Recent researches indicated that cyclooxygena se -2 (COX-2) expression was related not only to development of breast cancer but also to clinicopathological parameters and prognosis of advanced breast cancer. The preclinical and clinical studies on the use of selective COX-2 inhibitors f or the prevention and treatment of breast cancer have become the focus of invest igation.

Purpose:To investigate the prognostic factors for breast cancer patients with liver involvement.Methods:114 breast cancer patients with liver metastases,who were hospitalized in Fudan University Cancer Hospital between January,1996 and December,2003,were included in this study.Their survival data were analyzed.Results:The response rates with first-,second-,third-,fourth-line chemotherapy were 31.9%,27.8%,16.7% and 0%,respectively.Univariate analyses indicated that patients with impaired liver function and patients with a short interval between surgery and the first recurrence or metastasis had a poor prognosis.Multivariate analyses suggested that the presence of liver function impairment was an independent prognostic factor for overall survival.Conclusions:The response rates of chemotherapy drop with number of lines of chemotherapy.Breast cancer patients with liver involvement and impaired liver function have a poor prognosis.

Mutation, translocation and loss of some genes have been known to contribute to chemoresistance, epigenetic mechanisms may also play an important role. About 29 000 CpG islands are primarily distributed in the promoter and the first exon regions of protein coding genes in normal cells. However, cancer cells exhibit significant changes in terms of DNA methylation, which can be summarized as global hypomethylation of the genome accompanied by focal hypermethylation. The relationship between aberrant methylation of gene in the promoter and chemoresistance was discussed in the review. A brief summary was also introduced with regard to the advances how in reversing aberrant methylation and overcoming chemoresistance.

Objective To investigate the clinical characteristics of 31 patients suffering from ANCA associated vasculitis(AAV).Methods The clinical data of 31 patients with ANCA positive profiles diagnosed as AAV were analyzed,including ANCA spectrum,renal and other organs' clinical features.Results There were 16 males and 15 females,average admission age(54.19?20.00)years(18 to 84 years).Totally 27 MPA and 4 WG were diagnosed;onset symptoms of renal involvement were in 15 cases and others in 16 cases;18 patients had respiratory system involvements including 8 cases with pulmonary hemorrhage.In admission 27 MPA patients with average SCr(460.42?354.55)?mol/L,and WG group with(659.62?535.1)?mol/L.ANCA spectrum showed 24 P-ANCA cases and 7 C-ANCA cases,while ELISA method showed 25 anti-MPO cases and 6 anti-PR3 cases.Conclusion AAV has many kinds of manifestations and progresses in many variable ways.Kidney and respiratory system are most vulnerable in AAV.The treatment is very limited in advanced stage of AAV.The key to improving the outcome of AAV is early detection of ANCA and early diagnosis.

Sall4, a member of sall4 gene family, plays important roles in embryo development; organogenesis as well as pluripotency maintenance and re-establishment. There are two isoforms of Sall4, Sall4A and Sall4B. The sequence of porcine sall4 gene is still not reported. Because of its distinct role in maintaining the pluripotent state of stem cells, we cloned and sequenced porcine sall4 gene and assessed its expression in pig tissues and embryos. One 2 372 bp nucleotide sequence representing the full-length cDNA of pig sall4 was obtained by 5'and 3'RACE. Analyses of putative protein sequence showed a 70% to 80% identity with isoform Sall4B of human and mouse. Comparing with Sall4A, the identity reduced to 30% to 55% because of the loss of a zinc-finger domain-rich fragment. Assessment of sall4b expression in porcine tissues by Real-time PCR showed that it expressed most strongly in ovary and stronger in spleen, lung, heart and testis. For preimplantation embryos, the expression level was lower in 4-cell embryos compared with other stages. Immuno-fluorescence analysis of Sall4 on porcine preimplantation embryos indicated that it expressed in all the preimplantation embryos and located in nucleus, in blastocyst it preferentially limited in ICM cells. Expression pattern in early embryos suggest that pig sall4b is associated with pluripotency and might be a new and useful reprogramming factor for establishing pig induced pluripotent stem cell lines.
Amino Acid Sequence ; Animals ; Base Sequence ; Cloning, Molecular ; DNA-Binding Proteins ; genetics ; Embryonic Development ; genetics ; Female ; Gene Expression Regulation, Developmental ; Humans ; Mice ; Molecular Sequence Data ; Ovary ; metabolism ; Swine ; embryology ; genetics ; metabolism ; Transcription Factors ; genetics ; Transcription, Genetic ; physiology

