Hepatic fibrosis is a key pathological process in the development of chronic liver disease to cirrhosis, and its core mechanism involves the activation of hepatic stellate cells(HSC) and abnormal deposition of extracellular matrix(ECM). Although existing treatments, such as antiviral drugs, can delay disease progression, they have the problem of single therapeutic targets and cannot reverse fibrosis. Accordingly, multidimensional intervention strategies are urgently needed. Recent studies have shown that circadian rhythm disorders aggravate hepatic fibrosis by regulating metabolism, immunity, and inflammation. Traditional Chinese medicine(TCM) plays a unique role in restoring the circadian clock via multi-target and holistic regulation. This paper establishes a three-dimensional network by systematically integrating biological clock, metabolism, and immunity for the first time to elucidate the scientific connotation of the theory of time-concerned treatment of TCM, and proposes a new strategy for the development of time-targeted compound prescriptions, providing innovative ideas for the treatment of hepatic fibrosis.
Humans ; Liver Cirrhosis/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Circadian Rhythm/drug effects* ; Animals ; Medicine, Chinese Traditional ; Hepatic Stellate Cells/drug effects*

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Background: Advances in blood biomarker discovery have enabled the improved diagnosis and prognosis of Alzheimer's disease (AD). Most branched-chain amino acids, except isoleucine (Ile), are correlated with both mild cognitive impairment (MCI) and AD. Therefore, this study investigated the association between serum Ile levels and MCI/AD. Methods: This study stratified 700 participants from the Alzheimer's Disease Neuroimaging Initiative database into four diagnostic groups: cognitively normal, stable MCI, progressive MCI, and AD. Analysis of covariance and chi-square analyses were used to test the demographic data. Receiver operating curve analyses were used to calculate the diagnostic accuracy of different biomarkers and were compared by MedCalc 20. Additionally, Cox proportional hazards models were used to measure the ability of serum Ile levels to predict disease conversion. Finally, a linear mixed-effects model was used to evaluate the associations between serum Ile levels and cognition, brain structure, and metabolism. Results: Serum Ile concentration was decreased in AD and demonstrated significant diagnostic efficacy. The combination of serum Ile and cerebrospinal fluid (CSF) phosphorylated tau (P-tau) improved the diagnostic accuracy in AD compared to total tau (T-tau) alone. Serum Ile levels significantly predicted the conversion from MCI to AD (cutoff value of 78.3 μM). Finally, the results of this study also revealed a correlation between serum Ile levels and the Alzheimer's Disease Assessment Scale cognitive subscale Q4. Conclusions Serum Ile may be a potential biomarker of AD. Ile had independent diagnostic efficacy and significantly improved the diagnostic accuracy of CSF P-tau in AD. MCI patients with a lower serum Ile level had a higher risk of progression to AD and a worse cognition assessment.

