[Efficacy analysis of chemotherapy and endocrine therapy combined with targeted drugs after progression on cyclin-dependent kinase 4/6 inhibitor treatment in hormone receptor positive/human epidermal growth factor receptor 2-low metastatic breast cancer].

Objective: To evaluate the efficacy of chemotherapy and endocrine therapy combined with targeted drugs after progression on cyclin-dependent kinase 4/6 (CDK4/6) inhibitor treatment in hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2)-low metastatic breast cancer. Methods: Patients with metastatic breast cancer diagnosed with HR positive/HER2 low expression at the Fifth Medical Center of PLA General Hospital from October 1, 2018 to September 30, 2023 were retrospectively included. All patients received sequential chemotherapy or sequential endocrine therapy combined with targeted drugs after progression on CDK4/6 inhibitor treatment.The median follow-up was 9 months, and the follow-up ended on October 31, 2023. The patients were divided into chemotherapy group (receiving sequential chemotherapy) and endocrine therapy group (receiving sequential endocrine therapy combined with targeted drugs), according to the treatment plan. Information on demographic data, clinical and pathological diagnosis, treatment regimen, and efficacy evaluation was collected. The basic conditions of patients who may affect the curative effect of different treatment schemes were preset as stratified subgroups, including age, progesterone receptor (PR) status, HER2 status, disease-free survival, number of previous endocrine therapy and chemotherapy, and visceral metastasis. The primary endpoint was progression-free survival (PFS), the secondary endpoints were objective response rate (ORR), clinical benefit rate(CBR) and PFS based on stratification factors. The survival curve was plotted by Kaplan-Meier method, the comparison of PFS between groups was performed by log-rank test, and the comparison of ORR and CBR between groups were performed by χ2 test. Results: A total of 188 patients were included, including 126 patients in the chemotherapy group [all females, aged 29-74 (51±10) years] and 62 patients in the endocrine therapy group [1 male and 61 female, aged 29-77 (51±12) years]. ORR of chemotherapy group was 23.0% (29/126), higher than that of endocrine treatment group [3.2% (2/62)] (P<0.001); The CBR of chemotherapy group and endocrine therapy group were 46.8% (59/126) and 33.9% (21/62), respectively, with no statistical significance (P=0.091). The median PFS of chemotherapy group and endocrine therapy group were 5.0 (95%CI: 4.3-5.7) and 4.0 (95%CI: 1.6-6.4) months, respectively, with no statistical significance (P=0.484). In the preset stratified subgroups, the median PFS of chemotherapy [6.0 (95%CI: 5.4-6.6) months] was longer than that of endocrine combined with targeted therapy [2.0 (95%CI: 1.8-2.2) months] (P<0.001) in PR negative patients; In patients who had progressed on over 2 previous endocrine treatments, the median PFS of chemotherapy [5.0 (95%CI: 3.8-6.2) months] was longer than that of endocrine combined with targeted therapy [2.0 (95%CI: 0.6-3.4) months] (P=0.045). Conclusions: After progression on treatment with CDK4/6 inhibitors for HR-positive/HER2-low expression metastatic breast cancer, both chemotherapy and endocrine therpy combined with targeted drugs are viable treatment options. However, for patients with PR negative or ≥2 lines of endocrine therapy previously, priority should be accorded to chemotherapy.

Characteristics of flight delays during solar flares.

Solar flares are one of the severest solar activities that have important effects on near-Earth space. Previous studies have shown that flight arrival delays increase as a result of solar flares, but the intrinsic mechanism behind this relationship is still unknown. In this study, we conducted a comprehensive analysis of flight departure delays during 57 solar X-ray events by using a huge amount of flight data (~ 5 × 106 records) gathered over a 5-year period. It is found that the average flight departure delay time during solar X-ray events increased by 20.68% (7.67 min) compared to quiet periods. Our analysis also revealed apparent time and latitude dependencies, with flight delays being more serious on the dayside than on the nightside and longer (shorter) delays tending to occur in lower (higher) latitude airports during solar X-ray events. Furthermore, our results suggest that the intensity of solar flares (soft X-ray flux) and the Solar Zenith Angle directly modulate flight departure delay time and delay rate. These results indicate that communication interferences caused by solar flares directly affect flight departure delays. This work expands our conventional understanding of the impacts of solar flares on human society and provides new insights for preventing or coping with flight delays.

