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 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]

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

OBJECTIVE: This study assesses the impact of iodine-rich processed foods and dining places on the iodine nutritional status of children. METHODS: School-aged children (SAC) in seven provinces in China were selected by school-based multi-stage sampling. Urinary iodine, salt iodine, and thyroid volume (TVOL) were determined. Questionnaires were used to investigate dining places and iodine-rich processed foods. The water iodine was from the 2017 national survey. Multi-factor regression analysis was used to find correlations between variables. RESULTS: Children ate 78.7% of their meals at home, 15.1% at school canteens, and 6.1% at other places. The percentage of daily iodine intake from water, iodized salt, iodine-rich processed foods, and cooked food were 1.0%, 79.2%, 1.5%, and 18.4%, respectively. The salt iodine was correlated with the urinary iodine and TVOL, respectively (r = 0.999 and -0.997, P < 0.05). The iodine intake in processed foods was weakly correlated with the TVOL (r = 0.080, P < 0.01). Non-iodized salt used in processed foods or diets when eating out had less effect on children's iodine nutrition status. CONCLUSION Iodized salt remains the primary source of daily iodine intake of SAC, and processed food has less effect on iodine nutrition. Therefore, for children, iodized salt should be a compulsory supplement in their routine diet.
Humans ; Child ; Nutritional Status ; Cross-Sectional Studies ; Iodine ; Sodium Chloride, Dietary/analysis* ; China ; Water

Objective To predict the structure and antigenic epitope of the Strongyloides stercoralis serine protease inhibitor 1 (Ss-SRPN-1) protein using bioinformatics tools, and to construct prokaryotic expression plasmids for expression of recombinant Ss-SRPN-1 protein, so as to provide the basis for unraveling the function of the Ss-SRPN-1 protein. Methods The amino acid sequence of the Ss-SRPN-1 protein was downloaded from the NCBI database, and the physicochemical properties, structure and antigenic epitopes of the Ss-SRPN-1 protein were predicted using bioinformatics tools, including ExPASy, SWISS-MODEL and Protean. Primers were designed according to the nucleotide sequences of Ss-SRPN-1, and the Ss-SRPN-1 gene was amplified, cloned and sequenced with genomic DNA extracted from the infective third-stage larvae of S. stercoralis as a template. The Ss-SRPN-1 protein sequence was cloned into the pET28a (+) expression vector and transformed into Escherichia coli BL21 (DE) cells for induction of the recombinant Ss-SRPN-1 protein expression. The recombinant Ss-SRPN-1 protein was then purified and identified using Western blotting and mass spectrometry. Results Bioinformatics analysis showed that the Ss-SRPN-1 protein, which was composed of 372 amino acids and had a molecular formula of C₁₉₄₈H₃₀₄₆N₄₈₈O₅₇₅S₁₆, was a stable hydrophilic protein, and the subcellular localization of the protein was predicted to be extracellular. The Ss-SRPN-1 protein was predicted to contain 11 dominant B-cell antigenic epitopes and 20 T-cell antigenic epitopes. The Ss-SRPN-1 gene with a length of 1 119 bp was successfully amplified, and the recombinant plasmid pET28a (+)/Ss-SRPN-1 was constructed and transformed into E. coli BL21(DE) cells. The expressed recombinant Ss-SRPN-1 protein had a molecular weight of approximately 43 kDa, and was characterized as a Ss-SRPN-1 protein. Conclusions The recombinant Ss-SRPN-1 protein has been expressed successfully, and this recombinant protein may be a potential vaccine candidate against strongyloidiasis.

Bone defects caused by different causes such as trauma, severe bone infection and other factors are common in clinic and difficult to treat. Usually, bone substitutes are required for repair. Current bone grafting materials used clinically include autologous bones, allogeneic bones, xenografts, and synthetic materials, etc. Other than autologous bones, the major hurdles of rest bone grafts have various degrees of poor biological activity and lack of active ingredients to provide osteogenic impetus. Bone marrow contains various components such as stem cells and bioactive factors, which are contributive to osteogenesis. In response, the technique of bone marrow enrichment, based on the efficient utilization of components within bone marrow, has been risen, aiming to extract osteogenic cells and factors from bone marrow of patients and incorporate them into 3D scaffolds for fabricating bone grafts with high osteoinductivity. However, the scientific guidance and application specification are lacked with regard to the clinical scope, approach, safety and effectiveness. In this context, under the organization of Chinese Orthopedic Association, the Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair ( version 2023) is formulated based on the evidence-based medicine. The consensus covers the topics of the characteristics, range of application, safety and application notes of the technique of autologous bone marrow enrichment and proposes corresponding recommendations, hoping to provide better guidance for clinical practice of the technique.

Objective:To investigate the role of miRNA-4298/PADI4/p53 signal axis in mediating 4f-induced apoptosis of leukemia cells.Methods:The cell growth density was observed under inverted microscope and the proliferation of leukemia cells was detected by CCK-8 counting assay. The expression of PADI4 and P53 at mRNA level was detected by qRT-PCR. Cell cycle and apoptosis were measured with flow cytometry. The expression of PADI4, P53, Bcl-2, Bax, caspase-3 and caspase-9 at protein level was detected by Western blot. Differential miRNA and mRNA expression profiles was detected by next generation sequencing. Databases such as TargetScan were used to predict the potential upstream and downstream genes of PADI4. A luciferase reporter assay was used to detect the 3′UTR of PADI4 targeted by miRNA-4298. Cell transfection assay was used to detect the effect siRNA, PADI4 vector, miRNA mimics and miRNA inhibitor in interference and rescue.Results:Nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor 4f could inhibit the proliferation of THP-1, K562 and U937 cells, and induce the apoptosis of these leukemia cells. It downregulated the expression of PADI4 mainly through the binding activity of miRNA-4298 to miRNA sponges, which resulted in the proliferation inhibition and apoptosis of leukemia cells. The inhibited proliferation and apoptosis of leukemia cells by 4f were associated with the increase of P53 expression after the decrease of PADI4 expression. The PADI4-dependent upregulation of P53 led to the ratio inversion of downstream Bcl-2/Bax, which activated caspase-3 or caspase-9 to induce the apoptosis of leukemia cells.Conclusions:The apoptosis of leukemia cells induced by Nrf2 inhibitor 4f was mainly associated with the miRNA-4298/PADI4/p53 axis, suggesting that it might be a novel signaling pathway for targeted therapy.