Objective:To evaluate the clinical efficacy of intermediate frequency pulse electrical stimulation combined with TCM directional drug penetration therapy in the treatment of patients with lumbar spinal stenosis.Methods:Randomized controlled trial. Totally 90 patients with lumbar spinal stenosis who were treated between July 2018 and December 2021 in the hospital were selected according to randomized controlled trial design, and they were divided into the two groups through the random number table method, with 45 cases in each group. The control group was given non-steroidal anti-inflammatory drugs+conventional intermittent traction + intermediate frequency pulse electrical stimulation, and the combined group was treated with TCM directional drug penetration therapy on the basis of the control group. Both groups were continuously treated for 1 month. The TCM syndromes were scored before and after treatment, and Visual Analogue Scale (VAS) was used to evaluate the pain degree. Japanese Orthopedic Association (JOA) and Oswestry Disability Index (ODI) were applied to assess the dysfunction degree and quality of life, and the clinical efficacy was assessed.Results:The total effective rate was 95.56% (43/45) in combined group and was 82.22% (37/45) in control group, with statistical significance ( χ2=4.05, P=0.044). The scores of lumbago pain, articular soreness, knee soreness and weakness and impaired activity and total score in combined group after treatment were lower than those in the control group ( t=18.40, 15.81, 15.40, 26.50, 59.575, P<0.01), and the JOA score was higher than that of the control group ( t=5.62, P<0.01), while the ODI score was lower than that of the control group ( t=9.43, P<0.01). The time-point effect and between-group effect of VAS score in combined group were lower than those in the control group with the extension of time ( F=240.00, 17.19, P<0.01), and there was an interaction effect between decrease and treatment method ( F=6.66, P<0.01). Conclusion:Intermediate frequency pulse electrical stimulation combined with TCM directional drug penetration therapy is helpful to relieve the pain, improve the lumbar dysfunction degree and enhance the quality of life and clinical efficacy in patients with lumbar spinal stenosis.

