In this study, the pharmacokinetic characteristics and tissue distribution of cannabidiol(CBD)/γ-polyglutamic acid-g-cholesterol(γ-PGA-g-CHOL) nanomicelles [CBD/(γ-PGA-g-CHOL)NMs] were investigated by pharmacokinetic experiments, and the effect of CBD/(γ-PGA-g-CHOL)NMs on the lipopolysaccharide(LPS)-induced inflammatory damage of cells was evaluated by cell experiments. CBD/(γ-PGA-g-CHOL)NMs were prepared by dialysis. The CBD concentrations in the plasma samples of male SD rats treated with CBD and CBD/(γ-PGA-g-CHOL)NMs were investigated, and the pharmacokinetic parameters were calculated and compared. UPLC-MS/MS was employed to determine the concentration of CBD in tissue samples. The heart, liver, spleen, lung, kidney, and muscle samples were collected at different time points to explore the tissue distribution of CBD and CBD/(γ-PGA-g-CHOL)NMs. The Caco-2 cell model of LPS-induced inflammation was established, and the cell viability, transepithelial electrical resistance(TEER), and secretion levels of inflammatory cytokines were determined to compare the anti-inflammatory activity between the two groups. The results showed that CBD/(γ-PGA-g-CHOL)NMs had the average particle size of(163.1±2.3)nm, drug loading of 8.78%±0.28%, and encapsulation rate of 84.46%±0.35%. Compared with CBD, CBD/(γ-PGA-g-CHOL)NMs showed increased peak concentration(C_(max)) and prolonged peak time(t_(max)) and mean residence time(MRT_(0-t)). Within 24 h, the tissue distribution concentration of CBD/(γ-PGA-g-CHOL)NMs was higher than that of CBD. In addition, both CBD and CBD/(γ-PGA-g-CHOL)NMs significantly enhanced Caco-2 cell viability and TEER, lowered the secretion levels of inflammatory cytokines, and alleviated inflammation. Moreover, CBD/(γ-PGA-g-CHOL)NMs demonstrated stronger anti-inflammatory effect. It can be inferred that γ-PGA-g-CHOL blank nanomicelles are good carriers of CBD, being capable of prolonging the circulation time of CBD in the blood, improving the bioavailability and tissue distribution concentration of CBD, and protecting against LPS-induced inflammatory injury. The findings can provide an experimental basis for the development and clinical application of oral CBD preparations.
Animals ; Cannabidiol/administration & dosage* ; Polyglutamic Acid/analogs & derivatives* ; Humans ; Male ; Rats ; Rats, Sprague-Dawley ; Anti-Inflammatory Agents/administration & dosage* ; Micelles ; Caco-2 Cells ; Cholesterol/pharmacokinetics* ; Tissue Distribution ; Nanoparticles/chemistry*

