[Gemcitabine long-term maintenance chemotherapy benefits patients with survival: a multicenter, real-world study of advanced breast cancer treatment in China].

Objective: This study collected a real-world data on survival and efficacy of gemcitabine-containing therapy in advanced breast cancer. Aimed to find the main reasons of affecting the duration of gemcitabine-base therapy in advanced breast cancer patients. Methods: Advanced breast cancer patients who received gemcitabine-base therapy from January 2017 to January 2019 were enrolled(10 hospitals). The clinicopathological data, the number of chemotherapy cycles and the reasons for treatment termination were collected and analyzed. To identify the reasons related with continuous treatment for advanced breast cancer and the factors which affect the survival and efficacy. Results: A total of 224 patients with advanced breast cancer were enrolled in this study, with a median age of 52 years (26-77 years), 55.4%(124/224) was postmenopausal. Luminal type were 83 cases, TNBC were 97 cases, and human epidermal growth factor receptor 2 (HER's-2) overexpression were 44. At the analysis, 224 patients who received the gemcitabine-based regimens were evaluated, included 5 complete reponse (CR), 77 partial response (PR), 112 stable disease (SD) and 27 progressive disease (PD). The objective response rate (ORR) was 36.6%(82/224). Seventy patients had serious adverse diseases, including leukopenia (9), neutrophilia (49), thrombocytopenia (15), and elevated transaminase (2). The median follow-up time was 41 months (26~61 months), and the median PFS was 5.6 months. The reasons of termination treatment were listed: disease progression were 90 patients; personal reasons were 51 patients; adverse drug reactions were 18 patients; completed treatment were 65 patients. It was found that progression-free survival (PFS) was significantly longer in patients receiving >6 cycles than that in patients with ≤6 cycles (8.2 months vs 5.4 months, HR=2.474, 95% CI: 1.730-3.538, P＜0.001). Conclusions: Gemcitabine-based regimen is generally well tolerated in the Chinese population and has relatively ideal clinical efficacy in the real world. The median PFS is significantly prolonged when the number of treatment cycles are appropriately increased.

Design and experiments of a compact electrostatic low energy beam transport with a double Einzel-lens for a transportable neutron source.

A transportable, compact, accelerator-based neutron source is under development at Xian Jiaotong University. An electrostatic low energy beam transport (LEBT) structure with a double Einzel-lens setup was adopted due to its short length and low power consumption. It can transport a pulsed proton beam to the radio frequency quadrupole with a required beam current of 15 mA and an energy of 30 keV. We performed detailed structure optimization and beam tracking to achieve beam matching and small emittance growth. In addition, the fast chopper, beam steering, and diagnostic devices are integrated into the LEBT. The fabrication and assembly of the proton injector have been completed, and beam commissioning was carried out to measure the beam current and Twiss parameters. The design strategy, beam simulation, and experimental results are presented and discussed in this paper.

[Analysis on the secondary attack rates of SARS-CoV-2 Omicron variant and the associated factors].

Objective: To evaluate the secondary attack rates of the SARS-CoV-2 Omicron variant and the associated factors. Methods: A total of 328 primary cases and 40 146 close contacts of the SARS-CoV-2 Omicron variant routinely detected in local areas of Jiangsu Province from February to April 2022 were selected in this study, and those with positive nucleic acid test results during 7 days of centralized isolation medical observation were defined as secondary cases. The demographic information and clinical characteristics were collected, and the secondary attack rate (SAR) and the associated factors were analyzed by using a multivariate logistic regression model. Results: A total of 1 285 secondary cases of close contacts were reported from 328 primary cases, with a SAR of 3.2% (95%CI: 3.0%-3.4%). Among the 328 primary cases, males accounted for 61.9% (203 cases), with the median age (Q1, Q3) of 38.5 (27, 51) years old. Among the 1 285 secondary cases, males accounted for 59.1% (759 cases), with the median age (Q1, Q3) of 34 (17, 52) years old. The multivariate logistic regression model showed that the higher SAR was observed in the primary male cases (OR=1.632, 95%CI: 1.418-1.877), younger than 20 years old (OR=1.766, 95%CI: 1.506-2.072),≥60 years old (OR=1.869, 95%CI: 1.476-2.365), infected with the BA.2 strain branch (OR=2.906, 95%CI: 2.388-3.537), the confirmed common cases (OR=2.572, 95%CI: 2.036-3.249), and confirmed mild cases (OR=1.717, 95%CI: 1.486-1.985). Meanwhile, the higher SAR was observed in the close contacts younger than 20 years old (OR=2.604, 95%CI: 2.250-3.015),≥60 years old (OR=1.287, 95%CI: 1.052-1.573) and exposure for co-residence (OR=27.854, 95%CI: 23.470-33.057). Conclusion: The sex and age of the primary case of the Omicron variant, the branch of the infected strain, case severity of the primary case, as well as the age and contact mode of close contacts are the associated factors of SAR.