Humans ; Waldenstrom Macroglobulinemia ; Prospective Studies

Objective:To observe the clinical and fundus imaging features of acute macular neuroretinopathy (AMN) associated with COVID-19.Methods:A retrospective case study. A total of 32 eyes of 18 patients diagnosed of AMN associated with COVID-19 at Chengdu Aidi Eye Hospital from December 2022 to February 2023 were included. All patients had a history of fever 1 to 5 days prior to ocular onset and tested positive for SARS CoV-2 antigen. All patients were examined by best-corrected visual acuity (BCVA), color fundus photography, scanning laser ophthalmoscope (SLO), infrared fundus photography (IR), and optical coherence tomography (OCT); OCT angiography, visual field and multifocal electroretinogram (mf-ERG) were performed in 6 patients (11 eyes), 3 patients (6 eyes) and 1 patient (2 eyes), respectively. Follow-up time was 8-10 weeks. The clinical and fundus imaging features were observed and analyzed.Results:There were 6 males (12 eyes) and 12 females (20 eyes), aged from 15 to 36 years, with the mean age of (28.00±5.86) years. Fourteen patients were bilateral and 4 patients were unilateral. The time from the onset of eye symptoms to seeing a doctor was ranged from 1 day to 8 weeks. Among them, 6 patients (10 eyes) visited the doctor within 3 days of onset, while 12 patients (22 eyes) visited the doctor after 3 days of onset. The BCVA was 0.80±0.29. Fundus color photography and SLO examination showed that only 2 patients (4 eyes) showed sheet or petal-like dark red lesions in the macular area, and no obvious abnormal changes were observed in other patients. No obvious abnormalities were found in AF examination of all patients. IR examination showed no significant abnormality in 6 cases which came to hospital within 3 days after the onset, but irregular hyporeflective dark shadow lesions in the macular region of patients with more than 3-day course of disease was observed. OCT examinations of all eyes showed hyperreflective band or patchy lesion on the outer plexiform layer (OPL) and outer nuclear layer (ONL) and affect the ellipsoid zone (EZ) and interdigitation zone (IZ). In 11 eyes of 6 patients undergoing OCTA examination, the blood flow density of the choroidal capillary layer in the focal area decreased. In 6 eyes of 3 patients who underwent visual field examination, the physiologic scotoma was slightly enlarged. One patient (2 eyes) receiving mf-ERG showed a concave reduction in macular center amplitude. The hyperreflective band lesion on OPL and ONL disappear rapidly within 2 weeks, while the continuity of EZ recovered slowly, and the disruption of IZ kept existing for more than 10 weeks.Conclusions:Most AMN associated with COVID-19 are young women; IR showed irregular weak reflex in the lesion area. OCT showed strong OPL and ONL reflection. OCTA was characterized by decreased blood flow density in the choroidal capillary layer of the focal area.

Humans ; Melphalan/therapeutic use* ; Multiple Myeloma/therapy* ; Hematopoietic Stem Cell Transplantation ; Transplantation, Autologous ; Transplantation Conditioning

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ²=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male ; Humans ; Middle Aged ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV Infections/drug therapy* ; Drug Resistance, Viral/genetics* ; China/epidemiology* ; Mutation ; HIV-1/genetics* ; Protease Inhibitors/therapeutic use* ; Genotype

Objective: To explore the safety and effectiveness of stereotactic body radiation therapy (SBRT) for oligometastases from colorectal cancer (CRC). Methods: This is a prospective, single-arm phase Ⅱ trial. Patients who had histologically proven CRC, 1 to 5 detectable liver or lung metastatic lesions with maximum diameter of any metastases ≤5 cm were eligible. SBRT was delivered to all lesions. The primary endpoint was 3-year local control (LC). The secondary endpoints were treatment-related acute toxicities of grade 3 and above, 1-year and 3-year overall survival (OS) and progression free survival (PFS). Survival analysis was performed using the Kaplan-Meier method and Log rank test. Results: Petients from 2016 to 2019 who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Forty-eight patients with 60 lesions were enrolled, including 37 liver lesions and 23 lung lesions. Forty-six patients had 1 or 2 lesions, with median diameter of 1.3 cm, the median biologically effective dose (BED(10)) was 100.0 Gy. The median follow-up was 19.5 months for all lesions. Twenty-five lesions developed local failure, the median local progression free survival was 15 months. The 1-year LC, OS and PFS was 70.2% (95% CI, 63.7%~76.7%), 89.0% (95% CI, 84.3%~93.7%) and 40.4% (95%CI, 33.0%~47.8%). The univariate analysis revealed that planning target volume (PTV) and total dose were independent prognostic factors of LC (P<0.05). For liver and lung lesions, the 1-year LC, OS and PFS was 58.7% and 89.4% (P=0.015), 89.3% and 86.5% (P=0.732), 30.5% and 65.6% (P=0.024), respectively. No patients developed acute toxicity of grade 3 and above. Conclusion: SBRT is safe and effective treatment method for oligometastases from CRC under precise respiratory motion management and robust quality assurance.
Colorectal Neoplasms ; Humans ; Liver/pathology* ; Lung/pathology* ; Prospective Studies ; Radiosurgery/methods*

