OBJECTIVES: To investigate the effects of dihydroartemisinin (DHA) combined with doxorubicin (DOX) on proliferation and apoptosis of triple-negative breast cancer cells and explore the underlying molecular mechanism. METHODS: MDA-MB-231 cells were treated with 50, 100 or 150 μmol/L DHA, 0.5 μmol/L DOX, or with 50 μmol/L DHA combined with 0.5 μmol/L DOX. The changes in proliferation and survival of the treated cells were examined with MTT assay and colony-forming assay, and cell apoptosis was analyzed with flow cytometry. Western blotting was performed to detect the changes in protein expression levels of PCNA, cleaved PARP, Bcl-2, Bax, STAT3, p-STAT3, HIF-1α and survivin. RESULTS: The IC₅₀ of DHA was 131.37±29.87 μmol/L in MDA-MB-231 cells. The cells with the combined treatment with DHA and DOX showed significant suppression of cell proliferation. Treatment with DHA alone induced apoptosis of MDA-MB-231 cells in a dose-dependent manner, but the combined treatment produced a much stronger apoptosis-inducing effect than both DHA and DOX alone. DHA at 150 μmol/L significantly inhibited clone formation of MDA-MB-231 cells, markedly reduced cellular expression levels of PCNA, p-STAT3, HIF-1α and survivin proteins, and obviously increased the expression level of cleaved PARP protein and the Bax/Bcl-2 ratio, and the combined treatment further reduced the expression level of p-STAT3 protein and increased the Bax/Bcl-2 ratio. CONCLUSIONS DHA combined with DOX produces significantly enhanced effects for inhibiting cell proliferation and inducing apoptosis in MDA-MB-231 cells possibly as result of DHA-mediated negative regulation of the STAT3/HIF-1α pathway.
Humans ; STAT3 Transcription Factor/metabolism* ; Apoptosis/drug effects* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Doxorubicin/pharmacology* ; Triple Negative Breast Neoplasms/metabolism* ; Cell Line, Tumor ; Artemisinins/pharmacology* ; Female ; Cell Proliferation/drug effects* ; Signal Transduction/drug effects* ; Survivin

Objective To analyze the clinicopathological features, diagnosis and differential diagnosis of bronchiolar adenoma (BA) with primary lung cancer. Methods Data of 17 BA patients complicated with primary lung cancer in Dalian University Affiliated Xinhua Hospital from January 2020 to December 2022 were collected, and the clinical data, histopathological features and immunohistochemical features were summarized. Results 17 patients included 7 males and 10 females, with 49-82 years old. There were 2 squamous cell carcinoma and 15 adenocarcinoma. BA was mostly nodular, without capsule. It had a clear boundary with the surrounding lung tissue, with a major diameter of 0.3-1.5 cm. The section of BA was gray-white, gray-red, gray-brown, with medium-soft texture, and a few had obvious mucus. Microscopically, it was composed of luminal cell layer and basal cell layer, and luminal cells contain mucus cells, ciliated cells, cubic cells and columnar cells. According to the composition of luminal cells, BAs were divided into proximal type and distal type. There were 5 proximal type and 12 distal type, including 1 case of atypical distal BA. Immunohistochemistry results showed that in typical BAs, CK5/6, p63 and p40 were positive in basal cells, thyroid transcription factor-1 was positive in luminal cells and basal cells, and the proliferation index of Ki-67 was 1%. Conclusions BA is a benign tumor, and is a bilayer structure mainly composed of luminal cells and basal cells. However, when the absence or discontinuity of basal cells, BA is easily misdiagnosed as malignancy, which should be highly vigilant.

To meet the requirement of pathological practice and development, we systematically analyzed the situation of pathological residents training and the importance of initiating the clinical scientific research training. Additionally, we proposed the principle and implementation strategy for clinical scientific research training. According to features of pathological practice, we employed the modularized teaching to divide the training courses into several modules: discussion module for clinical pathology, lecture module for advanced research, and training modules for basic scientific theory, technology and writing skill. With these approaches, the systematic and structured system of standardized residents training is implemented to improve the clinical research ability of pathological residents.