OBJECTIVE: To explore the diagnostic value of shear wave elastography (SWE) for clinically significant prostate cancer (csPCa). METHODS: We retrospectively analyzed the clinical data of 359 cases with suspected prostate cancer (PCa) in Baoji Central Hospital from June 2017 to July 2023. All the patients underwent the following examinations in the order of serum prostate-specific antigen (PSA) testing, transrectal ultrasonography (TRUS), measurement of the stiffness of the entire prostate gland by SWE, and TRUS-guided prostate puncture biopsy. The stiffness of the entire prostate gland was defined as the average of Young's modulus at both sides of the base, middle, and apex of the prostate, including the maximum Young's modulus (Emax), mean Young's modulus (Emean), and minimum Young's modulus (Emin). We analyzed the correlation of the parameters of the stiffness of the entire prostate gland with the pathological results, focusing on their diagnostic performance for csPCa. RESULTS: Of the 359 cases, 189 were diagnosed by pathological puncture biopsy as BPH, 26 as non-csPCa, and 144 as csPCa. The PSA level, Emax, Emean and Emin were significantly higher in the csPCa than those in the BPH and non-csPCa groups (all P < 0.01), but showed no statistically significant difference between the BPH and non-csPCa groups (all P > 0.05). The area under the receiver operating characteristic curve (AUC), optimal cut-off value, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of Emax in the diagnosis of csPCa were 0.852, 143.92 kPa, 72.22%, 84.65%, 75.91%, 81.98% and 79.67%; those of Emean were 0.868, 82.42 kPa, 67.36%, 91.16%, 83.62%, 80.66% and 81.62%; and those of Emin were 0.682, 32.73 kPa, 47.22%, 89.30%, 73.91%, 71.54% and 72.14%, respectively. In the non-csPCa group, Emax, Emean and Emin were found below the optimal cut-off value in 73.08% (19/26), 92.31% (24/26) and 88.46% (23/26), respectively. CONCLUSION The stiffness of the entire prostate gland measured by SWE contributes to the diagnosis of csPCa, reduces unnecessary detection of non-csPCa, and provides some reference for its active surveillance.
Humans ; Male ; Prostatic Neoplasms/diagnosis* ; Elasticity Imaging Techniques ; Retrospective Studies ; Prostate/pathology* ; Prostate-Specific Antigen/blood* ; Aged ; Middle Aged

Objective:To evaluate the gene mutation profile and prognostic significance of adult cytogenetically normal acute myeloid leukemia (CN-AML) with CEBPA-bZIP mutation. Methods:Targeted sequencing was implemented on the diagnostic bone marrow DNA samples of 141 adult CN-AML subjects with CEBPA-bZIP mutation. The nomogram model for leukemia-free survival (LFS) rate was generated by combining genetic abnormalities and clinical data. Risk stratification was conducted based on prognostic variables and the effect of risk-adjusted consolidation therapy was investigated by Kaplan-Meier method. Results:Four variables were finally included in our nomogram model after multivariate Cox analysis,and an equation for risk score calculation was obtained,risk score=1.3002×white blood cell (WBC) (≥18.77×109/L)+1.4065×CSF3R mutation positive+2.6489×KMT2A mutation positive+1.0128×DNA methylation-related genes mutation positive. According to the nomogram model,patients were further divided into low-risk group (score=0,n=46) and high-risk group (score>0,n=95). Prognostic analysis showed that the 5-year LFS rate,5-year overall survival (OS) rate,and 5-year cumulative incidence of relapse (CIR) of patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the high-risk group were 93.5％,97.1％,and 3.5％,while those in patients who received maintenance chemotherapy were 32.9％,70.5％,and 63.4％,respectively. The differences were statistically significant (all P<0.05). Allo-HSCT could significantly improve the prognosis of patients in high-risk group. However,no corresponding benefit was observed in the low-risk group. Conclusion:Adult CN-AML with CEBPA-bZIP mutation has a complex co-mutation pattern. The nomogram model based on mutations of CFS3R,KMT2A and DNA methylation-related genes together with WBC count can further divide this subset of patients into a relatively low-risk group and a relatively high-risk group. For individuals in the high-risk group,allo-HSCT is proposed as post-remission therapy. The above data will benefit the prognosis estimation and treatment decision for adult CN-AML with CEBPA-bZIP mutation.

