to the second quarter of 2023. The adverse drug reaction （ADR） signal mining for three macrolide antibiotics was conducted using the Reporting Odds Ratio （ROR） and Bayesian Confidence Propagation Neural Network （BCPNN） methods. Special emphasis was placed on analyzing and contrasting the differences in adverse events among the three drugs. Results A total of 1 615 reports for children under 12 years old were retrieved from the FAERS database, including 1 024 reports of azithromycin, 460 reports of clarithromycin, and 131 reports of erythromycin. Among azithromycin and erythromycin, there were more reports from boys than girls, while for clarithromycin, there were more reports from girls than boys. Oral administration was the most common route of administration for all three drugs. Regarding the outcome of adverse events reported, azithromycin and clarithromycin were primarily associated with other serious adverse events, whereas erythromycin was mainly associated with hospitalization and other serious adverse events. The number of adverse events reported decreased with increasing age, with a higher number of reports in the 0-3 age group. Using the ROR and BCPNN methods for signal detection, 86 signals were identified for azithromycin, 91 for clarithromycin, and 34 for erythromycin. These signals involved 22 System Organ Classes （SOCs）, with azithromycin mainly concentrated in skin and subcutaneous tissue disorders （n=21）, clarithromycin in gastrointestinal disorders （n=15）, and erythromycin in gastrointestinal disorders （n=8）. Twenty-four signals of moderate to high risk were detected, with 13 for azithromycin, 9 for clarithromycin, and 2 for erythromycin. Conclusion The adverse events induced by the three drugs with different risks in different systems. When clinically treating Mycoplasma pneumoniae pneumonia in children, the risk profiles of drugs in different systems should be considered, and personalized dosing should be implemented.

BACKGROUND:Peripheral nerve axon rupture seriously affects patients' physical function and mental health.Microsurgery,nerve autograft,nerve allograft,fibrin glue and catheter technology are the main treatments for peripheral nerve injury,each of which has its own advantages and disadvantages,but the overall treatment effect is not satisfactory.Despite the clinical success of Schwann cells in promoting axonal regeneration,there are still many challenges in the treatment with Schwann cells,such as slow expansion of Schwann cells,immune rejection,and low survival rate of transplanted cells.OBJECTIVE:To summarize the role and mechanism of Schwann cells in promoting the regeneration of peripheral nerve axons,and the difficulties and challenges of Schwann cells in the process of nerve regeneration treatment.METHODS:PubMed,Medline,WanFang,VIP,and CNKI were searched by computer using the search terms of"Schwann cells,synaptic Schwann cell,macrophage,peripheral nerve axon rupture,Wallerian degeneration,Peripheral nerve axon regeneration,Central nervous system repair"in English and Chinese.Literature related to Schwann cell proliferation and differentiation,promotion of peripheral nerve regeneration,and clinical applications was retrieved from database inception to October 2024,and a total of 95 articles were finally included for review.RESULTS AND CONCLUSION:Schwann cells interact with macrophages,T cells and other cells,to initiate the regeneration process through signaling pathways,including Krox20/C-Jun,NRG-1/ErbB,Notch,MAPK,and PI3K/Akt/mTOR,synthesize and release nerve growth factors,and thus promote regeneration of the peripheral nervous system.Schwann cells have been experimentally demonstrated to have great potential in peripheral nerve repair and are expected to become the key target of therapeutic intervention.However,there are still problems such as difficulties in cell harvest and culture,as well as the occurrence of other diseases during the treatment process.

