OBJECTIVE To analyze the characteristics of pediatric medicines with priority review and approval for marketing in China， providing a reference for promoting enterprise R&D and production， as well as improving the supply guarantee mechanism for pediatric medicines. METHODS Based on publicly available data sources such as List of Approved Information for Pediatric Medications Subject to Priority Review and Approval， Pharnexcloud biomedical database， and National Medical Insurance Drug Directory， this study conducted a comprehensive analysis of the main characteristics of pediatric medicines with priority review and approval for marketing. RESULTS As of June 30， 2024， a total of 68 pediatric medicines had been approved through the priority review and approval process， covering 12 therapeutic areas， with oral dosage forms accounting for 64.71%. The median time from application to inclusion in priority review was 35.50 days， with an average of 41.69 days. The median time from inclusion in priority review to market approval was 1.24 years， with an average of 1.42 years. This included 12 domestic new medicines， 21 domestic generic medicines， 35 imported medicines， as well as 29 pediatric-specific medicines and 21 orphan medicines. Additionally， 31 of these medicines had been included in the medical insurance catalog， representing a proportion of 45.59%. CONCLUSIONS Currently， a trend of differentiated competition is emerging between domestic and imported pediatric medicines. The therapeutic areas for pediatric medicines are continuously expanding， and the dosage forms are becoming more tailored to children’s needs. However， there are still issues such as slow progress in new medicine development， insufficient stability in the medicine review and approval process， and a need to increase the proportion of medicines included in medical insurance.

BACKGROUND:Human periodontal stem cells have a certain inhibitory effect on the pro-inflammatory function of M1-type macrophages,and it is not clear whether icariin,which has anti-inflammatory and other pharmacological activities,can enhance the inhibitory effect of human periodontal stem cells on M1-type macrophages. OBJECTIVE:To investigate the effect of icariin on M1 macrophages after pretreatment of human periodontal stem cells. METHODS:Primary human periodontal stem cells were isolated,cultured and characterized.THP-1 was induced and M1-type macrophages were identified by immunofluorescence staining and PCR.Human periodontal stem cells were cultured with α-MEM complete medium containing concentrations of 10-7,10-6,10-5,and 10-4 mol/L icariin,and the cytotoxicity of Icariin on human periodontal stem cells was detected by the CCK-8 assay at 1,3,5,and 7 days,respectively.α-MEM complete medium,untreated α-MEM conditioned medium for human periodontal stem cells and α-MEM conditioned medium for human periodontal stem cells pretreated with icariin for 24 hours were conditioned with RPMI-1640 complete medium in a 1:1 ratio for M1-type macrophages in the control,untreated,and pretreated groups,and 24 hours later,the mRNA expression of inflammatory factors in M1 macrophages was detected by RT-PCR.The protein expression of inflammatory factors in M1 macrophages was detected by ELISA.The expression of surface markers and nuclear factor-κB pathway-related proteins in M1/M2 macrophages was detected by western blot assay. RESULTS AND CONCLUSION:(1)CCK-8 assay results showed that 10-7,10-6,10-5,10-4 mol/L icariin was not cytotoxic to the human periodontal stem cells,and from day 5 onwards,all the concentrations increased the cell viability,and promoted the cell proliferation.10-4 mol/L icariin was selected for follow-up experiment.(2)RT-PCR and ELISA results showed that compared with the control group,the untreated group and the pretreated group both decreased the expression and secretion of interleukin-1β,interleukin-6,and tumor necrosis factor-α of M1-type macrophages(P<0.05),and the pretreated group was lower than the untreated group(P<0.05).(3)Western blot assay results showed that compared with the untreated group,the expression of CD86 was significantly lower in the pretreated group(P<0.05);compared with the control group,the expression of CD206,a surface marker of M2-type macrophages,was elevated in both the untreated and pretreated groups(P<0.01),and it was significantly higher in the pretreated group than in the untreated group(P<0.01).In M1-type macrophages after 24 hours of conditioned culture,compared with the control group,the expression of nuclear factor-κB/P65 was decreased in the untreated group and the pretreated group(P<0.01),and the expression of p-IκBα was decreased only in the pretreated group(P<0.01);the expression of both nuclear factor-κB/P65 and p-IκBα was significantly reduced in the pretreated group compared with the untreated group(P<0.05),while the difference of IκBα in the three groups was not statistically significant.(4)These results indicated that icariin enhanced the inhibitory effect of human periodontal stem cells on M1-type macrophages,and this effect may be related to the inhibition of the nuclear factor-κB signaling pathway of macrophages.

