BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome

Based on ultra-high performance liquid chromatography-quadrupole-Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) technology and network pharmacology, this study explored the pharmacodynamic substances and potential mechanisms of Huazhuo Sanjie Chubi Decoction in the treatment of gouty arthritis(GA). UPLC-Q-Exactive Orbitrap-MS technology was used to identify the components in Huazhuo Sanjie Chubi Decoction, and the qualitative analysis of its active ingredients was carried out, with a total of 184 active ingredients identified. A total of 897 active ingredient targets were screened through the PharmMapper database, and 491 GA-related disease targets were obtained from the OMIM, GeneCards, CTD databases. After Venn analysis, 60 intersecting targets were obtained. The component target-GA target network was constructed through the Cytoscape platform, and the STRING database was used to construct a protein-protein interaction network, with 16 core targets screened. The core targets were subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses, and the component-target-pathway network was constructed. It was found that the main active ingredients of the formula for the treatment of GA were phenols, flavonoids, alkaloids, and terpenoids, and the key targets were SRC, MMP3, MMP9, REN, ALB, IGF1R, PPARG, MAPK1, HPRT1, and CASP1. Through GO analysis, it was found that the treatment of GA mainly involved biological processes such as lipid response, bacterial response, and biostimulus response. KEGG analysis showed that the pathways related to the treatment of GA included lipids and atherosclerosis, neutrophil extracellular traps(NETs), IL-17, and so on. In summary, phenols, flavonoids, alkaloids, and terpenoids may be the core pharmacodynamic substances of Huazhuo Sanjie Chubi Decoction in the treatment of GA, and the pharmacodynamic mechanism may be related to SRC, MMP3, MMP9, and other targets, as well as lipids and atherosclerosis, NETs, IL-17, and other pathways.
Drugs, Chinese Herbal/therapeutic use* ; Network Pharmacology ; Arthritis, Gouty/metabolism* ; Chromatography, High Pressure Liquid/methods* ; Humans ; Mass Spectrometry/methods* ; Protein Interaction Maps/drug effects*

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Background: Given the association between nonalcoholic fatty liver disease and metabolic risks, a new term, metabolic dysfunction- associated steatotic liver disease (MASLD) has been proposed. We aimed to explore the association between MASLD and all-cause, cause-specific mortalities. Methods: We included individuals with steatotic liver disease (SLD) from the Korean National Health Insurance Service. Moreover, SLD was defined as a fatty liver index ≥30. Furthermore, MASLD, metabolic alcohol-associated liver disease (MetALD), and alcoholic liver disease (ALD) with metabolic dysfunction (MD) were categorized based on alcohol consumption and MD. We also analyzed all-cause, liver-, cancer-, hepatocellular carcinoma (HCC)- and cardiovascular (CV)-related mortalities. Results: This retrospective nationwide cohort study included 1,298,993 individuals aged 40 to 79 years for a mean follow-up duration of 9.04 years. The prevalence of MASLD, MetALD, and ALD with MD was 33.11%, 3.93%, and 1.00%, respectively. Relative to the “no SLD” group, multivariable analysis identified that MASLD (adjusted hazard ratio [aHR], 1.28; 95% confidence interval [CI], 1.26 to 1.31), MetALD (aHR, 1.38; 95% CI, 1.32 to 1.44), and ALD with MD group (aHR, 1.80; 95% CI, 1.68 to 1.93) have a significantly higher risk of all-cause mortality. Furthermore, MASLD, MetALD, ALD with MD groups showed higher liver-, cancer- and HCC-related mortality than “no SLD” group. While all-cause specific mortalities increase from MASLD to MetALD to ALD with MD, the MetALD group shows a lower risk of CV-related mortality compared to MASLD. However, ALD with MD group still have a higher risk of CV-related mortality compared to MASLD. Conclusion SLD is associated with an increased risk of all-cause, liver-, cancer-, HCC-, and CV-related mortalities.

Background: We aimed to investigate the predictive values of plasma C-peptide levels and the continuous glucose monitoring (CGM)-defined coefficient of variation (CV) in risk prediction for hypoglycemia in Korean people with diabetes with normal and impaired kidney function. Methods: We analyzed data from 1,185 participants diagnosed with type 1 and type 2 diabetes who underwent blinded professional CGM between January 2009 and May 2021 at outpatient clinics. We explored correlations among CGM-defined CV, plasma C-peptide levels, and time below range at <70 and 54 mg/dL across different kidney function categories. Results: In patients with chronic kidney disease (CKD) stages 1–2 (n=934), 89.3% who had a random plasma C-peptide level higher than 600 pmol/L exhibited a CV of ≤36%. Among those in CKD stage 3 (n=161) with a random plasma C-peptide level exceeding 600 pmol/L, 66.7% showed a CV of ≤36%. In stages 4–5 of CKD (n=90), the correlation between random C-peptide levels and CV was not significant (r=–0.05, P=0.640), including cases with a CV greater than 36% despite very high random plasma C-peptide levels. Random plasma C-peptide levels and CGM-assessed CV significantly predicted hypoglycemia in CKD stages 1–2 and 1–5, respectively. Conclusion The established C-peptide criteria in Western populations are applicable to Korean people with diabetes for hypoglycemic risk prediction, unless kidney function is impaired equivalent to CKD stage 3–5. The CGM-defined CV is informative for hypoglycemic risk prediction regardless of kidney function.

