OBJECTIVES: To evaluate preterm white matter injury (PWMI) in neonatal rats using multimodal magnetic resonance imaging (MRI) combined with histological assessments and to explore its underlying mechanisms. METHODS: Healthy 3-day-old Sprague-Dawley neonatal rats were randomly divided into a sham operation group and a PWMI group (n=12 in each group). A PWMI model was established in neonatal rats through hypoxia-ischemia. Laser speckle imaging was used to observe changes in cerebral oxygen saturation and blood flow at different time points post-modeling. Multimodal MRI was employed to assess the condition of white matter injury, while hematoxylin-eosin staining was utilized to observe morphological changes in the striatal area on the injured side. Immunofluorescence staining was performed to detect the proliferation and differentiation of oligodendrocyte precursor cells. RESULTS: At 0, 6, 12, 24, and 72 hours post-modeling, the relative blood flow and relative oxygen saturation on the injured side in the PWMI group were significantly lower than those in the sham operation group (P<0.05). At 24 hours post-modeling, T2-weighted imaging showed high signals in the white matter of the injured side in the PWMI group, with relative apparent diffusion coefficient values and Lorenz differential values being lower than those in the sham operation group (P<0.001); additionally, the arrangement of nerve cells in the PWMI group was disordered, and the number of EdU⁺PDGFR-α⁺ cells was higher than that in the sham operation group (P<0.001). At 28 days post-modeling, the relative fractional anisotropy values, the number of EdU⁺Olig2⁺ cells, and the fluorescence intensity of myelin basic protein and neurofilament protein 200 in the white matter region of the PWMI group were all lower than those in the sham operation group (P<0.001). CONCLUSIONS Multimodal MRI can evaluate early and long-term changes in PWMI in neonatal rat models in vivo, providing both imaging and pathological evidence for the diagnosis and treatment of PWMI in neonates. Hypoxia-ischemia inhibits the proliferation and differentiation of oligodendrocyte precursor cells in neonatal rats, leading to PWMI.
Animals ; Rats, Sprague-Dawley ; Magnetic Resonance Imaging/methods* ; Rats ; White Matter/injuries* ; Animals, Newborn ; Female ; Multimodal Imaging ; Male ; Hypoxia-Ischemia, Brain/pathology*

Glioblastoma (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis. Conventional chemo-radiotherapy demonstrates limited therapeutic efficacy and is often accompanied by significant side effects, largely due to factors such as drug resistance, radiation resistance, the presence of the blood-brain barrier (BBB), and the activation of DNA damage repair mechanisms. There is a pressing need to enhance treatment efficacy, with BRD4 identified as a promising target for increasing GBM sensitivity to therapy. Lacking small molecule inhibitors, BRD4 can be degraded using PROteolysis Targeting Chimera (PROTAC), thereby inhibiting DNA damage repair. To deliver PROTAC, SIAIS171142 (SIS) effectively, we designed a responsive nanocapsule, MPL_(SS)P@SIS, featuring GBM-targeting and GSH-responsive drug release. Modified with 1-methyl-l-tryptophan (MLT), nanocapsules facilitate targeted delivery of SIS, downregulating BRD4 and sensitizing GBM cells to radiotherapy and chemotherapy. After intravenous administration, MPL_(SS)P@SIS selectively accumulates in tumor tissue, enhancing the effects of radiotherapy and temozolomide (TMZ) by increasing DNA damage and oxidative stress. GSH activates the nanocapsules, triggering BRD4 degradation and hindering DNA repair. In mouse models, the nanosensitizer, combined with TMZ and X-ray irradiation, efficiently inhibited the growth of GBM. These findings demonstrate a novel PROTAC-based sensitization strategy targeting BRD4, offering a promising approach for effective GBM therapy.

Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.