Background The neck, shoulders, and lower back are the primary affected areas of work-related musculoskeletal disorders. In manual tasks, combinations of hand functional height (defined as working height below the waist), awkward postures, and cognitive load are common risk factors. However, there is limited literature documenting how these factors specifically alter biomechanical load on the neck, shoulders, and lower back when working at hand functional height. Objective To explore quantitative differences in biomechanical load on the neck, shoulders, and lower back of workers performing manual tasks at hand functional height under different postures and cognitive load combinations. Methods A 3x2 within-subject design was implemented, with three postures (squat, kneeling, and stoop) and two levels of cognitive load (with cognitive load induced by a 2back task and without cognitive load). Ten male university students were recruited to perform a predetermined assembly task (a sequence of loosening and tightening screws) at hand functional height. Surface electromyography (sEMG) and 3D motion capture system were employed to assess the participants’ trunk biomechanical load in executing the tasks. Additionally, subjective perception, including fatigue, muscle pain, and cognitive load, were evaluated using scales. Results Significant variations in biomechanical load were observed across the three postures (P<0.05). The stoop posture exhibited the lowest muscle activation in most target muscles, except for the sternocleidomastoid, and showed the fastest decline in instantaneous median frequency (IMF) of the erector spinae, with a rate of (-0.050±0.008) Hz per unit time (0.128 s), and the greatest trunk flexion angle (35.14°±4.40°). Performing the task by squatting resulted in the highest muscle activation, especially in the upper trapezius, where maximum voluntary contraction percentage reached 20.07%±1.26%. In addition, the squatting posture also resulted in larger joint angles in the sagittal plane for the neck (−7.03°±2.70°), shoulders (60.20°±7.89°), and lower back (34.42°±4.20°). The kneeling posture showed intermediate muscle activation, the slowest IMF decline for the erector spinae in the lower back (−0.005±0.008) Hz per unit time (0.128s), and the joint angles were closest to neutral. The task performance results were also superior in the kneeling posture. Regarding cognitive load, no significant differences were found for most biomechanical indicators, except for subjective cognitive load scores, neck flexion, and shoulder external rotation angles. Conclusion In assembly tasks performed at hand functional height, kneeling results in moderate biomechanical load on the neck, shoulders, and lower back while also improves task performance compared to squatting and forward bending. Additionally, no significant effects of cognitive load under the 2back condition on biomechanical load are observed.

Background At present, high level of depression is a serious problem in medical staff and may affect their immune function. The role of psychological resilience between depression and immunity cannot be ignored. However, it is still lack of research report in this area. Objective To explore the mediating effect of psychological resilience on the association between depression and humoral immunological biomarkers in medical staff. Methods A total of 108 medical staff from a tertiary hospital in Henan Province were selected using stratified cluster sampling from September 2022 to December 2022. The Connor-Davidson Resilience Scale and Patient Health Questionnaire-9 were used to evaluate their psychological resilience and depression. Serum immunoglobulin (Ig) M (IgM), IgG, IgA, complement 3 (C3), and complement 4 (C4) were detected in fasting venous blood samples. Mann-Whitney U test, Kruskal-Wallis H test, independent-samples t-test, and One-way ANOVA were used for comparisons among different demographic groups. Spearman correlation was used to evaluate correlations among measured variables. PROCESS plug-in was used to verify potential mediating effect of psychological resilience on the relationship between depression and humoral immunological biomarkers. Results The M (P₂₅, P₇₅) score of psychological resilience was 65.50 (53.25, 75.00) in the participating medical staff. The ratios of low, medium, and high levels of psychological resilience were 2.78% (3/108), 51.85% (56/108), and 45.37% (49/108), respectively. The M (P₂₅, P₇₅) score of depression was 6.00 (2.00, 8.00). The positive rate of depression was 61.11% (66/108). The correlation analysis results showed that psychological resilience was negatively correlated with depression and serum complement C3 (r=−0.416 and −0.309, P＜0.01), positively correlated with serum IgG and serum IgA (r=0.302 and 0.517, P＜0.01); optimism, self-improvement, and resilience were negatively correlated with depression (r=−0.387, −0.446, and −0.312, P<0.01), positively correlated with IgG (r=0.194, 0.284, and 0.239, P<0.05), and positively correlated with IgA (r=0.377, 0.378, and 0.444, P<0.01), respectively; resilience was negatively correlated with C3 (r=−0.304, P<0.01), and depression was negatively correlated with serum IgG and serum IgA (r=−0.516 and −0.522, P＜0.01), positively correlated with serum complement C3 (r=0.195, P＜0.05). The mediating effect test showed that psychological resilience showed mediating effects on the relationship between depression and serum IgA and serum complement C3, with mediating effect values of −0.148 (95%CI: −0.051, −0.012) and 0.111 (95%CI: 0.001, 0.010), and their mediating effect ratios were 28.30% and 56.92%. Conclusion The mental health status of the target medical staff is not optimistic. Depression is associated with changes in some humoral immunological biomarkers. Psychological resilience can mediate the correlations between depression and humoral immunological biomarkers. The managers should take measures to improve the levels of psychological resilience and promote the physical and mental health of medical staff.