Additional flight delays and magnetospheric-ionospheric disturbances during solar storms.

Although the sun is really far away from us, some solar activities could still influence the performance and reliability of space-borne and ground-based technological systems on Earth. Those time-varying conditions in space caused by the sun are also called solar storm or space weather. It is known that aviation activities can be affected during solar storms, but the exact effects of space weather on aviation are still unclear. Especially how the flight delays, the top topic concerned by most people, will be affected by space weather has never been thoroughly researched. By analyzing huge amount of flight data (~ 4 × 106 records), for the first time, we quantitatively investigate the flight delays during space weather events. It is found that compared to the quiet periods, the average arrival delay time and 30-min delay rate during space weather events are significantly increased by 81.34% and 21.45% respectively. The evident negative correlation between the yearly flight regularity rate and the yearly mean total sunspot number during 22 years also confirms such correlation. Further studies show that the flight delay time and delay rate will monotonically increase with the geomagnetic field fluctuations and ionospheric disturbances. These results indicate that the interferences in communication and navigation during space weather events may be the most probable reason accounting for the increased flight delays. The above analyses expand the traditional field of space weather research and could also provide us with brand new views for improving the flight delay predications.

A pilot study on preoperative vascular anatomy and clinical application in rectal cancer resection.

AIM: To assess the utility of preoperatively evaluating the vascular anatomy using multisection spiral computed tomography angiography (CTA) and image fusion technology in the treatment of obese patients undergoing laparoscopic radical resection for rectal cancer. MATERIALS AND METHODS: This randomised prospective study included 56 patients who underwent laparoscopic surgery for rectal cancer. Patients were randomly divided into two groups: the fusion imaging group (preoperative CTA and image fusion reconstruction [n=28]) and the control group (not performed CTA and image fusion reconstruction before the operation [n=28]). Duration of surgery was defined as the primary endpoint, and the volume of bleeding, the number of lymph node dissections, conversion to laparotomy, time to recovery of postoperative flatus, length of hospitalisation as well as perioperative complications were defined as secondary endpoints. RESULTS: Compared with the control group, the duration of surgery in the image fusion group was shorter, bleeding volume was reduced, and the number of lymph node dissections was greater (p<0.05); however, there was no significant differences between the two groups regarding time to postoperative flatus recovery, conversion to laparotomy, length of hospitalisation, and perioperative complications (p>0.05). CONCLUSIONS: Preoperative assessment of the vascular anatomy was an effective method and avoided some invisible risks during surgery, and resulted in a better therapeutic effect.

[Evaluation of papilledema and visual improvement in patients with idiopathic intracranial hypertension after venous sinus stenting].

Objective: To evaluate the improvement of papilledema and visual acuities in patients with idiopathic intracranial hypertension (IIH) after venous sinus stenting. Methods: The clinical data of 8 IIH patients who met the inclusion criteria underwent venous sinus stenting between January 2013 and December 2016 at Department of Neurosurgery, Tianjin Huanhu Hospital were analyzed retrospectively. There were 6 females and 3 males,aged (32.9±14.4)years (range:19 to 57 years).The thickness of the retinal nerve fiber layer (RNFL) was measured by optical coherence tomography. Fundus,visual acuity and visual field examination were performed before and after operation. If pressure gradient ≥10 mmHg(1 mmHg=0.133 kPa) across the venous stenosis was indicated by intraoperative pressure measurement,the patient would be treated with venous sinus stenting. Intracranial pressure was measured by lumbar puncture 3 to 7 days after operation. RNFL thickness and eye examination were detected 6 months after surgery. CT venogram was used to observe the sinus venous conditions. Paired t test was used to compare the data before and after surgery. Results: All the 8 patients underwent venous sinus stenting successfully. The mean pressure gradient across the venous stenosis was reduced from (24±9.2) mmHg to (2.6±2.0) mmHg (t=8.02,P<0.01). Intracranial pressure decreased from preoperative (41.4±12.7) cmH2O(1 cmH2O=0.098 kPa) to postoperative (12.9±3.3) cmH2O (t=7.08, P<0.01). The RNFL thickness decreased from (275.3±68.3)µm to (131.4±31.8)µm(t=5.80,P<0.05) 6 months after surgery and the baseline visual acuity was improved from(M(QR))0.24 (0.25) to 0.65 (0.23)(Z=-2.52,P<0.05).Papilledema was significantly improved in 6 patients,and no significant change in 2 patients. CT venogram indicated adjacent stent restenosis in 1 patient. Conclusion: Venous sinus stenting can effectively improve papilledema and visual acuity caused by IIH.