Objective To compare the application of two endoscopic retrograde appendicitis therapies(ERAT)in acute uncomplicated appendicitis.Methods 100 patients with acute uncomplicated appendicitis from January 2021 to Jun 2023 were randomly divided into the direct vision group(50 cases)and the control group(50 cases).The control group was treated with conventional ERAT,and the direct vision group was treated with EyeMax Insight pancreaticobiliary imaging system assisted ERAT.The operation time,appendiceal intubation time,success rate of appendiceal intubation,abdominal pain relief time,body temperature recovery time,white blood cell recovery time,hospitalization time,and incidence of surgical complications were compared between the two groups.Results Comparison of appendiceal intubation time and operation time between the two groups:The appendiceal intubation time(5.43±3.51)min and operation time(45.50±10.65)min in the direct vision group were shorter than those in the control group(8.76±5.43)min and(54.32±13.45)min,and the differences were statistically significant(P=0.000).There were no significant differences in the success rate of intubation,recurrence rate,abdominal pain relief time,body temperature recovery time,white blood cell recovery time,hospitalization time and incidence of surgical complications between the two groups(P>0.05).Conclusion ERAT assisted by EyeMax Insight pancreaticobiliary imaging system can shorten the time of appendiceal intubation and operation,without increasing the incidence of complications,avoiding radiation exposure for patients and medical staff.It is safe and effective and worthy of clinical promotion.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To observe the effects of melatonin on autophagy in cortical neurons of neonatal rats with hypoxic-ischemic brain damage(HIBD)and to explore its mechanisms via the PI3K/AKT signaling pathway,aiming to provide a basis for the clinical application of melatonin.Methods Seven-day-old Sprague-Dawley neonatal rats were randomly divided into a sham operation group,an HIBD group,and a melatonin group(n=9 each).The neonatal rat HIBD model was established using the classic Rice-Vannucci method.Neuronal morphology in the neonatal rat cerebral cortex was observed with hematoxylin-eosin staining and Nissl staining.Autophagy-related protein levels of microtubule-associated protein 1 light chain 3(LC3)and Beclin-1 were detected by immunofluorescence staining and Western blot analysis.Phosphorylated phosphoinositide 3-kinase(p-PI3K)and phosphorylated protein kinase B(p-AKT)protein expression levels were measured by immunohistochemistry and Western blot.The correlation between autophagy and the PI3K pathway in the melatonin group and the HIBD group was analyzed using Pearson correlation analysis.Results Twenty-four hours post-modeling,neurons in the sham operation group displayed normal size and orderly arrangement.In contrast,neurons in the HIBD group showed swelling and disorderly arrangement,while those in the melatonin group had relatively normal morphology and more orderly arrangement.Nissl bodies were normal in the sham operation group but distorted in the HIBD group;however,they remained relatively intact in the melatonin group.The average fluorescence intensity of LC3 and Beclin-1 was higher in the HIBD group compared to the sham operation group,but was reduced in the melatonin group compared to the HIBD group(P<0.05).The number of p-PI3K+and p-AKT+cells decreased in the HIBD group compared to the sham operation group but increased in the melatonin group compared to the HIBD group(P<0.05).LC3 and Beclin-1 protein expression levels were higher,and p-PI3K and p-AKT levels were lower in the HIBD group compared to the sham operation group(P<0.05);however,in the melatonin group,LC3 and Beclin-1 levels decreased,and p-PI3K and p-AKT increased compared to the HIBD group(P<0.05).The correlation analysis results showed that the difference of the mean fluorescence intensity of LC3 and Beclin-1 protein in the injured cerebral cortex between the melatonin and HIBD groups was negatively correlated with the difference of the number of p-PI3K+and p-AKT+cells between the two groups(P<0.05).Conclusions Melatonin can inhibit excessive autophagy in cortical neurons of neonatal rats with HIBD,thereby alleviating HIBD.This mechanism is associated with the PI3K/AKT pathway.