Objective:Evaluation of the effectiveness of domestic ultrapulsed thulium laser ablation of isolated porcine kidneys.Methods:Forty-two fresh porcine kidneys were taken. One porcine kidney was dissected along the sagittal plane at the renal hilum, and then dissected along the coronal plane and divided into four pieces.A total of 168 pieces of renal tissues were obtained, of which 162 pieces were selected for the domestic hyperpulsed thulium laser ablation of isolated porcine kidneys using the single-needle method and the double-needle method, respectively. The ablation was carried out with different ablation modes (single-needle and double-needle methods), ablation power (4, 5, and 6 W), ablation modes (continuous, low-energy and high-frequency mode, and high-energy and low-frequency mode), and ablation time (10, 15, and 20 s). The size of the ablation area in terms of the long diameter, the short diameter, and the thick diameter were measured and recorded. The embedded tissues were sectioned and stained with HE to study the microscopic pathological characteristics of the ablation foci. The ablation foci volume and sphericity coefficient (Φ) were calculated, and the ablation foci volume and sphericity coefficient were statistically analyzed by analytic factorial design and one-way ANOVA.Results:The gross specimen showed that the single-needle ablation foci were elliptical in shape, containing black carbonized areas and gray-white necrotic areas with clear boundaries, and the peripheral renal tissues were pink, and the ablation focus was clearly demarcated from the normal tissues. The double-needle ablation foci were a large ellipse containing two small ellipse ablation foci, and the structure was similar to that of the single-needle method. Under the light microscope, the center of the ablation focus was a "cavity-like" carbonized area, outside of which was an area of coagulation necrosis, with deepened cell staining, reduced cell volume, disorganized arrangement, loose nuclei, nuclear consolidation, and some cell nuclei were cleaved and ablated. Ablation mode ( P<0.001), ablation pattern ( P <0.001), ablation time ( P <0.001), and ablation power ( P <0.001) all significantly affected ablation focus volume. The volume of the ablation foci increased with increasing number of needle feeds, longer ablation time, higher ablation power, and with the ablation mode being continuous mode. Single-needle ablation produced the largest volume of ablation foci (259.56 mm 3) in continuous mode, ablation time of 20 s, and ablation power of 6 W. Double-needle ablation produced the largest volume of ablation foci (452.00 mm 3) in continuous mode, ablation time of 20 s, and ablation power of 6 W. The analysis of the sphericity coefficient showed that in single-needle ablation, the sphericity coefficient was the largest (Φ=0.76) under the conditions of continuous mode, ablation power of 4 W, and ablation time of 15 s. The sphericity coefficient was the smallest (Φ=0.56) under the conditions of high-energy, low-frequency mode, ablation time of 10 s, and ablation power of 6 W, and the morphology of the ablation foci were more close to ellipsoid shape. When ablated by the double-needle method, the ablation foci morphology was closer to spherical shape (Φ=0.91) under the conditions of continuous mode, ablation time of 10 s, and ablation power of 5 W. The combined main effect and interaction results showed that ablation mode ( P<0.001), ablation pattern ( P<0.001), and ablation power ( P<0.001) significantly affected the sphericity coefficient of the ablation foci, and ablation time did not affect the ablation foci morphology. Conclusions:Domestic ultrapulsed thulium laser ablates isolated porcine kidney tissues with precise effect, the tissue morphology of the unablated area is normal, the thulium laser ablated foci have a definite safe boundary. Choosing double needle method, continuous mode, ablation power 6 W for 20 s, can ablate spherical cancer foci within 1 cm in diameter, which can be used for spherical small kidney cancer ablation. Selecting the single-needle method, high-frequency, low-energy mode and ablation power of 6 W, the ablation foci were similar to the oval volume, and could be used for the ablation of oval small renal cancer. However, this study is only limited to the animal ex vivo model, which needs to be confirmed by further study.

AIM: To investigate the efficacy and safety of dexamethasone versus conbercept in the treatment of diabetic macular edema(DME)with different optical coherence tomography(OCT)subtypes.METHODS: A total of 160 DME patients(160 eyes)admitted to our hospital from January 2021 to March 2023 were prospectively selected, and the patients were randomly divided into dexamethasone intravitreal implant group and conbercept group, with 80 cases(80 eyes)in each group, and DME patients were divided into 51 eyes with serous retinal detachment(SRD), 55 eyes with cystoid macular edema(CME), and 54 eyes with diffuse retinal thickening(DRT)according to OCT characteristics. The best corrected visual acuity(BCVA), central macular thickness(CMT), intraocular pressure and adverse reactions were compared before treatment and at 2, 3 and 6 mo postoperatively.RESULTS: There were differences in BCVA, CMT and intraocular pressure between the two groups at 2, 3 and 6 mo compared with those before operation(all P<0.05). There were differences in BCVA, CMT and intraocular pressure between the dexamethasone intravitreal implant group and the conbercept group in the treatment of patients with different types of DME(all P<0.05). The BCVA of patients with DRT and SRD types in the dexamethasone intravitreal implant group was improved at 3 and 6 mo after treatment compared with that in the conbercept group(all P<0.05). At 6 mo after treatment, the CMT of patients with DRT type in the dexamethasone intravitreal implant group was lower than that in the conbercept group(P<0.05). During the follow-up period, none of the patients experienced adverse events such as cataract exacerbation or retinal detachment.CONCLUSION: Both dexamethasone intravitreal implant and conbercept treatment can improve visual function and macular retinal morphology in patients with different OCT subtypes of DME with good safety, but the dexamethasone intravitreal implant is better than conbercept in the treatment of DRT type.