Gastrodin protects against high glucose-induced cardiomyocyte toxicity via GSK-3ß-mediated nuclear translocation of Nrf2.

Diabetic cardiomyopathy (DCM) is one of the major complications of diabetes that causes mortality and morbidity in diabetic patients. Gastrodin (GSTD) is a bioactive phenolic glucoside component of an ancient Chinese herb Tianma (Gastrodia elata Bl.), which is widely used for cardiovascular and cerebrovascular diseases by ancient Chinese. Up to now, whether GSTD has a beneficial effect on DCM is unclear. Therefore, this study aimed to investigate the effect of GSTD on high glucose-induced injury in H9c2 rat cardiomyocytes and HL-1 mouse cardiomyocytes, and its underlying mechanisms. High glucose (33 mM) treatment caused cardiomyocyte toxicity, oxidative stress and apoptosis in both H9c2 and HL-1 cells. Under both normal (5.5 mM glucose) and high glucose conditions, GSTD showed protective effect against high glucose-induced cytotoxicity and promoted the nuclear translocation of Nrf2 in a concentration and time-dependent manner in H9c2 and HL-1 cells. Knockdown of Nrf2 expression using siRNA specifically targeting Nrf2 attenuated the protective effect of GSTD. Furthermore, GSTD promoted the nuclear translocation of Nrf2 via activating glycogen synthase kinse-3ß (GSK-3ß) signaling pathway. 4-benzyl, 2-methyl, 1, 2, 4-thiadiazolidine, 3, 5 dione (TDZD-8), an inhibitor of GSK-3ß, inhibited the nuclear translocation of Nrf2 induced by GSTD, and attenuated the protective effect of GSTD as Nrf2 knockdown did. In summary, GSTD could protect against high glucose-induced cardiomyocyte toxicity via GSK-3ß-mediated nuclear translocation of Nrf2.

[Phase â ¢ randomized controlled, multicenter, prospective study of recombinant anti-HER2 humanized monoclonal antibody (Cipterbin) combined with vinorelbine in patients with HER2 positive metastatic breast cancer: the HOPES Study].

Objective: To evaluate the clinical efficacy and safety of recombinant anti-HER2 humanized monoclonal antibody (Cipterbin) combined with vinorelbine in patients with HER2 positive metastatic breast cancer. Methods: Patients were randomized 2∶1 to test group and control group. Patients in test group received Cipterbin (4 mg/kg loading dose and 2 mg/kg maintenance dose each week, IV) combined with vinorelbine (25 mg/m(2) on days 1,8 and 15 of each 28 days, IV). Patients in control group received vinorelbine (25 mg/m(2) on days 1,8 and 15 of each 28 days, IV).The primary end point was progression free survival (PFS). Results: A total of 315 patients were enrolled from Jan 2009 to Jan 2013 (212 in test group and 103 in control group). The median PFS of test group was significantly longer than that of control group, 39.1 weeks vs 14.0 weeks (HR=0.24; 95%CI, 0.16-0.36; P<0.000 1). The objective response rate (ORR) and disease control rate (DCR) in test group were significantly higher than those in control group, ORR was 46.7% vs 18.45% (P<0.000 1) and DCR was 79.72% vs 45.63% (P<0.000 1). The incidence of neutropenia, leucopenia and erythrocytopenia were higher in both groups, but there was no significant difference between two groups.The most common adverse events associated with Cipterbin were infusion reactions. Left ventricular ejection fraction reduced to less than 50% in 5 patients, which were recovered. No serious cardiotoxicity. Conclusion: The recombinant anti-HER2 humanized monoclonal antibody (Cipterbin) combined with vinorelbine has significant efficacy and good safety. It is the optimized therapy regime for patients with taxane-pretreated HER2 positive metastatic breast cancer, which provides more targeted therapy opportunities for HER2 positive breast cancer patients in China.