Objective:To analyze the current status of red blood cell transfusion in very preterm infants (VPI) (gestational age at birth <32 weeks) from Chinese Neonatal Network (CHNN) in 2022.Methods:This cross-sectional study was based on the CHNN VPI cohort. It included 6 985 VPI admitted to CHNN 89 participating centers within 24 hours after birth in 2022. VPI with major congenital anomalies or those transferred to non-CHNN centers for treatment or discharged against medical advice were excluded. VPI were categorized based on whether they received red blood cell transfusions, their gestational age at birth, the type of respiratory support received during transfusion, and whether the pre-transfusion hemoglobin levels exceeded the thresholds. General characteristics, red blood cell transfusion rates, number of transfusions, timing of the first transfusion, and pre-transfusion hemoglobin levels were compared among different groups. The incidence of adverse outcomes between the group of VPI who received transfusions above the threshold and those who received transfusions below the threshold were compared. Comparison among different groups was conducted using χ2 tests, Kruskal-Wallis H tests, Mann-Whitney U test, and so on. Trends by gestational age at birth were evaluated by Cochran-Armitage tests and Jonckheere-Terpstra tests for trend. Results:Among the 6 985 VPI, 3 865 cases(55.3%) were male, with a gestational age at birth of 30.0 (28.6, 31.0) weeks and a birth weight of (1 302±321) g. Overall, 3 617 cases (51.8%) received red blood cell transfusion, while 3 368 cases (48.2%) did not. The red blood cell transfusion rate was 51.8% (3 617/6 985), with rates of 77.7% (893/1 150) for those born before 28 weeks gestational age and 46.7% (2 724/5 835) for those born between 28 and 31 weeks gestational age. A total of 9 616 times red blood cell transfusions were administered to 3 617 VPI, with 632 times missing pre-transfusion hemoglobin data, and 8 984 times included in the analysis. Of the red blood cell transfusions, 25.6% (2 459/9 616) were administered when invasive respiratory support was required, 51.3% (4 934/9 616) were receiving non-invasive respiratory support, while 23.1% (2 223/9, 616) were given when no respiratory support was needed. Compared to the non-transfusion group, the red blood cell transfusion group had a higher rate of pregnancy-induced hypertension in mothers, lower rates of born via cesarean section and mother′s antenatal steroid administration, smaller gestational age, lower birth weight, a higher proportion of small-for-gestational-age, multiple births, and proportions of Apgar score at the 5 th minute after birth ≤3 (all P<0.05). They were also less likely to be female, born in hospital or undergo delayed cord clamping (all P<0.01). Additionally, higher transport risk index of physiologic stability score at admission were observed in the red blood cell transfusion group ( P<0.001). The number of red blood cell transfusion was 2 (1, 3) times, with the first transfusion occurring at an age of 18 (8, 29) days, and a pre-transfusion hemoglobin level of 97 (86, 109) g/L. For VPI ≤7 days of age, the pre-transfusion hemoglobin levels for invasive respiratory support, non-invasive respiratory support, or no respiratory support, respectively, with no statistically significant differences between groups ( H=5.59, P=0.061). For VPI aged 8 to 21 days and≥22 days, the levels with statistically differences between groups (both P<0.01). Red blood cell transfusions above recommended thresholds were observed in all respiratory support categories at different stages of life, with the highest prevalence in infants aged 8 to 21 days and≥22 days who did not require respiratory support, at 90.1% (264/273) and 91.1%(1 578/1 732), respectively. The rate of necrotizing enterocolitis was higher in the above-threshold group ( χ2=10.59, P=0.001), and the duration of hospital stay was longer in the above-threshold group ( Z=4.67, P<0.001) compared to the below-threshold group. Conclusions:In 2022, the red blood cell transfusion rate was relatively high among VPI from CHNN. Pre-transfusion hemoglobin levels frequently exceeded recommended transfusion thresholds.

Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

Objective : To investigate the effect of chromosome instability(CIN) associated gene polypeptide N-acetylgalactosaminyltransferase 7(GALNT7) on proliferation and apoptosis of HCT116 colon cancer cells. Methods : The HCT116 cell line withGALNT7knockdown was constructed by lentiviral infection. The correlation betweenGALNT7and CIN was verified by chromosome spread assay. The effect ofGALNT7on cell proliferation was detected by live cell counting, and the effect ofGALNT7on cell cycle distribution was detected by flow cytometry and Western blot. Caspase-3 activity and Western blot assays were used to detect the effect ofGALNT7on apoptosis. Results : HCT116 cells showed a slower proliferation rate upon knocking down ofGALNT7, and exhibited a more scattered karyotype distribution and a phenotype of increased degree of CIN. Inhibition ofGALNT7in HCT116 cells resulted in cell cycle arrest, upregulation of P21 and downregulation of CDK6 protein levels, as well as increased levels of Caspase-3 activity, cleaved PARP1 and PUMA protein expression, and decreased levels of BCL-2 protein expression. Conclusion TheGALNT7gene may promote proliferation and inhibit apoptosis of HCT116 colon cancer cells through the suppression of CIN generation.

Objective To explore the relationship between PANoptosis and hepatic ischemia-reperfusion injury (HIRI), and to screen the key genes of PANoptosis in HIRI. Methods PANoptosis-related differentially expressed genes (PDG) were obtained through the Gene Expression Omnibus database and GeneCards database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore the biological pathways related to PDG. A protein-protein interaction network was constructed. Key genes were selected, and their diagnostic value was assessed and validated in the HIRI mice. Immune cell infiltration analysis was performed based on the cell-type identification by estimating relative subsets of RNA transcripts. Results A total of 16 PDG were identified. GO analysis showed that PDG were closely related to cellular metabolism. KEGG analysis indicated that PDG were mainly enriched in cellular death pathways such as apoptosis and immune-related signaling pathways such as the tumor necrosis factor signaling pathway. GSEA results showed that key genes were mainly enriched in immune-related signaling pathways such as the mitogen-activated protein kinase (MAPK) signaling pathway. Two key genes, DFFB and TNFSF10, were identified with high accuracy in diagnosing HIRI, with areas under the curve of 0.964 and 1.000, respectively. Immune infiltration analysis showed that the control group had more infiltration of resting natural killer cells, M2 macrophages, etc., while the HIRI group had more infiltration of M0 macrophages, neutrophils, and naive B cells. Real-time quantitative polymerase chain reaction results showed that compared with the Sham group, the relative expression of DFFB messenger RNA in liver tissue of HIRI group mice increased, and the relative expression of TNFSF10 messenger RNA decreased. Cibersort analysis showed that the infiltration abundance of naive B cells was positively correlated with DFFB expression (r=0.70, P=0.035), and the infiltration abundance of M2 macrophages was positively correlated with TNFSF10 expression (r=0.68, P=0.045). Conclusions PANoptosis-related genes DFFB and TNFSF10 may be potential biomarkers and therapeutic targets for HIRI.