The long-term survival outcomes of radical prostatectomy (RP) in Chinese prostate cancer (PCa) patients are poorly understood. We conducted a single-center, retrospective analysis of patients undergoing RP to study the prognostic value of pathological and surgical information. From April 1998 to February 2022, 782 patients undergoing RP at Queen Mary Hospital of The University of Hong Kong (Hong Kong, China) were included in our study. Multivariable Cox regression analysis and Kaplan-Meier analysis with stratification were performed. The 5-year, 10-year, and 15-year overall survival (OS) rates were 96.6%, 86.8%, and 70.6%, respectively, while the 5-year, 10-year, and 15-year PCa-specific survival (PSS) rates were 99.7%, 98.6%, and 97.8%, respectively. Surgical International Society of Urological Pathology PCa grades (ISUP Grade Group) ≥4 was significantly associated with poorer PSS (hazard ratio [HR] = 8.52, 95% confidence interval [CI]: 1.42-51.25, P = 0.02). Pathological T3 stage was not significantly associated with PSS or OS in our cohort. Lymph node invasion and extracapsular extension might be associated with worse PSS (HR = 20.30, 95% CI: 1.22-336.38, P = 0.04; and HR = 7.29, 95% CI: 1.22-43.64, P = 0.03, respectively). Different surgical approaches (open, laparoscopic, or robotic-assisted) had similar outcomes in terms of PSS and OS. In conclusion, we report the longest timespan follow-up of Chinese PCa patients after RP with different approaches.
Male ; Humans ; Retrospective Studies ; Prostatic Neoplasms/pathology* ; Prostate/pathology* ; Prostatectomy ; Prognosis ; Neoplasm Grading

Male ; Humans ; Germ-Line Mutation ; Prostatic Neoplasms/genetics* ; BRCA2 Protein/genetics* ; Genetic Predisposition to Disease

OBJECTIVES: To investigate the efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection in the treatment of retinopathy of prematurity (ROP) and the risk factors for recurrence. METHODS: A retrospective analysis was performed on the medical data of 159 infants with ROP who were born in the First Affiliated Hospital of Zhengzhou University and underwent anti-VEGF treatment from January 2016 to December 2021. According to the presence or absence of recurrence within the follow-up period after initial anti-VEGF treatment, they were divided into a recurrence group with 24 infants and a non-recurrence group with 135 infants. The medical data were compared between the two groups, and a multivariate logistic regression analysis was used to investigate the risk factors for the recurrence of ROP after anti-VEGF treatment. RESULTS: After one-time anti-VEGF treatment, all 159 infants showed regression of plus disease. Recurrence was observed in 24 infants (15.1%) after anti-VEGF treatment, with a mean interval of (8.4±2.6) weeks from treatment to recurrence. The multivariate logistic regression analysis showed that preoperative fundus hemorrhage and prolonged total oxygen supply time were risk factors for the recurrence of ROP (P<0.05), while gestational hypertension was a protective factor (P<0.05). CONCLUSIONS Intravitreal anti-VEGF injection is effective for ROP. Preoperative fundus hemorrhage and long duration of oxygen therapy may increase the risk of ROP recurrence, and further studies are needed to investigate the influence of gestational hypertension on the recurrence of ROP.
Female ; Humans ; Infant ; Infant, Newborn ; Pregnancy ; Angiogenesis Inhibitors/therapeutic use* ; Endothelial Growth Factors/therapeutic use* ; Hemorrhage ; Hypertension, Pregnancy-Induced ; Oxygen/therapeutic use* ; Retinopathy of Prematurity/drug therapy* ; Retrospective Studies ; Risk Factors ; Vascular Endothelial Growth Factor A

Coronavirus disease-2019 (COVID-19) outbreaks were spreading rapidly around the world in early 2020. This disease is within the category of "damp epidemic" and "damp toxin epidemic" in traditional Chinese medicine, with lung and spleen as the lesion focuses, while dampness and toxin as especially prominent properties. Through clinical observation, we found that dampness would often transform into damp heat during the development and evolution of the disease, and the "triple energizer" treatment was an important therapeutic method, eliminating pathogens through purgation and diuresis: for those with damp-heat accumulation toxin diffused to the triple energizer, we could use Ganlu Xiaodudan as primary prescription, which can spread the upper part, smooth the middle part and infiltrate the lower part, so as to provide a way out for the pathogenic factors and regulate Qi movement. For those with damp-heat in Shaoyang channel, we could use Haoqin Qingdantang to clear heat and promote diuresis, harmonize Shaoyang, eliminate damp-heat and epidemic pathogenic factor. For those with pathogen hidden in membrane source dampness trapping and hidden heat, we could use Dayuanyin to eliminate pathogens between interior and exterior parts, and regulate Qi movement. At the same time we shared three typical cases treated in Wuhan, and conducted an in-depth analysis in this study. Clinically, the method of elimination of pathogens through purgation and diuresis is mainly used in the early and middle stage of this disease. When the disease is still located in Qi system, it also can be applied to mild, ordinary patients and severe patients that have accurate syndrome differentiation. In such cases, it can effectively improve symptoms, reduce pathogenic toxin, truncate and reverse the course of disease, give way to pathogen, and avoid disease aggravating.