Objective To evaluate the effect of contrast medium on the renal function in patients with cerebrovascular disease accompanied by diabetes mellitus after receiving neuro - interventional therapy. Methods The clinical data of a total of 108 patients with cerebrovascular disease complicated by diabetes mellitus type 2, who were treated with neuro - interventional therapy during the period from March 2013 to March 2016, were retrospectively analyzed. The contrast dose used in interventional procedures was less than 250ml in each patient. The preoperative and 24 h -postoperative serum creatinine (sCr), serum cystatin C (Cys C) levels were determined, and based on the modification of dietary renal disease (MDRD) equation and Larsson equation the estimated glomerular filtration rates (eGFR) were separately calculated. Results Compared with preoperative values, the 24 h - postoperative mean sCr and Cys C levels were increased significantly (P=0. 001, P=0. 015 respectively), while the average eGFR rates were remarkably decreased (P＜ 0. 000 1 by using MDRD equation, and P=0. 021 by using Larsson equation). No kidney damage that needed to be treated occurred in all patients. Conclusion The contrast dose used in neuro - interventional procedures can cause decline of renal function in patients with type 2 diabetes mellitus. The combined determination of sCr and Cys C levels is helpful for the detection of contrast - induced changes in renal function as early as possible. The use of conventional dose of contrast agent in neuro - interventional procedures is safe for patients with type 2 diabetes mellitus. (J Intervent Radiol, 2018, 27:277-280)

BACKGROUND:Traditional core decompression and al ograft fibula supporting can reduce the stress load within femoral head and improve mechanical properties of femoral head. However, it cannot provide supports for maintaining the stability of five pathological areas fol owing femoral head necrosis. OBJECTIVE:To observe the clinical effect of fan-shaped decompression and al ograft fibula supporting internal fixation in treatment of early femoral head necrosis in adults, taking al ograft fibula grants as the control. METHODS:Forty patients with early femoral head necrosis were randomly divided into treatment group and control group, receiving fan-shaped decompression plus al ograft fibula supporting internal fixation and traditional decompression plus al ograft fibula grafting, respectively. The therapeutic effects in two groups were observed and compared. After treatment, patients were detected by bilateral hip anteroposterior films, Harris scoring and X-ray ARCO staging to evaluate the col apse severity and restoration of necrosis. RESULTS AND CONCLUSION:At the last fol ow-up, Harris scores in the treatment group were significantly higher and the repairing effect was better than control group (P<0.05). In treatment group, 18 hips restored wel (72%) and 7 hips delayed or failed to restore (28%);in control group, 9 hips restored wel (60%) and 6 hips delayed or failed to restore (40%). Our findings indicate that, fan-shaped decompression plus al ograft fibula supporting internal fixation yields a more complete decompression, a higher stability of femoral head and a more reliable supporting, compared with traditional decompression plus al ograft fibula grafting.

Objective To study the effects of oxytocin antagonists-atosiban on pregnancy outcome after thaw embryo transfer (TET).Methods Between Jul.and Dec.2012,a total of 120 women undergoing TET in Reproductive Medical Center,General Hospital of Tianjin Medical University were randomly allocated into atosiban and control group.They were all transferred 2 or 3 top quality embryos at phase of 7-8 cells.Patients in atosiban group were administered by intravenous administration of atosiban before 30 minutes of embryo transfer with a total administered dose of 37.5 mg.In the control group,no special treatment was given before embryo transfer.All patients in 2 groups underwent progesterone luteal support regularly after embryo transfer,then the clinical rate of pregnancy,implantation and early abortion was compared.Results The clinical pregnancy rate per cycle and implantation rate per transfer were 60％(36/60) and 30.0％ (48/160) in the atosiban group,which were higher than 42％ (25/60) and 20.3％ (31/153) in the control group (all P ＜ 0.05).Early abortion rate was 6％ (2/36)in the atosiban group,which was no statistical difference comapring with control group [16％ (4/25),P ＞ 0.05].Conclusion It was suggested that atosiban treatment before embryo transfer can improve the outcome of pregnancy,and increase clinical pregnancy rate and implantation rate after TET.

Objective To analyze the efficacy and safety of glimepiride treatment as initial monotherapy in newly diagnosed patients with type 2 diabetes mellitus (T2DM).Methods This was a subgroup analysis of the GREAT study,which investigated the efficacy and safety of glimepiride as initial monotherapy in Chinese patients with T2DM.This analysis was performed in 209 patients with disease duration less than 6 months and never received any anti-diabetic drugs.The change of HbA1C,fasting plasm glucose (FPG),2 h postprandial blood glucose (2hPPG),homeostasis model assessment for β-cell function index (HOMA-β),homeostasis model assessment for insulin-resistance index(HOMA-IR),the percentage of patients with HbA1C ＜ 7.0％ at endpoint and the incidence of hypoglycemia were evaluated after 16-weeks treatment.Results After 16-weeks glimepiride treatment,HbA1C value reduced significantly from baseline to endpoint,the reduction was statistically significant (9.21％ ± 1.65％ to 6.69％±0.83％,P＜0.001),69.7％ of the patients achieved HbA1C ＜7.0％ at study endpoint.Glimepiride-treated patients also achieved a significant improvement in FPG [from (10.15 ± 2.13) mmol/L to (7.23 ± 1.50) mmol/L,P＜0.001] and 2hPPG [from (17.21 ±4.14) mmol/L to (11.62 ± 3.34) mmol/L].HOMA-β was improved from 17.21± 15.19 [11.62 (2.90,115.8)] to 41.13 ± 44.12 [28.00 (5.1,360.00)],and HOMA-IR was reduced from 2.32± 1.90 [1.76 (0.60,12.80)] to 2.07 ± 1.74 [1.63 (0.4,12.3)].The incidence of all reported symptomatic hypoglycemia was 18.2％,and the incidence of confirmed hypoglycemia was 3.8％.Conclusion This analysis showed that glimepiride treatment as an initial mono-therapy could effectively improve blood glucose control in newly diagnosed patients with T2DM,and the treatment may improve islet β cell function,and the safety profile is reasonably good.