BACKGROUND:Peripheral nerve axon rupture seriously affects patients' physical function and mental health.Microsurgery,nerve autograft,nerve allograft,fibrin glue and catheter technology are the main treatments for peripheral nerve injury,each of which has its own advantages and disadvantages,but the overall treatment effect is not satisfactory.Despite the clinical success of Schwann cells in promoting axonal regeneration,there are still many challenges in the treatment with Schwann cells,such as slow expansion of Schwann cells,immune rejection,and low survival rate of transplanted cells.OBJECTIVE:To summarize the role and mechanism of Schwann cells in promoting the regeneration of peripheral nerve axons,and the difficulties and challenges of Schwann cells in the process of nerve regeneration treatment.METHODS:PubMed,Medline,WanFang,VIP,and CNKI were searched by computer using the search terms of"Schwann cells,synaptic Schwann cell,macrophage,peripheral nerve axon rupture,Wallerian degeneration,Peripheral nerve axon regeneration,Central nervous system repair"in English and Chinese.Literature related to Schwann cell proliferation and differentiation,promotion of peripheral nerve regeneration,and clinical applications was retrieved from database inception to October 2024,and a total of 95 articles were finally included for review.RESULTS AND CONCLUSION:Schwann cells interact with macrophages,T cells and other cells,to initiate the regeneration process through signaling pathways,including Krox20/C-Jun,NRG-1/ErbB,Notch,MAPK,and PI3K/Akt/mTOR,synthesize and release nerve growth factors,and thus promote regeneration of the peripheral nervous system.Schwann cells have been experimentally demonstrated to have great potential in peripheral nerve repair and are expected to become the key target of therapeutic intervention.However,there are still problems such as difficulties in cell harvest and culture,as well as the occurrence of other diseases during the treatment process.

Objective To explore the role of X chromosome encoded epigenetic regulator UTX in NK cell-mediated anti-tumor activity.Methods Male Ncr1-iCre mice were crossed with female UTXfl/fl mice to generate F1 Ncr1-iCre+UTXfl/-male mice,which were further crossed with female UTXfl/fl mice to obtain male Ncr1-iCre-UTX fl/-control mice(M-Con)and NK-specific deletion of UTX male mice Ncr1-iCre+UTXfl/-(M-KO),as well as female Ncr1-iCre-UTXfl/fl control mice(F-Con)and UTX-deficient female mice Ncr1-iCre+UTXfl/fl(F-KO).UTX-deficient mice were injected with melanoma cell line B16F10 via tail vein to observe pulmonary metastatic tumor nodules.Moreover,flow cytometry was applied to detect the proportion and quantity of pulmonary NK cells(CD3-CD19-NK1.1+),maturation makers KLRG1 and CD11b,activation receptors NKG2D and CD69,and effector molecules,including perforin,granzyme B,CD107a,and IFN-γ.Then pulmonary NK cells were sorted and co-cultured with B16F10 cells,and the apoptosis of the melanoma cells was measured with flow cytometry.Results Compared with the M-Con mice,the M-KO mice presented less number of pulmonary tumor nodules(P<0.05),increased proportion and quantity of NK cells in the tumor microenvironment(P<0.01),though no obvious changes in the ratio of NK maturation makers KLRG1 to CD11b,enhanced expression level of cytotoxic molecule perforin(P<0.01),but no changes in the expression of effector molecule granzyme B,degranulation marker CD107a and cytokine IFN-γ in NK cells.Co-culture of NK cells and B16F10 cells promoted the apoptosis of tumor cells(P<0.05).Compared with the F-Con mice,the F-KO mice had no statistical difference in the number of pulmonary tumor nodules,but larger proportion and number of NK cells(P<0.05),decreased ratio of KLRG1 to CD11b(P<0.01),elevated level of perforin but decreased levels of granzyme B,CD107a and IFN-γ in NK cells(P<0.01).The co-culture of NK cells and B16F10 cells reduced the apoptosis of tumor cells in F-KO female mice(P<0.05).Conclusion NK-specific deletion of UTX regulates pulmonary metastasis of melanoma in a sex-dependent manner.

