Objective To investigate the clinical effect of dysmenorrhea in patients with adenomyosis treated by high intensity focused ultrasound (HIFU) ablation combined with gonadotropin-releasing hormone agonist (GnRH-a) and levonorgestrel-releasing intrauterine system (LNG-IUS). Methods From April 2012 to December 2015, 477 cases of adenomyosis patients with dysmenorrhea were treated by HIFU in the Third Xiangya Hospital. Among them, some patients were treated with HIFU alone, some of them were treated with HIFU combined with GnRH-a and (or) LNG-IUS, thus were classified as H group, H+G group, H+M group and H+G+M group. The improvements of clinical results were compared among the four groups and the influencing factors of HIFU treatment for adenomyosis were also analyzed. Results During the follow-up period, the overall effective rates of the treatment decreased with time, 3 months 89.4% (345/386), 12 months 84.0%(221/263), 24 months 74.2%(98/132), and the overall recurrence rate was 12.9%(39/303). The significant difference in the curative at 3 months [H group 83.7%(170/203), H+M group 95.0%(95/100), H+G group 100.0%(43/43), H+G+M group 96.8%(30/31)], 12 months [H group 79.4%(123/155), H+M group 93.2%(69/74), H+G group 11/12, H+G+M group 15/17], and 24 months [H group 68.0%(51/75), H+M group 96.4% (27/28), H+G group 6/12, H+G+M group 15/15] after HIFU treatment and recurrence rate [H group 19.0%(29/153), H+M group 3.3%(3/90), H+G group 19.4%(6/31), H+G+M group 4.5%(1/22)] were observed among the four groups (P<0.05). Pairwise comparison further showed that, in 3 months after the treatment, the effect of H group was significantly lower than those of H+M group and H+G group (P=0.003, P=0.005);in 12 months after the treatment, the effect of H group was significantly lower than that of H+M group (P=0.006);while in 24 months after treatment, the effect of H group was significantly lower than that of H+G+M group (P=0.005), and the effect of H+G group was lower than that of H+G+M group (P=0.001); and the recurrence rate of H group was significantly higher than that of H+M group (P<0.008). In patients of group H, the effect of HIFU was related to uterine size, the effect of patients with large uterine volume was significantly higher than that of small volume of uterine of patients (P=0.017, OR=2.739, 95%CI:1.200-6.251); with increasing of age, the improvement of dysmenorrhea had a increasing trend (P<0.05). Conclusions HIFU combined with GnRH-a and (or) LNG-IUS could improve the treatment effect in relief of dysmenorrhea. Based on our results, individual treatment protocol should be selected for different patients.

Objective To use real-time three-dimensional echocardiography(RT-3DE) to compare the cardiac function related indicators between before operation and at postoperative 2 months in the patients with left ventricular aneurysm(LVA) undergoing emergency percutaneous coronary intervention(PCI),and to assess the PCI short term effect.Methods RT-3DE was applied to observe the left ventricular end-diastolic volume(LVEDV),end systolic volume(LVESV),cardiac output(CO),end-diastolic volume index(EDVI),end systolic volume index (ESVI),cardiac index (CI),left ventricular ejection fraction (LVEF) and left ventricular spherical index(SPI) before operation and at postoperative 2 months in 31 cases of acute anterior myocardial infarction(AAMI) complicating LVA.The patients were divided into the functional LVA group(A),anatomical LVA group (B) and complicating thrombus LVA group(C).The cardiac function parameters in various groups conducted the intra-group and inter group comparisons.Results Compared with before operation,LVEF at postoperative 2 months in the group A was increased and SPI was decreased(P＜0.05);CO,CI and LVEF before operation and at postoperative 2 months in the group B were increased and SPI was decreased(P＜0.05);SPI at postoperative 2 months in the group C was decreased(P＜0.05);EF and SPI before operation and at postoperative 2 months had no statistical difference among 3 groups(P＞0.05).SPI before operation and at postoperative 2 months was negatively correlated with LVEF and positively correlated with EDV,ESV,EDVI,ESVI,CO and CI.Conclusion The left ventricular morphology and overall systolic function at 2 months after PCI in the patients with functional and anatomical LVA are improved,but the curative effect in the patients with complicating thrombus LVA is unobvious.

Toxoplasma gondii, an intracellular protozoan parasite that infects one-third of the world’s population, has been reported to hijack host cell apoptotic machinery and promote either an anti- or proapoptotic program depending on the parasite virulence and load and the host cell type. However, little is known about the regulation of human FHs 74 small intestinal epithelial cell viability in response to T. gondii infection. Here we show that T. gondii RH strain tachyzoite infection or ESP treatment of FHs 74 Int cells induced apoptosis, mitochondrial dysfunction and ER stress in host cells. Pretreatment with 4-PBA inhibited the expression or activation of key molecules involved in ER stress. In addition, both T. gondii and ESP challenge-induced mitochondrial dysfunction and cell death were dramatically suppressed in 4-PBA pretreated cells. Our study indicates that T. gondii infection induced ER stress in FHs 74 Int cells, which induced mitochondrial dysfunction followed by apoptosis. This may constitute a potential molecular mechanism responsible for the foodborne parasitic disease caused by T. gondii.

