OBJECTIVE: This study investigates the sleep-modulating effects of ginsenoside Rg1 (Rg1, C₄₂H₇₂O₁₄), a key bioactive component of ginseng, and elucidates its underlying mechanisms. METHODS: C57BL/6J mice were intraperitoneally administered doses of Rg1 ranging from 12.5 to 100 mg/kg. Sleep parameters were assessed to determine the average duration of each sleep stage by monitoring the electrical activity of the brain and muscles. Further, orexin neurons in the lateral hypothalamus (LH) and corticotropin-releasing hormone (CRH) neurons in the paraventricular hypothalamic nucleus (PVH) were ablated using viral vector surgery and electrode embedding. The excitability of LH^orexin and PVH^CRH neurons was evaluated through the measurement of cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-Fos) expression. RESULTS: Rg1 (12.5-100 mg/kg) augmented the duration of non-rapid eye movement (NREM) sleep phases, while reducing the duration of wakefulness, in a dose dependent manner. The reduced latency from wakefulness to NREM sleep indicates an accelerated sleep initiation time. We found that these sleep-promoting effects were weakened in the LH^orexin and PVH^CRH neuron ablation groups, and disappeared in the orexin and CRH double-ablation group. Decreased c-Fos protein expression in the LH and PVH confirmed that Rg1 promoted NREM sleep by inhibiting orexin and CRH neurons. CONCLUSION Rg1 increases the duration of NREM sleep, underscoring the essential roles of LH^orexin and PVH^CRH neurons in facilitating the sleep-promoting effects of Rg1. Please cite this article as: Wang YY, Wu Y, Yu KW, Xie HY, Gui Y, Chen CR, Wang NH. Ginsenoside Rg1 promotes non-rapid eye movement sleep via inhibition of orexin neurons of the lateral hypothalamus and corticotropin-releasing hormone neurons of the paraventricular hypothalamic nucleus. J Integr Med. 2024; 22(6): 721-730.
Animals ; Ginsenosides/pharmacology* ; Orexins/metabolism* ; Mice, Inbred C57BL ; Neurons/metabolism* ; Paraventricular Hypothalamic Nucleus/metabolism* ; Male ; Hypothalamic Area, Lateral/metabolism* ; Corticotropin-Releasing Hormone/metabolism* ; Mice ; Sleep/drug effects*

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.
Humans ; Aged ; Treatment Outcome ; Retrospective Studies ; Combined Modality Therapy ; Chemoradiotherapy/methods* ; Urinary Bladder Neoplasms/radiotherapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Neoplasm Staging

OBJECTIVE: We aimed to assess the feasibility and superiority of machine learning (ML) methods to predict the risk of Major Adverse Cardiovascular Events (MACEs) in chest pain patients with NSTE-ACS. METHODS: Enrolled chest pain patients were from two centers, Beijing Anzhen Emergency Chest Pain Center Beijing Bo'ai Hospital, China Rehabilitation Research Center. Five classifiers were used to develop ML models. Accuracy, Precision, Recall, F-Measure and AUC were used to assess the model performance and prediction effect compared with HEART risk scoring system. Ultimately, ML model constructed by Naïve Bayes was employed to predict the occurrence of MACEs. RESULTS: According to learning metrics, ML models constructed by different classifiers were superior over HEART (History, ECG, Age, Risk factors, & Troponin) scoring system when predicting acute myocardial infarction (AMI) and all-cause death. However, according to ROC curves and AUC, ML model constructed by different classifiers performed better than HEART scoring system only in prediction for AMI. Among the five ML algorithms, Linear support vector machine (SVC), Naïve Bayes and Logistic regression classifiers stood out with all Accuracy, Precision, Recall and F-Measure from 0.8 to 1.0 for predicting any event, AMI, revascularization and all-cause death ( vs. HEART ≤ 0.78), with AUC from 0.88 to 0.98 for predicting any event, AMI and revascularization ( vs. HEART ≤ 0.85). ML model developed by Naïve Bayes predicted that suspected acute coronary syndrome (ACS), abnormal electrocardiogram (ECG), elevated hs-cTn I, sex and smoking were risk factors of MACEs. CONCLUSION Compared with HEART risk scoring system, the superiority of ML method was demonstrated when employing Linear SVC classifier, Naïve Bayes and Logistic. ML method could be a promising method to predict MACEs in chest pain patients with NSTE-ACS.
Humans ; Acute Coronary Syndrome/epidemiology* ; Bayes Theorem ; Feasibility Studies ; Risk Assessment/methods* ; Chest Pain/etiology* ; Myocardial Infarction/diagnosis*