[Evaluating the long-term prognosis of coronary artery disease patients undergoing percutaneous coronary intervention by risk stratification with ACC/AHA classification of coronary lesions].

Objective: To evaluate the long-term prognosis of coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI) by risk stratification with American College of Cardiology (ACC)/American Heart Association (AHA) classification of coronary lesions. Methods: Data used in this study derived from the I-LOVE-IT 2 trial. I-LOVE-IT 2 trial was a prospective, multicenter, randomized, assessor-blinded, noninferiority study. A total of 1 255 patients in I-LOVE-IT 2 trial with only one lesion and underwent biodegradable polymer drug-eluting stent implantation were included and grouped according to ACC/AHA classification of coronary lesions, namely type A/B1 lesion group (n=184), type B2 lesion group (n=457) and type C lesion group (n=614). The primary endpoint was 48-month patient-oriented composite endpoint (PoCE), a composite of all-cause mortality, all myocardial infarction, stroke, and/or any revascularization. The secondary endpoints were target lesion failure (TLF), components of PoCE, major bleeding (bleeding academic research consortium(BARC) type 3-5) and definite/probable stent thrombosis within 48 months. The incidences of endpoint events were compared in the three groups. The multivariable Cox hazard ratio model was used to analyze the independent predictors of PoCE and TLF at 48 months. Results: Incidences of PoCE at 48 months were significantly higher in patients with type C lesion compared with patients with type A/B1 (24.43%(150/614) vs. 14.13%(26/184), P<0.05) or B2 lesion (24.43%(150/614) vs. 15.97%(73/457), P<0.05). The multivariable Cox hazard ratio model showed that the type C lesion were the independent predictors of 48-month PoCE (HR=1.59, 95%CI 1.21-2.08, P<0.001) and TLF (HR=2.31, 95%CI 1.53-3.49, P<0.001). After multivariable adjustment, the HRs of PoCE for patients with type C lesion versus type A/B1 and type B2 were 1.91 (95%CI 1.25-2.92, P=0.003) and 1.64 (95%CI 1.23-2.20, P<0.001), respectively. Meanwhile, the HRs of TLF for patients with type C lesion versus type A/B1 and type B2 were 2.45 (95%CI 1.29-4.64, P=0.006) and 2.55 (95%CI 1.62-4.02, P=0.001), respectively. Conclusions: The ACC/AHA classification of coronary lesions has good discrimination with long-term outcomes for CAD patients undergoing PCI. The type C lesion is associated with a worse prognosis, enough attention should be paid in these patients during routine clinical management.

[Long-term efficacy of a second generation biodegradable polymer sirolimus-eluting stent (EXCEL2) in treating patients with de novo coronary artery diseases].

Objective: To evaluate the long-term efficacy of a second generation biodegradable polymer sirolimus-eluting stent (EXCEL2) in treating patients with de novo coronary artery diseases. Methods: CREDIT Ⅱ trial was a prospective, multicenter, randomized, controlled study, conducted at 15 Chinese cardiac centres from November 2013 to December 2014. In this analysis, eligible patients for coronary stenting (n=419) were randomized to receive either the EXCEL2 stent (n=208) or the EXCEL stent (n=211). The primary endpoint was target lesion failure (TLF) at 3 years after PCI defined as a composite endpoints of cardiac death, target vessel myocardial infarction (TVMI), or clinically indicated target lesion revascularization (CI-TLR). Secondary endpoints included patient-oriented composite endpoint (PoCE) including all-cause death, all MI, or any revascularization at 3 years and independent components, and stent thrombosis according to Academic Research Consortium's (ARC) definition. Results: Among 419 enrolled patients, 413 (98.6%) patients completed 3-year clinical follow-up. Compared with the EXCEL group, 3-year TLF (5.4%(11/204) vs. 11.5% (24/209), P=0.025) and PoCE (9.8% (20/204) vs. 20.1% (42/209), P=0.003) were significantly lower in the EXCEL2 group. The cumulative event rate of CI-TLR (2.0% (4/204) vs. 5.7% (12/209), P=0.042) and any revascularization (4.9% (10/204) vs. 14.4% (30/209), P=0.001) were statistically lower in the EXCEL2 group than in the EXCEL group. There were no significant difference between two groups in terms of all-cause death and all MI. Rates of stent thrombosis were low without significant difference between the two groups (EXCEL2 vs. EXCEL, 1.0% (2/204) vs. 2.9% (6/209), P=0.285). Conclusion: 3-year clinical follow-up results demonstrate that EXCEL2 stents are effective and safe in treating CAD patients with de novo coronary lesions.

