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

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

While multiple step saccades (MSS) are occasionally reported in the healthy population, they are more evident in patients with Parkinson's disease (PD). Therefore, MSS has been suggested as a biological marker for the diagnosis of PD. However, the lack of clarity on the neural mechanism underlying the generation of MSS largely impedes their application in the clinic. We have proposed recently that MSS are triggered by the discrepancy between desired and executed saccades. Accordingly, brain regions involved in saccadic planning and execution might play a role in the generation of MSS. To test this hypothesis, we explored the role of the prefrontal (PFC) and posterior parietal cortex (PPC) in generating MSS by conducting two experiments: electroencephalographic recording and single-pulse transcranial magnetic stimulation in the PFC or PPC of humans while participants were performing a gap saccade task. We found that the PFC and PPC are involved in the generation of MSS.
Humans ; Parietal Lobe/physiology* ; Saccades/physiology* ; Prefrontal Cortex/physiology* ; Male ; Transcranial Magnetic Stimulation ; Female ; Electroencephalography ; Adult ; Young Adult

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*

OBJECTIVE To investigate the HRCT and MRI characteristic of external auditory canal cholesteatoma(EACC)in children.METHODS A total of 40 patients(45 lesions)with EACC confirmed by pathology were retrospectively analyzed with HRCT and MRI characteristics and clinical therapeutic value.Imaging findings of 40 patients(45 lesions)with EACC were retrospectively analyzed.RESULTS Soft tissues were found in all the external auditory canal(EAC).Of the forty-five soft tissues,7 manifested as inhomogeneous strip soft tissues and 38 as lesions solid soft tissues;30 located in medial part of the EAC and covered the tympanic membrane,while the other 15 presented as tympanic membrane perforation and involved the tympanic cavity.The MRI of the 3 ears showed high signal on T2/T1 iso-intensity,high signal on DWI,and low signal on ADC.Normal whole bony EAC was observed in 17 cases and enlarged medial EAC in 28 cases.Seven cases only involved in the superior wall,but 38 cases displayed as multiple bone wall involved,of which 6 involved in circumferential walls.Thirty-three cases displayed atactic ear bone margin,11 displayed blunted or disappeared drum shield plate.Destroy of long crus of incus and manubrium mallei occurred in 15 cases,of short crus of incus in 8 cases,of stapes in 2 cases,and mastoiditis in 5 cases.According to the pneumatization degree of mastoid air cell,37 cases were classified into pneumatic type,7 cases into mixed type,and the last one into diploic type.CONCLUSION The children EACC tends to be limited and rarely involved in middle ear and mastoid process.No patient with peri-ear infection was found.Application of HRCT and MRI help accurate location and determination of cholesteatoma.According to the extent of the lesion,selecting the appropriate surgical method is an effective method to remove cholesteatoma,improve hearing and reduce recurrence.

Objective:To explore the early predictive value of umbilical cord blood S100β protein and lactate combined with amplitude integrated electroencephalogram（aEEG）in small for gestational age（SGA）preterm infants with brain injury.Methods:One hundred and six cases of SGA preterm infants were enrolled in this study in Neonatology Department of Inner Mongolia People's Hospital from January 2019 to December 2021. Umbilical cord blood serum S100β protein and lactate at birth of All SGA preterm infants were tested，and aEEG was monitored at 6h and 72 h after birth，corrected gestational age of 32 weeks and 37 weeks. According to the diagnostic criteria of brain injury in preterm infants，SGA preterm infants were divided into brain injury group（45 cases）and non-brain injury group（61 cases），and compared the differences of S100β protein，lactate and the designated time aEEG between the two groups.SGA preterm infants with brain injury were further divided into symmetrical group（28 cases）and non-symmetrical group（15 cases）. The differences of umbilical cord blood S100β protein and lactate level between the two groups were compared，and the diagnostic value in different types of SGA preterm infants with brain injury was also compared.Results:SGA preterm infants in the brain injury group had significantly higher levels of umbilical cord blood S100β protein［（0.826±0.218）μg/L vs（0.397±0.196）μg/L， t=8.316， P<0.05］and lactate［（8.5±1.3）mmol/L vs（3.8±0.9）mmol/L， t=3.281， P<0.05］than those in non-brain injury group.Symmetric SGA group had higher level of S100β protein than the asymmetric SGA group［（0.924±0.205）μg/L vs（0.438±0.196）μg/L， t=5.734， P<0.05］.But there was no statistically significant difference in lactate levels［（5.6±1.4）mmol/L vs（3.9±1.2）mmol/L， t=0.932， P>0.05］between symmetric SGA group and asymmetric SGA group. The abnormal rates of aEEG in brain injury group and non-brain injury group were respectively 100%（45/45）vs 22.95%（14/61）at 6 h after birth，95.56%（43/45）vs 16.39%（10/61）at 72 h after birth，62.22%（28/45）vs 6.56%（4/61）at 32 weeks of corrected gestational age，22.22%（10/45）vs 3.28%（2/61）at 37 weeks of corrected gestational age. The abnormal rate of brain injury group was higher than the non-brain injury group in the same nodal time，and the differences were statistically significant（ χ 2 value respectively 62.292，64.913，38.074，9.257，all P<0.05）. Conclusion:There were significant value in umbilical cord blood S100β protein，lactate level and aEEG monitoring in the early diagnosis in preterm infants SGA with brain injury. The combination of the three might be more helpful for the early diagnosis and timely treatment of brain injury in SGA preterm infants.