[Objective] To investigate the effect of Shenmai injection on the preservation quality of suspended red blood cells of high hemoglobin population in Xizang plateau. [Methods] Whole blood (400 mL, n=8) collected by the Xizang Autonomous Region Blood Center was centrifuged at 3 000 g for 10 minutes to remove most of the plasma, followed by the addition of 100 mL of MAP preservation solution to obtain plateau suspended red blood cells, which were then divided into three equal portions. One portion was the control group, and another part had 15 mL of MAP preservation solution added, which was the dosage group. The third portion involved diluting Shenmai injection with MAP, followed by addition of 15 mL of MAP preservation solution containing Shenmai to the red blood cells, resulting in a final concentration of Shenmai injection of 1%, which was the Shenmai group. Blood routine, pH value, electrolytes, glucose, lactate, free Hb, adenosine triphosphate (ATP), P50, phosphatidylserine (PS) and other indicators were detected at day 1, 21 and 35, respectively. [Results] The Hb concentration and Hct of the dosage group and the Shenmai group were significantly lower than those of the control group, with values of (179.3±17.8) vs (181.0±17.1) vs (199.1±19.5) g/L for Hb concentration and (53.2±2.6)% vs (53.3±2.5)% vs (58.4±3.1)% for Hct. The three groups maintained this pattern until the end of storage. In the middle and late stages of preservation, the glucose and Na⁺ contents in the dosage group and the Shenmai group were higher than those in the control group, while the lactate and K⁺ contents were lower than those in the control group. At the end of storage, the glucose and Na⁺ content of the Shenmai group was higher than that of the dosage group, while the lactate and K⁺ content were lower than that of the dosage group. From day 1 to day 35 of storage, the hemolysis rate of the Shenmai group was significantly lower than that of the control group and the dosage group. On day 21 and 35 of storage, the PS expression rate in the Shenmai group was significantly lower than that in the control group and the dosage group, which were (6.52±0.40)% vs (7.24±0.91)% vs (8.27±0.93)% and (7.29±0.53)% vs (9.37±0.82)% vs (8.39±0.76)%, respectively. [Conclusion] The hemolysis rate and PS of suspended red blood cells of Xizang high altitude prepared by adding Shenmai injection were significantly lower than those in the control group and the dosage group, which was conducive to reducing hemolysis and slowing down the aging of red blood cells, and had a certain improvement on the preservation quality of suspended red blood cells in Xizang plateau people.

ObjectiveTo investigate the role of mature-tRNA-Asp-GTC and pre-tRNA-Arg-TCT in the ferroptosis phenotype of ovarian cancer （OC） cells and the regulatory mechanism of gypenoside L （Gyp-L） on mature-tRNA-Asp-GTC and pre-tRNA-Arg-TCT in OC cells. MethodsThe proliferation of human ovarian adenocarcinoma OVCAR3 cells was detected by cell counting kit-8 （CCK-8） assay， and the half-maximal inhibitory concentration （IC₅₀） values of cisplatin （DDP）， Gyp-L， and DDP in the presence of Gyp-L were calculated to determine the intervention concentration for subsequent experiments. Cell cloning assay and scratch assay reflected the proliferation and migration ability of OVCAR3 cells. PANDORA-seq small RNA sequencing was used to detect the differentially expressed transfer RNA-derived small RNAs （tsRNAs） in the cells after Gyp-L intervention， and the corresponding target genes of the tsRNAs were found by the RNAhybrid software. Malondialdehyde （MDA）， glutathione （GSH）， and lipid peroxide （LPO） levels were measured by colorimetry or enzyme linked immunosorbent assay （ELISA） method， Fe²⁺ content by FerroOrange fluorescent probe， and reactive oxygen species （ROS） content by DCFH-DA fluorescent probe to reflect the occurrence of ferroptosis in OVCAR3 cells. OVCAR3 