[Value of SYNTAX revascularization index on evaluating the long-term prognosis of coronary artery disease patients with biodegradable polymer drug-eluting stents implantation].

Objective: To explore the value of SYNTAX revascularization index (SRI) on evaluating the long-term prognosis of coronary artery disease (CAD) patients implanted with biodegradable polymer drug-eluting stents (BP-DES) and define the best threshold of SRI for predicting all-cause mortality in these patients. Methods: Data used in this study derived from the I-LOVE-IT 2 trial (evaluate safety and effectiveness of the Tivoli DES and the Firebird DES for treatment of coronary). I-LOVE-IT 2 trial was a prospective, multicenter, randomized, assessor-blinded, non-inferiority study. A total of 1 829 patients implanted with BP-DES were divided into 3 groups, namely SRI=100% group (n=963), 50%≤SRI<100% group (n=527) and SRI<50% group (n=339). The primary endpoint was 48-month patient-oriented composite endpoint (PoCE), a composite of all-cause mortality, myocardial infarction(MI), stroke, and/or any revascularization. The secondary endpoints were components of PoCE and definite/probable stent thrombosis at 48 months. The receiver operating characteristic curve was used to investigate the best cut-off point of SRI for 48-month all-cause mortality. The Cox regression analysis was used to identify independent predictors of the all-cause death and PoCE at 48 months. Results: Incidence of PoCE at 48 months was significantly lower in SRI=100% group than patients with 50%≤SRI<100%(17.34% (167/963) vs. 22.20% (117/527), P<0.05) and SRI<50% (17.34% (167/963) vs. 24.78% (84/339), P<0.05). Comparing with SRI=100% group, the patients with 50%≤SRI<100% suffered higher rates of all MI (7.78% (41/527) vs. 4.26% (41/963), P<0.05) and target vessel MI (6.45% (34/527) vs. 4.26% (41/963), P<0.05); patients with SRI<50% had higher rates of all-cause mortality (5.90% (20/339) vs. 3.12% (30/963), P<0.05) and any revascularization (14.16% (48/339) vs. 3.12% (30/963), P<0.05). The receiver operating characteristic curve analysis showed that the SRI=65% was the best cut-off point to predict the all-cause mortality at 48 months (area under the curve was 0.58, sensitive was 0.47, specificity was 0.70). Meanwhile, SRI<65% was an independent predictor of 48-month all-cause mortality (HR=2.06, 95%CI 1.25-3.38) and PoCE (HR=1.34, 95%CI 1.09-1.66). Conclusions: SRI serves as a good index for predicting long-term prognosis and SRI<65% is an independent predictor of 48-month PoCE and all-cause mortality for CAD patients with BP-DES implantation. Meanwhile, SRI≥65% might be a reasonable threshold of incomplete revascularization.

[Comparison of ultrasound-guided serratus anterior plane block and erector spinae plane blockperioperatively in radical mastectomy].