Coronavirus disease-2019 (COVID-19) is highly contagious. In the early stages of the disease, the symptoms of coldness, dampness and depression in the lungs often appear, including fever, fatigue, soreness, dry cough, poor appetite, and white greasy tongue coating. During the development of the disease, the damp toxin epidemic often enters the inner and generates heat, and the damp heat epidemic toxin blocks pleurodiaphragmatic sites, the triple energizer and lungs, with manifestations of chest tightness, shortness of breath, exacerbation after exercise, or high fever without bringing down, poor appetite, bitterness in mouth, fatigue, diarrhea, loose stools, and yellow and thick tongue fur. As the pathogen can go outward or enter more deeply inside to cause death at the moment, it is the crucial time to treat the disease. In this study, Haoqin Qingdantang was used to clear dampness and heat, reconcile Shaoyang channel and recover the triple energizer, detoxify the dampness fever epidemic toxin, and block the toxin inside, with a good efficacy. This prescription focuses on smoothing the Shaoyang gallbladder channel and the triple energizer, and regards the spleen and stomach as the acquired essence. In the prescription, Erchentang reconciles the spleen and stomach, elevates clear Qi and lower turbid Qi. Bupleuri Radix is added to increase its detoxification function, and Paeoniae Rubra Radix is added to circulate the blood and prevent pathogen from the blood. When the condition improves, Sweet Wormwood Herb and talc are often withdrawn, and Codonopsis is added to nourish the spleen and stomach, to strengthening vital qi to eliminate pathogenic factor. Based on the cases of COVID-19 treated in Wuhan Jinyintan Hospital, this paper summarized some experience of applying Haoqin Qingdantang.

