ObjectiveTo investigate the intervention effects of Suanzaoren Tang on depression model rats induced by isolation combined with chronic unpredictable mild stress （CUMS）， and to examine its influence on the c-Jun N-terminal kinase （JNK）/proto-oncogene protein （c-Myc）/tumor suppressor protein 53 （p53） signaling pathway， thereby revealing its potential functional mechanism. MethodsA total of 72 male SD rats were randomly divided into six groups using a strict random number table： blank group， model group， fluoxetine group （3.6 mg·kg^-1）， and high-， medium-， and low-dose Suanzaoren Tang groups （10， 5， 2.5 g·kg^-1），with 12 rats in each group. A depression model was established using isolation combined with CUMS. Fluoxetine and different doses of Suanzaoren Tang were administered continuously for 28 days. Behavioral indicators such as sucrose water consumption and open field test scores were recorded. Western blot and immunohistochemistry （IHC） were employed to analyze the expression of key proteins in the JNK/c-Myc/p53 signaling pathway， and the terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） assay was used to evaluate the number of apoptotic cells in the hippocampus. ResultsCompared with the blank group， the model group exhibited a significantly reduced sucrose preference index （P<0.01）， a lower total score of horizontal and vertical movements in the open field test （P<0.01）， significantly increased expression of JNK， c-Myc， and p53 proteins in the hippocampus （P<0.01）， and a higher number of TUNEL-positive cells in the hippocampus （P<0.01）. Compared with the model group， the sucrose preference index and the total score of horizontal and vertical movements in the open field test significantly increased in the high- and medium-dose Suanzaoren Tang groups and the fluoxetine group （P<0.05， P<0.01）. The expression of JNK， c-Myc， and p53 proteins significantly decreased in all Suanzaoren Tang groups （high， medium， and low doses） and the fluoxetine group （P<0.05， P<0.01）. The number of TUNEL-positive cells in the hippocampus also significantly decreased in these groups （P<0.01）. ConclusionSuanzaoren Tang can regulate the expression of JNK/c-Myc/p53 proteins in the hippocampus of depression model rats， and its antidepressant mechanism may be related to its protective effect on hippocampal neurons.

Objective: To explore the efficacy of focal radiofrequency ablation (RFA) in the treatment of low-to-intermediate risk localized prostate cancer and its impact on postoperative urinary control and sexual function recovery，in order to explore the feasibility of minimally invasive methods for the treatment of localized prostate cancer. Methods: Clinical data of 28 patients with low-to-intermediate risk localized prostate cancer who underwent RFA in Nanjing Drum Tower Hospital，Affiliated Hospital of Medical School during Jun.2017 and Feb.2021 were retrospectively analyzed.The 5-year failure-free survival (FFS) rate，surgery related complications，postoperative urinary control and sexual function were collected.The differences between the survival curves of patients in the low-risk and intermediate-risk subgroups were assessed with log-rank test and Breslow test. Results: All surgeries were successfully completed under local anesthesia.During the median follow-up of 43 (40-49) months，the 5-year FFS rate predicted by Kaplan-Meier method was 78.57%; 25 patients (89.29%) did not experience surgery-related complications; 27 patients (96.43%) were able to control urination; 1 patient developed new-onset sexual dysfunction.There was no significant difference in the survival curves between patients in the low-risk and intermediate-risk groups (P>0.05). Conclusion: RFA for patients with low-to-intermediate risk localized prostate cancer has good clinical efficacy，little impact on urinary control and sexual function recovery，and few postoperative complications，which can be used as one of the treatment options for these patients.