Gegen Qinlian Decoction (GQD), a traditional Chinese medicine (TCM) formula, has long been used for the treatment of common metabolic diseases, including type 2 diabetes mellitus. However, the main limitation of its wider application is ingredient complexity of this formula. Thus, it is critically important to identify the major active ingredients of GQD and to illustrate mecha-nisms underlying its action. Here, we compared the effects of GQD and berberine, a hypothetical key active pharmaceutical ingredient of GQD, on a diabetic rat model by comprehensive analyses of gut microbiota, short-chain fatty acids, proinflammatory cytokines, and ileum transcriptomics. Our results show that berberine and GQD had similar effects on lowering blood glucose levels, modulating gut microbiota, inducing ileal gene expression, as well as relieving systemic and local inflammation. As expected, both berberine and GQD treatment significantly altered the overall gut microbiota structure and enriched many butyrate-producing bacteria, including Faecalibacterium and Roseburia, thereby attenuating intestinal inflammation and lowering glucose. Levels of short-chain fatty acids in rat feces were also significantly elevated after treatment with ber-berine or GQD. Moreover, concentration of serum proinflammatory cytokines and expression of immune-related genes, including Nfkb1, Stat1, and Ifnrg1, in pancreatic islets were significantly reduced after treatment. Our study demonstrates that the main effects of GQD can be attributed to berberine via modulating gut microbiota. The strategy employed would facilitate further stan-dardization and widespread application of TCM in many diseases.

Activated fibroblasts and M2-polarized macrophages may contribute to the progression of pulmonary fibrosis by forming a positive feedback loop. This study was aimed to investigate whether fibroblasts and macrophages form this loop by secreting SDF-1 and TGF-β and the impacts of neotuberostemonine (NTS) and tuberostemonine (TS). Mice were intratracheally injected with 3 U·kg^-1 bleomycin and orally administered with 30 mg·kg^-1 NTS or TS. Primary pulmonary fibroblasts (PFBs) and MH-S cells (alveolar macrophages) were used in vitro. The animal experiments showed that NTS and TS improved fibrosis related indicators, inhibited fibroblast activation and macrophage M2 polarization, and reduced the levels of TGF-β and SDF-1 in alveolar lavage fluid. Cell experiments showed that TGF-β1 may activated fibroblasts into myofibroblasts secreting SDF-1 by activating the PI3K/AKT/HIF-1α and PI3K/PAK/RAF/ERK/HIF-1α pathways. It was also found for the first time that SDF-1 was able to directly polarize macrophages into M2 phenotype secreting TGF-β through the same pathways as mentioned above. Moreover, the results of the cell coculture confirmed that fibroblasts and macrophages actually developed a feedback loop to promote fibrosis, and the secretion of TGF-β and SDF-1 was crucial for maintaining this loop. NTS and TS may disturb this loop through inhibiting both the PI3K/AKT/HIF-1α and PI3K/PAK/RAF/ERK/HIF-1α pathways to improve pulmonary fibrosis. NTS and TS are stereoisomeric alkaloids with pyrrole[1,2-a]azapine skeleton, and their effect on improving pulmonary fibrosis may be largely attributed to their parent nucleus. Moreover, this study found that inhibition of both the AKT and ERK pathways is essential for maximizing the improvement of pulmonary fibrosis.
Animals ; Mice ; Pulmonary Fibrosis/metabolism* ; Transforming Growth Factor beta/pharmacology* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; MAP Kinase Signaling System ; Alkaloids/pharmacology* ; Fibroblasts ; Macrophages/metabolism*