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]

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.

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.

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.

OBJECTIVE: To observe clinical efficacy of percutaneous endoscopic transforaminal discectomy (PETD) and target radioffrequency thermal coblation nucleoplasty(CN) on inclusive lumbar disc herniation(LDH) in different age groups, and provide a basis for clinical formulation of precise and individualized treatments. METHODS: A retrospective analysis of 219 patients with lumbar disc herniation treated with PETD and CN between January 2018 and June 2021 was performed, in which 107 patients were treated with PETD and 112 with CN. Patients were stratified by age into young group(≤45 years old), middle-aged group(>45 years old and <60 years old) and older group(≥60 years old). Before treatment, 3 days, 1 month and 6 months after treatment, visual analogue scale (VAS), Japanese Orthopaedic Association (JOA) score, infrared thermal imaging temperature difference (△T) and lumbar range of motion (ROM) were evaluated and clinical efficacy were compared in the different age groups between two treatment methods. RESULTS: ①VAS and JOA score outcomes, in the same age group and the same treatment method, the VAS and JOA scores at different time points postoperatively were obviously improved (P<0.05). For the same age group and the different treatment methods, the older group had lower VAS and higher JOA scores after PETD than after CN (P<0.05), and there was no significant difference between the young group and middle-aged group (P>0.05). There was no significant difference in VAS and JOA scores at the same time between age groups by PETD treatment (P>0.05). The VAS was higher and the JOA score was lower in older group than in young group and middle-aged group at 1, 6 months after CN treatment(P<0.05). ②△T and ROM outcomes, in the same age group and same treatment method, postoperative △T and ROM at different time points were obviously improved(P<0.05). There was no significant difference in △T between two methods of PETD and CN at the same age(P>0.05), there was no significant difference in ROM between young group and middle-aged group(P>0.05), ROM was higher after PETD treatment than after CN treatment(P<0.05). There was no significant difference in △T and ROM at the same time between age groups by PETD treatment(P>0.05). There was no significant difference in △T between age groups by CN treatment, but the ROM was smaller in older group than in young group and middle-aged group after CN treatment(P<0.05). CONCLUSION Both PETD and CN for inclusive LDH have good efficacy, the curative benefit for older patients receiving PETD within 6 months after surgery more than CN, and CN is more appropriate for young and middle-aged patients.
Middle Aged ; Humans ; Aged ; Intervertebral Disc Displacement/surgery* ; Retrospective Studies ; Lumbar Vertebrae/surgery* ; Diskectomy, Percutaneous/methods* ; Treatment Outcome ; Endoscopy/methods* ; Diskectomy/methods*

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

OBJECTIVE: To investigate the inflammatory effects of Cinobufotalin on monocytes in resting state and macrophages in activated state and its molecular mechanism. METHODS: THP-1 cells were stimulated with Phorbol 12-myristate 13-acetate to induce differentiation into macrophages. Lipopolysaccharides was added to activate macrophages in order to establish macrophage activation model. Cinobufotalin was added to the inflammatory cell model for 24 h as a treatment. CCK-8 was used to detect cell proliferation, Annexin V /PI double staining flow cytometry was used to detect cell apoptosis, flow cytometry was used to detect macrophage activation, and cytometric bead array was used to detect cytokines. Transcriptome sequencing was used to explore the gene expression profile regulated by Cinobufotalin. Changes in the significantly regulated molecules were verified by real-time quantitative polymerase chain reaction and Western blot. RESULTS: 1∶25 concentration of Cinobufotalin significantly inhibited the proliferation of resting monocytes(P<0.01), and induced apoptosis(P<0.01), especially the activated macrophages(P<0.001, P<0.001). Cinobufotalin significantly inhibited the activation of macrophages, and significantly down-regulated the inflammatory cytokines(IL-6, TNF-α, IL-1β, IL-8) released by activated macrophages(P＜0.001). Its mechanism was achieved by inhibiting TLR4/MYD88/P-IκBa signaling pathway. CONCLUSION Cinobufotalin can inhibit the inflammatory factors produced by the over-activation of macrophages through TLR4/MYD88/P-IκBa pathway, which is expected to be applied to the treatment and research of diseases related to the over-release of inflammatory factors.
Humans ; Toll-Like Receptor 4/metabolism* ; Myeloid Differentiation Factor 88/genetics* ; Macrophages/metabolism* ; Cytokines/metabolism* ; Lipopolysaccharides/pharmacology* ; NF-kappa B

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