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 evaluate the risk of bias and reporting quality in randomized controlled trials(RCTs)of the Chinese medicine injection for acute cerebral infarction in the last five years.Methods RCTs literature on Chinese medicine injection in the treatment of acute cerebral infarction was systematically searched in CNKI,Wanfang Data,VIP,China Biology Medicine Database(CBM),PubMed,Embase and Cochrane Library from April 20,2018 to April 20,2023.The risk of bias and reporting quality of included RCTs were evaluated using the Cochrane Risk of Bias Tool(ROB 1.0)and CONSORT-CHM Formulas 2017,respectively.Results A total of 4 301 articles were retrieved,and 408 RCTs were included according to inclusion and exclusion criteria.The ROB evaluation results showed that the the majority of studies were rated as having an unclear risk of bias due to the lack of reporting on allocation concealment,blind method,trial registration information,and funding sources.The evaluation results of CONSORT-CHM Formulas 2017 showed that the number of reported papers of 17 items was greater than or equal to 50%,and the number of reported papers of 25 items was less than 10%,and most of the RCTs did not show the characteristics of TCM syndrome differentiation and treatment.Conclusion The quality of Chinese medicine injection in the treatment of acute cerebral infarction RCTs is generally low.It is recommended that researchers refer to the methodology design of RCTs and international reporting standards,improve the trial design,standardize the trial report,and highlight the characteristics of TCM syndrome differentiation and treatment.

The number of benign prostatic obstruction (BPO) patients in China is increasing, and patients tend to be younger and younger. The former "gold standard" scheme of transurethral resection of the prostate (TURP) is more suitable for patients with prostate volume ranging from 40 mL to 80 mL, which may lead to excessive resection in patients with small prostate volume and low efficiency in patients with large prostate volume. New minimally invasive techniques have been introduced,including prostate artery embolization, laser surgery (such as holmium, green, diode, and thulium), minimally invasive simple prostatectomy, transperineal laser ablation, prostatic urethral lift,and robot-assisted water jet ablation of the prostate. These methods are alternatives to TURP and increasingly used in the treatment of BPO. This article reviewed the advances in minimally invasive treatment of BPO.

Humans ; Aged ; Processing Speed ; Cross-Sectional Studies ; Cognition ; Hearing Loss/psychology* ; Cohort Studies ; Cognitive Dysfunction

In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease (PD). However, difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1. Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains. CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and morphology. Importantly, PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and survival. Our findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD.

Objective:To investigate the development of intrapulmonary vascular volume (IPVV) in normal preschool children based on quantitative measurement on chest CT.Methods:The CT data of 407 normal preschool children (236 males and 171 females, aged 1-72 months, with a median of 36 months) who underwent chest CT examination from January 2014 to May 2017 in the "Digital Lung" imaging database were retrospectively collected. The pulmonary vessels were segmented by the "Digital Lung" automatic detection tool, and the IPVV of the whole lung, the right lung, the left lung and each lobe were obtained, and the IPVV upper/lower and IPVV left/right were calculated. According to the age, the subjects were divided into infant period (0-12 months), early childhood period (13-36 months) and preschool period (37-72 months), with 30 cases (17 males and 13 females), 175 cases (95 males and 80 females) and 202 cases (124 males and 78 females) respectively. Spearman correlation analysis was used to evaluate the correlation between IPVV and month age. One-way analysis of variance or Kruskal-Wallis H test was used to compare the differences of IPVV, IPVV upper/lower and IPVV left/right between different months of age. Independent sample t test or Mann-Whitney U test was used to compare the differences of IPVV between different genders, and the normal reference range of IPVV in normal preschool children of different months of age was established. Results:The IPVV of the whole lung, right lung, left lung and each lung lobe were positively correlated with age, the correlation coefficient was 0. 638-0.820 in males and 0. 683-0.791 in females (all P<0.001). There was no significant difference in IPVV of whole lung, right lung, left lung and each lobe between male and female from 0 to 12 months (all P>0.05), but there was significant difference in IPVV of whole lung, right lung, left lung and each lobe between male and female from 13 to 36 months (all P<0.05). There were significant differences in IPVV of the whole lung, right lung, left lung and upper lobe of both lungs between boys and girls from 37 to 72 months (all P<0.05). IPVV upper/lower in the right lung (χ 2=14.00, 12.87, P=0.001, 0.002) and IPVV upper/lower in the left lung (χ 2=6.65, 22.84, P=0.036,<0.001) were significantly different in both boys and girls among 3 months of age. And with the increase of age, it showed a decreasing trend. There was no significant difference in IPVV upper/lower between boys and girls at the same age (all P>0.05).There was no significant difference in IPVV left/right among different months and between different sexes (all P>0.05). Finally, the normal reference value range of IPVV of different genders in infancy, early childhood and preschool age was calculated. Conclusions:The increase of pulmonary vessels in normal preschool children is positively correlated with age. There is no significant difference in IPVV between boys and girls in infant period, but IPVV in boys is larger than that in girls in early childhood period and preschool period. IPVV in the lower lung increased faster than that in the upper lung, but there was no significant difference between the left and right lungs.