Objective:To enhance comprehension of undifferentiated embryonal sarcoma of the liver(UESL)in children by analyzing ultra-sound,CT,and MRI imaging features.Methods:A retrospective analysis was conducted on 11 cases of UESL in children,confirmed through surgery and pathology,at the Children's Hospital,Affiliated Capital Institute of Pediatrics from December 2009 to December 2021.We ana-lyzed the ultrasound,CT,and MRI imaging features of all patients and summarized their characteristics.Results:All 11 cases presented with solitary hepatic masses ranging from 11.5 to 19.8 cm in diameter.Imaging manifestations of UESL correlated with component proportion and distribution within the masses.Lesions displayed clear boundaries in all cases.CT scans revealed mixed low density in 11 cases,with ir-regular floc soft tissue density shadows observed at the edge of cystic density areas or around partitions in a few cases.Ultrasound images of all six cases showed solid space-occupying masses,with varying sizes of anechoic regions within the solid mass.MRI T1WI showed mixed low intensity signal in three cases and strip/large high intensity signal areas in the lesion.T2WI revealed mixed high intensity signal and strip low intensity signal areas in 3 lesions.In the arterial phase,lesions displayed slightly to moderately heterogeneous strip/patch enhancement,primarily marginal enhancement in nine cases and thickened,tortuous arterial shadows in eight cases.In the delayed phase,lesions showed continuous uneven enhancement,with enhancement at the edge and peripheral-to-central filling observed in eight cases.Additionally,the enhancement range continuously increased in eight cases,with the false capsule sign identified in eight cases in the delayed stage.Conclu-sions:Imaging features of UESL in children exhibit distinct characteristics.Understanding these features,in conjunction with clinical findings,may aid in early diagnosis.

Objective:To explore the MR enterography (MRE) features of intestinal Behcet disease (BD) and Crohn disease (CD) in pediatric patients.Methods:This study was a cross-sectional study. The BD patients and CD patients were retrospectively enrolled from Children′s Hospital Affiliated to Capital Institute of Pediatrics from January 2019 to October 2022. There were 17 children with intestinal BD, including 6 males and 11 females, aged 5-12 (8.4±2.6) years, and 23 children with CD, including 15 males and 8 females, aged 7-15 (10.2±2.7) years. The MRE images were observed, and the evaluation contents included the diseased intestine (terminal ileum, ileum+ascending colon, ileum+ascending colon+transverse colon, whole colon), the form of intestinal wall thickening (uniform/eccentric thickening), MRI signal (fat suppression T 2WI, DWI), the enhancement mode (uniform/layered enhancement), intestinal stenosis, intestinal dilatation, mesentery comb sign, mesentery fatty fibrosis, lymph node enlargement, and the extraintestinal complication (anal fistula, fluid collection). The comparison of MRE signs between groups was performed using the χ2 test or Fisher exact test. Results:All children were completed MRE examination with good intestinal filling, and no adverse reactions. The significant differences were found in the scope of the diseased bowel, the form of intestinal wall thickening, DWI signal, intestinal dilatation, lymph node enlargement, anal fistula and fluid collection between the intestinal BD and CD patients ( P<0.05), while no significant differences were found in the fat suppression T 2WI signal, enhancement mode of the lesion, intestinal stenosis, mesentery comb sign, and mesentery fatty fibrosis ( P>0.05). Conclusion:MRE is safe and effective, and there are certain significantly different MRE features between children with intestinal BD and CD.

Objective To systematically evaluate and integrate the experiences of people living with HIV in peer support,and to provide references and suggestions for improving peer support for HIV patients in clinical practice.Methods The computer retrieval was performed in PubMed,CINAHL(EBSCO),Web of Science,ProQuest,CNKI and Wanfang Data from January 1,1996 to September 30,2022,to collect qualitative studies in the experience of people living with HIV participating in peer support.This qualitative systematic review was conducted under the Joanna Briggs Institute guideline.This paper was written according to the enhancing transparency in reporting the synthesis of qualitative research(ENTREQ).Results A total of 7 qualitative studies were included,and 26 findings were extracted,which were summarized into 12 categories and integrated into 4 synthesized findings.Findings included that peer support provides patients with information and help them establish and maintain a healthy lifestyle;patients receive emotional support in peer support;patients receive instrumental support in peer support;the objective requirements and scenarios of peer support.Conclusion AIDS peer support has a positive effect on AIDS prevention and treatment,and it is important to address the practical needs of people living with HIV/AIDS.The practice of HIV peer support needs further theoretical support and scientific guidance.Building an HIV peer support model,providing systematic training and professional guidance to HIV peers is conducive to improving the accuracy of HIV peer support behaviors,the development of HIV peer support activities,and optimizing the effectiveness and sustainability of peer support for people living with HIV/AIDS.