cells were divided into a control group， a 50 µmol·L^-1 Gyp-L group， and a 100 µmol·L^-1 Gyp-L group. Quantitative real-time polymerase chain reaction （PCR） was performed to detect the expression of mature-tRNA-Asp-GTC， mature-tRNA-Leu-CAA， mature-mt_tRNA-Tyr-GTA_5_end， mature-tRNA-Val-CAC， mature-mt_tRNA-Glu-TTC， pre-tRNA-Arg-TCT， mature-tRNA-Asn-GTT， hydroxymethylbilane synthase （HMBS）， Wnt， β-catenin， glutathione peroxidase 4 （GPX4）， Kelch-like ECH-associated protein 1 （KEAP1）， nuclear factor erythroid 2-related factor 2 （Nrf2）， activating transcription factor 3 （ATF3）， cystine/glutamate antiporter xCT， lysophosphatidylcholine acyltransferase 3 （LPCAT3）， and arachidonate 15-lipoxygenase （ALOX15）. Western blot was performed to detect the expression of HMBS， Wnt， β-catenin， GPX4， KEAP1， Nrf2， ATF3， xCT， LPCAT3， and ALOX15 proteins. ResultsThe 50 µmol·L^-1 Gyp-L， 100 µmol·L^-1 Gyp-L， DDP， 50 µmol·L^-1 Gyp-L+DDP， and 100 µmol·L^-1 Gyp-L+DDP groups showed significantly inhibited proliferation and migration of OVCAR3 cells （P<0.05） and exacerbated cell ferroptosis as reflected by the increase in the content of ROS， MDA， LPO， and Fe²⁺， as well as a decrease in the content of GSH （P<0.05）. Compared with the control group， Gyp-L effectively interfered with the expression of 25 tsRNAs in OVCAR3 cells （P<0.05， |log₂Fc|>1）. Pre-tRNA-Arg-TCT/HMBS/Wnt/β-catenin/GPX4， pre-tRNA-Arg-TCT/KEAP1/NRF2/xCT， mature-tRNA-Asp-GTC/ATF3/KEAP1/NRF2/xCT， and mature-tRNA-Asp-GTC/LPCAT3/ALOX15 axial expression was significantly aberrant after Gyp-L intervention （P<0.05）. ConclusionThe pre-tRNA-Arg-TCT/HMBS/Wnt/β-catenin/GPX4， pre-tRNA-Arg-TCT/KEAP1/Nrf2/xCT， mature-tRNA-Asp-GTC/ATF3/KEAP1/Nrf2/xCT， and mature-tRNA-Asp-GTC/LPCAT3/ALOX15 signaling pathways are involved in OC development. Gyp-L inhibits OC development by activating OVCAR3 cell ferroptosis onset mainly through the mature-tRNA-Asp-GTC/ATF3/KEAP1/Nrf2/xCT and mature-tRNA-Asp-GTC/LPCAT3/ALOX15 signaling axes.

ObjectiveTo investigate the role of mature-tRNA-Asp-GTC and pre-tRNA-Arg-TCT in the ferroptosis phenotype of ovarian cancer （OC） cells and the regulatory mechanism of gypenoside L （Gyp-L） on mature-tRNA-Asp-GTC and pre-tRNA-Arg-TCT in OC cells. MethodsThe proliferation of human ovarian adenocarcinoma OVCAR3 cells was detected by cell counting kit-8 （CCK-8） assay， and the half-maximal inhibitory concentration （IC₅₀） values of cisplatin （DDP）， Gyp-L， and DDP in the presence of Gyp-L were calculated to determine the intervention concentration for subsequent experiments. Cell cloning assay and scratch assay reflected the proliferation and migration ability of OVCAR3 cells. PANDORA-seq small RNA sequencing was used to detect the differentially expressed transfer RNA-derived small RNAs （tsRNAs） in the cells after Gyp-L intervention， and the corresponding target genes of the tsRNAs were found by the RNAhybrid software. Malondialdehyde （MDA）， glutathione （GSH）， and lipid peroxide （LPO） levels were measured by colorimetry or enzyme linked immunosorbent assay （ELISA） method， Fe²⁺ content by FerroOrange fluorescent probe， and reactive oxygen species （ROS） content by DCFH-DA fluorescent probe to reflect the occurrence of ferroptosis in OVCAR3 cells. OVCAR3 cells were divided into a control group， a 50 µmol·L^-1 Gyp-L group， and a 100 µmol·L^-1 Gyp-L group. Quantitative real-time polymerase chain reaction （PCR） was performed to detect the expression of mature-tRNA-Asp-GTC， mature-tRNA-Leu-CAA， mature-mt_tRNA-Tyr-GTA_5_end， mature-tRNA-Val-CAC， mature-mt_tRNA-Glu-TTC， pre-tRNA-Arg-TCT， mature-tRNA-Asn-GTT， hydroxymethylbilane synthase （HMBS）， Wnt， β-catenin， glutathione peroxidase 4 （GPX4）， Kelch-like ECH-associated protein 1 （KEAP1）， nuclear factor erythroid 2-related factor 2 （Nrf2）， activating transcription factor 3 （ATF3）， cystine/glutamate antiporter xCT， lysophosphatidylcholine acyltransferase 3 （LPCAT3）， and arachidonate 15-lipoxygenase （ALOX15）. Western blot was performed to detect the expression of HMBS， Wnt， β-catenin， GPX4， KEAP1， Nrf2， ATF3， xCT， LPCAT3， and ALOX15 proteins. ResultsThe 50 µmol·L^-1 Gyp-L， 100 µmol·L^-1 Gyp-L， DDP， 50 µmol·L^-1 Gyp-L+DDP， and 100 µmol·L^-1 Gyp-L+DDP groups showed significantly inhibited proliferation and migration of OVCAR3 cells （P<0.05） and exacerbated cell ferroptosis as reflected by the increase in the content of ROS， MDA， LPO， and Fe²⁺， as well as a decrease in the content of GSH （P<0.05）. Compared with the control group， Gyp-L effectively interfered with the expression of 25 tsRNAs in OVCAR3 cells （P<0.05， |log₂Fc|>1）. Pre-tRNA-Arg-TCT/HMBS/Wnt/β-catenin/GPX4， pre-tRNA-Arg-TCT/KEAP1/NRF2/xCT， mature-tRNA-Asp-GTC/ATF3/KEAP1/NRF2/xCT， and mature-tRNA-Asp-GTC/LPCAT3/ALOX15 axial expression was significantly aberrant after Gyp-L intervention （P<0.05）. ConclusionThe pre-tRNA-Arg-TCT/HMBS/Wnt/β-catenin/GPX4， pre-tRNA-Arg-TCT/KEAP1/Nrf2/xCT， mature-tRNA-Asp-GTC/ATF3/KEAP1/Nrf2/xCT， and mature-tRNA-Asp-GTC/LPCAT3/ALOX15 signaling pathways are involved in OC development. Gyp-L inhibits OC development by activating OVCAR3 cell ferroptosis onset mainly through the mature-tRNA-Asp-GTC/ATF3/KEAP1/Nrf2/xCT and mature-tRNA-Asp-GTC/LPCAT3/ALOX15 signaling axes.

Objective To analyze the situation of insecticide-treated nets (ITNs) ownership in malaria-endemic African countries from 2010 to 2023, so as to provide insights into China’s deeper participation in malaria control in Africa. Methods The study period from 2010 to 2023 was divided into three phases: the baseline phase (from 2010 to 2015), the middle phase (from 2016 to 2019), and the final phase (from 2020 to 2023), a total of 11 African countries with at least one Demographic and Health Survey (DHS) in each phase were included. Data pertaining to ITNs in 33 surveys of the above 11 African counties from 2010 to 2023 were captured from the DHS database, and the proportions of sources of ITNs and ITN ownership in each phase (number of ITNs ownership per person, overall ownership rate, and ownership rate per two residents) were calculated. The differences in numbers of ITNs per person between urban and rural areas and specified by socioeconomic status were analyzed. Results The proportions of ITNs from distribution campaigns were 60.24% to 94.01% and 50.46% to 85.04% in 11 African countries in the middle and final phases, respectively. The median numbers (interquartile range) of INTs ownership per person were 0.22 (0.50), 0.33 (0.50) and 0.33 (0.50) in the baseline, middle, and final phases, and the overall ownership rates [95% confidence interval (CI)] were 59.77% (59.50%, 60.05%), 70.32% (70.06%, 70.57%), and 69.21% (68.95%, 69.47%), while the ownership rates per two residents were 26.91% (26.66%, 27.16%), 38.07% (37.80%, 38.34%), and 36.56% (36.29%, 36.84%), respectively. The number of ITNs per person showed a significant increase followed by a significant decrease in 7 countries during all three phases (H = 102.518 to 2 327.440, all P < 0.05; Z = -48.886 to -4.653, all P < 0.016 7 after Bonferroni correction). In 33 surveys, there were 31 (Z = -26.719 to -2.472, P < 0.05) and 28 surveys (Z = -27.316 to -4.068, P < 0.001) with significant differences in numbers of ITNs ownership per person between households in urban and rural areas and with different socioeconomic status, including 20 surveys with a significantly higher number of ITNs ownership per person in households in rural areas than in urban areas, and 17 surveys with a significantly higher number of ITNs ownership per person among the poorest households than among the richest households. Conclusions There are substantial disparities in ITNs ownership in 11 African countries. Intensified co-operation on malaria prevention and control measures, such as ITNs, is recommended between China and African countries to build a global community of health for all.