Objective: To compare the perioperative effects of ultrasound-guided serratus anterior plane block (SAPB) and erector spinae plane block (ESPB) in radical mastectomy. Methods: One hundred and fifty patients,undergoing radical mastectomy from May 2016 to Jan 2019,the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, were randomly divided into SAPB group, ESPB group and control group. Patients in SAPB group and ESPB group were received corresponding blocks before induction of general anesthesia. The control group was only received routine general anesthesia without any block. Patient-controlled intravenous analgesia (PCIA) was performed in all the patients postoperatively. The VAS score at rest or coughing and Ramsay score at 2, 4, 8, 12, 24, 48 h after operation were compared among the three groups. The intraoperative dosages of propofol and remifentanil,press times and sufentanil cumulative dosage of PCIA in 48 hours after operation, postoperative rehabilitation indicators and adverse effects were all compared. Results: In all the three groups,the VAS scores at rest and coughing increased first and then decreased 2 h to 48 h after operation. The VAS scores in SAPB group and ESPB group were lower than that in control group (P<0.05), whereas, no significant difference was observed between SAPB group and ESPB group (P>0.05). For Ramsay score, among the three groups, there were no significances of the main effects of group and time point, as well as interaction effect (all P>0.05). The intraoperative dosages of propofol and remifentanil in SAPB group and ESPB group were lower than those in control group (P<0.05), the press times and sufentanil cumulative dosage of PCIA after operation were also lower than those in control group (P<0.05). There was no significant difference in feeding time after operation among the three groups (P>0.05). The times of first anal exhaust, ambulation and hospitalization after operation in ESPB group and SAPB group were significantly shorter than those in control group (P<0.05). However, there was no significant difference between ESPB group and SAPB group in postoperative rehabilitation indicators mentioned above (P>0.05). The incidences of skin itching and nausea in ESPB and SAPB groups were lower than those in control group (P<0.05). There was no difference in the incidence of vomiting among the three groups (P>0.05). Conclusions: Both SAPB and ESPB can provide good and safe analgesia for radical mastectomy,with equivalent performances in analgesia and adverse effect.

Macrophages Promote Growth of Squamous Cancer Independent of T cells.

Oral cancers, primarily squamous cell carcinomas (SCCs), progress either slowly or aggressively. Here we assessed the role of macrophages in SCC behavior. We used mouse SCC cells derived from tumors harboring a KrasG12D activation mutation and Smad4 deletion in keratin 15-positive stem cells and a human oral SCC cell line, FaDu, which has NRAS amplification and SMAD4 deletion. SCC cells were transplanted into immune-compromised or immune-competent (syngeneic) recipients. After tumors were established, we used clodronate liposomes to ablate macrophages. We found that the number of tumor-associated macrophages (TAMs) was not affected by the presence of T cells but differed considerably among tumors derived from different SCC lines. Clodronate significantly reduced TAMs and splenic macrophages, resulting in reduced SCC volumes. Tumors with clodronate treatment did not show decreased proliferation but did exhibit increased apoptosis and reduced vascular density. FLIP (Fas-associated via death domain-like interleukin 1ß-converting enzyme inhibitory protein), an apoptosis inhibitor abundantly produced in tumor cells and TAMs, was reduced in tumor cells of clodronate-treated mice. Reduced FLIP levels correlated with reductions in phosphorylated nuclear NFκB p65 and NFκB inhibitor attenuated FLIP protein levels in SCC cells. Furthermore, TGFß1 serum levels and pSmad3 were reduced in clodronate-treated mice, but their reductions were insufficient to reverse epithelial-mesenchymal transition or TGFß-mediated angiogenesis in endothelial cells. Consequently, metastasis was not significantly reduced by macrophage reduction. However, reduced pSmad3 correlated with reduction of its transcriptional target, vascular endothelial growth factor A, in clodronate-treated tumor cells, which correlated with reduced vascular density in clodronate-treated tumors. Taken together, our study revealed that macrophages contribute to SCC expansion through interactions with tumor cells but are dispensable for SCC metastasis. Our study provides novel insights into understanding the contributions and limitations of TAMs in SCC progression.

[Surgical treatment for Cushing's disease with negative results in high dose dexamethasone suppression tests].