[Potential application of improved hard tissue section technique in the clinical pathological diagnosis of bone and bone marrow].

Objective: To discuss the application value of hard tissue section in the clinicopathology diagnosis. Methods: From March 2021 to December 2021, bone slices of 19 patients (1 patient with osteochondroma, 2 patients with chondrosarcoma, 4 patients with osteosarcoma, 2 patients with fibrous dysplasia, 2 patients with bone metastasis from thyroid papillary carcinoma, 2 patients with osteomyelitis, 4 patients with giant cell tumor of bone, 2 patients with Ewing sarcoma) and 16 hemopathy patients were collected from the Department of Pathology, Shanghai Sixth People's Hospital. Of the osteopathy patients, there were 14 male and 5 female with a median age of 31 (10-66) years. Meanwhile, there were 7 male and 9 female with a median age of 28 (16-65) years among these hemopathy patients. Thirty-five cases were treated with modified hard tissue slicing technique and paraffin embedding technique, respectively. The advantages and disadvantages of the two methods for clinical diagnosis of bone disease were compared by Hematoxylin-Eosin staining (H&E staining), immunohistochemical staining (IHC), fluorescence in situ hybridization (FISH) and Sanger sequencing. Results: The improved resin-embedded method showed better histological morphology and cell structure. Besides, the expression of Ki67, SATB2, CD34, SMA, CD68,MPO,CD4 and CD33 in immunohistochemical staining in bone tissues which were embedded in resin were more clear in the accurate positive localization than those using paraffin-embedded. MDM2 of FISH exhibited a higher fluorescence intensity and more accurate location. Meanwhile, both methods treated with Sanger sequencing met the requirements of DNA purity and mutation detection. Conclusion: The improved hard tissue section method is simple and short time-consuming, which is suitable for optimizing the clinical bone and bone marrow pathological diagnosis process.

[Relationship between opacity of cytomegalovirus retinitis lesion borders and aqueous viral load among patients after allogeneic hematopoietic stem cell transplantation].

Objective: To evaluate the relationship between lesion features of cytomegalovirus (CMV) retinitis, including lesion size and degree of opacity of lesion borders, and aqueous CMV-DNA load in patients after allogeneic hematopoietic stem cell transplantation. Methods: It was a retrospective case series study. Data of patients diagnosed as CMV retinitis after allogeneic hematopoietic stem cell transplantation at the Department of Ophthalmology, Peking University Third Hospital from January 2018 to October 2020 were reviewed. Lesion size was detected by ultra-wide-field fundus image and measured by ImageJ, an image processing and analysis software. Opacity of lesion borders was evaluated by a masked reader. The CMV retinitis lesions were divided into 3 types according to the opacity degree of the border of the lesions: suspected active lesion mildly to moderately opacified lesion and severely opacified lesion. All eyes were diagnosed as active cytomegalovirus retinitis. CMV-DNA in aqueous humor was detected at the first visit and at the end of the induction period of antiviral drugs. CMV-DNA load was quantitatively detected by polymerase chain reaction after 100 µl of aqueous humor was extracted, and were converted to common logarithmic representations. Pearson correlation analysis was used to analyze the correlation between lesion area, opacity degree of lesion border and aqueous humor CMV-DNA load. Results: A total of 71 eyes from 46 patients were included and 26 was male and 20 was female. The age of the patients was 27(13, 33)years. The active lesion size of CMV retinitis was 40(12, 65) disc areas. Eight eyes (11.3%) had a suspected active lesion, 51 eyes (71.8%) had a mildly to moderately opacified lesion border, and 12 eyes (16.9%) had a severely opacified border. At the first visit, 67 eyes (94.4%) were CMV-positive, and the CMV-DNA load was 2.04×104 (6.24× 102, 1.48 ×105) copies/ml. After 2 weeks of induction therapy, the viral load was 2.47×102 (1.08× 10, 6.87 ×103) copies/ml. The correlation analysis showed that the CMV-DNA load in aqueous humor was significantly correlated with the lesion border opacity both at presentation and 2 weeks after intravitreal antiviral treatment (r=0.765, P<0.001; r=0.761, P<0.001), but was not related with the size of active fundus lesions (r=0.209, P=0.095; r=0.220, P=0.078). Conclusion: Degrees of lesion border opacity can reflect levels of aqueous viral load of CMV retinitis in patients after allogeneic hematopoietic stem cell transplantation and can become a useful measurement for investigation of CMV retinitis activity.

