Chromodomain-helicase-DNA-binding protein 1 (CHD1) deletion is among the most common mutations in prostate cancer (PCa), but its role remains unclear. In this study, RNA sequencing was conducted in PCa cells after clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9)-based CHD1 knockout. Gene set enrichment analysis (GSEA) indicated upregulation of hypoxia-related pathways. A subsequent study confirmed that CHD1 deletion significantly upregulated hypoxia-inducible factor 1α (HIF1α) expression. Mechanistic investigation revealed that CHD1 deletion upregulated HIF1α by transcriptionally downregulating prolyl hydroxylase domain protein 2 (PHD2), a prolyl hydroxylase catalyzing the hydroxylation of HIF1α and thus promoting its degradation by the E3 ligase von Hippel-Lindau tumor suppressor (VHL). Functional analysis showed that CHD1 deletion promoted angiogenesis and glycolysis, possibly through HIF1α target genes. Taken together, these findings indicate that CHD1 deletion enhances HIF1α expression through PHD2 downregulation and therefore promotes angiogenesis and metabolic reprogramming in PCa.
Male ; Humans ; Von Hippel-Lindau Tumor Suppressor Protein/metabolism* ; DNA-Binding Proteins/metabolism* ; Prolyl Hydroxylases/metabolism* ; Hypoxia ; Prostatic Neoplasms/pathology* ; Glycolysis ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Cell Line, Tumor ; DNA Helicases/metabolism*

OBJECTIVES: To compare the efficacy of needle retaining after electroacupuncture combined with cognitive training and electroacupuncture combined with cognitive training in the treatment of post-stroke cognitive impairment (PSCI). METHODS: A total of 206 patients with PSCI were randomized into a needle retaining group (103 cases, 9 cases dropped out) and an electroacupuncture group (103 cases, 6 cases dropped out). In addition to the conventional basic medical treatment and the rehabilitation treatment, in the needle retaining group, electroacupuncture at Shenting (GV 24) and Baihui (GV 20) was applied, with continuous wave of 50 Hz in the first 15 min and with disperse-dense wave of 2 Hz/50 Hz in the last 15 min, the needles were continuously retained for 1 h after electroacupuncture, during which cognitive training was adopted; in the electroacupuncture group, cognitive training was performed after the same electric stimulation exerted for 30 min, without additional needles retaining. The treatment was given once a day, 5 times a week for totally 8 weeks in the two groups. Before and after 8-week treatment, the TCM syndrome score was observed; before and after 4,8-week treatment, the scores of mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA) and ability of daily living were observed in the two groups. The clinical efficacy of the two groups was evaluated after 8-week treatment. RESULTS: After 8-week treatment, the TCM syndrome scores were increased compared with those before treatment in both groups (P<0.05); the TCM syndrome score in the needle retaining group was higher than that in the electroacupuncture group (P<0.05).After 4,8-week treatment, the scores of MMSE, MoCA and ability of daily living were increased compared with those before treatment in both groups (P<0.05); MMSE, MoCA scores after 4,8-week treatment and ability of daily living score after 8-week treatment in the needle retaining group were higher than those in the electroacupuncture group (P<0.05). The total effective rate was 90.4% (85/94) in the needle retaining group, which was superior to 82.5% (80/97) in the electroacupuncture group (P<0.05). CONCLUSIONS Both needle retaining after electroacupuncture combined with cognitive training and electroacupuncture combined with cognitive training can effectively treat PSCI, improve the clinical symptom, cognitive function and ability of daily living in PSCI patients. Needle retaining after electroacupuncture combined with cognitive training has a better therapeutic effect.
Humans ; Electroacupuncture ; Acupuncture Therapy ; Cognitive Training ; Acupuncture Points ; Cognitive Dysfunction/therapy* ; Stroke/complications* ; Treatment Outcome