Objective: To analyze the indication and the outcome of trans-sphenoidal surgery (TSS) in Cushing's disease (CD) with negative high dose dexamethasone suppression tests (HDDST) results. Methods: Eighteen cases of ACTH-dependent Cushing's syndrome (CS) with negative HDDST results in the Department of Neurosurgery in Shanghai Ruijin Hospital from January 2015 to December 2017 were retrospectively reviewed. All patients underwent TSS. There were 5 males and 13 females, with an average age of (41±14) years. Results: All patients underwent bilateral inferior petrosal sinus sampling (BIPSS) before the surgery and got evidence of pituitary origin of ACTH secretion. They were thus indicated for TSS. Immediate post-operative remission was achieved in ratio 17/18. There were no recurrences within a flow-up of 1 to 3 years. Pituitary ACTH secreting adenomas were pathologically confirmed in 15 cases, including the one who did not achieve post-operative remission. Thus, all 18 patients with negative HDDST results can finally be confirmed as CD. Conclusions: HDDST alone is not sufficient to eliminate CD. For patients with ACTH-dependent CS with negative HDDST results, BIPSS should be further performed. The fact of post-operative remission and the pathological confirm of ACTH secreting pituitary adenoma may add final evidence to the diagnosis of CD.

Efficacy and safety of rituximab therapy for membranous nephropathy: a meta-analysis.

OBJECTIVE: Membranous nephropathy (MN) is a leading cause of nephrotic syndrome in adults, but the treatment of MN remains controversial. Rituximab, a possible alternative treatment option, represented a new therapeutic hope for the treatment of membranous nephropathy (MN). We performed a meta-analysis to perform the efficacy and safety of rituximab therapy. MATERIALS AND METHODS: Either randomized controlled trials (RCTs), cohort studies or case studies were eligible for review and were performed in Medline, Embase, Web of Science, Cochrane database with the computerized searches. The primary outcome measure was remissions and the endpoint outcomes. We assessed the following studies methodological quality independently by using the Cochrane Collaboration tool for assessing risk of bias scale. The primary meta-analyses were performed using fixed or random effects models due to a1n expected clinical diversity. RESULTS: Five trials with a total of 351 patients were included. We found significant difference between rituximab and the placebo group on complete remissions rate (OR=1.6, 95%; CI=0.96, 2.66; I2 of 0% indicating no heterogeneity) and eGFR (MD=-0.69, 95% CI=-14.53, 0.73). The factors of remission and no remission MN patients who received treatment with rituximab on remission were proteinuria and albumin, which reported different (MD=7.20, 95% CI=-9.07, -5.33) (MD=10.70, 95% CI=7.23, 14.17). But remains high risk of infusion reactions (OR= 81.37, 95% CI=4.89, 1354.41). No evidence of significant risk of bias was reported. CONCLUSIONS: Rituximab had a beneficial effect and remissions of proteinuria on MN during follow-up times, but some adverse events were still unknown. Taking consideration of long-term therapeutic side effects and dose of the drug, we suggest that rituximab might replace cyclophosphamide and steroids as first-line immunosuppressive therapy in MN patients.

MiR-550a-3p promotes non-small cell lung cancer cell proliferation and metastasis through down-regulating TIMP2.

OBJECTIVE: MicroRNAs (miRNAs) have been identified to play a crucial regulatory role in the development and progression of malignant tumors, including lung cancer. However, the function of miR-550a-3p on the progression of non-small cell lung cancer (NSCLC) remains poorly understood. PATIENTS AND METHODS: Quantitative Real-time polymerase chain reaction was employed to estimate the expression level of miR-550a-3p in NSCLC tissue and cell samples. Cell proliferation was measured by using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and colony formation assays. Transwell assay was recruited to demonstrate the abilities of cell invasion and migration. Luciferase analysis and Western-blot assay were performed to elucidate the underlying mechanism of miR-550a-3p in NSCLC. RESULTS: The level of miR-550a-3p expressed in NSCLC tissues was significantly higher than that in para-tumor control tissues. Over-expression of miR-550a-3p significantly promoted proliferation, invasion, and migration of A549 cells while knockdown of miR-550a-3p inhibited growth and metastasis of H460 cells. TIMP2 was verified as a direct target of miR-550a-3p in NSCLC. Restoration of TIMP2 rescued the influence of miR-550a-3p over-expression. CONCLUSIONS: We demonstrated that miR-550a-3p regulated the progression of NSCLC cells through TIMP2. Thus, miR-550a-3p axis could serve as a potential therapeutic target for NSCLC treatment.

[Study of bioequiavailability of paclitaxel for Injection (Albumin Bound) and abraxane and the efficacy of extension treatments in patients with metastatic breast cancer].