[Clinical and endoscopic characteristics of gastrointestinal mantle cell lymphoma].

Objective: To study the clinical and endoscopic features of mantle cell lymphoma (MCL). Methods: The clinical data and endoscopic characteristics of 20 patients with gastrointestinal MCL treated in the Affiliated Hospital of Zunyi Medical University and the Digestive Endoscopy Center of Guizhou Medical University from January 2011 to January 2021 were collected, and the histological and immunohistochemical characteristics of the tumor were observed. Meanwhile, 44 cases of non-gastrointestinal MCL in the above two hospitals in the same period were also enrolled. The clinical and endoscopic differences between the two groups were compared. Results: Among the 20 patients with gastrointestinal MCL, the male to female ratio was 4∶1 (16/4), the average age was (60.3±9.7) years, and 11 patients (55.0%, 11/20) were over 60 years old. The main clinical manifestations of 20 patients at the onset of the disease were bloody stool or black stool in 9 cases (45.0%), abdominal pain in 8 cases (40.0%). Moreover, 5.0% (1/20) had B symptoms (fever, night sweat and weight loss). The most frequently involved site was colorectum (50.0%). Endoscopic findings showed mucosal polypoid lesions in 13 cases (65.0%, 13/20), involving multiple intestinal segments, with polyp diameter of 0.2-3.5 cm. Two cases (10%) were in stage Ⅲ and 18 cases (90%) were in stage Ⅳ according to Ann Arbor staging. Seven cases (35.0%, 7/20) had the involvement of the peritoneal and retroperitoneal lymph nodes, 9 cases (45.0%, 9/20) had the involvement of the superficial lymph nodes in 45.0% (9/20), and 4 cases (20%, 4/20) had other extranodal invasion. Splenomegaly accounted for 35.0% (7/20). CD20, Bcl-2 and CD5 were positive or strongly positive in all gastrointestinal MCL tumor cells in 20 cases. Cyclin D1 was positive or strongly positive, accounting for 90.0% (18/20). The sex-determining region of Y chromosome-related high-mobility-group box 11 (SOX11) was positive or strongly positive, accounting for 65.0% (13/20). The positive index of Ki-67 was 5%-80%. Twenty cases (100%, 20/20) were followed up. The median follow-up was 41.2 months (1-74 months). There was no significant difference in the 3-year overall survival rate between the gastrointestinal MCL patients (70.0%) and non-gastrointestinal MCL patients (72.7%) (χ2=0.051, P=0.822). Conclusions: Abdominal discomfort is the main symptom of gastrointestinal MCL, which often occurs in the colorectum and often presents with multiple polypoid lesions. There are relatively few cases with B symptoms and extranodal invasion, and the prognosis is not different from that of patients with non-gastrointestinal MCL.

[Effect of a novel radio-frequency atmospheric-pressure glow discharge plasma jet treatment on crosslinking of dentin collagen].