OBJECTIVE To investigate the potential of glycyrrhizic acid(GL)to improve the solubility and bioavailability of ost-hole(Ost),and to explore the underlying mechanism of the potential solubility and pharmacokinetic interactions.METHODS Male Sprague-Dawley rats were orally given osthole(20 mg·kg-1)alone or with glycyrrhizic acid(45 mg·kg-1).Blood and liver samples were collected at specific time points and determined by an LC-MS/MS method.The effect of glycyrrhizic acid on the solubility of ost-hole,and physical characterizations,including X-ray diffraction(XRD)and Fourier transform infrared(FT-IR)spectroscopy,were performed to reveal the mechanism of the solubilization of GL.In addition,bidirectional transport study using Caco-2 cell monolayer model was employed to study the effects of glycyrrhizic acid and its active metabolite glycyrrhetinic acid(GC)on the absorption of ost-hole.In incubation studies,rat enterocyte S9 and liver S9 were used to explore the potential effect of GL and GC on the metabolism of osthole.RESULTS The results of pharmacokinetics in rats showed that co-administration of glycyrrhizic acid could significantly in-crease the AUC of osthole as compared with osthole administered alone.The results of rat liver tissue samples indicated that glycyrrhizic acid increased the distribution of osthol in liver tissue.Solubility study found that glycyrrhizic acid could significantly enhance the solu-bility of osthole in water due to the decreased crystallinity of osthole and the formation of hydrogen bonding between Ost and GL.Caco-2 cell monolayer model demonstrated that neither GL nor GC could enhance osthole absorption.Further in vitro incubation study re-vealed that there was little metabolic interaction between osthole and GL or GC in phaseⅠmetabolism.CONCLUSION Increased AUC and liver concentration of osthole are probably due to the increased solubility of osthole by GL.The current study has significant implications for further investigation on the potential combination use of natural solubilizing agent GL and drugs with solubility as the rate-limiting step to absorption from the gastrointestinal tract.

ObjectiveTo observe the effects of the water extracts of Trichosanthis Radix-Polygonati Rhizoma at different ratios on glucose and lipid metabolism in KKAy mice with spontaneous type 2 diabetes and explore the mechanism of the extract in alleviating insulin resistance based on phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/forkhead box O1 （FoxO1） signaling pathway. MethodThe 8-week-old C57BL/6J male mice were taken as the normal control group， and KKAy male mice of the same age were randomly assigned into a model group， a metformin group， Trichosanthis Radix-Polygonati Rhizoma groups at the ratios of 1∶1 （Trichosanthis Radix 30 g， Polygonati Rhizoma 30 g）， 1∶3 （Trichosanthis Radix 15 g， Polygonati Rhizoma 45 g）， and 1∶5 （Trichosanthis Radix 10 g， Polygonati Rhizoma 50 g） according to blood glucose level and body weight， with 6 mice in each group. The administration lasted for 8 weeks， and the body weight （BW） and fasting blood glucose （FBG） of mice were recorded at the same time points of the 2nd， 4th， 6th， and 8th weeks， respectively. Oral glucose tolerance test （OGTT） was performed at the 7th week. After drug administration， the serum levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， and fasting insulin （FINS） were measured， and homeostasis model assessment-insulin resistance （HOMA-IR） index was calculated. The liver tissue samples were stained with hematylin-eosin （HE） and periodic acid-Schiff （PAS） for observation of the fat distribution and glycogen content. The protein levels of PI3K， Akt， p-Akt， FoxO1， and p-FoxO1 in the liver were determined by Western blot. ResultCompared with the normal group， the model group showed increased food intake， FBG， glucose tolerance， FINS， HOMA-IR， TC， TG， and LDL-C （P<0.01）， and down-regulated protein levels of PI3K， Akt， phosphorylaison （p）-Akt， FoxO1， and p-FoxO1 in the liver （P<0.01）. Compared with the model group， Trichosanthis Radix-Polygonati Rhizoma lowered FBG and HOMA-IR （P<0.05， P<0.01）. In particular， the combination at the ratio of 1∶3 showed the best performance （P<0.01） comparable to metformin. Furthermore， Trichosanthis Radix-Polygonati Rhizoma at different ratios lowered blood glucose at different time points of OGTT （P<0.05） and TC and LDL-C （P<0.01）. Additionally， the combination at the ratio of 1∶3 reduced TG （P<0.01）. The liver of mice in the drug administration groups showed regular morphology， with few lipid droplets and rich glycogen. Western blot showed that Trichosanthis Radix-Polygonati Rhizoma up-regulated the protein levels of PI3K and p-Akt， down-regulated the protein level of FoxO1， and up-regulated the protein level of p-FoxO1 （P<0.05）. ConclusionTrichosanthis Radix-Polygonati Rhizoma， especially at the ratio of 1∶3， lowered the FBG， TC， LDL-C， and HOMA-IR index， promoted liver glycogen synthesis， and reduced steatosis in KKAy mice， which may be related to the regulation of PI3K/Akt/FoxO1 signaling pathway in the liver.