Objective To investigate the effect of STAT3 knockdown on the sensitivity of breast cancer cells with drug-resistant to adriamycin (MCF-7/ADR). Methods Levels of STAT3 and p-STAT3 in MCF-7/ADR and MCF-7 cells were detected by Western Blot. The MCF-7/ADR cells were infected with lentivirus expressing STAT3-shRNA and the negative control vectors in the STAT3-RNAi group and NC group, respectively, wihle the cells in the blank group received no treatment. The transfection efficiency was observed with fluorescence microscope, the mRNA level of STAT3, protein levels of STAT3 and p-STAT3 were detected by qRT-PCR and Western Blot, respectively. MCF-7/ADR cells were treated with different concentrations of adriamycin for 48 hours, cell proliferation was detected by MTT assay and cell apoptosis was detected by flow cytometry. Results Levels of STAT3 and p-STAT3 in MCF-7/ADR cells were significantly higher than those in the MCF-7 cells (P < 0.05). The levels of STAT3 mRNA, STAT3 and p-STAT3 in the STAT3-RNAi group were significantly lower than those in the Con group and the NC group (P<0.05, respectively). The Adriamycin IC50 in the Con group, NC group and STAT3-RNAi group was (56.1 ± 3.00)ug/mL,(54.9 ± 11.9)ug/mL and (7.6 ± 0.2)ug/mL, respectively. The flow cytometry results showed that the cell apoptosis in the Con group, the NC group and the STAT3-RNAi group was (10.5+0.7)%, (11.7+0.7)%and (34+3.1)%, respectively. Conclusion LV-shRNA-STAT3 can significantly inhibit STAT3 expression and enhance the sensitivity of breast cancer cells to adriamycin, and the underlying mechanism may be related to cell apoptosis.

The leading cause of drug withdrawal from market and clinical trials failure is drug-induced liver injury (DILI). Varying clinical, histological and laboratory features of DILI, as well as undefined underlying mechanisms, hinder patients to be diagnosed in the early-stage of the disease and receive effective treatments. Conventional indicators, like serum transaminases and bilirubin, have inevitable limitations referring to sensitive prediction and specific detection of DILI. In order to reduce the occurrence of DILI, researchers have attempted to discover potential biomarkers with higher specificity and sensitivity from blood and urine in recent years. This article aims to review recent advances in biomarkers of DILI.

Objective To investigate whether TG2 promotes drug resistance to epirubicin through AKT signal pathway in breast cancer. Methods MCF-7 cells with constant expression of TGM2 gene(TGM2-LV)were established via the lentiviral vector. The breast cancer cells were divided into five groups,including the NC group, TG2 group and MK2206 group. The MCF-7/adr cells were divided into ADR group and MKadr group. The expres-sion of TG2 ,AKT ,Bcl-2 and P53 was detected by Western blot assay. Cells were treated with epirubicin. MTT assay was performed to assess cell proliferation. The inhibition ratio of cancer cell proliferation was evaluated. TUNEL analysis was performed to identify the apoptosis of the breast cancer cells. Results Lvels of TG2,p-AKT and Bcl-2 in NC group were significantly lower than those in TG2 group,while the expression of P53 in NC group was much higher. In MK2206(or MK/adr )group,p-AKT and Bcl-2 were down-regulated,while P53 was markedly up-regulated compared with TG2(or ADR)group(P<0.05). The results of the MTT assay showed a strong inhibi-tion in cell proliferation rate in MK2206(or MKadr )group. Compared with the NC group,TG2 promoted prolifera-tion of MCF-7 cells in TG2 group. The cell apoptosis rate in MK2206(or MKadr )group was significantly higher than that in TG2(or ADR)group(P<0.05). TG2 significantly inhibit the apoptosis of breast cancer cells ,com-pared to the control group. Conclusion TG2 might promote drug resistance to epirubicin through AKT signal path-way in breast cancer

OBJECTIVETo improve the oral bioavailability of patchoulic alcohol in rats by using self-microemulsifying drug delivery systems (SMEDDS).

METHODPatchoulic alcohol was separated and purified from patchoulic oil, and the SMEDDSs including patchoulic alcohol or patchoulic oil were optimized by pseudo-ternary phase diagrams via central composite design-response surface methodology. Pharmacokinetics of both SMEDDSs and patchoulic alcohol itself in rats were investigated.

RESULTThe patchoulic alcohol SMEDDS (Cremophor EL-Tween 80-PEG 400-isopropyl myristate-patchoulic alcohol, 2:2:0.8:1.95:0.65) was considered as the optimized formulation. The mean drop size of the system was 30. 1 nm after diluted 100 folds in water. The average self-microemulsifying time was 142 s. Patchoulic alcohol SMEDDS and patchoulic oil SMEDDS showed no signficant difference in Tmax compared with patchoulic alcohol with around 60 minutes, while the AUCs of both SMEDDSs (2001 745.6 +/- 329 663.6) and (1594 005.6 +/- 280 150.3) microg x min x L(-1) were significantly higher than that of patchoulic alcohol (1 163 153.3 +/- 232 324.3) microg x min x L(-1).