OBJECTIVE: To investigate the effect of a noval radio-frequency atmospheric-pressure glow discharge (RF-APGD) plasma jet on crosslinking of dentin collagen. METHODS: (1) Twenty intact third molars were collected. The middle dentin discs were prepared for each tooth by low-speed water-cooled Isomet saw, and then immersed in 10% (mass fraction) H3PO4 solution for 16 h to obtain fully demine-ralized dentin collagen. The twenty dentin discs were then randomly divided into five groups. The control group was untreated while the four experimental groups were treated by plasma jet with gas temperature of 4 ℃ for different times (20 s, 30 s, 40 s, and 50 s). The structure and crosslinking degree of dentin collagen were characterized by attenuated total reflection-Fourier transform infrared spectroscopy. The surface morphology of demineralized dentin was observed by scanning electron microscope, and the microstructure was observed by transmission electron microscope. (2) Fourty non-caries third molars were collected to prepare 5 g fine dentin powder, then completely demineralized with 10% H3PO4 solution. The control group was untreated, while the four experimental groups were treated by plasma jet for 20 s, 30 s, 40 s and 50 s. The crosslinking degree of each group was determined by ninhydrin colorimetric method. (3) Forty intact third molars were collected to obtain dentin strips. Only two central symmetrical dentin strips (nasty 80) were taken from each tooth and immersed in 10% H3PO4 solution for 16 h to obtain fully demineralized dentin collagen. Eighty dentine collagen fiber strips were randomly divided into five groups. The control group was untreated and the axial surfaces of dentin collagen fiber strips in the expe-rimental groups were treated with the plasma jet for 20 s, 30 s, 40 s and 50 s. The ultimate tensile strength of dentin was measured by universal mechanical machine. RESULTS: (1) The surface morphology of demineralized dentin observed by scanning electron microscope showed that the network structure of collagen fibers on the surface of demineralized dentin treated with the plasma jet for 20 s, 30 s and 40 s could maintain the uncollapsed three-dimensional structure, and part of the microstructure was destroyed after plasma jet treated for 50 s. After being treated by plasma jet for 20 s, 30 s and 40 s, the three-dimensional structure was uncollapsed, and the typical periodic transverse pattern of natural type Ⅰ collagen fiber could be seen. The results of infrared spectra showed that the secondary conformation of dentin collagen fibers was the same as that of the control group after being treated with the plasma jet, and the intensity of amide band was significantly increased after being treated for 30 s and 40 s. (2) The results of ninhydrin crosslinking test showed that the crosslinking ratio of dentin collagen treated by plasma jet for 30 s and 40 s was the highest, and the difference was statistically significant (P < 0.05). (3) The results of dentin ultimate tensile strength showed that the control group was (1.67±0.24) MPa, and the plasma jet treated 20 s, 30 s, 40 s and 50 s groups were (4.21±0.15) MPa, (7.06±0.30) MPa, (7.32±0.27) MPa, and (6.87±0.17) MPa, which were significantly different from that of the control group (P < 0.05). CONCLUSION: The novel RF-APGD plasma jet treatment can promote the crosslinking degree of demineralized dentin collagen and improve their ultimate tensile strength.

[Effect of high-fat diet on respiratory function and diaphragm fibers in mice and its mitochondrial mechanism].

Objective: To investigate the effect of high-fat diet (HFD) on respiratory function and its mitochondrial mechanism in mice. Methods: Twenty 4-week-old healthy male C57BL/6 mice were divided by simple random grouping into two groups, 10 mice for each group. Mice were raised with normal diet (NFD) and HFD for 16 weeks, respectively, and weighed once every two weeks. At the end of the intervention, respiratory parameters were measured by whole-body plethysomography, serum and diaphragm tissue lipid species were measured, diaphragm tissue was stained to observe diaphragmmatic morphology, muscle fiber phenotype and mitochondrial ultrastructure. Real-time fluorescence quantitative PCR and immunoblotting were used to detect myosin heavy chain(MHC) and mitochondrial dynamics-related genes and protein expression. Results: The baseline body weights of NFD and HFD mice were (19.17±0.59) and (19.12±0.64) g, respectively, with no statistically significant differences (P=0.857). After 16 weeks of feeding, the body weight of mice in the HFD group was (41.28±2.21) g, which was higher than NFD group [(27.14±0.53) g, P<0.001]. The peak inspiratory flow rate, tidal volume and minute ventilation of mice in the HFD group were (5.72±0.64) ml/s, (0.23±0.04) ml and (97.49±21.68) ml, respectively, which were lower than NFD group [(7.70±1.52) ml/s, (0.31±0.07) ml and (129.99±28.87) ml, respectively, all P values<0.05]. Penh value was 1.16±0.07, which was higher than NFD group (0.98±0.09, P<0.001). The diaphragmatic triglyceride content of mice in the HFD group was (20.43±6.36) mmol/mg, which was higher than NFD group [(11.62±1.78) mmol/mg] (P=0.003), and lipid droplets were deposited in the diaphragm fibers. The percentage of MHC-Ⅰ muscle fibers in the diaphragm of mice in the HFD group was 13.33%±2.95%, which was lower than NFD group (19.20%±1.23%, P=0.034). The mitochondria of the diaphragm in the NFD group were arranged in rows with clear structures, while in the HFD group showed swelling, cristae breakage and vacuoles. The relative expression level of mitochondrial fusion protein 2 in the diaphragm of the HFD group was 0.61±0.16, which was lower than NFD group (1.28±0.03, P<0.001); the relative expression of mitochondrial dynamin-related protein 1 were 1.18±0.06 and 0.91±0.11, respectively, both higher than NFD group (0.61±0.07 and 0.60±0.04, respectively, P<0.001). Conclusion: HFD impairs respiratory function in mice by the mechanism associated with the MHC-Ⅰ muscle fibers decrease and the mitochondrial dynamics imbalance of diaphragm.