This paper focuses on the application of health big data in cancer screening. Firstly, the sources and characteristics of health big data are introduced, then the commonly used epidemiological designs and analytical techniques in hospital-based cancer screening studies are summarized and the application scenarios of such studies are described. Finally, the challenges and future development in the application of health big data are analyzed to provide reference for the future studies.

Objective:To evaluate the role of necroptosis in paclitaxel-induced cognitive dysfunction in mice.Methods:Thirty SPF healthy male C57BL/6N mice, aged 6-8 weeks, weighing 20-25 g, were divided into 3 groups ( n=10 each) using a random number table method: vehicle control group (Veh group), paclitaxel group (PTX group), and paclitaxel+ a specific inhibitor of necroptosis Necrostatin-1 group (P+ N group). In PTX group and P+ N group, paclitaxel 10 mg/kg (diluted to 5 mg/ml in anhydrous ethanol and castor oil [1∶1], and further diluted to 1 mg/ml in 0.9% normal saline before use) was intraperitoneally injected daily for 7 consecutive days to induce cognitive dysfunction. P+ N group received an intraperitoneal injection of Necrostatin-1 6.5 mg/kg (diluted to 10 mg/ml in dimethyl sulfoxide, and further diluted to 1 mg/ml in 0.9% normal saline before use) at 2 h before paclitaxel administration every other day, 4 times in total. Veh group received the equal volume of solvent at the matched time points as previously described in P+ N group. After establishment of the model, spontaneous locomotor activity was assessed using the open field test, followed by the novel object recognition test and the Morris water maze to evaluate the cognitive function. The animals were sacrificed after the end of the Morris water maze test, and the hippocampal tissues were collected for determination of the expression of necroptosis-related proteins receptor-interacting serine/threonine-protein kinase 1 (RIPK1), RIPK3, mixed lineage kinase domain-like protein (MLKL), and phospho-MLKL (p-MLKL) (by Western blot analysis) and contents of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) (double immunofluorescence staining) and for observation of the localization of programmed necrosis cells (using enzyme-linked immunosorbent assay). Results:There were no significant differences in the total distance traveled and mean movement speed in the open field test or swimming speed in the Morris water maze test among the three groups ( P>0.05). Compared to Veh group, the time spent in the central zone in the open field and time spent in the original platform quadrant were significantly shortened, the discrimination index was decreased, the escape latency was prolonged, the number of crossing the original platform was reduced, the expression of RIPK1, RIPK3, MLKL and p-MLKL was up-regulated, the contents of TNF-α and IL-1β were increased, and the number of RIPK1-positive neurons was increased in PTX group ( P<0.05). Compared to PTX group, the time spent in the central zone in the open field test and time spent in the original platform quadrant were significantly prolonged, the discrimination index was increased, the escape latency was shortened, the number of crossing the original platform was increased, the expression of RIPK1, RIPK3, MLKL and p-MLKL was down-regulated, the contents of TNF-α and IL-1β were decreased, and the number of RIPK1-positive neurons was decreased in P+ N group ( P<0.05). Conclusions:Necroptosis in hippocampal neurons can lead to neuroinflammation, thus contributeing to paclitaxel-induced cognitive dysfunction in mice.