CONCLUSIONSMEDDS can effectively improve the oral bioavailability of patchoulic alcohol in rats.

Administration, Oral ; Animals ; Biological Availability ; Chemistry, Pharmaceutical ; Drug Delivery Systems ; methods ; Drug Stability ; Emulsifying Agents ; chemistry ; Ethanol ; chemistry ; Female ; Particle Size ; Rats ; Rats, Sprague-Dawley ; Self Administration ; Sesquiterpenes ; chemistry ; Solubility

Objective To explore the clinical effect of the endoscopic electrocoagulation combined with nasal micro packing in the treatment of refractory epistaxis .Methods 120 patients with refractory epistaxis were selected as the research subjects ,and they were divided into two groups by the single blind randomly methods ,60 cases in each group.The control group was given vaseline gauze for hemostasis of nasal cavity ,and the observation group received endoscopic electrocoagulation combined with nasal packing hemostasis micro treatment .The cure rate ,the incidence of complications ,recovery of nasal mucosa of nasal ventilation time , recovery time , the total amount of bleeding , pain score and recurrence rate of the two groups were compared .Results The cure rate in the observation group was 96.67％,which was significantly higher than 81.67％ in the control group(χ2 =6.988,P<0.05).The incidence rate of complications and pain score in the observation group were 8.33％,(3.65 ±1.09)points,respectively,which were significantly lower than 21.67％,(5.23 ±1.72) points in the control group (χ2 =4.183,t =6.010,all P<0.05).The total amount of bleeding significantly reduced (t=6.344,P<0.05),the recovery of nasal ventilation time and recovery time of nasal mucosa significantly decreased (t=7.119,6.183,all P<0.05).The patients were followed up for 6 months,the recurrence rate in the observation group was 1.67％,which was significantly lower than 11.67％in the control group(χ2 =4.821,P<0.05).Conclusion The endoscopic electric coagulation combined with nasal micro packing in the treatment of refractory epistaxis has significant effect ,it can effectively promote the recovery of patients,reduce complications and recurrence ,the prognosis is good .

Objective To assess the factors associated with the restoration of spontaneous circulation (ROSC) and 2-year survival prognosis in patients with cardiac arrest (CA) after acute myocardial infarction (AMI),and after ROSC,the effects of various factors on midian survival time and on 2-year survival.Methods In a registry study from January 2005 to January 2015,all consecutive AMI-induced CA patients treated with cardiopulmonary resuscitation (CPR) admitted to our hospital were enrolled.The survivors were followed-up for 2 years.Univariate analysis was applied to evaluate factors associated with rate of ROSC and 2-year survival.Multivariable logistic regression analysis was applied to evaluate statistically significant factors in the univariate analysis.Medians with inter-quartile ranges were used to describe 2-year survival time affected by various factors after ROSC.Kaplan-Meier survival curve analysis was used to evaluate the effect of factors on 2-year survival.Results A total of 254 cases with CA after AMI were enrolled,including 129 cases of ROSC and 71 cases of 2-year survival.Univariate analysis showed age ≥ 70 years,CA occurred during 22:00-8:00,the duration time ofCPR ≥ 15 min and adrenaline dosage ＞ 5 mg were unfavorable predictors of ROSC;while,left ventricular ejection fraction (LVEF) ≥ 40％ before CA,shockable rhythm and percutaneous coronary intervention (PCI) therapy were favorable predictors.Besides,age ≥ 70 years,intubation during CPR,adrenaline dosage ＞ 5 mg and cardiogenic shock were unfavorable predictors of 2-year survival;While,male,normal daily activity before CA and PCI treatment were favorable predictors.Multivariable analysis showed age,the duration of CPR,adrenaline dosage,LVEF before CA,the rhythm during CPR and PCI therapy were independent predictors of ROSC.Age and PCI therapy were independent predictors of 2-year survival.Among patients,the survival time was affected by various factors after ROSC,and the factors with minimum 25％ and small median value were associated with cardiac rupture,cancer,adrenaline dosage ＞ 5 mg and cardiogenic shock.The factor with maximum 25％ value was PCI treatment (216 days).Kaplan-Meier survival analysis suggested that age ≥ 70 years was an unfavorable factor of 2-years survival (Log-rank test,P=0.007);while,PCI treatment was a favorable factor (Log-rank test,P＜0.01).PCI-related prognosis analysis showed that the effectiveness of PCI was related to the timing of PCI,the number of infarctrelated artery and the difference in culprit lesion.Conclusions The age ≥ 70 years was disadvantageous to both ROSC and 2-year survival.PCI treatment was favorable to both ROSC and 2-year survival.