AIM To investigate the effects of total Astragalus saponins on the improvement of sarcopenia in a rat model of type 2 diabetes mellitus(T2DM).METHODS The rats were divided into the normal group for a normal feeding and the model group for the feeding of high-sugar and high-fat diet combined with intraperitoneal injection of STZ to establish a T2DM model.The successful model rats were randomly divided into the model group,the metformin group(0.2 g/kg)and the total Astragalus saponins group(80 mg/kg),and given corresponding doses of drugs by gavage.After 12 weeks administration,the rats had their FBG,postprandial blood glucose(PG2h)and wet weight of skeletal muscle measured;their serum levels of INS,C-peptide(C-P),IGF-1,TNF-α and IL-1β detected by ELISA;their morphological changes of skeletal muscle observed by HE staining;their protein expressions of PI3K,p-Akt,mTOR,S6K1,FoxO1 and Murf1 in skeletal muscle detected by Western blot;and their mRNA expressions of Pi3k,Akt and mtor in skeletal muscle detected by RT-qPCR method.RESULTS Compared with the model group,the total Astragalus saponins group displayed decreased levels of FBG,PG2h,OGTT-AUC,HOMA-IR,TNF-α and IL-1β(P＜0.01);increased levels of INS,C-P,IGF-1 and wet weight of skeletal muscle(P＜0.05,P＜0.01);improved skeletal muscle atrophy and increased protein expressions of PI3K,p-Akt,mTOR and S6K1 in skeletal muscle(P＜0.05,P＜0.01);decreased protein expressions of FoxO1 and Murf1(P＜0.05,P＜0.01);and increased mRNA expressions of Pi3k,Akt and mtor(P＜0.01).CONCLUSION The improvement effects of total Astragalus saponins on sarcopenia in T2DM rats may be associated with the regulation of PI3K/Akt/mTOR and PI3K/Akt/FoxO1 pathways.

To explore the effect of Internet+diet self-management intervention technology on the blood pressure control of hypertension high-risk population through the intervention of hypertension high-risk population in Haikou City community, so as to provide scientific evidence for the prevention and treatment of cardiovascular diseases (CVD). The multi-stage cluster sampling method was used, and 295 hypertension high-risk participants were recruited from 15 communities in Haikou City from July to December 2021. The 15 communities were randomly divided into three groups: blank group, traditional group and Internet plus group by random number table method. The blank group referred to the group (99 participants) that did not take special intervention measures but the routine interventions in accordance with the "National Basic Public Health Service Standards (the Third Edition) Health Education Service Standards". On the basis of the blank group, the traditional group (95 participants) was intervened by giving additional traditional methods such as holding lectures and distributing popular science books. The Internet plus group (101 participants) was given additional Internet measures on the basis of the intervention of the traditional group. After 6 months, questionnaires, laboratory biochemical tests, and physical measurements were conducted. SPSS 25.0 software was applied for data analysis. Measurement data that followed normal distribution were statistically described by using mean±standard deviation, analysis of variance was used for inter group comparisons before intervention, analysis of covariance was used for inter group comparisons after intervention, and Bonferroni adjustment was used for pairwise comparisons between groups. Measurement data that did not follow the Normal distribution were represented by M (Q₁, Q₃). The rank sum test was used for inter group comparison. The k sample Kruskal Wallis single factor ANOVA was used to compare the distribution between different groups. Counting data were described by composition ratio or rate. Under the premise of balanced comparison between groups before intervention, Chi-squared test was used for inter group comparison after intervention, and Bonferroni adjustment method was used for pairwise comparison between groups. The results showed that a total of 295 participants were included, with males accounting for 35.6% (105) and females accounting for 64.4% (190). The age ranged from 55 to 74 years old, with an average age of (64.69±5.73) years. The number of married accounted for 95.6% (282 participants). There were no statistically significant differences in gender, age, family history, education level, occupation, marital status, drinking