Objectives: This study investigated the relationship between exposure to endocrine-disrupting chemicals (EDCs), specifically phthalates, bisphenol A, bisphenol F, and bisphenol S, and the severity of attention-deficit/hyperactivity disorder (ADHD) symptoms using neuropsychological tests in children diagnosed with ADHD. Methods: This study included 67 medication-naïve children with ADHD aged 6–16 years. The urinary concentrations of EDCs were measured, and ADHD symptom severity was evaluated using neuropsychological tests and clinical symptom scale measurements. The Jonckheere–Terpstra test, Pearson and Spearman correlation analyses, linear regression models, and multiple regression models were used to examine the relationship between EDC exposure and ADHD symptoms. Results: A significant correlation was observed between urinary phthalate metabolite concentrations and commission error T-scores in the visual Advanced Test of Attention test. No significant associations were found with other neuropsychological indicators or bisphenol levels. Conclusion Phthalate exposure affects impulsivity in children with ADHD, which is consistent with the results of previous studies that used parental surveys. However, bisphenols are not clearly associated with ADHD symptoms, which is consistent with the results of previous studies.

Objective To explore the application effect of ultrasound-assisted localization in spinal anesthesia for elderly patients with hip fractures.Methods A total of 114 elderly patients undergoing hip fracture surgery with spinal anesthesia in our hospital from September 2022 to June 2024 were enrolled.The random number table method was applied to allocate participants into two groups:surface anatomical landmark localization group and ultrasound-assisted localization group,with 57 patients in each group.Both groups of patients underwent spinal anesthesia via the paramedian approach for puncture.The first-attempt puncture success rate,success rate of the initial puncture site,number of skin punctures,number of adjusted epidural needle direction,positioning time of the puncture point,puncture time(puncture success time,anesthesia time,and total time),adverse events during the puncture process(nerve hypersensitivity and accidental puncture of the dura mater),spinal anesthesia related complications(back pain,headache,and nerve injury),patient satisfaction and hospital stay were observed and compared between the two groups.The quality of early postoperative recovery was evaluated by using the 15-Item Quality of Recovery(QOR-15)scale at 24 h after surgery.Results The first-attempt puncture success rate in the ultrasound-assisted localization group was 71.9％(41/57),which was significantly higher than that in the surface anatomical landmark localization group[28.1％(16/57),x2=21.930,P=0.000].The success rate of the initial puncture site in the ultrasound-assisted localization group was 87.7％(50/57),which was significantly higher than that in the surface anatomical landmark localization group[54.4％(31/57),x2=15.396,P=0.000].The number of skin punctures and adjusted epidural needle direction in the ultrasound-assisted localization group were 1(1,1)and 0(0,1)times,while in the surface anatomical landmark localization group were 2(1,3)and 3(0,5)times,with statistically significant differences(all P=0.000).The puncture positioning time in the ultrasound-assisted localization group was 2.2(1.7,3.2)min,which was significantly longer than that in the surface anatomical landmark localization group[0.8(0.5,1.2)min,Z=-8.418,P=0.000].The puncture success time,anesthesia time,and total time of the ultrasound-assisted localization group were 1.9(1.7,2.3),4.9(4.3,5.3),and 7.1(6.3,8.7)min,while of the surface anatomical landmark localization group were 5.1(2.3,8.0),7.9(5.7,11.0),and 8.6(6.6,12.0)min,with statistically significant differences(all P＜0.05).There were no statistically significant differences in the incidence of nerve hypersensitivity during operation(3.5％vs.7.0％,x2=0.176,P=0.675),accidental puncture of the dura mater by epidural needles(0％vs.3.5％,P=0.496),postoperative headache(0％vs.3.5％,P=0.496),and back pain(1.8％vs.10.5％,x2=2.435,P=0.119)between the two groups.Both groups of patients showed no symptoms of nerve injury after surgery.There were no statistically significant differences in QOR-15 scores at 24 h postoperatively[119(115,124)points vs.116(112,121)points,Z=-1.858,P=0.063]and length of hospital stay[10.0(9.0,12.5)dvs.10.0(8.0,13.0)d,Z=-0.043,P=0.966]between the two groups.The satisfaction of patients in the ultrasound-assisted localization group was significantly higher than that in the surface anatomical landmark localization group(P=0.004).Conclusion Application of ultrasound-guided localization in spinal anesthesia for elderly patients with hip fractures significantly improves the first-attempt puncture and initial puncture site success rates,reduces skin puncture attempts and adjustments of the epidural needle direction,shortens time of anesthetic procedure,and enhances patient satisfaction,making it highly recommendable for clinical use.

