The global myopia epidemic presents a significant public health challenge, necessitating diverse intervention strategies. The primary objective of myopia management is to achieve a dual therapeutic effect: providing children with clear, comfortable, and sustained vision, while also curbing rapid myopic progression to prevent high myopia. Optical interventions based on the theory of peripheral retinal defocus have become first-line treatments owing to their dual capacity for vision correction and axial elongation control. For children with myopia who show suboptimal response to defocus-based optical interventions, combination therapy has gradually emerged as a new clinical trend. Current combination strategies primarily include defocus-based optical interventions combined with low-concentration atropine, red-light therapy, and vision training, among others. This review summarizes available evidence on these three combination strategies, focusing on clinical efficacy, safety, and underlying mechanisms, with the aim of supporting evidence-based and personalized myopia management plans for clinicians.

Objective To investigate the safety and feasibility of en-bloc resection of a primary sacral chordona based on a 3-dimensional printing model.Methods 31 patients with primary sacral chordoma underwent en-bloc resection via a onestage posterior approach or combined anterior and posterior approaches in our oncology department from January 2013 to December 2014.They comprised 21 males and 10 females of mean age (49.2±12.5) years (range,26-67 years).Preoperative 3-D printing models were created by 3D printing technology,it included tumor tissue,the around vascular and nerves involved in sacral chordoma.The sacral chordomas were en-bloc resection with decompression and internal fixation.Results With the mean (29.0±6.8)months follow-up (range from 19 to 41),all patients underwent en bloc excision via 26 cases with posterior approach,5 cases combined posterior and anterior approaches in one stage.The mean operative time and estimated blood loss were (275.0±58.1) min and (3 250.0±1 304.4) ml,respectively.The visual analogue scale (VAS) score was (5.6±1.9) in average (range from 3 to 9) at preoperation,and (2.0±1.5) at post-operation,which was significantly lower than that of preoperation,and the pain was relief obviously.There were 13 cases in grade C,11 cases in grade D,7 cases in grade E of American Spinal Injury Association (ASIA) grade neurological function before surgery,compared with the pre-operation,there were 5 cases in grade C,6 cases in grade D,20 cases in grade E of post-operation,which was significantly improved.MSTS (Musculoskeletal Tumor Society) 93 score was 6-29 points (20.0％-96.7％) at the follow-up 3 months after surgery,with the average of (19.8 ± 5.8) points,which excellent in 8 cases,good in 14 cases,general in 5 cases,poor in 4 cases.Two cases of dysporia for the reasons of resecting on one side of the S1,2 nerve roots involved by the sacral chordoma,after sacrificing the nerve root of complete tumor resection,the urine left dysfunctional,while the pain of other 29 patients were thoroughly relief after surgery.The ones were relieved with the disturbance of sensation of the perineum before the operation.2 cases were recovery of leakage of cerebrospinal by the drainage of lumbar cistern with normal temperature.One hypostatic pneumonia patient was cured by anti-inflammatory.One with the urinary infection got better by the effective bladder irrigation,which had diabetics mellitus with the bladder stoma before.1 case of skin necrosis due to vascular thrombosis before operation,recevied flap translocation half month after surgery,got recovery 3 months later.Only one underwent tumor resection for the recurrence at 15 months follow-up.Conclusion It is feasible and safe to perform en bloc resection of primary sacral chordoma.This is the most effective means of managing method of the marginal resection of the tumor.Preoperative 3-D printing modeling enables better anatomical understanding of the relationship between the tumor,and can avoid vascular and nerves tissue injury,which can also assist in planning the surgical procedure,and be worth recommendation.