habits, regular exercise, dietary status, SBP (systolic blood pressure), DBP (diastolic blood pressure), pulse pressure difference, BMI (body mass index), folic acid, and 24-hour urine sodium among the three groups upon enrollment (P values>0.05). After the intervention, the drinking rate was as follows: Internet plus group (29, 28.7%)2=28.948, P<0.001); Regular exercise rate was higher in the Internet plus group (37, 36.6%) than in the traditional group (18, 18.9%) and the blank group (16, 16.2%) (χ²=13.476, P=0.001). After the intervention, compared with the participants in the blank group, the intake of energy, carbohydrate, dietary fiber, sodium and folic acid in the Internet plus group were significantly different (all P<0.05); Compared with the participants in the traditional group, the energy, carbohydrate and dietary fiber intake of the participants in the Internet plus group were significantly different (all P<0.05). After the intervention, the blood pressure levels in the Internet plus group [ SBP: (128.95±6.55) mmHg, DBP: (79.88±5.75) mmHg ] and the traditional group [ SBP: (129.63±8.41) mmHg, DBP: (79.77±7.73) mmHg ] were lower than those in the blank group [ SBP: (132.93±8.41) mmHg, DBP: (82.42±7.76) mmHg ] (SBP: F=9.417, P<0.001; DBP: F=6.967, P=0.001), the 24-hour urinary sodium level in the Internet plus group (143.63±38.58) mmol/24 h was lower than that in the traditional group (163.31±35.67) mmol/24 h and the blank group (154.14±35.52) mmol/24 h (F=11.509, P<0.001). In conclusion, compared with the traditional intervention mode, the "Internet plus diet self-management intervention" mode is more likely to promote the development of a healthy lifestyle for people at high risk of hypertension, effectively improve blood pressure and 24-hour urine sodium level, and facilitate CVD prevention.
Male ; Female ; Humans ; Middle Aged ; Aged ; Blood Pressure ; Self-Management ; Hypertension/prevention & control* ; Cardiovascular Diseases/prevention & control* ; Diet ; Sodium ; Internet ; Folic Acid

To explore the effect of Internet+diet self-management intervention technology on the blood pressure control of hypertension high-risk population through the intervention of hypertension high-risk population in Haikou City community, so as to provide scientific evidence for the prevention and treatment of cardiovascular diseases (CVD). The multi-stage cluster sampling method was used, and 295 hypertension high-risk participants were recruited from 15 communities in Haikou City from July to December 2021. The 15 communities were randomly divided into three groups: blank group, traditional group and Internet plus group by random number table method. The blank group referred to the group (99 participants) that did not take special intervention measures but the routine interventions in accordance with the "National Basic Public Health Service Standards (the Third Edition) Health Education Service Standards". On the basis of the blank group, the traditional group (95 participants) was intervened by giving additional traditional methods such as holding lectures and distributing popular science books. The Internet plus group (101 participants) was given additional Internet measures on the basis of the intervention of the traditional group. After 6 months, questionnaires, laboratory biochemical tests, and physical measurements were conducted. SPSS 25.0 software was applied for data analysis. Measurement data that followed normal distribution were statistically described by using mean±standard deviation, analysis of variance was used for inter group comparisons before intervention, analysis of covariance was used for inter group comparisons after intervention, and Bonferroni adjustment was used for pairwise comparisons between groups. Measurement data that did not follow the Normal distribution were represented by M (Q₁, Q₃). The rank sum test was used for inter group comparison. The k sample Kruskal Wallis single factor ANOVA was used to compare the distribution between different groups. Counting data were described by composition ratio or rate. Under the premise of balanced comparison between groups before intervention, Chi-squared test was used for inter group comparison after intervention, and Bonferroni adjustment method was used for pairwise comparison between groups. The results showed that a total of 295 participants were included, with males accounting