OBJECTIVE: To investigate the effect of BECN1 expression on proliferation and invasion of human multiple myeloma (MM) cell line RPMI-8226. METHODS: RPMI-8226 cells were cultured in vitro, the recombinant plasmid pcDNA3.1-BECN1 was constructed and transfected into RPMI-8226 cells, then the cells were divided into three groups: control group, negative transfection group and BECN1 transfection group. The expression of BECN1 mRNA in cells of each group was detected by real-time fluorescent quantitative polymerase chain reaction (qRT-PCR); the effect of BECN1 overexpression on cell proliferation inhibition rate was detected by cell counting kit 8 (CCK-8); the effect of BECN1 overexpression on the colony formation rate was detected by plate cloning assay; the effect of BECN1 overexpression on cell invasion was detected by Transwell assay; the effects of BECN1 overexpression on the expression of cell proliferation, invasion and autophagy-related proteins were detected by Western blot. RESULTS: The expression of BECN1 mRNA in BECN1 transfection group was significantly higher than that in control group and negative transfection group (P<0.05); the inhibition rate of cell proliferation and the expression of autophagy-related proteins Beclin1, Atg5 and invasion-related protein E-cadherin in BECN1 transfection group were significantly higher than those in control group and negative transfection group; the colony formation rate, invasion number and the expression of proliferation-related proteins CyclinD1, β-catenin and invasion-related protein N-cadherin were significantly lower than those in control group and negative transfection group (P<0.05). CONCLUSION Overexpression of BECN1 can inhibit the proliferation and invasion of human MM cells RPMI-8226, which may be a potential research target of MM.
Beclin-1/metabolism* ; Cadherins/metabolism* ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Humans ; Multiple Myeloma/genetics* ; RNA, Messenger/metabolism* ; Sincalide/metabolism* ; beta Catenin/genetics*

Objective: To examine the clinical feasibility of mixed reality navigation (MRN) technology based on multimodal imaging for the resection of intracranial eloquent lesions. Methods: Fifteen patients with intracranial eloquent lesions admitted to the Department of Neurosurgery, the First Medical Center, People's Liberation Army General Hospital from September 2020 to September 2021 were retrospectively enrolled. There were 7 males and 8 females, aged (50±16) years (range: 16 to 70 years). Postoperative pathological diagnosis included meningioma (n=7), metastatic carcinoma (n=3), cavernous hemangioma, glioma, ependymoma, aneurysmal changes and lymphoma (n=1, respectively). The open-source software was used to perform the three-dimensional visualization of preoperative images, and the self-developed MRN system was used to perform the fusion and interaction of multimodal images, so as to formulate the surgical plan and avoid damaging the eloquent white matter fiber tracts. Traditional navigation, intraoperative ultrasound and fluorescein sodium angiography were used to determine the extent of lesion resection. The intraoperative conditions of MRN-assisted surgery were analyzed, and the setup time and localization error of MRN system were measured. The changes of postoperative neurological function were recorded. Results: MRN based on multimodal imaging was achieved in all patients. The MRN system setup time (M(IQR)) was 36 (12) minutes (range: 20 to 44 minutes), and the localization error was 3.2 (2.0) mm (range: 2.6 to 6.7 mm). The reliability of eloquent white matter fiber tracts localization based on MRN was rated as "excellent" in 11 cases, "medium" in 3 cases, and "poor" in 1 case. There were no perioperative death and no new impairment in motor, language, or visual functions after operation. Transient limb numbness occurred in 1 patient after operation, and recovered to the preoperative state in 2 weeks after operation. Conclusion: The MRN system based on multimodal imaging can improve the surgical accuracy and safety, and reduce the incidence of iatrogenic neurological dysfunction.
Humans ; Augmented Reality ; Reproducibility of Results ; Retrospective Studies ; Multimodal Imaging