Objective: To prospectively explore the relationship between resting heart rate (RHR) and risk of new-onset heart failure. Methods: It was a prospective cohort study. People who attended the physical examination of Kailuan Group Company in 2006 and with complete electrocardiography (ECG) recordings were eligible for this study. A total of 88 879 participants aged 18 years old or more who were free of arrhythmia, a prior history of heart failure and were not treated with β-blocker were included. Participants were divided into 5 groups according to the quintiles of RHR at baseline (Q(1) group, 40-60 beats/minutes (n=18 168) ; Q(2) group, 67-70 beats/minutes (n=18 970) ; Q(3) group, 71-74 beats/minutes (n=13 583) ; Q(4) group, 75-80 beats/minutes (n=22 739) ; and Q(5) group,>80 beats/minutes (n=15 419) ) .The general clinical data and laboratory test results were collected. The outcome was the first occurrence of heart failure at the end of follow-up (December 31, 2016) .We used Cox regression model to examine the association between RHR and the risk of new-onset heart failure. Hazard ratio (HR) with 95% confidence intervals (CI) were calculated using Cox regression modeling. Results: Among the included patients 68 411 participants were male, mean age was (51.0±12.3) years old, and RHR was (74±10) beats/minutes. Statistically significant differences among the RHR quintiles were found for the following variables: age, gender, systolic blood pressure, diastolic blood pressure, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting blood glucose, body mass index, the level of high-sensitivity C-reactive protein, education status, physical activity, smoking status, drinking status, history of diabetes, history of hypertension and history of use antihypertensive drugs (all P<0.01) . Higher RHR was linked with higher prevalence of diabetes, hypertension history, and higher systolic blood pressure, diastolic blood pressure and FBG levels (all P<0.01). After a mean follow-up of 9.5 years, the incidence of new-onset heart failure in Q(1), Q(2), Q(3), Q(4) and Q(5) groups was 1.60%(290/18 168), 1.36%(258/18 970), 1.80%(245/13 583), 1.76%(400/22 739) and 2.35%(362/15 419),respectively (P<0.01) . The person-year incidence of heart failure in Q(1), Q(2), Q(3), Q(4) and Q(5) groups was 1.7, 1.5, 1.9, 1.9 and 2.6 per 1 000 person-years respectively. Compared with the Q(2) group, multivariate analysis with adjustment for major traditional cardiovascular risk factors showed that HRs of Q(3),Q(4),and Q(5) group were 1.23 (95%CI 1.03-1.48, P<0.05) , 1.19 (95%CI 1.01-1.41, P<0.05) , 1.39 (95%CI 1.18-1.65, P<0.01) , respectively. In the absence of hypertension, diabetes, smoking and acute myocardial infarction, the Cox regression model showed that compared with Q(2) group, the HR of new-onset heart failure in Q(5) group was 1.58 (95%CI 1.02-2.45, P<0.05) . Conclusion: Increased RHR is associated with increased risk of new-onset heart failure in this cohort.
Adult ; Blood Pressure ; Cohort Studies ; Female ; Heart Failure ; Heart Rate ; Humans ; Male ; Middle Aged ; Prospective Studies ; Risk Factors

OBJECTIVE: To explore expression of β-catenin and NF-κB signaling pathway in synovial tissue of rats with different degrees of knee osteoarthritis (KOA). METHODS: Forty-eight SPF male rats weighed (200±20) g were randomly divided into three groups, namely model group (32 rats), sham operation group (8 rats) and control group (8 rats). KOA model rats were established by Hulth method, and 8 rats were killed at 2, 4, 8, 12 weeks respectively after modeling, in order to establish KOA model rats with moderate, early, mild and severe degree. Sham operation group was only cut off capsule of knee joint and suture to exclude interference factor, control group was untreated. Behavior, synovial hyperplasia and cartilage degeneration of rats among each group were observed. Expression of NF-κB and signaling pathway and β-catenin in synovial tissue of rats were detected by real-time PCR. RESULTS: KOA rat model was successfully established, and synovial hyperplasia was observed in KOA model at mild and early degree, and then gradually decreased; while cartilage degeneration in the early moderate and severe KOA model was significantly expressed, and gradually aggravated with time. The results of PCR showed that expression of β-catenin in 4-week group (8.57±0.46) and 8-week group (4.23±0.09) were higher than those in control group (<0.05); expression of TLR-2 in 2-week group (12.04±4.02) and 4-week group (8.54±2.13) were higher than those in control group(<0.05), and TLR-4 in 2-week group(5.04±0.93), 4-week group (3.29±0.58) and 8-week group (1.63±0.12) were higher than those in control group; expression of NF-κB was significantly higher in 2-week group (10.15±2.04), 4-week group (15.97±4.17), 8-week group (7.69±1.48) and 12-week group (6.70±1.58) than that in control group (<0.05), and expression of IL-1β was significantly higher in 4-week group (2.79±0.25) and 8-week group (2.46±0.32) than that of control group (<0.05). CONCLUSIONS On the RNA expression level, both of β-catenin and NF-κB signaling pathways are involved in synovial inflammation in KOA model rats, and they play a regulatory role in expression of IL-1β, degeneration of KOA.
Animals ; Inflammation ; Male ; NF-kappa B ; Osteoarthritis, Knee ; Rats ; Signal Transduction ; beta Catenin