ObjectiveTo investigate the therapeutic effect of Baihe Wuyaotang （BWT） on non-alcoholic fatty liver disease （NAFLD） and elucidate its underlying mechanism. MethodC57BL/6J mice were randomly assigned to six groups： normal control， model， positive drug （pioglitazone hydrochloride 1.95×10^-3 g·kg^-1）， and low-， medium-， and high-dose BWT （1.3，2.5 and 5.1 g·kg^-1）. Following a 12-week high-fat diet （HFD） inducement， the mice underwent six weeks of therapeutic intervention with twice-daily drug administration. Body weight was monitored weekly throughout the treatment period. At the fifth week， glucose tolerance （GTT） and insulin tolerance （ITT） tests were conducted. Subsequently， the mice were euthanized for the collection of liver tissue and serum， and the subcutaneous adipose tissue （iWAT） and epididymal adipose tissue （eWAT） were weighed. Serum levels of total triglycerides （TG） and liver function indicators，such as alanine aminotransferase （ALT） and aspartate aminotransferase （AST）， were determined. Histological examinations， including oil red O staining， hematoxylin-eosin （HE） staining， Masson staining， and transmission electron microscopy， were performed to evaluate hepatic lipid deposition， pathological morphology， and ultrastructural changes， respectively. Meanwhile， Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were employed to analyze alterations， at both gene and protein levels， the insulin signaling pathway molecules， including insulin receptor substrate 1/2/protein kinase B/forkhead box gene O1 （IRS1/2/Akt/FoxO1）， glycogen synthesis enzymes phosphoenolpyruvate carboxy kinase （Pepck） and glucose-6-phosphatase （G6Pase）， lipid metabolism-related genes stearoyl-coA desaturase-1 （SCD-1） and carnitine palmitoyltransferase-1 （CPT-1）， fibrosis-associated molecules α-smooth muscle actin （α-SMA）， type Ⅰ collagen （CollagenⅠ）， and the fibrosis canonical signaling pathway transforming growth factor-β₁/drosophila mothers against decapentaplegic protein2/3（TGF-β₁/p-Smad/Smad2/3）， inflammatory factors such as interleukin（IL）-6， IL-8， IL-11， and IL-1β， autophagy markers LC3B Ⅱ/Ⅰ and p62/SQSTM1， and the expression of mammalian target of rapamycin （mTOR）. ResultCompared with the model group， BWT reduced the body weight and liver weight of NAFLD mice（P<0.05， P<0.01）， inhibited liver lipid accumulation， and reduced the weight of white fat： it reduced the weight of eWAT and iWAT（P<0.05， P<0.01） as well as the serum TG content（P<0.05， P<0.01）. BWT improved the liver function as reflected by the reduced ALT and AST content（P<0.05， P<0.01）. It improved liver insulin resistance by upregulating IRS2， p-Akt/Akt， p-FoxO1/FoxO1 expressions（P<0.05）. Besides， it improved glucose and lipid metabolism disorders： it reduced fasting blood glucose and postprandial blood glucose（P<0.05， P<0.01）， improved GTT and ITT（P<0.05， P<0.01）， reduced the expression of Pepck， G6Pase， and SCD-1（P<0.01）， and increased the expression of CPT-1（P<0.01）. The expressions of α-SMA， Collagen1， and TGF-β₁ proteins were down-regulated（P<0.05， P<0.01）， while the expression of p-Smad/Smad2/3 was downregulated（P<0.05）， suggesting BWT reduced liver fibrosis. BWT inhibited inflammation-related factors as it reduced the gene expression of IL-6， IL-8， IL-11 and IL-1β（P<0.01） and it enhanced autophagy by upregulating LC3B Ⅱ/Ⅰ expression（P<0.05）while downregulating the expression of p62/SQSTM1 and mTOR（P<0.05）. ConclusionBWT ameliorates NAFLD by multifaceted improvements， including improving IR and glucose and lipid metabolism， anti-inflammation， anti-fibrosis， and enhancing autophagy. In particular， BWT may enhance liver autophagy by inhibiting the mTOR-mediated signaling pathway.