PURPOSE: C-terminal binding protein 1 (CtBP1) is a transcriptional co-repressor that is overexpressed in many cancers. CtBP1 transcriptionally represses a broad array of tumor suppressors, which promotes cancer cell proliferation, migration, invasion, and resistance to apoptosis. Recent studies have demonstrated that CtBP1 is a potential target for cancer therapy. This study was designed to screen for compounds that potentially target CtBP1. METHODS: Using a structure-based virtual screening for CtBP1 inhibitors, we found protocatechuic aldehyde (PA), a natural compound found in the root of a traditional Chinese herb, Salvia miltiorrhiza, that directly binds to CtBP1. Microscale thermophoresis assay was performed to determine whether PA and CtBP1 directly bind to each other. Further, clustered regularly interspaced short palindromic repeats associated Cas9 nuclease-mediated CtBP1 knockout in breast cancer cells was used to validate the CtBP1 targeting specificity of PA. RESULTS: Functional studies showed that PA repressed the proliferation and migration of breast cancer cells. Furthermore, PA elevated the expression of the downstream targets of CtBP1, p21 and E-cadherin, and decreased CtBP1 binding affinity for the promoter regions of p21 and E-cadherin in breast cancer cells. However, PA did not affect the expression of p21 and E-cadherin in the CtBP1 knockout breast cancer cells. In addition, the CtBP1 knockout breast cancer cells showed resistance to PA-induced repression of proliferation and migration. CONCLUSION Our findings demonstrated that PA directly bound to CtBP1 and inhibited the growth and migration of breast cancer cells through CtBP1 inhibition. Structural modifications of PA are further required to enhance its binding affinity and selectivity for CtBP1.

Toxoplasma gondii is an intracellular parasite that causes severe disease when the infection occurs during pregnancy. Adenosine is a purine nucleoside involved in numerous physiological processes; however, the role of adenosine receptors in T. gondii-induced trophoblast cell function has not been investigated until now. The goal of the present study was to evaluate the intracellular signaling pathways regulated by adenosine receptors using a HTR-8/SVneo trophoblast cell model of T. gondii infection. HTR8/SVneo human extravillous trophoblast cells were infected with or without T. gondii and then evaluated for cell morphology, intracellular proliferation of the parasite, adenosine receptor expression, TNF-α production and mitogen-activated protein (MAP) kinase signaling pathways triggered by adenosine A3 receptor (A3AR). HTR8/SVneo cells infected with T. gondii exhibited an altered cytoskeletal changes, an increased infection rate and reduced viability in an infection time-dependent manner. T. gondii significantly promoted increased TNF-α production, A3AR protein levels and p38, ERK1/2 and JNK phosphorylation compared to those observed in uninfected control cells. Moreover, the inhibition of A3AR by A3AR siRNA transfection apparently suppressed the T. gondii infection-mediated upregulation of TNF-α, A3AR production and MAPK activation. In addition, T. gondii-promoted TNF-α secretion was dramatically attenuated by pretreatment with PD098059 or SP600125. These results indicate that A3AR-mediated activation of ERK1/2 and JNK positively regulates TNF-α secretion in T. gondii-infected HTR8/SVneo cells.

Fetal heart rate plays an essential role in maternal and fetal monitoring and fetal health detection. In this study, a method based on Poincare Plot and LSTM is proposed to realize the high performance classification of abnormal fetal heart rate. Firstly, the original fetal heart rate signal of CTU-UHB database is preprocessed via interpolation, then the sequential fetal heart rate signal is converted into Poincare Plot to obtain nonlinear characteristics of the signals, and then SquenzeNet is used to extract the features of Poincare Plot. Finally, the features extracted by SqueezeNet are classified by LSTM. And the accuracy, the true positive rate and the false positive rate are 98.00%, 100.00%, 92.30% respectively on 2 000 test set data. Compared with the traditional fetal heart rate classification method, all respects are improved. The method proposed in this study has good performance in CTU-UHB fetal monitoring database and has certain practical value in the clinical diagnosis of auxiliary fetal heart rate detection.
Databases, Factual ; Female ; Fetal Monitoring ; Fetus ; Heart Rate, Fetal ; Humans ; Pregnancy

Objective:To evaluate the accuracy of ultrasound-measured pulsatility index (PI) of central retinal arteries in diagnosing low cerebral perfusion pressure (CPP) in the patients with traumatic brain injury.Methods:Fifty-five patients who were admitted to the surgical intensive care unit due to traumatic brain injury with continuous intracranial pressure monitoring were selected.At 72 h after surgery, continuous incracranial pressure and mean arterial pressure were recorded, and peak systolic velocity and end diastolic velocity of central retinal arteries were measured by ultrasound.The invasive CPP and PI were calculated.The correlation between PI and CPP was analyzed.The accuracy of central retinal pulse index in diagnosing low CPP was evaluated by the receiver operating characteristic curve.Results:PI was negatively correlated with CPP ( r=-0.655, P<0.01). The area under the receiver operating characteristic curve of PI in diagnosing low CPP was 0.863 (95% confidence interval 0.761-0.965), and the threshold value was 0.97, sensitivity 92.3%, and specificity 66.7%. Conclusion:Ultrasound-measured PI is more accurate in diagnosing low CPP in the patients with traumatic brain injury.