Objective:To investigate the characteristics of fragility fractures of pelvis(FFP) in the elderly and compare the clinical efficacy between conservative treatment and minimally invasive surgery.Methods:A retrospective study was conducted in the 56 elderly FFP patients who had been treated at Department of Orthopaedics, The General Hospital of Chinese People＇s Liberation Army from January 2017 to January 2019. They were 16 males and 40 females, with an age of 73.4 years (from 65 to 93 years). By the American Society of Anesthesiologists (ASA) classification, there were 12 cases of grade Ⅰ, 16 cases of grade Ⅱ, 20 cases of grade Ⅲ, and 8 cases of grade Ⅳ; by the FFP classification, there were 6 cases of type Ⅰ, 10 cases of type Ⅱ, 36 cases of type Ⅲ, and 4 cases of type Ⅳ. The morphological characteristics and injury mechanisms of FFP were analyzed. According to the treatment methods, the patients were divided into a conservative treatment group of 32 cases and a minimally invasive surgery group of 24 cases. The 2 groups were compared in terms of complication incidence, mortality and the Koval attenuation rate of walking ability after one-year follow-up.Results:There were mostly the fractures of pubic branches on both sides of the pubic symphysis and compression fractures of the sacral wing caused by lateral crush injury. The 2 groups were comparable due to no significant differences in the preoperative general data between them other than FFP classification ( P>0.05). By one year after treatment, the conservative treatment group had a complication incidence of 34.4% (11/32), a mortality of 9.4% (3/32) and a Koval attenuation rate of walking ability of 13.8% (4/29) while the minimally invasive surgery group had a complication incidence of 20.8% (5/24), a mortality of 4.2% (1/24) and a Koval attenuation rate of walking ability of 8.7%(2/23), showing no significant difference between the 2 groups ( P>0.05). Conclusions:The injury mechanism of geriatric FFP is mostly lateral compression injury. The fracture sites are mostly located on both sides of the pubic symphysis, pubic branches and the sacral wing of anterior and posterior rings simultaneously. Although there may be no significant difference in complication incidence, mortality or Koval attenuation rate of walking ability between conservative treatment and minimally invasive surgery after one year, the minimally invasive surgery deals with more unstable fracture types.

Objective:To systematically evaluate the clinical efficacy of compound α-ketoacid tablets in the treatment of diabetic kidney disease (DKD).Methods:CNKI, Wanfang database, EMBASE, PubMed and Cochrane Library database were searched for eligible records published from the establishment of individual database to November 13 th, 2022. The quality of the included studies were assessed, data were extracted, and meta-analysis was conducted using RevMan5.3. Results:A total of 26 randomized controlled trials were included, with a total of 2 790 DKD patients (1 465 in the experimental group and 1 325 in the control group). Multiple parameters were significantly improved in the experimental group compared with the control group, including 24-hour urinary protein, blood creatinine, urea nitrogen, nutritional index, oxidative stress level, fasting blood glucose, glycated hemoglobin, homocysteine, HGF, VEGF, TGF-β1, and systolic blood pressure.Conclusions:Limited low-quality evidence showed that compound α-ketoacid tablets combined with low-protein diet may be related to the improved 24-hour urinary protein, renal function, and glucose metabolism in patients with DKD. Due to the lack of randomized controlled trials designed for respective stages of DKD, the inclusion criteria of our study were relatively general, possibly leading to the lack of pertinence of the results. Some indicators showed apparent heterogeneity among different groups, and more high-quality multi-center studies with large sample sizes are still needed to verify our findings.

BACKGROUND:In recent years,the development of liver organoids has made it a hot spot in the field of international liver disease research,but there is still no article on the bibliometric analysis of liver organoids. OBJECTIVE:To explore the hot trends in liver organoids in the last 20 years based on bibliometrics and visualization analysis. METHODS:We searched the articles about liver organoids in the Web of Science Core Collection from January 1,2002 to November 12,2022.Origin,Office,and CiteSpace software were used for bibliometrics and visualization analysis.We statistically analyzed the number of annually published articles,countries,institutions,authors,journals,and keywords of the articles by generating charts. RESULTS AND CONCLUSION:The number of articles,citation frequency,institutions and personnel involved in the research about liver organoids showed an overall upward trend in the last 20 years,indicating that the field was growing rapidly and attention was increasing.The USA had published the most papers and had the strongest influence in this field.Although it had invested a lot of time and energy,the number of papers published by a single research institution in the USA was not the highest among many research institutions.China was second only to the USA in the number of publications,with the Chinese Academy of Sciences and Fudan University leading the list.Utrecht University in the Netherlands was the institution with the most publications.Clevers H was the author with the highest number of articles.The article with the highest co-citation frequency was"Long-term culture of genome-stable bipotent stem cells from adult human liver".The main fields of study for liver organoids were Molecular Science,Biology,and Immunology.The most frequently occurring keywords were stem cell,in vitro,and culture.The research hotspots in the liver organoids field were mainly focused on in vitro stem cell three-dimensional culture,differentiation and gene expression.

Bone Transplantation/adverse effects* ; Transplantation, Autologous/adverse effects*