ObjectiveTo study the differences in volatile oil content of bran-processed Atractylodes lancea and its standard decoction concentrate and freeze-dried powder， as well as the differences in the types and contents of chemical components in volatile oil， and to clarify the quality value transmitting. MethodTen batches of A. lancea rhizoma were collected and prepared into raw products and bran-processed products of A. lancea， standard decoction concentrate and freeze-dried powder of bran-processed A. lancea in order to extract the volatile oil， and the transfer rate of volatile oil in each sample was calculated. Quantitative analysis of the main chemical components（β-eudesmol， atractylon， atractylodin） in each volatile oil was performed by gas chromatography（GC） on the HP-5 quartz capillary column（0.32 mm×30 m， 0.25 μm） with a flame ionization detector（FID）， a split ratio of 10∶1 and a temperature program（initial temperature at 80 ℃， hold for 1 min， rise to 150 ℃ at 10 ℃·min^-1， hold for 10 min， rise to 155 ℃ at 0.5 ℃·min^-1， hold for 5 min， rise to 240 ℃ at 8.5 ℃·min^-1， hold for 8 min）. Cluster analysis and principal component analysis（PCA） were used to explore the overall differences in types and contents of chemical components between the standard decoction concentrate and freeze-dried powder. ResultThe transfer rates of volatile oil in the bran-processed products， standard decoction concentrate and freeze-dried powder were 70.51%， 1.57% and 40.90%， respectively. The average transfer rates of β-eudesmol， atractylon and atractylodin in the volatile oil of bran-processed A. lancea were 58.45%， 48.49% and 55.64%， respectively. In the standard decoction concentrate， only β-eudesmol and atractylodin were detected， and their average transfer rates were 0.22% and 0.10%， respectively. And only β-eudesmol was detected in the freeze-dried powder with the average transfer rate of 8.37%. The results of cluster analysis and PCA showed that there are obvious differences in the types and contents of chemical components between the standard decoction concentrate and freeze-dried powder. ConclusionThe quality value transmitting between bran-processed A. lancea and its standard decoction concentrate and freeze-dried powder is stable， and if the freeze-dried powder is selected as the reference material of dispensing granules， appropriate amount of volatile oil should be added back to make it consistent with the quality of the standard decoction concentrate.

BACKGROUND: Breast cancer patients with ipsilateral supraclavicular lymph node metastasis (ISLNM) but without distant metastasis are considered to have a poor prognosis. This study aimed to develop a nomogram to predict the overall survival (OS) of breast cancer patients with ISLNM but without distant metastasis. METHODS: Medical records of breast cancer patients who received surgical treatment at the Affiliated Cancer Hospital of Zhengzhou University, Jiyuan People's Hospital and Huaxian People's Hospital between December 21, 2012 and June 30, 2020 were reviewed retrospectively. Overall, 345 patients with pathologically confirmed ISLNM and without evidence of distant metastasis were identified. They were further randomized 2:1 and divided into training (n = 231) and validation (n = 114) cohorts. A nomogram to predict the probability of OS was constructed based on clinicopathologic variables identified by the univariable and multivariable analyses. The predictive accuracy and discriminative ability were measured by calibration plots, concordance index (C-index), and risk group stratification. RESULTS: Univariable analysis showed that estrogen receptor-positive (ER+), progesterone receptor-positive (PR+), human epidermal growth factor receptor 2-positive (HER2+) with Herceptin treatment, and a low axillary lymph node ratio (ALNR) were prognostic factors for better OS. PR+, HER2+ with Herceptin treatment, and a low ALNR remained independent prognostic factors for better OS on multivariable analysis. These variables were incorporated into a nomogram to predict the 1-, 3-, and 5-year OS of breast cancer patients with ISLNM. The C-indexes of the nomogram were 0.737 (95% confidence interval [CI]: 0.660-0.813) and 0.759 (95% CI: 0.636-0.881) for the training and the validation cohorts, respectively. The calibration plots presented excellent agreement between the nomogram prediction and actual observation for 3 and 5 years, but not 1 year, OS in both the cohorts. The nomogram was also able to stratify patients into different risk groups. CONCLUSIONS In this study, we established and validated a novel nomogram for predicting survival of patients with ISLNM. This nomogram may, to some extent, allow clinicians to more accurately estimate prognosis and to make personalized therapeutic decisions for individual patients with ISLNM.
Breast Neoplasms ; Female ; Humans ; Lymph Nodes ; Lymphatic Metastasis ; Nomograms ; Retrospective Studies