Objective To analyze the 10-year survival outcome and failure patterns for patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT),aiming to provide reference for optimized treatment for NPC.Methods Clinical data of 866 patients with NPC receiving IMRT from January 2001 to December 2008 were retrospectively analyzed.Survival analysis was performed using the Kaplan-Meier estimator.Univariate analysis was carried out by log-rank test and multivariate analysis was performed using Cox proportional hazards model.Results The median follow-up time was 132 months.The 10-year local recurrence-free survival (LRFS),distant metastasis-free survival (DMFS),progression-free survival (PFS) and disease specific survival (DSS) were 92.0％,83.4％,75.7％ and 78.6％,respectively.A total of 210 patients died including 124 patients (59.0％) from distant metastasis,which was the primary cause of death,and 47 (22.3％) from local regional recurrence.Independent negative factors of DSS included age＞50 years (P=0.00),LDH ≥ 245 IU/L (P=0.00),Hb＜ 120 g/L (P=0.01),T2-T4 staging (P=0.00),N1-N3 staging (P=0.00) and GTV-nx＞20 cm3(P=0.00).The 10-year LRFS,DMFS and DSS of stage Ⅱ NPC patients did not significantly differ after IMRT alone and chemoradiotherapy (P=0.83,0.22,0.23).For patients with stage Ⅲ NPC,the 10-year LRFS and DSS in the chemoradiotherapy arm were significantly higher than those in the IMRT alone (P=0.01,0.01),whereas no statistical significance was observed in the DMFS between two groups (P=0.14).The overall survival of stage Ⅳa+Ⅳb NPC patients is relatively poor.Conclusions IMRT can improve the long-term survival of NPC patients.Distant metastasis is the primary failure pattern.Patients with stage Ⅰ-Ⅱ NPC can obtain satisfactory survival outcomes after IMRT alone.The addition of chemotherapy can further enhance the LRFS and DSS of stage Ⅲ NPC patients.However,the optimal therapeutic strategy remains to be urgently investigated for stage a+ Ⅳb NPC patients.

Hepatic fibrosis is a pathological process of chronic liver injury. Without timely intervention and treatment， liver fibrosis may eventually lead to liver cirrhosis and cancer. Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling pathway is closely associated with the occurrence and development of liver fibrosis. Based on this， this paper summarized and analyzed the mechanism and effects of active ingredients and compounds of traditional Chinese medicine improving liver fibrosis based on JAK/STAT signaling pathway. It is found that the active ingredients and compounds of traditional Chinese medicine that promote blood circulation and remove blood stasis （ingredients such as ethanol extract of Euonymus alatus and paclitaxel， as well as compounds such as Ershiwuwei songshi pill and Ganfukang）， clear away heat and toxic material （ingredients such as betulinic acid， total flavonoids from Persicaria perfoliata， as well as compounds such as Pianzaihuang and Kehuang capsules）， and sooth the liver and promote qi circulation （ingredients such as fraxetin and cucurbitacin B， as well as compounds such as Chaihu shugan powder and Xiaochaihu decoction） can all relieve liver fibrosis by inhibiting the activity of the JAK/STAT signaling pathway， reducing inflammatory reactions， and inhibiting the proliferation of hepatic stellate cells.

OBJECTIVE To establish and optimize tablets adding mechanism of automatic tablet dispensing machine in the inpatient pharmacy, realize tablets checking and fine management for tablets inventory and expiration date in process of tablets adding, reduce incidence of errors, improve work efficiency, and ensure the safety of tablets use for patients. METHODS Intelligent software combined with barcode scanning technology was used to carry out intelligent intervention on the error-prone link in the process of tablets adding of automatic drug dispensing machine. The error ratio of tablets adding(%), average of daily tablets adding time(min), error ratio of tablets quantity in monthly inventory check(%) were compared before and after intelligent intervention. RESULTS Compared with before optimization, the error ratio of tablets adding decreased from 0.11 % to 0%, average of daily tablets adding time decreased from (96.50±21.84)min to (64.23±19.59)min(P<0.01), which saved 32.27 min on average, and error ratio of tablets quantity in monthly inventory check decreased from (9.42±1.13)% to (3.42±0.88)%(P<0.01) after optimizing the dosing process of the automatic drug dispensing machine. CONCLUSION The optimized process of tablets adding of automatic drug dispensing machine is simple and rapid to operate, which has high accuracy. The tablets inventory and expiration date can be tracked and managed in real time, which ensures the safety of tablets use for patients, promotes development of digital pharmacy management system, and improves quality of pharmaceutical care.