Objective To establish docetaxel (Doc) resistant MDA‐MB‐231/Doc model and epirubicin (Epi) resistant MDA‐MB‐231/Epi mode from triple negative breast cancer cell line MDA‐MB‐231 and to explore their biological characteristics .Methods The MDA‐MB‐231/Doc and MDA‐MB‐231/Epi drug‐resistant cell lines were respectively established by gradually increasing Doc or Epi concentrations induction method in 12 months .The biological characteristics of the cell lines were compared by the cell mor‐phological observation ,MTT and flow cytometry ;the real‐time fluorescent quantitative PCR was used to detect multi‐drug resist‐ance gene (MDR1) mRNA expression;the expression of P glycoprotein(P‐gp) ,estrogen receptor (ER) ,progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her‐2) was detected by Western Blot .Results After the 12‐month induction ,the established MDA‐MB‐231/Doc could grow stably in the medium containing 12 nmol/L Doc ,and MDA‐MB‐231/Epi could grow stably in the medium containing 800 nmol/L Epi;in the same drug concentration ,the growth proliferation rate of the drug resistant cell line was significantly higher than that of the parental generation cells ,their drug resistance indexes were 8 .32 times and 64 .93 rimes of parental generation sensitive cells ,moreover which showed the mutual cross drug resistant status .Compared to the parental generation cells ,the cells of stage G1 and G2 in two cell lines were increased and the cells of stage S were decreased ,with the prolon‐gation of drug withdrawal time ,the cell proliferation speed was accelerated .The expression level of MDR1 gene was increased in the two drug‐resistant cell lines ,which were 4 .05 times and 5 .96 times of parental generation cells respectively ,P‐gp protein expression was positive .Compared with the MCF‐7 cell line ,ER ,PR and Her2 expression in the MDA‐MB‐231 cell line was negative and typi‐cal triple negative breast cancer cell line .Conclusion The drug resistance cell lines of MDA‐MB‐231/Doc and MDA‐MB‐231/Epi are successfully established with stable growth and drug resistance .

OBJECTIVETo explore whether docetaxel-resistant cells (MCF-7/Doc) and doxorubicin-resistant cells (MCF-7/ADM) can secrete Exosomes and their potential role in cell-cell drug-resistance transfer.

METHODSExosomes were extracted from the cell culture supernatants of MCF-7/Doc and MCF-7/ADM cells by fractionation ultracentrifugation, and were identified by transmission electron microscopy and Western blot analysis. GFP-MCF-7/S, a breast cancer parental sensitive cell line stably expressing green fluorescent protein (GFP), was constructed by recombinant lentiviral vector with GFP. Then the resistance experiment of cells and the experiment of resistance transfer by exosomes were designed to observe the phenomenon of cell-to-cell drug-resistance transfer.

RESULTSSimilar to the breast cancer parental sensitive cells (MCF-7/S), the breast cancer resistant sublines could secrete exosomes, which exhibited round or elliptic shape ranging from 30 to 100 nm in diameter with intact membrane, and only expressed the protein marker of exosomes, Tsg101, did not express the endoplasmic reticulum marker calnexin. After MCF-7/S, MCF-7/DOC and MCF-7/ADM cells we cocultured with GFP-MCF-7/S cells for 72 h, there were no significant differences in the expression of fluorescence-labeled cells among the four groups. When treated by the drug ADM or DOC for 24 hours, the MCF-7/DOC+GFP-MCF-7/S group was in favor of a significant higher survival rate of fluorescence-labeled cells compared with the MCF-7/S+GFP-MCF-7/S group (65.5% vs. 25.5%, P < 0.001), and so did the MCF-7/ADM+GFP-MCF-7/S group (53.6% vs. 25.4%, P < 0.001). The exosomes extracted from MCF-7/S, MCF-7/DOC and MCF-7/ADM cells were cultured with the GFP-MCF-7/S cells for 48 h. Among these groups, no significant differences in the expression of fluorescence-labeled cells were found. After treated by the drug ADM or DOC for 24 hours, the exosomes extracted from MCF-7/DOC+GFP-MCF-7/S group was associated with a significant higher survival rate of fluorescence-labeled cells compared with the exosomes extracted from MCF-7/S+GFP-MCF-7/S group (59.9% vs. 32.4%, P < 0.001), and so did the exosomes extracted from the MCF-7/ADM)+GFP-MCF-7/S group (58.3% vs. 27.2%, P < 0.001).

CONCLUSIONOur results suggest that drug-resistance can be transferred between breast cancer cells, and exosomes are probably the transporter of the drug resistance.

