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 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.

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.

The accumulation of uremic toxins such as urea nitrogen, blood creatinine, and uric acid of patients with renal failure in vivo would lead to aggravated kidney damage. In this study, coated aldehyde oxy-starch (CAO) was used as an adsorbent to investigate its in vitro adsorption performance on renal failure indexes for urea, indoxyl sulfate (INS), monomethylamine (MMA), dimethylamine (DMA), uric acid (UA), and creatinine (Cr). The effects of variables such as pH, temperature, concentration, dosage, and time on the adsorption capacity of CAO were systematically investigated, employing analytical techniques of high-performance liquid chromatography (HPLC) and gas chromatography (GC). The results revealed that CAO exhibited a strong adsorption capacity for urea, INS, and MMA, alongside a moderate adsorption capacity for DMA, UA, and Cr. The adsorption kinetics and thermodynamic studies indicated that the adsorption of urea and UA by CAO were fitted in pseudo-first-order kinetics, and the adsorption isotherm aligned with the Freundlich adsorption model. The enthalpy change ΔH of urea in adsorption was in the range of 40 to 60 kJ·mol^-1, which demonstrated the presence of strong adsorption force due to the interactions of coordinating groups. The ΔH of UA was greater than 80 kJ·mol^-1, indicating the generation of chemical bonds during the adsorption. Both of them, Gibbs free energy ΔG was less than 0, within the range of -20 to 0 kJ·mol^-1, suggested that the adsorption of urea and UA by CAO occurred spontaneously as physical adsorption process. The adsorption entropy ΔS of urea and UA was > 0, which indicated an increase in entropy throughout the adsorption. The infrared spectroscopygram showed the formation of a chemical bond, specifically the imine bond, following the adsorption of urea by CAO, thereby indicating a chemical reaction during the adsorption. This study elucidates the adsorption mechanism of CAO on various indexes of renal failure, providing a scientific basis for its clinical usage.

ObjectiveTo compare colonoscopy compliance rates under different screening strategies, to explore ways to enhance colonoscopy compliance among residents with colorectal carcinoma. MethodsResidents aged between 50‒80 years were recruited through extensive community outreach and voluntary participation. A total of 210 630 residents who participated in the colorectal carcinoma screening program in Jiading District, Shanghai, between 2013 and 2019 were selected as the research subjects. All subjects underwent a colorectal carcinoma risk assessment questionnaire survey and two fecal occult blood tests (FOBT). Positive results in the initial screening were defined as a positive questionnaire survey or a positive result in at least one FOBT. Participants with positive initial screening results were advised to undergo colonoscopy screening in a hospital. Colonoscopy results were collected from hospital reports and physician follow-ups. Compliance with colonoscopy was analyzed under different screening strategies to identify possible factors influencing residents’ willingness to undergo the procedure. ResultsA total of 21 403 individuals (10.16%) were identified as positive with the questionnaire survey, 31 595 individuals (15.00%) tested positive with at least one FOBT. Combined questionnaire and FOBT positivity was observed in 3 501 individuals (1.66%). Among the 48 453 individuals with positive initial screening results, 17 230 (35.56%) underwent colonoscopy, and a total of 315 cases of colorectal cancer were detected. The sensitivity, specificity value of FOBT initial screening were 83.81% and 84.66%, respectively. According to the combined risk assessment and FOBT initial screening preliminary screening, the lowest colonoscopy compliance rate (25.63%) was observed among individuals with only a positive questionnaire, and the highest compliance rate (52.55%) was among those with both positive questionnaire survey and two positive FOBT results. Multivariate analysis revealed that FOBT positivity had the greatest impact on colonoscopy compliance. Those with one positive FOBT test result were 2.64 times more likely to undergo colonoscopy screening than those with negative FOBT results, while individuals with two positive FOBT results were 3.18 times more likely to do so. After adjusting for FOBT results, individuals with positive questionnaire survey results were 1.43 times more likely to undergo colonoscopy screening than those with negative results (95%CI: 1.34‒1.52). Compared to questionnaire-based risk assessment, FOBT results were more influential in determining compliance with colonoscopy. ConclusionThe choice of initial screening method significantly impacts residents’ compliance with colonoscopy. While implementing colorectal carcinoma screening programs, it is necessary to strictly adhere to screening protocols, including risk assessment and FOBT. Additionally, efforts should be made to raise public awareness, encouraging residents to actively participate in risk assessments and FOBT, thereby improving their compliance with colonoscopy.

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.

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.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background/Aims: Endoscopic radiofrequency ablation (ERFA) is a treatment option for superficial esophageal squamous cell neoplasia (ESCN), with a relatively low risk of stenosis; however, the long-term outcomes remain unclear. We aimed to compare the long-term outcomes of patients with widespread superficial ESCN who underwent endoscopic submucosal dissection (ESD) or ERFA. Methods: We retrospectively analyzed the clinical data of patients with superficial ESCN who underwent ESD or ERFA between January 2015 and December 2021. The primary outcome measure was recurrence-free survival. Results: Ninety-two and 33 patients with superficial ESCN underwent ESD and ERFA, respectively. The en bloc, R0, and curative resection rates for ESD were 100.0%, 90.2%, and 76.1%, respectively. At 12 months, the complete response rate was comparable between the two groups (94.6% vs 90.9%, p=0.748). During a median follow-up of 66 months, recurrence-free survival was significantly longer in the ESD group than in the ERFA group (p=0.004), while no significant differences in overall survival (p=0.845) and disease-specific survival (p=0.494) were observed.Preoperative diagnosis of intramucosal cancer (adjusted hazard ratio, 5.55; vs high-grade intraepithelial neoplasia) was an independent predictor of recurrence. Significantly fewer patients in the ERFA group experienced stenosis compare to ESD group (15.2% vs 38.0%, p=0.016). Conclusions The risk of recurrence was higher for ERFA than ESD for ESCN but overall survival was not affected. The risk of esophageal stenosis was significantly lower for patients who underwent ERFA.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.