Objective:To summarize the case data of endometrial cancer (EC), analyze the related factors of lymph node metastasis, and establish the prediction model, so as to provide reference for clinical practice.Methods:191 patients with endometrial cancer who were diagnosed and treated in department of gynecology of Baoding Maternal and Child Health Hospital from January 2010 to December 2019 were selected as the research objects. The demographic and surgical pathological information of the patients were analyzed retrospectively. The risk factors of lymph node metastasis were analyzed by univariate and logistic regression analysis, and the predictive model was established.Results:A total of 191 patients with EC, aged 26-76(53.1±9.5)years old, body mass index (BMI)18.70-40.20(25.84±3.94)kg/m 2, 13 cases (6. 81%) had lymph node metastasis. Univariate analysis showed that lymph node metastasis was associated with obesity (BMI≥28 kg/m 2), pathological type (non endometrioid adenocarcinoma), degree of differentiation, depth of myometrial invasion (>1/2) and vascular invasion ( P<0.05). Logistic multivariate analysis showed that low differentiation ( OR=9.475, 95% CI: 1.840-48.799), vascular invasion ( OR=6.614, 95% CI: 1.457-30.024) and deep muscle invasion ( OR=4.997, 95% CI: 1.342-18.600) were independent risk factors ( P<0.05). The regression equation: Logit P=-4.488+ 1.609× myometrial infiltration depth+ 1.889×vascular infiltration+ 2.249×degree of tissue differentiation. The area under the receiver operating characteristic (ROC) curve (AUC) of EC lymph node metastasis probability P was 0.813 (95% CI: 0.688-0.938). The cut off value of 0.56 was ideal. At this time, the prediction sensitivity was 76.9% and the specificity was 79.2%. Conclusions:In clinical practice, gynecologists should consider the condition of EC patients and make operation plan to avoid over treatment or under treatment.

【Objective】 To explore the role of RYBP in activating PARP-1 dependent Parthanatos and promoting response to YM155 in esophageal squamous cell carcinoma. 【Methods】 CCK-8 and flow cytometry were used to analyze the inhibition ratio and cell death percentage after YM155 treatment in both RYBP overexpression group and control group. Western blotting was used to detect the expression of Parthanatos-related proteins. 【Results】 Compared with control group, RYBP overexpression group showed higher inhibition ratio and cell death percentage after YM155 treatment. Overexpression of RYBP activated PARP-1 with or without YM155 treatment. Besides, after YM155 treatment, KYSE170-RYBP showed more PAR accumulation in the nucleus, AIF translocation from mitochondria to the nucleus than control cells. 【Conclusion】 RYBP can activate PARP-1/PAR/AIF-dependent induced Parthanatos in esophageal squamous cell carcinoma and enhance response to YM155.

Objective To explore the damage mechanism of dopamine cells induced by amphetamine (AMPH). Methods The damage model of dopaminergic cells in mice was established by intraperitoneal injection of AMPH. The mice were randomly grouped into control, saline, amphetamine treatment for 1 day, 7 days, 14 days and 28 days. Each group contained 10 mice. The model of cell injury was established by use of AMPH in PC12 cells. The dopaminergic fibers of corpus striatum and PC12 cells were observed by the immunohistochemistry and immunofluorescence method, and changes of proteins in the protein kinase B (Akt) / glycogen synthase kinase 3β(GSK-3β) / collapsin response mediator protein 2 (CRMP-2) signal pathway were detected by Western blotting. Results AMPH caused the damage of dopaminergic fibers in the mouse corpus striatum and PC12 cells. Meanwhile, AMPH inhibited Akt and GSK-3β phosphorylation levels, and increased phosphorylated CRMP-2 level. Nerve growth factor(NGF), an agonist of Akt, or SB216763, an inhibitor of GSK-3β protected PC12 cells against AMPH-induced toxicity through upregulation of Aat and GSK-3β phosphorylation and downregulated of phosphorylation CRMP-2. Conclusion AMPH causes damage of dopamine cells via inhibition of Akt/ GSK-3β/ CRMP-2 signal pathway.