STAT1-induced upregulation of lncRNA LINP1 promotes cell proliferation and inhibits apoptosis via AMPK signaling pathway in papillary thyroid cancer.

OBJECTIVE: The purpose of this study was to detect the relative expression of long non-coding ribonucleic acid (lncRNA) in non-homologous end joining pathway 1 (LINP1) in papillary thyroid cancer (PTC) tissues and cells, and to investigate the molecular mechanisms of abnormal expression and biological function of LINP1. PATIENTS AND METHODS: The relative expression of LINP1 in PTC tissues and cells was detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR), and the impact of small interfering (si)-LINP1 on the proliferative capacity of PTC cells was studied using Cell Counting Kit-8 (CCK-8) and colony formation assays. After the expression of LINP1 in PTC cells was interfered, flow cytometry was applied to determine the changes in cell cycle distribution and apoptosis rate. The transcription factors binding to the promoter region of LINP1 were predicted by bioinformatics. Next, qRT-PCR assay was adopted to measure the changes in LINP1 expression after interference in the expression of signal transducer and activator of transcription 1 (STAT1). Finally, the changes in the expressions of molecular markers of the adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling pathway were examined via Western blotting assay after the expressions of STAT1 and LINP1 were interfered. RESULTS: It was shown in qRT-PCR results that LINP1 expression was upregulated in 42 out of 53 cases of PTC tissues and in all PTC cells. After interference in the expression of LINP1 in PTC cells, the results of CCK-8 and colony formation assays indicated that the proliferative capacity of the cells was repressed. According to the results of flow cytometry, the cell cycle was arrested at the G1/G0 phase, and the apoptosis rate was increased. In addition, the bioinformatics predicted that STAT1 could bind to the promoter region of LINP1, and the results of qRT-PCR indicated that the expression of LINP1 declined after STAT1 expression was interfered. Moreover, it was indicated in the Western blotting assay after interference in the expressions of STAT1 and LINP1 that the expression of molecular marker (Phosphorylation AMPK, p-AMPK) of the AMPK signaling pathway was altered but the expression of total AMPK did not change. CONCLUSIONS: The transcription factor STAT1 promotes the expression of LINP1 in PTC, and highly expressed LINP1 facilitates the proliferation and inhibits the apoptosis of PTC by suppressing the AMPK signaling pathway.

FBW7 inhibits nucleus pulposus cells proliferation by downregulation of cyclin E in the intervertebral disc degeneration.

The article "FBW7 inhibits nucleus pulposus cells proliferation by downregulation of cyclin E in the intervertebral disc degeneration, by J.-W. Xu, J. Wang, K. Yang, S. Guo, C.-S. Feng, H.-Y. Chen, H.-P. Li, published in Eur Rev Med Pharmacol Sci 2020; 24(2):508-516. DOI: 10.26355/eurrev_202001_20026. PMID: 32016952" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause.

[Efficacy and safety of oral pyrotinib in HER2 positive metastatic breast cancer: real-world practice].

OBJECTIVE: Pyrotinib, a novel irreversible pan-ErbB receptor tyrosine kinase inhibitor, showed promising antitumor activity and acceptable tolerability in phase II and phase III randomized clinical trials. We assessed the activity and safety of oral pyrotinib for human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer patients in the real world. METHODS: We retrospectively analyzed 72 HER2 positive metastatic breast cancer (MBC) patients who received oral pyrotinib based regimens at Beijing Cancer Hospital and other four hospitals (Peking University First Hospital, China-Japan Friendship Hospital, General Hospital of PLA, Peking University Third Hospital) from August 2018 to September 2019. Progression free survival (PFS), objective response rate (ORR), adverse events (AE) of pyrotinib were investigated. RESULTS: Seventy-two patients with HER2 positive MBC were enrolled. The median age of the patients was 55 years (range: 32-79 years). Sixty-nine (95.8%) patients had received anti-HER2 treatment in the metastatic and/or (neo) adjuvant settings; 61 (84.7%) patients had received anti-HER2 treatments in the metastatic setting in terms of trastuzumab 56 (77.8%) patients, lapatinib 36 (50.0%) patients, and T-DM1 4 (5.6%) patients. Among these 72 patients who received oral pyrotinib based regimens, 62 (86.1%) patients received pyrotinib (±trastuzumab) in combination with chemotherapy, 6 (8.3%) patients received pyrotinib (± trastuzumab) in combination with endocrine therapy and 4 (5.6%) patients received pyrotinib (±trastuzumab). Sixty-five (90.3%) patients received 400 mg pyrotinib once daily as initial dose, and 7 (9.7%) patients received 320 mg. OBJECTIVE response and safety to pyrotinib based therapy were evaluable in all the 72 patients. One (1.4%) patient achieved complete response (CR), 18 (25.0%) patients achieved partial response (PR), 41 (56.9%) patients had stable disease (SD), and 12 (16.7%) patients had progressive disease (PD). The ORR (CR+PR) was 26.4% and the median PFS was 7.6 months (95%CI: 5.5-9.7 months). Among the 36 patients with prior lapatinib therapy, the median PFS was 7.9 months (95%CI: 4.1-11.7 months). Among the 15 patients with brain metastasis, the median PFS was 6.0 months (95%CI: 2.2-9.8 months). The main toxicities related to pyrotinib were diarrhea in 57 (79.2%) cases, and 48 (66.7%) cases with grade 1-2 as well as 9 (12.5%) cases with grade 3. CONCLUSION: Pyrotinib based therapy is an effective treatment for patients with HER2 positive MBC, including patients with lapatinib treatment failure and brain metastasis, and the toxicities can be tolerated.