Objective: To investigate the relationship between the expression levels of Plakoglobin protein in residual lesions after neoadjuvant chemotherapy (NAC) and the prognosis of breast cancer patients. Methods: Clinical and pathological data from 174 breast cancer patients who underwent surgery after receiving NAC at the Cancer Hospital of Chinese Academy of Medical Sciences from January 2009 to December 2017 were collected. The expression level of Plakoglobin in residual cancer lesions was evaluated by immunohistochemistry. The correlation between Plakoglobin expression level and clinicopathological features was analyzed. Survival analysis was performed using the Kaplan-Meier method, and Cox proportional hazard regression models were used for factor analysis. Results: Among the 174 patients, 140 had low expression of Plakoglobin, and 34 had high expression. The median disease-free survival (DFS) and overall survival (OS) in the Plakoglobin low expression group were 59.46 and 71.68 months, respectively, both of which were higher than those in the high expression group (36.58 and 47.26 months, respectively, both P<0.05). Univariate analysis showed that Plakoglobin expression, pathological N stage, lymphovascular invasion status, histological grade, Ki-67, and molecular subtypes were associated with OS (all P<0.05), while pathological N stage, histological grade, and Ki-67 were associated with DFS (all P<0.05). Multivariate analysis revealed that Plakoglobin expression (HR=2.438, 95% CI: 1.256-4.735, P=0.008) was an independent predictor for OS, and Ki-67 (HR=2.228, 95% CI: 1.316-3.773, P=0.003) was an independent predictor for DFS. Conclusion: In breast cancer patients with residual lesions after NAC, those with low Plakoglobin expression have relatively longer OS and Plakoglobin is an independent prognostic factor for OS.
Humans ; Female ; Prognosis ; Breast Neoplasms/surgery* ; Ki-67 Antigen/analysis* ; Neoadjuvant Therapy/methods* ; gamma Catenin ; Neoplasm, Residual ; Disease-Free Survival ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Objective: To investigate the relationship between the expression levels of Plakoglobin protein in residual lesions after neoadjuvant chemotherapy (NAC) and the prognosis of breast cancer patients. Methods: Clinical and pathological data from 174 breast cancer patients who underwent surgery after receiving NAC at the Cancer Hospital of Chinese Academy of Medical Sciences from January 2009 to December 2017 were collected. The expression level of Plakoglobin in residual cancer lesions was evaluated by immunohistochemistry. The correlation between Plakoglobin expression level and clinicopathological features was analyzed. Survival analysis was performed using the Kaplan-Meier method, and Cox proportional hazard regression models were used for factor analysis. Results: Among the 174 patients, 140 had low expression of Plakoglobin, and 34 had high expression. The median disease-free survival (DFS) and overall survival (OS) in the Plakoglobin low expression group were 59.46 and 71.68 months, respectively, both of which were higher than those in the high expression group (36.58 and 47.26 months, respectively, both P<0.05). Univariate analysis showed that Plakoglobin expression, pathological N stage, lymphovascular invasion status, histological grade, Ki-67, and molecular subtypes were associated with OS (all P<0.05), while pathological N stage, histological grade, and Ki-67 were associated with DFS (all P<0.05). Multivariate analysis revealed that Plakoglobin expression (HR=2.438, 95% CI: 1.256-4.735, P=0.008) was an independent predictor for OS, and Ki-67 (HR=2.228, 95% CI: 1.316-3.773, P=0.003) was an independent predictor for DFS. Conclusion: In breast cancer patients with residual lesions after NAC, those with low Plakoglobin expression have relatively longer OS and Plakoglobin is an independent prognostic factor for OS.
Humans ; Female ; Prognosis ; Breast Neoplasms/surgery* ; Ki-67 Antigen/analysis* ; Neoadjuvant Therapy/methods* ; gamma Catenin ; Neoplasm, Residual ; Disease-Free Survival ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Objective: To study the impact of regional positive lymph node ratio (LNR) on prognosis of patients with gallbladder carcinoma. Methods: The clinicopathological and survival data of 53 patients with gallbladder carcinoma who underwent radical resection with regional lymph node metastasis in Ningbo University Affiliated Lihuili Hospital from May 2012 to December 2020 were collected, and receiver operating characteristic curve (ROC) was used to determine the optimal cut-off value of LNR for predicting postoperative survival status in patients with gallbladder carcinoma. According to the critical value, the patients were divided into low LNR group and high LNR group. The clinicopathological features and prognosis of the two groups were compared. Log rank test was used for univariate analysis of prognostic factors in patients with gallbladder carcinoma, and Cox proportional hazards model was used for multivariate analysis. Results: A total of 417 regional lymph nodes were dissected in 53 patients, of which 144 lymph nodes were positive, with a positive rate of 34.5%. The optimal cut-off value of LNR for predicting postoperative survival status of patients with gallbladder carcinoma was 0.33. According to this cut-off value, patients were divided into low LNR group (LNR≤0.33, 28 cases) and high LNR group (LNR>0.33, 25 cases). The recurrence rates were 64.3% (18/28) and 88.0 % (22/25) in low LNR group and high LNR group, respectively. The median recurrence-free survival (RFS) was 8 and 7 months, respectively (P=0.032). In the low LNR group, the 1-, 3-, and 5-year survival rates were 56.2%, 38.4%, and 32.0%, respectively, and the median overall survival (OS) was 16 months. In the high LNR group, the 1-, 3-, and 5-year survival rates were 37.9%, 5.4%, and 0, respectively, and the median OS was 9 months. The postoperative survival rate of patients in the low LNR group was better than that in the high LNR group (P=0.008). Univariate analysis showed that LNR was even associated with RFS and OS in patients with gallbladder carcinoma (P<0.05). Multivariate analysis showed that LNR>0.33 was an independent risk factor for postoperative RFS (HR=1.977, 95% CI: 1.045-3.740), but not for OS (HR=1.561, 95% CI: 0.685-3.553). Conclusion: On the basis of clearing a sufficient number of regional lymph nodes, patients with gallbladder carcinoma with regional LNR>0.33 are more likely to relapse after operation, but the predictive value of LNR>0.33 OS is insufficient.
Humans ; Lymph Node Ratio ; Gallbladder Neoplasms/pathology* ; Lymph Node Excision ; Lymphatic Metastasis/pathology* ; Neoplasm Staging ; Retrospective Studies ; Lymph Nodes/pathology* ; Prognosis