Objective:To investigate the predictive value of lactate concentration within 1 h after admission combined with lactate clearance rate (LC) at 6 h after fluid resuscitation in prognosis of neonatal septic shock.Methods:In this retrospective study, 58 newborns with septic shock admitted to the Neonatal Intensive Care Unit of Xi′an Children′s Hospital,Xi′an Jiao Tong University from June 2016 to March 2020 were enrolled. According to the mortality within 60 days after admission,which was also set as the end point, the patients were divided into death group and survival group. The general demographic data and clinical variables including blood cell counts, procalcitonin, C-reactive protein, D-dimer, serum creatinine, and lactate concentration within 1 h after admission (Lac1) and at 6 h after fluid resuscitation (Lac2) were collected. The differences in the clinical variables between the survival and death group were compared by independent sample t test or Rank-Sum test, and the risk factors of poor prognosis were analyzed by binary Logistic regression. The predictive values of these risk factors were tested by receiver operating characteristic (ROC) curve. Furthermore, the cut-off of the risk factors were used to analyze the accumulative survival rate by Kaplan-Meier curve. Results:A total of 58 neonates were enrolled, among whom 24 survived and 34 died within 60 days after admission. The rate of premature rupture of membranes in the death group was higher than that in the survival group (41% (14/34) vs.13%(3/24), P=0.021). There were also significant differences in infection site, pathogenic characteristics, total fluid volume of resuscitation, vasoactive drug index, rate and complications of mechanical ventilation between the two groups (all P<0.05). The levels of Lac1, Lac2, procalcitonin, D-dimer and serum creatinine in the death group were higher than those in the survival group ((12±6) vs. (7±4) mmol/L, (14±6) vs. (4±2) mmol/L, (59±23) vs.(24±14) ng/L, (24±11) vs.(11±6) mg/L, (167±31) vs.(92±23) μmol/L, t=3.549, 3.112, 3.859, 4.499, 3.288, all P<0.05). While the blood pressure and LC at 6 h after fluid resuscitation were lower than those in the survival group ((41±12) vs. (52±5) mmHg (1 mmHg=0.133 kPa), t =4.230;-16 (-40, 20) % vs. 40 (18, 70) %, Z= 3.558, all P<0.05). Binary Logistic regression analysis showed that LC was negatively associated with the risk of death in neonates with septic shock (odds ratio ( OR) and 95% confidence interval ( CI): 0.679 (0.662-0.999), P<0.05), while Lac1 was the risk factor and positively associated with the risk of death ( OR and 95% CI: 1.203 (0.965-1.500), P<0.05). Furthermore, the predictive values of LC, Lac1 and the combination of these two variables in the prognosis of neonatal septic shock were analyzed by ROC curve analysis, and the area under the curve (AUC) were 0.699, 0.875, 0.965, respectively, with the sensitivity of 83.32%, 89.65% and 94.31%, and the specificity of 72.52%, 77.18% and 88.76%, respectively. According to the cut-off value of Lac1, the newborns with Lac1>4 mmol/L had significantly lower accumulative survival rate than those with Lac1≤4 mmol/L by Kaplan-Meier analysis (21% (8/38) vs. 80% (16/20), χ 2=54.520, P<0.05). According to the cut-off value of LC, the newborns with LC ≤ 10% had significantly lower accumulative survival rate than those with LC>10% by Kaplan-Meier analysis (19% (6/32) vs. 69% (18/26), χ 2=14.140, P<0.05). Conclusion:The combination of lactate concentration and lactate clearance rate have an optimal predictive value in the prognosis of neonatal septic shock.

Objective To establish the cardiac arrest (CA) model in rats by modified transcutaneous electrical stimulation on epicardium. Methods This study was performed in the Emergency Medicine laboratory in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. After 10 Sprague-Dawley male rats weighing 330-380 g were anesthetized, two acupuncture needles connected to the anode and cathode of a stimulator were transcutaneously inserted into the epicardium as electrodes. The puncture points were located quantitatively according to the anatomical structure of the rat chest. The electrical stimulation was maintained for 3 minutes to induce ventricular fibrillation(VF). Cardiopulmonary resuscitation (CPR) included chest compressions, intravenous adrenaline and defi brillation operated at 6 min after a period of nonintervention. Results CA was induced after the implement of the effective electrical stimulation in all ten rats in this experiment. The average current intensity to induce VF was (1.80 ± 0.59) mA, the average time to induce CA was (5.07 ± 2.37)s,the average time of the total electrical stimulation was(187.50 ± 12.75)s and the total time of CA was 6 min. At the end of the electrical stimulation, 9 rats presented VF and 1 rat showed pulseless electrical activity. The restoration of spontaneous circulation was achieved in all 10 rats. The average time of CPR was(190.90±68.60) s, the mean numbers of defi brillation were(1.20 ± 0.63) , and he average number of adrenaline application were (1.20 ± 0.42) times. Neither visible hemorrhage on epicardium nor gross pulmonary congestion was observed. Conclusions The modified transcutaneous electrical stimulation on epicardium to produce CA model in rats is an easily applicable and effective technique. This model may provide an alternative for experimental research of CPR.