FBW7 inhibits nucleus pulposus cells proliferation by downregulation of cyclin E in the intervertebral disc degeneration.

OBJECTIVE: TF-box and WD repeat domain-containing 7 (FBW7), a component of SCF ubiquitin ligase complex, usually acts as a tumor suppressor because it has an ability in the inhibition of cell proliferation. Nevertheless, the role of FBW7 in intervertebral disc degeneration (IDD) is not quite understood. MATERIALS AND METHODS: The total protein and RNA were isolated from patients' disc tissues. WB was carried out to analyze the collagen II and FBW7 protein levels of different Pfirrmann grades disc degeneration. Reverse transcription-polymerase chain reaction (RT-PCR) was used to test the collagen II and FBW7 mRNA expression in these disc samples. NP cells were transfected with siRNA-FWB7 to downregulate the FBW7 expression. SiRNA-NC was used as the sham group. Cyclin E, E2F1, and E2F2 were analyzed with WB and RT-PCR. RESULTS: In this study, different kinds of degenerated disc tissues were analyzed, and it was found that FBW7 was overexpressed in much severe degeneration condition, which was also proved by the IL-1ß stimuli nucleus pulposus (NP) cells degeneration model in vitro. Interestingly, the results showed that FBW7 suppression could reverse the degeneration of NP cells. Furthermore, we found that FBW7 induced NP cell cycle arrest in the G1 phase of and inhibited cell proliferation by upregulating p27 expression in vitro. The overexpression of p27 resulted in the inhibition of cyclin E, which promotes cell proliferation. CONCLUSIONS: Taken together, our study uncovered that FBW7 played an essential inhibitory role in NP cells proliferation, providing new insights that FBW7 may be a potential strategy for IDD treatments.

Long noncoding RNA SNHG14 accelerates cell proliferation, migration, invasion and suppresses apoptosis in colorectal cancer cells by targeting miR-944/KRAS axis through PI3K/AKT pathway.

OBJECTIVE: Colorectal cancer (CRC) is a gastrointestinal tract cancer, which threatens the well-being of million of patients due to high metastasis. Recently, numerous studies have recognized nuclear RNA host gene 14 (SNHG14) as a remarkable oncogene in different cancers. However, the regulatory mechanism of SNHG14 in CRC development is mostly unclear. PATIENTS AND METHODS: The expression of SNHG14, miR-944 and Kirsten rat sarcoma (KRAS) in tissues and cells was measured by quantitative Real-time polymerase chain reaction (qRT-PCR). Cell viability and apoptosis were evaluated by cell counting kit-8 (CCK-8) and flow cytometry assay, respectively. Cell migration and invasion were assessed using transwell assay. Protein expression of KRAS, AKT, phosphorylated AKT (p-AKT), phosphatidylinositol-3-kinase (PI3K) and phosphorylated PI3K (p-PI3K) was detected by Western blot. Animal models were constructed by subcutaneously injecting SW620 cells stably transfected with sh-SNHG14 and sh-NC. The interaction among SNHG14, miR-944 and KRAS was determined by luciferase reporter assay and RIP assay. RESULTS: The expression of SNHG14 and KRAS was up-regulated whereas miR-944 was down-regulated in CRC tumors and cells compared with normal tissues and cells. In addition, SNHG14 silencing attenuated cell proliferation, migration and invasion, while accelerated apoptosis in CRC cells by suppressing PI3K/AKT pathway. Consistently, SNHG14 knockdown hindered tumor growth in vivo. MiR-944 was a target of SNHG14 and directly targeted KRAS. Moreover, miR-944 inhibitor abrogated silenced SNHG14-mediated inhibition on proliferation, migration and invasion, as well as promotion on apoptosis in CRC cells. Similarly, miR-944 regulated CRC cell progression by targeting KRAS through PI3K/AKT pathway. CONCLUSIONS: SNHG14 contributed to cell proliferation, migration and invasion, while suppressed apoptosis in CRC cells by targeting miR-944/KRAS axis through PI3K/AKT pathway, representing novel biomarkers for CRC therapy.