Objective:To analyze the clinical value of delayed solidification of cement at freezing point combined with establishment of cement channels in the treatment of further leakage of cement in percutaneous kyphoplasty (PKP).Methods:A retrospective analysis was performed for the medical records of 261 patients with osteoporotic vertebral fracture in the thoracolumbar segment who underwent PKP treatment in Beijing Puren Hospital from April 2019 to April 2023. According to the method of dealing with PKP cement leakage, it was divided into freezing point group (using bone cement combined with cement channel reconstruction treatment at freezing point temperature) and temperature gradient group (using temperature gradient method). There were 128 cases in the freezing point group, including 37 males and 91 females, aged 75.57±4.60 years (range, 65-85 years), and fracture locations were 18 cases in T 10, 30 cases in T 11, 44 cases in T 12, 23 cases in L 1 and 13 cases in L 2. There were 133 cases in the temperature gradient group, including 36 males and 97 females, aged 75.66±4.51 years (range, 65-85 years), and fracture locations were 17 cases in T 10, 32 cases in T 11, 51 cases in T 12, 22 cases in L 1, and 11 cases in L 2. The intraoperative blood loss, operation time, intravertebral cement area, cement leakage area, cement leakage area increase, cement bolus time and incidence of injection difficulty, as well as the pain visual analogue scale (VAS), Oswestry disability index (ODI), kyphosis angle, the height of the anterior edge of the injured vertebral body and the difference between it before and after surgery were compared. Results:All patients were followed up for 3 consecutive months. The intraoperative blood loss and initial cement leakage area were 9.48±2.64 ml and 32.56±7.05 mm 2 in the freezing point group and 9.04±2.25 ml and 32.86±7.00 mm 2 in the temperature gradient group, respectively, and the difference was not statistically significant ( P>0.05) ; The operation time, the area of bone cement in the vertebral body, the final leakage area of bone cement, and the increase of bone cement leakage in the freezing point group were 55.08±4.13 min, 1 175.45±117.11 mm 2, 35.84±8.67 mm 2, and 0.00(0.00, 13.32) mm 2, respectively, and the temperature gradient group were 53.02±3.96 min, 823.70±144.79 mm 2, and 73.38±29.16 mm 2 and 44.39(20.13, 56.61) mm 2, the differences were statistically significant ( P<0.05). The height of the anterior edge of the vertebral body was 21.54±2.06 mm and 21.24±2.33 mm immediately after surgery and 3 months after surgery in the freezing point group, which were higher than those in the temperature gradient group 21.10±1.60 mm and 18.92±1.51 mm, respectively, and the difference was statistically significant ( P<0.05). The VAS scores of the freezing point group were 2.29±0.62 and 1.03±0.66 points, ODI were 23.20%±3.97%, 10.43%±4.33%, and the kyphosis angles were 9.09°±2.80° and 9.44°±2.93°, respectively, which were lower than those of the temperature gradient group (4.11±0.79 and 2.79±0.65 points), ODI (35.97%±6.42%, and 23.73%±5.72%), and the kyphosis angles (10.24°±2.33° and 13.22°±2.56°), the differences were statistically significant ( P<0.05). The operating time of bone cement in the freezing point group was 10.89±2.35 min, which was longer than that in the temperature gradient group 5.77±0.52 min, and the difference was statistically significant ( t=24.021, P<0.001). The incidence of cement injection difficulty was 0 in the freezing point group and 27.1% (36/133) in the temperature gradient group. Conclusion:The establishment of bone cement combined with bone cement channel at freezing point temperature can effectively prolong the bolus time of bone cement and reduce the re-leakage of bone cement, which is conducive to increasing the injection volume and distribution area of bone cement in the vertebral body, effectively reducing the amount of bone cement leakage and obtaining better clinical efficacy.

This study investigated the drug resistance and genetic relationships among strains co-existing in animals,the environ-ment,and the living quarters of employees at large-scale pig farms in certain regions of Shandong Province,to provide a scientific ba-sis for elucidating the transmission mechanisms of drug-resistant bacteria through bacterial traceability analysis.Samples were col-lected from two pig farms,and bacteria were isolated and purified.The species of the isolated strains were identified via 16S rRNA gene sequencing.Antimicrobial susceptibility testing was conducted with a VITEK-2 Compact system and the disk diffusion method for strains present in pigs,the environment,and living areas.Furthermore,whole-genome sequencing was performed on the Illumina Miniseq platform to annotate drug resistance genes,and multilocus sequence typing(MLST)and core genome single nucleotide poly-morphism(cgSNP)analyses were used to trace the resistant strains.Three species—Staphylococcus aureus,Pseudomonas aeruginosa,and Bacillus cereus—were isolated and cultured from animals,the environment,and employee living areas,and their distributions were analyzed.These strains exhibited diverse drug resistance spectra and genetic diversity.Additionally,the strains displayed highly consistent resistance profiles,resistance genes,ST types,and SNP loci in pig urine,soil both inside and outside the facility,human drinking water,and the cafeteria and dormitories.Our findings indicated a potential risk of transmission of opportunistic pathogens be-tween the pig farming area and the living quarters.Particular attention should be paid to the environmental transmission of methicillin-resistant Staphylococcus aureus.