ObjectiveTo investigate the effects of artemisinin （ART） on histopathological damage and salivary secretion in the submandibular gland （SMG） of mice with Sjögren's syndrome （SS） model，and on the expression of aquaporin 5 （AQP5） in SMG cells. MethodsThe NOD/Ltj mice were used as a model of SS and randomly divided into the SS model group，the ART group，and the hydroxychloroquine sulfate （HCQ） group，with six mice per group. Another 6 female BALB/c mice at the same week were selected as the control group. Mice in the ART group was fed with the ART solution daily in the dosage of 50 mg·kg^-1，and mice in the HCQ group was given with the HCQ solution （1 300 mg·kg^-1）. Mice in the SS model and control groups were given saline daily. The treatment lasted for 8 weeks. The 24-hour average water intake，salivary flow rate，SMG pathology scores of mice in each group were measured，as well as the expression levels of AQP5 protein and gene in the SMG tissues. ResultsCompared with the control group，the 24-hour average water intake of mice in the model group was significantly increased （P<0.01），and the saliva flow rate was significantly decreased （P<0.01）. Compared to the SS model group，the 24-hour average water intake of mice in the ART and HCQ groups was significantly reduced （P<0.01），and the salivary flow rate was significantly increased in the ART group（P<0.01），comparisons between groups showed that the ART was superior to the HCQ in reducing water intake and improving saliva flow rate in SS model mice （P<0.05）. The HE staining results showed that，compared with the normal group，the number of lymphocyte infiltration foci in SMG tissue in the model group increased，and the pathological score increased （P<0.01）. Compared to the SS model group，after the intervention of the ART and HCQ，the number of lymphocytic infiltration foci in the SMG tissue decreased，the area of the lymphocytic infiltration foci was reduced，and the pathology score of the SMG tissues was lowered in the ART group（P<0.01）. However，there was no difference in pathological scores between the ART and HCQ groups . The results of IHC，Western blot，and Real-time PCR showed that，compared with the normal group，the expression levels of AQP5 protein and gene in SMG tissue in the model group significantly decreased （P<0.05）. Comparing with the SS model group，the ART and HCQ groups could significantly up-regulated the expression levels of AQP5 protein and mRNA in the SMG tissue，and the treatment effect was better than that of HCQ. ConclusionART was able to ameliorate SMG structural damage and salivary secretion function in SS model mice，and its mechanism of action may be related to the up-regulation of AQP5 protein and gene expression levels in SMG cells.

Objective To investigate serum β2-MG, sCHE, and PSGL-1 expression in patients with esophageal cancer and their relationship to lung infection after mediastinoscopy. Methods A total of 118 patients with esophageal cancer were selected and divided into infected and uninfected groups according to whether they developed lung infection after surgery. An automatic microbiological identification system was used to detect the pathogenic bacteria of lung infection. ELISA was used to detect the levels of β2-MG, sCHE, and PSGL-1. Multivariate logistic regression was used to analyze the influencing factors of postoperative lung infection in patients with esophageal cancer. ROC curves were plotted to analyze the assessment value of serum β2-MG, sCHE, and PSGL-1 on postoperative lung infection. Results Fifty-two strains of bacteria were isolated from the sputum of 38 patients with postoperative lung infections, and these included 35 (67.31%) Gram-negative, 14 (26.92%) Gram-positive, and 3 (5.77%) fungal strains. The difference in long-term smoking history between the infected and uninfected groups was statistically significant (P<0.05). Serum β2-MG and PSGL-1 levels were significantly higher and sCHE levels were significantly lower in the infected group than in the uninfected group (P<0.05). Serum β2-MG and PSGL-1 levels were sequentially higher (P<0.05) and sCHE levels were sequentially lower (P<0.05) in the mild, moderate, and severe lung infection groups. Long-term smoking history, β2-MG, and PSGL-1 were risk factors affecting postoperative lung infection in patients with esophageal cancer (P<0.05), and sCHE was a protective factor (P<0.05). The AUCs of serum β2-MG, sCHE, and PSGL-1 for assessing postoperative lung infections were 0.807, 0.845, and 0.800, respectively, and the AUC of the three combined factors for assessing postoperative lung infections was 0.954, which was superior to that assessed individually (Z_{combination vs. β2-MG}=2.576, Z_{combination vs. sCHE}=2.623, Z_{combination vs. PSGL-1}=2.574, all P<0.05). Conclusion The serum levels of β2-MG and PSGL-1 increase and the sCHE level decreases in patients with esophageal cancer and postoperative pulmonary infection, which are also related with lung infection. Combined testing can improve the evaluation value of postoperative pulmonary infection in patients.