[Effect of different plasma treated zirconia on the adhensive behaviour of human gingival fibroblasts].

OBJECTIVE: To evaluate the effect of different cold atmospheric plasma (CAP) treatment on the surface chemical and physical properties of zirconia and adhensive behaviour of human gingival fibroblasts (HGFs) cultured on zirconia disks. METHODS: The zirconia disks were divided into four groups and treated using helium, argon and mixture of argon and oxygen cold atmospheric plasma for 90 s or left untreated. The surface morphology, wettability and chemical elements were analyzed right after treatment. Human gingival fibroblasts were grown from biopsies obtained from a periodontally healthy human subject during periodontal surgery. HGFs were seeded on zirconia disk, and cells density was measured at the time point of 3 hours. Indirect immunofluorescence (IIF) was performed for morphometric examination at the time point of 3 hours. RESULTS: The crystallographic structure of zirconia was analyzed previously and the results suggested that it fitted the properties of zirconium yttrium oxide. After helium, argon and mixture of argon and oxygen cold atmospheric plasma treatment, the surface morphology and roughness of zirconia disks remained the same. The contact angle of zirconia decreased significantly(P<0.05)after CAP treatment: from 68.38° to 17.90°. After different CAP plasmas treatment, the atomic percentage of carbon on the outermost surface of the three groups decreased, as did the surface C/O ratio. The surface C/O ratio of zirconia decreased from 1.07 to 0.33. Fibroblasts density increased on CAP treated disks, especially the ones treated by mixture of argon and oxygen CAP(P<0.05). Cells of the three CAP plasma treatment groups spread better and had more protrusions, as well as larger surficial areas. CONCLUSION: Based on the results of this study after being treated by different kinds of CAP plasmas for 90 s, the surface wettability increased and the elements changed significantly with no changes in the tomography and roughness of the materials. The CAP treatment enhances the adhensive behavior of fibroblasts on zirconia by increasing the oxygen functional groups and promoting the cell density. Wettability of zirconia, an important physicochemical property, has a vital influence on the cell behaviors.

[Effect of a novel cold atmospheric plasma jet treatment with different temperatures on resin-dentin bonding].

OBJECTIVE: To investigate the effect of different treatment temperatures of a novel cold atmospheric plasma jet treatment on the resin-dentin bonding. METHODS: (1) Fifty-two freshly extracted, non-carious and intact third molars were collected. The occlusal one-third of the crown was removed by means of a water-cooled low-speed Isomet saw. One dentin disc [(900 ±100) µm] was prepared for each tooth. The fifty-two dentin discs were randomly divided into control group and experimental groups, of which four were in control group, and forty-eight were divided into four experimental groups according to the different treatment temperatures (4 °C, 10 °C, 20 °C and 30 °C) of the novel radio-frequency atmospheric-pressure glow discharge (RF-APGD) plasma jet, twelve in each group. Each experimental group was divided into three subgroups according to different treatment time (10 s, 20 s and 30 s), with four in each subgroup. The occlusal one-third of the crown was removed by means of a water-cooled low-speed Isomet saw. The morphology of demineralized dentin surfaces was analyzed using field emission scanning electron microscopy. (2) Twenty unerupted, non-carious and intact third molars were randomly divided into five groups, four in each group: control group, untreated; 4 °C, 10 °C, 20 °C and 30 °C experimental groups, each group was treated with the RF-APGD plasma jet for 20 s. The micro-tensile resin dentin bond strength was tested after 20 s RF-APGD plasma jet treatment with different temperatures, using a universal mechanical machine. RESULTS: (1) The field emission scanning electron microscopy results indicated that when compared with the control group, a 10 s RF-APGD plasma jet treatment with 30 °C and 20 °C collapsed the collagen scaffold. Collagen fibrils maintained an uncollapsed three-dimensional structure after the 4 °C RF-APGD plasma jet treatment for even 30 s treatment. (2) The microtensile resin dentin bond strength results of the 4 °C RF-APGD plasma jet treatment group (57.8±0.7) MPa were significantly higher than that of the control group [(47.4±0.5) MPa] and 10 s, 20 s and 30 s RF-APGD plasma treatment group [(51.9±0.7) MPa,(29.7±1.0) MPa and (22.2±1.5) MPa] with statistically significant difference (P<0.05). Compared with the control group, the micro-tensile bond strength increased about 21.9% and 9.5% after 4 °C and 10 °C RF-APGD plasma jet treatment, respectively. CONCLUSION: Compared with other treatment temperatures, this novel RF-APGD plasma jet treatment with the temperature of 4 °C can preserve the three-dimensional morphology of demineralized dentin better, and can improve the resin-dentin bonding.