OBJECTIVE: To explore the relationship between drug treatment and outcomes in patients with late-onset severe pneumonia (LOSP) after allogeneic stem cell transplantation (allo-SCT). METHODS: We retrospectively analyzed the effects of the initiation time of treatment drugs, especially antiviral drugs and glucocorticoids on the clinical outcomes in 82 patients between January 2016 and August 2021 who developed LOSP after allo-SCT in Peking University People's Hospital. Univariate analysis was performed by Mann-Whitney U test and χ² test, and multivariate analysis was performed by Logistic regression. When multiple groups (n>2) were involved in the χ² test, Bonferroni correction was used for the level of significance test. RESULTS: Of all 82 patients in this study, the median onset time of LOSP was 220 d (93-813 d) after transplantation, and the 60-day survival rate was 58.5% (48/82). The median improvement time of the survival patients was 18 d (7-44 d), while the median death time of the died patients was 22 d (2-53 d). Multivariate analysis showed that the initiation time of antiviral drugs from the onset of LOSP (< 10 d vs. ≥10 d, P=0.012), and the initiation time of glucocorticoids from antiviral drugs (< 10 d vs. ≥10 d, P=0.027) were the factors affecting the final outcome of the patients with LOSP at the end of 60 d. According to the above results, LOSP patients were divided into four subgroups: group A (antiviral drugs < 10 d, glucocorticoids ≥10 d), group B (antiviral drugs < 10 d, glucocorticoids < 10 d), group C (antiviral drugs ≥10 d, glucocorticoids ≥10 d) and group D (antiviral drugs ≥10 d, glucocorticoids < 10 d), the 60-day survival rates were 91.7%, 56.8%, 50.0% and 21.4%, respectively. CONCLUSION Our study demonstrated that in patients who developed LOSP after allo-SCT, the initiation time of antiviral drugs and glucocorticoids were associated with the prognosis of LOSP, and the survival rate was highest in patients who received antiviral drugs early and glucocorticoids later. It suggested that for patients with LOSP of unknown etiology should be highly suspicious of the possibility of a secondary hyperimmune response to viral infection.
Antiviral Agents/therapeutic use* ; Glucocorticoids/therapeutic use* ; Hematopoietic Stem Cell Transplantation/methods* ; Humans ; Pneumonia/etiology* ; Prognosis ; Retrospective Studies ; Transplantation, Homologous/adverse effects*

The relevant provisions of bloodletting for expelling pathogens are collected from the works of the medical representative scholars in Jin-Yuan Dynasties and Ming-Qing Dynasties respectively to construct the databases of bloodletting for expelling pathogens of Jin-Yuan Dynasties and Ming-Qing Dynasties. Using frequency analysis, the bloodletting device, bloodletting location, bloodletting volume, the related pathogens and indications are compared between these two times so that the evidences could be provided for the inheritance and development of the academic thought of bloodletting for expelling pathogens. It is found that the three-edge needle is the most commonly used device for bloodletting in Jin-Yuan Dynasties and Ming-Qing Dynasties and
Acupuncture Points ; Bloodletting ; China ; Medicine, Chinese Traditional ; Meridians ; Needles

OBJECTIVE: To analyze the overall survival (OS) of elderly acute myeloid leukemia (AML) patients treated with oral arsenic-containing Qinghuang Powder (, QHP) or low-intensity chemotherapy (LIC). METHODS: Forty-two elderly AML patients treated with intravenous or subcutaneous LIC (1 month for each course, at least 3 courses) or oral QHP (3 months for each course, at least 2 courses) were retrospectively analyzed from January 2015 to December 2017. The main endpoints of analysis were OS and 1-, 2-, 3-year OS rates of patients, respectively. And the adverse reactions induding bone marrow suppression, digestive tract discomfort and myocardia injury were observed. RESULTS: Out of 42 elderly AML patients, 22 received LIC treatment and 20 received QHP treatment, according to patients' preference. There was no significant difference on OS between LIC and QHP patients (13.0 months vs. 13.5 months, >0.05). There was no significant difference on OS rates between LIC and QHP groups at 1 year (59.1% vs. 70.0%), 2 years (13.6% vs. 15%), and 3 years (4.6% vs. 5.0%, all >0.05). Furthermore, there was no significant difference of OS on prognosis stratification of performance status > 2 (12 months vs. 12 months), age> 75 year-old (12.0 months vs. 12.5 months), hematopoietic stem cell transplant comorbidity index >2 (12 months vs. 13 months), poor cytogenetics (12 months vs. 8 months), and diagnosis of secondary AML (10 months vs. 14 months) between LIC and QHP patients (>0.05). CONCLUSION QHP may be an alternative treatment for elderly AML patients refusing LIC therapy.
Aged ; Aged, 80 and over ; Antineoplastic Agents ; therapeutic use ; Arsenicals ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; mortality ; Male ; Middle Aged ; Powders ; Retrospective Studies