Animal models are essential for investigating the pathogenesis and developing the treatment of human diseases. Identification of genetic mutations responsible for neurodegenerative diseases has enabled the creation of a large number of small animal models that mimic genetic defects found in the affected individuals. Of the current animal models, rodents with genetic modifications are the most commonly used animal models and provided important insights into pathogenesis. However, most of genetically modified rodent models lack overt neurodegeneration, imposing challenges and obstacles in utilizing them to rigorously test the therapeutic effects on neurodegeneration. Recent studies that used CRISPR/Cas9-targeted large animal (pigs and monkeys) have uncovered important pathological events that resemble neurodegeneration in the patient's brain but could not be produced in small animal models. Here we highlight the unique nature of large animals to model neurodegenerative diseases as well as the limitations and challenges in establishing large animal models of neurodegenerative diseases, with focus on Huntington disease, Amyotrophic lateral sclerosis, and Parkinson diseases. We also discuss how to use the important pathogenic insights from large animal models to make rodent models more capable of recapitulating important pathological features of neurodegenerative diseases.
Amyotrophic Lateral Sclerosis/genetics* ; Animals ; Brain/pathology* ; Disease Models, Animal ; Gene Editing ; Neurodegenerative Diseases/pathology* ; Swine

OBJECTIVE To explore the factors influencing the failure of tigecycline in the treatment of multidrug-resistant Acinetobacter baumannii （MDRAb） pneumonia， and to provide a basis for the rational use of tigecycline. METHODS The information of patients with MDRAb pneumonia who were treated with tigecycline in the ICU of our hospital during Aug. 2020-Jun. 2022 were collected retrospectively. The patients were divided into treatment failure group and treatment success group according to the curative effect. The basic information， acute physiology and chronic health evaluation Ⅱ （APACHE-Ⅱ） score， laboratory indicators， and medication-related information were recorded and compared between 2 groups. Logistic regression analysis was conducted for analyzing the influential factors inducing the failure of tigecycline in the treatment of MDRAb pneumonia. RESULTS A total of 102 cases of MDRAb pneumonia received tigecycline therapy， with 71 in the treatment success group and 31 in the treatment failure group. Compared with the treatment success group， the patients in the treatment failure group had higher APACHE Ⅱ score （P＜0.05）， and more cases with abnormal coagulation function and comorbidities ≥2 types （P＜0.05）. After the treatment of tigecycline， procalcitonin level of the treatment failure group was significantly higher than that of the treatment success group （P＜0.05）. Logistic regression analysis showed that the independent risk factors for the failure of tigecycline in the treatment of MDRAb pneumonia included abnormal coagulation function and APACHE-Ⅱ score ≥20 （P＜0.05）； doubling the first dose was a protective factor （P＜0.05）. CONCLUSIONS In patients with MDRAb pneumonia with APACHE-Ⅱ score ≥20 and abnormal coagulation function， tigecycline therapy is more likely to fail； doubling the first dose of tigecycline has better efficacy in the treatment of MDRAb pneumonia.

Cerebral edema and its caused elevated intracranial pressure are one of the main causes of death in patients with acute ischemic stroke. The main pathogeneses of brain edema include cytotoxic edema, ionic edema, and angiogenic edema. At present, the treatment strategies used to control brain edema and reduce intracranial pressure are mainly osmotic drugs and hemicraniectomy decompression, which are symptomatic treatments to reduce intracranial pressure. In recent years, it has been proposed to inhibit the ion channel in the formation of brain edema as a therapeutic target, which provides a new direction for the treatment of brain edema.