for 35.6% (105) and females accounting for 64.4% (190). The age ranged from 55 to 74 years old, with an average age of (64.69±5.73) years. The number of married accounted for 95.6% (282 participants). There were no statistically significant differences in gender, age, family history, education level, occupation, marital status, drinking habits, regular exercise, dietary status, SBP (systolic blood pressure), DBP (diastolic blood pressure), pulse pressure difference, BMI (body mass index), folic acid, and 24-hour urine sodium among the three groups upon enrollment (P values>0.05). After the intervention, the drinking rate was as follows: Internet plus group (29, 28.7%)2=28.948, P<0.001); Regular exercise rate was higher in the Internet plus group (37, 36.6%) than in the traditional group (18, 18.9%) and the blank group (16, 16.2%) (χ²=13.476, P=0.001). After the intervention, compared with the participants in the blank group, the intake of energy, carbohydrate, dietary fiber, sodium and folic acid in the Internet plus group were significantly different (all P<0.05); Compared with the participants in the traditional group, the energy, carbohydrate and dietary fiber intake of the participants in the Internet plus group were significantly different (all P<0.05). After the intervention, the blood pressure levels in the Internet plus group [ SBP: (128.95±6.55) mmHg, DBP: (79.88±5.75) mmHg ] and the traditional group [ SBP: (129.63±8.41) mmHg, DBP: (79.77±7.73) mmHg ] were lower than those in the blank group [ SBP: (132.93±8.41) mmHg, DBP: (82.42±7.76) mmHg ] (SBP: F=9.417, P<0.001; DBP: F=6.967, P=0.001), the 24-hour urinary sodium level in the Internet plus group (143.63±38.58) mmol/24 h was lower than that in the traditional group (163.31±35.67) mmol/24 h and the blank group (154.14±35.52) mmol/24 h (F=11.509, P<0.001). In conclusion, compared with the traditional intervention mode, the "Internet plus diet self-management intervention" mode is more likely to promote the development of a healthy lifestyle for people at high risk of hypertension, effectively improve blood pressure and 24-hour urine sodium level, and facilitate CVD prevention.
Male ; Female ; Humans ; Middle Aged ; Aged ; Blood Pressure ; Self-Management ; Hypertension/prevention & control* ; Cardiovascular Diseases/prevention & control* ; Diet ; Sodium ; Internet ; Folic Acid

This study aims to investigate the role of slient mating-type information regulation 2 homolog 1(SIRT1)/tuberous sclerosis complex 2(TSC2)/mammalian target of rapamycin(mTOR) signaling pathways in the Periplaneta americana extract CⅡ-3-induced senescence of human leukemia K562 cells. K562 cells were cultured in vitro and treated with 0(control), 5, 10, 20, 40, 80, and 160 μg·mL~(-1) of P. americana extract CⅡ-3. Cell counting kit-8(CCK-8) and flow cytometry were employed to examine the proliferation and cell cycle of the K562 cells. Senescence-associated β-galactosidase stain kit(SA-β-gal) was used to detect the positive rate of senescent cells. Mitochondrial membrane potential was detected by flow cytometry. The relative mRNA level of telomerase reverse transcriptase(TERT) was determined by fluorescence quantitative PCR. The mRNA and protein levels of SIRT1, TSC2, and mTOR were determined by fluorescence quantitative PCR and Western blot, respectively. The results showed that CⅡ-3 significantly inhibited the proliferation of K562 cells and the treatment with 80 μg·mL~(-1) CⅡ-3 for 72 h had the highest inhibition rate. Therefore, 80 μg·mL~(-1) CⅡ-3 treatment for 72 h was selected as the standard for subsequent experiments. Compared with the control group, CⅡ-3 increased the proportion of cells arrested in G_0/G_1 phase, decreased the proportion of cells in S phase, increased the positive rate of SA-β-Gal staining, elevated the mitochondrial membrane potential and down-regulated the mRNA expression of TERT. Furthermore, the mRNA expression of SIRT1 and TSC2 was down-regulated, while the mRNA expression of mTOR was up-regulated. The protein expression of SIRT1 and p-TSC2 was down-regulated, while the protein expression of p-mTOR was up-regulated. The results indicated that P. americana extract CⅡ-3 induced the senescence of K562 cells via the SIRT1/mTOR signaling pathway.
Humans ; Animals ; Periplaneta ; Sirtuin 1/genetics* ; K562 Cells ; Signal Transduction ; TOR Serine-Threonine Kinases/genetics* ; RNA, Messenger ; Mammals