AIM:To observe the expression of microRNA-126-5p during myocardial injury and its role in myo-cardial cell injury induced by adriamycin(also called doxorubicin, DOX).METHODS: The BALB/c mouse model of DOX-induced acute and chronic myocardial injury was established via intraperitoneal injection of DOX.HE staining was applied to observe the morphological changes of myocardial tissues.Lactate dehydrogenase(LDH)in serum was detected and PowerLab system was used to detect the influence of DOX on the changes of ±dp/dtmax.The expression of microRNA-126-5p in injured myocardial tissues and the H 9c2 cells exposed to DOX was detected by real-time PCR.Gain-and loss-of-function experiments were conducted to detect the role of microRNA-126-5p in H9c2 cells treated with DOX on LDH release and caspase-3 activation.RESULTS:In acute and chronic DOX myocardial damage models in mice,HE staining showed disarranged myocardial fibers, dissolved myofibril and inflammatory cell infiltration.Higher serum LDH level and lower ±dp/dtmaxin DOX-treated mice than those in normal mice were found.Compared with the normal mice, the expression level of microRNA-126-5p was significant increased in the myocardium with DOX-induced injury.Similarly,the expression level of microRNA-126-5p was significant increased in the H9c2 cells treated with DOX.In addition, over-expression of microRNA-126-5p decreased cell viability and promoted apoptosis,while microRNA-126-5p ablation promoted the viability and inhibited the apoptosis of H9c2 cells.CONCLUSION:The microRNA-126-5p expression is up-regulated in myocar-dial injury induced by DOX,and microRNA-126-5p inhibits cell viability and promotes apoptosis induced by DOX.

Objective To evaluate the dose distribution and clinical efficacy of hippocampal-sparing prophylactic cranial irradiation ( HS-PCI ) in patients with small cell lung cancer by using helical tomotherapy. Methods Clinical data of 49 patients with small cell lung cancer receiving HS-PCI using helical tomotherapy in Cancer Hospital between 2014 and 2017 were retrospectively analyzed. All patients received brain MRI to exclude the possibility of brain metastasis within 1 month after standard surgery or radio-and chemo-therapy. The prescription dose was 95% PTV,25 Gy in 10 fractions. The adverse reactions and cognitive functions of patients were observed before,6 months and 1 year after treatment,and the dose distribution in the hippocampal gyrus,survival rate and brain metastasis rate were analyzed. Results The median follow-up time was 16 months. The average dose in the hippocampal gyrus was 7. 23 Gy and 8. 46 Gy in the reduction region,which was reduced by 71. 88% and 66. 16% compared with the prescription dose. The maximum dose in the hippocampal gyrus was 10. 66 Gy and 15. 43 Gy in the reduction region. Among 49 patients,8 died,the 1-year survival rate was 85. 1% and the 2-year survival rate was 70. 3%.Nine patients (18. 3%) had brain metastases,and one of them with extensive multiple brain metastases (n＝13) presented with metastasis adjacent to the hippocampal gyrus. The main adverse reactions included mild headache, dizziness and brain edema,whereas no ≥ grade 2 adverse reactions occurred. At 6 months after treatment, the HVLT-R score was significantly decreased,and declined by 6. 78% at 12 months after treatment. The HVLT-R scores did not significantly differ in patients without brain metastasis before and 12 months after treatment ( P＞0. 05 ). Conclusion Application of HS-PCI using helical tomotherapy meets the dose requirement,effectively protects the cognitive function and yields slight adverse reactions.