Antibiotics, Antineoplastic ; pharmacology ; Antineoplastic Agents ; pharmacology ; Cell Survival ; Coculture Techniques ; DNA-Binding Proteins ; metabolism ; Doxorubicin ; pharmacology ; Drug Resistance, Neoplasm ; Endosomal Sorting Complexes Required for Transport ; metabolism ; Exosomes ; metabolism ; pathology ; Green Fluorescent Proteins ; metabolism ; Humans ; MCF-7 Cells ; pathology ; Taxoids ; pharmacology ; Transcription Factors ; metabolism

Objective To summarize our experience on diagnosis and treatment of bilateral primary breast cancer (BPBC). Methods Clinicopathologic records, including clinical manifestations, diagnosis and immunohistochemical expressions of 16 patients with BPBC, treated from 2001 to 2009 in Jiangsu Provincial Cancer Hospital, were analyzed retrospectively. Results The 16 patients with BPBC accounted for 0.47% of all patients diagnosed as malignant tumors of breast during the same period in our hospital. All of the 16 patients were women, with the median age of 53 years (ranged 41-69 years). 7 patients were in bilateral synchronous breast cancer (BSBC), with the median age 47 years (ranged 41-54 years), among whom 5 patients got BSBC just before menopause. 9 patients were in bilateral asynchronous breast cancer (BABC), with the median age 58 years (ranged 43-69 years), among whom 1 patient got BABC before menopause. The median interval between the first and second breast carcinoma of BABC was 52 months (ranged 14-196 months). Conclusions Compared with BABC, the occurrence age of the patients with BSBC was smaller. BABC was more common in premenopausal women. The interval time of BABC was irregular. The active follow-up after the occurrence of contralateral breast cancer and endocrine therapy for estrogen receptor-positive patients were recommended.

Objective To investigate the effect of noggin on BrdU labeled cells in the adult rat hippocampus. Methods The expressions of noggin and bone morphogenetic protein 4 (BMP4) in rat hippocampus were detected using in situ hybridization histochemistry (ISHH) and reverse transcription polymerase chain reaction (RT PCR). By using antisense technique combined with bromodeoxyuridine!(BrdU) labeling, the effect of noggin on hippocampal neurogenesis in adult rats was explored. Results The number of noggin mRNA positive cells in the adult rat hippocampus decreased significantly after treatment with antisense noggin but no change was found in the number of BMP4 mRNA positive cells. In addition, the number of BrdU labeled cells decreased significantly in the adult rat hippocampus after treatment with antisense noggin, but the sense noggin had no such effect. Conclusion Noggin can promote proliferation of neural precursor cells in adult rat hippocampus.

Objective To observe the expression changes of noggin mRNA and BMP4 mRNA in the hippocampus and frontal cortex of rats at different stages. Methods The expressions of noggin mRNA and BMP4 mRNA were analyzed by the method of reverse transcriptase polymerase chain reaction (RT PCR).Results It was revealed that the level of noggin mRNA in the frontal cortex decreased significantly in P1W rats but high level of BMP4 mRNA was detected in P1M and P3M rats. The expressions of noggin mRNA and BMP4 mRNA in the hippocampus showed the opposite expression pattern. The peak of noggin mRNA expression in the hippocampus was found in E13 and E16 rats. The expression of noggin mRNA decreased gradually but that of BMP4 mRNA in hippocampus increased gradually during the developmental stage. The peak of the expression of BMP4 mRNA was found in P1M rats. Conclusion There are expressions of noggin mRNA and BMP4 mRNA in the frontal cortex and hippocampus in rats at different developmental stages. The expression level is closely correlated with the developmental age. This indicates that noggin and BMP4 play important roles in the development of rat frontal cortex and hippocampus.

Objective To examine the expression of Noggin in CNS of the developing rat. Methods In situ hybridization histochemistry(ISHH) was performed using digoxigenin-labeled cRNA as probes. Results It was revealed that densely and deeply stained noggin positive cells were detected in cortex,hippocampus,cerebellum,and nucleus of hypothalamus and thalamus in embryonic day(E)16 rats.The number of noggin positive cells was increased in the thalamus and medulla oblongata at postnatal day(P)1-2,whereas decreased in the hippocampus and cortex.The number of noggin positive cells was decreased significantly in brain at 1 week postnatal(P1W),and began to increase at P2W,especially in the cortex and hippocamps.Strong positive signal can be detected in the frontal cortex,parietal cortex,cingulated cortex,hippocampus,olfactory and cerebellum at 1 month postnatal(P1M).The expression of noggin begins to decline at P3M,only sparse noggin positive cells can be seen in CNS at P18M.Furthermore,there is no noggin positive cells seen in the spinal cord of rats during development.Conclusion Our results indicated that noggin could play an important role in CNS development of rats.