[Transmission cluster and network of HIV-1 CRF01_AE strain in China, 1996-2014].

Objective: To understand the transmission patterns and risk factors of HIV-1 strain CRF01_AE subtypes in China, and to provide guidance for the implementation of precise intervention. Methods: A total of 2 094 CRF01_AE pol sequences were collected in 19 provinces in China between 1996 and 2014. Phylogenetic tree was constructed by PhyML 3.0 software to select the transmission clusters. Transmission network was constructed by Cytoscape 3.6.0, which was further used for exploring of the major risk factors. Results: Of the 2 094 sequences, 12.18% (255/2 094) were in clusters. A total of 82 transmission clusters were identified. The numbers of clusters and contained sequences in intra-provincial transmission (61, 173) were significantly more than those in inter-provincial transmission (21, 82). The ratio of transmission clustering in MSM increased over time from 2.41% (2/83) during 1996-2008 to 23.61% (72/305) during 2013-2014, showing a significant upward trend (χ(2)=27.800, df=1, P=0.000). The proportion of MSM with inter-provincial transmission clusters were higher than those with intra-provincial transmission clusters, which increased from 0.67% (2/297) during 1996-2008 to 6.36%(30/472) during 2013-2014, showing a significant upward trend (χ(2)=20.276, df=1, P=0.000). The transmission rate in homosexuals of the inter-transmission clusters (86.59%, 71/82) was higher than that of intra-provincial transmission clusters (56.65%, 98/173), and the difference was statistically significant (χ(2)=22.792, P=0.000). The proportion of inter-provincial transmission clusters with more than 2 transmission routes (33.33%, 7/21) was higher than that of intra-provincial clusters (13.11%, 8/61), and the difference was statistically significant (χ(2)=4.273, P=0.039). Results from the transmission network analysis indicated that the proportion of high risk population (degree≥4) with inter-provincial transmission clusters (51.22%, 42/82) was significantly higher than that with intra-provincial transmission clusters (26.59%, 46/173), and the difference was statistically significant (χ(2)=14.932, P=0.000). Inter-provincial clusters were mainly detected in and and MSM. Conclusions: Complex transmission networks were found for HIV-1 CRF01_AE strains in the mainland of China. Inter-provincial transmission clusters increased rapidly, MSM played an important role in the wide spread of the strain. More researches in transmission networks are needed to guide the precision intervention.

[The role of prophylactic use of pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF) in breast cancer receiving adjuvant chemotherapy].

Objectives: To investigate the efficacy and safety of prophylactic use of pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF) in breast cancer receiving docetaxel as adjuvant chemotherapy. Methods: A total of 58 patients with breast cancer receiving adjuvant chemotherapy with docetaxel were included between January 2014 to October 2017. Prophylactic use of PEG-rhG-CSF was administered.Patients were further divided into two groups according to the frequency of PEG-rhG-CSF use: frequent use group (≥3 cycles) and non-frequent use group (<3 cycles). Results: There were significant differences in the incidence rates of grade 3/4 neutropenia between the prophylactic group and non-prophylactic group in cycle 1-3(P<0.05). Less febrile neutropenia (FN) was also noted in the prophylactic group compared with the non-prophylactic group in cycle 1 and cycle 3 (P<0.05). Grade 3/4 neutropenia and FN were less in the frequent use of group compared with the non-frequent use group(P<0.001). The most common side effects of PEG-rhG-CSF included fatigue (10.2%), bone joint pain(50.8%), and 2 patients (3.4%) refused further treatment because of bone joint pain. Conclusions: PEG-rhG-CSF should be prophylactically used for preventing neutropenia and febrile neutropenia in breast cancer patients receiving adjuvant chemotherapy with docetaxel regimen.