Objective: To assess the feasibility of HEAD-US scale in the clinical application of hemophilic arthropathy (HA) and propose an optimized ultrasound scoring system. Methods: From July 2015 to August 2017, 1 035 joints ultrasonographic examinations were performed in 91 patients. Melchiorre, HEAD-US (Hemophilic Early Arthropathy Detection with UltraSound) and HEAD-US-C (HEAD-US in China) scale scores were used respectively to analyze the results. The correlations between three ultrasound scales and Hemophilia Joint Health Scores (HJHS) were evaluated. The sensitivity differences of the above Ultrasonic scoring systems in evaluation of HA were compared. Results: All the 91 patients were male, with median age of 16 (4-55) years old, including 86 cases of hemophilia A and 5 cases hemophilia B. The median (P₂₅, P₇₅) of Melchiorre, HEAD-US and HEAD-US-C scores of 1 035 joints were 2(0,6), 1(0,5) and 2(0,6), respectively, and the correlation coefficients compared with HJHS was 0.747, 0.762 and 0.765 respectively, with statistical significance (P<0.001). The positive rates of Melchiorre, HEAD-US-C and HEAD-US scale score were 63.0% (95%CI 59.7%-65.9%), 59.5% (95%CI 56.5%-62.4%) and 56.6% (95%CI 53.6%-59.6%) respectively, and the difference was statistically significant (P<0.001). Even for 336 cases of asymptomatic joints, the positive rates of Melchiorre, HEAD-US-C and HEAD-US scale score were 25.0% (95%CI 20.6%-29.6%), 17.0% (95%CI 12.6%-21.1%) and 11.9% (95%CI 8.4%-15.7%) respectively, and the difference was statistically significant (P<0.001). There were significant changes (P<0.05) in the ultrasonographic score of HA before and after onset of hemorrhage in 107 joints of 40 patients. The difference in variation amplitude of HEAD-US-C scores and HEAD-US scores before and after joint bleeding was statistically significant (P<0.001). Conclusion: Compared with Melchiorre, there were similar good correlations between HEAD-US, HEAD-US-C and HJHS. HEAD-US ultrasound scoring system is quick, convenient and simple to use. The optimized HEAD-US-C scale score is more sensitive than HEAD-US, especially for patients with HA who have subclinical state, which make up for insufficiency of sensitivity in HEAD-US scoring system.
Adolescent ; Adult ; Child ; Child, Preschool ; China ; Hemarthrosis ; Hemophilia A ; Hemophilia B ; Humans ; Male ; Middle Aged ; Ultrasonography ; Young Adult

Based on the relationship between government and market,this paper analyzed the development process of large medical equipment configuration management strategy,and forecasted the trend of management.It is found that the development process of large equipment management in China can be divided into four stages:sprouting stage,management window period,growth stage,and transition period.The management model of the four stages,respectively,are integrated management,market-oriented management,quantitative control-based comprehensive supervision,and legal supervision.As per the analysis of this work,it was found that the sprouting of the regulation of industry standards,training professionals,management efficiency are low;market-oriented led to rapid growth in the number of equipment,with a low configuration efficiency;growth period of the number of regulatory norms of the market and equipment is reasonable to use;and the legal supervision in transition is taking shape.Currently,the lack of rational allocation of large-scale equipment in the hospitals is the main factor leading to market failure.In the legal framework,the government intervention with configuration permits is the major large-scale equipment configuration management model in the future.

Objective: To investigate the impact of discontinued dual antiplatelet therapy(DAPT) of aspirin combining clopidogrel within 5 days on peri-operative bleeding in patients with coronary artery bypass grafting (CABG). Methods: A total of 2012 patients with off-pump CABG were retrospectively enrolled in our study including 1506 male and the mean age was at 61.92 years. All patients received regular DAPT previously and discontinued the medication≤5 days due to emergency or prior limited CABG. Based on the days from discontinued DAPT to operation, the patients were divided into 6 groups: 0-day group, n=220, 1-day group, n=240, 2-day group, n=360, 3-day group, n=332, 4-day group, n=428 and 5-day group, n=432. Relationships between risk factors of bleeding and discontinued DAPT time were studied. Results: Bleeding was defined by BARC (bleeding academic research consortium) standard. The incidences of bleeding events in 0-day group, 1-day group, 2-day group, 3-day group, 4-day group and 5-day group showed a decreasing trend as 29.1%, 24.6%,19.4%, 13.0%, 14.5% and 13.0% respectively, P<0.01. Post-operative chest drainage volume≥2L within 24h (P=0.13) and intracranial bleeding (P=0.60) had no obvious tendency changes; occurrence rates of 48h peri-operative transfusion≥5 U whole blood or red blood cells (P<0.01) and re-operation(P<0.01) had a decreasing trend by prolonged time of discontinued medication. The minor endpoint events were similar. Compared to (3-5) days discontinued medication, the patients with (0-2) days discontinued DAPT were with the higher incidences of overall bleeding, re-operation and 5U transfusion, the differences had statistical meaning. Conclusion: The incidence of bleeding presented a decreasing trend by prolonged time of discontinued DAPT before CABG;transfusion and re-operation had the statistical meaning for bleeding. Discontinued medication less than 3 days may increase bleeding events and therefore, in high risk patients, prior CABG discontinued medication should be more than 3 days.