ObjectiveTo investigate expression distribution of mutant connexin 32 (Cx32) protein in human endothelial cells in patients with X-linked Charcot-Marie-Tooth disease type 1 ( CMTX1 ) .MethodsNerve biopsies were performed in 3 patients with CMTX1 and in 3 non-CMTX1 controls. Cx32 mutations of c. 379A ＞ T( I127F), c. 533A ＞ G(D178G) and c. 590C ＞ T(A197V) were identified in these 3 patients respectively.Immunofluorescent (IMF) staining of nerve blood vessel was processed with antibodies against Cx32, Yon Willebrand factor and Cx40. The mutant Cx32 was constructed in pEGFP-N plasmid (pEGFP-N1-Cx32) and was transfected in HeLa cells. Cx32 and GRP78, a marker of endoplasmic reticulum ( ER), were stained by IMF in HeLa cells to investigate expression of mutant Cx32. ResultsIn 3 control cases, Cx32 was visualized by IMF staining as dots along gap junction of vascular endothelial cells,and it was coexisted with Cx40.However, immunoreactivity of Cx32 in 3 patients was predominantly decreased and was not located in endothelial gap junction. The transfection of 3 Cx32 mutants into HeLa cells demonstrated thepathogenic changes.The cells withthemutationc. 379A ＞T found Cx32 accumulations in the cytoplasm; the cells with mutation c. 533A ＞G showed few staining positive dots surrounding the nuclear and the cells with c. 590C ＞ T showed dot-like expression of Cx32 both in the cytoplasmicand cell membrane. The mutant Cx32 was not overlapped with expression of the marker of ER.ConclusionsMutant Cx32 might cause dysfunction of endothelial gap-junctions due to the abnormal expression of Cx32 in level and location in the vascular endothelial cells of CMTX1 patients.

A simple,rapid and sensitive liquid chromatography-mass spectrometry (LC-MS) method was developed for the determination of salidroside in rat plasma and study of its pharmacokinetics after oral administration of suspension of Erzhi Wan and Fructus Ligustri lucidi into Wistar rats.Plasma sample of 200 μL was extracted with acetic etherisopropanol (2:1) and the extraction was performed on a Kromasil C18 column (150 mm×4.6mm,5 μm) with the mobile phase of methanol-water (41:59,v/v) within a run time of 6.0min.The analyte was monitored with positive electrospray ionization (ESI) by selected ion monitoring (SIM) mode.The target ions were m/z 323.05 for salidroside and m/z 411.05 for internal standard (IS) geniposide.A good linear relationship was obtained over the range of 5.0-500.0 ng/mL and the lower limit of quantification was 5.0 ng/mL.The validated method was successfully applied to the pharmacokinetic study of salidroside in rat plasma after oral administration of suspension of Erzhi Wan and Fructus Ligustri lucidi.

This paper aimed to study clinical effectiveness of gabapentin in the treatment for pruritus and insomnia among patients with hemodialysis. Eighty patients with severe pruritus and insomnia during regular hemedialysis in Jiaozhou People's Hospital, Jiangsu were randomly divided into two groups with 40 patients each. Gahapentin 0. 1 g were given each patient every night for 4 weeks in one group and a modified-re]ease capsule of 8 mg chiorphenamine maleate was given each patient daffy for 4 weeks in the other group. Effectiveness of treatment was evaluated by improvement of itching symptoms and Pittsburgh Sleep Quality Index (PSQI) scores for insomnia in the patients. Itching improvement was observed in 85%(34/40) of the patients and PSQI scores obviously lowered in them four weeks after gabapentin treatment.However, itching improvement was observed only in 42% ( 17/40 ) of the patients and little change was observed in PSQI scores in them four weeks after chlorphenamine treatment It suggests that gabapentin can significantly improve quality of sleeping and itching symptoms in patients with hemodialysis and it is worthy popularizing in those with it.