Objective: To compare the bioequiavailability of paclitaxel for injection (albumin bound) (PAB) and reference listed drug abraxane in the patients with metastatic breast cancer, and to investigate the safety and efficacy in the extension treatments of PAB. Methods: This study was random, two cycles, self-crossover control study in the bioequiavailability stage. PAB was the investigational drug T and Abraxane was the reference drug R. Patients were randomly assigned to two cycles therapy of either R→T or T→R(260 mg/m(2)/21d). Non-PD patients entered in the extension treatments of the investigational drug PAB(260 mg/m(2)/21d) until the disease progression or the intolerance toxicity. Results: From Mar 1, 2016 to May 24, 2016, we enrolled 40 patients. The blood concentration-time curve and the parameters of pharmacokinetics indicated the two drugs were the bioequivalent drug products in the initial two cycles crossover-therapy.The incidence of adverse drug reactions were 89.7% vs 97.4% in investigational drug vs reference drug and grade 3/4 toxicities were 20.5% vs 21.1%(P=1.000). Patients received a median of 7 treatment cycles(range 1-23) and a median of 260mg/m(2) actual drug dose (range 220-260 mg/m(2)). Seven patients (17.5%) had dose reductions because of toxicities (260 mg/m(2) reduce to 220 mg/m(2)). Twenty-two patients (55%) discontinued treatment prematurely because of toxicity.Overall response rates (ORR) were 40% (95% CI, 24.8%-55.2%). For patients who received PAB as first-line vs non-first-line therapy, the ORR were 43.8% vs 25%. For patients who taxane-naïve vs taxane-pretreated, the ORR were 45.5% vs 37.9%. Median PFS was 49 weeks(95% CI, 30weeks-NA). Conclusion: The paclitaxel for injection (albumin bound) (PAB) and reference listed drug abraxane are the bioequivalent drug products.The toxicity and efficacy of the PAB are similar with abraxane.The more therapy chances for Chinese patients will come by the research and development of domestic drugs.

Evidence of Premating Isolation Between Two Sibling Moths: Ectropis grisescens and Ectropis obliqua (Lepidoptera: Geometridae).

The sex pheromones of Ectropis grisescens Warren and Ectropis obliqua Prout were both reported to contain (Z,Z,Z)-3,6,9-octadecatriene (Z3,Z6,Z9-18:H) and (Z,Z)-3,9-cis-6,7-epoxy-octadecadiene (Z3,epo6,Z9-18:H). To clarify how these two sibling geometrids maintain premating isolation, the female sex pheromones of the two species were reexamined. Gas chromatography-electroantennographic detection (GC-EAD) and gas chromatography-mass spectrometry revealed two GC-EAD-active compounds, Z3,Z6,Z9-18:H and Z3,epo6,Z9-18:H, in E. grisescens female pheromone glands as well as an additional GC-EAD-active compound, (Z,Z)-3,9-cis-6,7-epoxy-nonadecadiene (Z3,epo6,Z9-19:H), in E. obliqua female pheromone glands. Synthesized Z3,Z6,Z9-18:H and Z3,epo6,Z9-18:H elicited dose-dependent electroantennogram (EAG) responses from male antennae of both E. grisescens and E. obliqua. However, Z3,epo6,Z9-19:H only elicited dose-dependent EAG responses from E. obliqua and limited EAG responses from E. grisescens at all doses. In wind-tunnel studies, lures that contained Z3,Z6,Z9-18:H and Z3,epo6,Z9-18:H attracted E. grisescens males and had no effect on E. obliqua males. The addition of Z3,epo6,Z9-19:H to the blend of Z3,Z6,Z9-18:H and Z3,epo6,Z9-18:H strongly attracted E. obliqua males but had a limited attraction for E. grisescens males. Thus, Z3,Z6,Z9-18:H and Z3,epo6,Z9-18:H were sex pheromone components of E. grisescens, whereas Z3,Z6,Z9-18:H, Z3,epo6,Z9-18:H and Z3,epo6,Z9-19:H were sex pheromone components of E. obliqua. The presence or absence of Z3,epo6,Z9-19:H played a central role in the premating isolation of these two sibling species.