Objective To investigate the clinicopathological features and prognosis of chromophobe renal cell carcinoma(ChRCC). Methods The clinical and pathological data of 126 patients with ChRCC treated in Cancer Hospital of Chinese Academy of Medical Sciences were retrospectively analyzed. Results The patients included 64 males and 62 females,with the age of 22-80 years(median of 52 years).The tumor was located on the right side in 70 cases and on the left side in 56 cases.Ultrasound,CT or magnetic resonance imaging(MRI)were performed.Of the 110 cases receiving ultrasound examination,63,23,13,10,and 1 cases showed hypoecho,hyperecho,isoecho,uneven or mixed echo,and dark hypoecho,respectively.Color Doppler flow imaging showed no blood flow signal in 42 cases and low blood flow signal in 60 cases out of 68 cases with blood flow signal.Among the 54 cases receiving CT,50 cases showed equal density or low density and 4 cases showed high density with clear boundary.The enhanced scanning showed mild to moderate uniform or non-uniform reinforcement,mostly below the renal parenchyma,and still showed reinforcement in the delayed period.Among the 97 cases receiving MRI,96 cases showed hypo-or isointense signals and 1 case showed hyperintense signal in T1 weighted images;71 cases showed hyper-or isointense signals and 26 cases showed hypo-or isointense signals in T2 weighted images;93 cases showed hyperintense signals with obvious limited diffusion and 4 cases showed unobvious limited diffusion in diffusion weighted images.Mild to moderate uniform or non-uniform reinforcement was observed in most of the enhanced scans.All the 126 patients underwent surgical treatment,including 64 cases of nephron sparing surgery and 62 cases of radical surgery.Pathological examinations confirmed ChRCC for all the patients,including 91 cases of T1N0M0,15 cases of T2N0M0,and 20 cases of T3N0M0.The immunohistochemical assay demonstrated the positive expression rate of 48.2%(54/112)for CD10,92.3%(96/104)for CD117,8.0%(9/112)for vimentin,85.6%(95/111)for CK7,and 97.6%(83/85)for colloidal iron.Conclusions ChRCC is less common,with low level of malignancy and good prognosis.Since the clinical symptoms of ChRCC are not typical,MRI is an important means of imaging differential diagnosis,and the disease can be confirmed depending on pathological diagnosis.Surgery is the preferred treatment method,and currently there is no standard treatment regimen for metastatic patients.
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Renal Cell/diagnostic imaging* ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Kidney Neoplasms/surgery* ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER NCT02063100 on ClinicalTrials.gov.

Objective: To evaluate the safety and efficacy of catheter ablation in patients with new-onset atrial arrhythmia after surgical excision of left atrial myxoma. Methods: Nine patients with new onset atrial arrhythmia and a prior history of left atrial myxoma, who received surgical myxoma excision and catheter ablation between September 2014 and November 2019, were included in the present study. Baseline characteristics, procedural parameters during catheter ablation, severe perioperative adverse events, recurrence rate of arrhythmia and clinical prognosis were analyzed. Kaplan Meier survival analysis was used to define the maintenance rate of sinus rhythm after catheter ablation in this patient cohort. Results: Nine patients were included. The average age was (55.8 ± 9.1) years old (3 male), there were 3 patients (3/9) with paroxysmal atrial fibrillation (PAF) and 6 patients (6/9) with atrial flutter or atrial tachycardia (AFL or AT). Ablation was successful in all patients, there were no perioperative complications such as stroke, pericardial effusion, cardiac tamponade, vascular complications or massive hemorrhage. During a mean follow-up time of 40.0 (27.5, 55.5) months, sinus rhythm was maintained in six patients (6/9) after the initial catheter ablation. The overall sinus rhythm maintenance rate was 2/3. In addition, 1 out of the 3 AF patients (1/3) developed recurrence of AF at 3 month after ablation, and 2 out of the 6 AFL or AT patients (2/6) developed late recurrence of AF or AFL (19 months and 29 months after ablation), two out of three patients with recurrent AFs or AFL received repeated catheter ablation and one patient remained sinus rhythm post repeat ablation. Meanwhile, there was no recurrence of atrial myxoma, no death, stroke, acute myocardial infarction and other events during the entire follow-up period. Conclusions: Catheter ablation is a safe and feasible therapeutic option for patients with new-onset atrial arrhythmia after surgical excision of left atrial myxoma.