Risk factors for ketoacidosis in children/adolescents with type 1 diabetes mellitus and establishment of a predictive model / 中国当代儿科杂志

OBJECTIVES@#To investigate the risk factors for diabetic ketoacidosis (DKA) in children/adolescents with type 1 diabetes mellitus (T1DM) and to establish a model for predicting the risk of DKA.@*METHODS@#A retrospective analysis was performed on 217 children/adolescents with T1DM who were admitted to General Hospital of Ningxia Medical University from January 2018 to December 2021. Among the 217 children/adolescents,169 cases with DKA were included as the DKA group and 48 cases without DKA were included as the non-DKA group. The risk factors for DKA in the children/adolescents with T1DM were analyzed, and a nomogram model was established for predicting the risk of DKA in children/adolescents with T1DM.@*RESULTS@#For the 217 children/adolescents with T1DM, the incidence rate of DKA was 77.9% (169/217). The multivariate logistic regression analysis showed that high levels of random blood glucose, hemoglobin A1c (HbA1c), blood ketone body, and triglyceride on admission were closely associated with the development of DKA in the children/adolescents with T1DM (OR=1.156, 3.2031015, 20.131, and 9.519 respectively; P<0.05). The nomogram prediction model had a C-statistic of 0.95, with a mean absolute error of 0.004 between the risk of DKA predicted by the nomogram model and the actual risk of DKA, indicating that the model had a good overall prediction ability.@*CONCLUSIONS@#High levels of random blood glucose, HbA1c, blood ketone body, and triglyceride on admission are closely associated with the development of DKA in children/adolescents with T1DM, and targeted intervention measures should be developed to reduce the risk of DKA.

A real-world study on the efficacy and safety analysis of paclitaxel liposome in advanced breast cancer / 中华肿瘤杂志

Objective: To explore the application and efficacy of paclitaxel liposome in the treatment of advanced breast cancer among Chinese population in the real world. Methods: The clinical characteristics of patients with advanced breast cancer who received paclitaxel liposome as salvage treatment from January 1, 2016 to August 31, 2019 in 11 hospitals were collected and retrospectively analyzed. The primary outcome was progression free survival (PFS), and the secondary outcome included objective response rate (ORR) and safety. The survival curve was drawn by Kaplan-Meier analysis and the Cox regression model were used for the multivariate analysis. Results: Among 647 patients with advanced breast cancer who received paclitaxel liposome, the first-line treatment accounted for 43.3% (280/647), the second-line treatment accounted for 27.7% (179/647), and the third-line and above treatment accounted for 29.1% (188/647). The median dose of first-line and second-line treatment was 260 mg per cycle, and 240 mg in third line and above treatment. The median period of paclitaxel liposome alone and combined chemotherapy or targeted therapy is 4 cycles and 6 cycles, respectively. In the whole group, 167 patients (25.8%) were treated with paclitaxel liposome combined with capecitabine±trastuzumab (TX±H), 123 patients (19.0%) were treated with paclitaxel liposome alone (T), and 119 patients (18.4%) were treated with paclitaxel liposome combined with platinum ± trastuzumab (TP±H), 108 patients (16.7%) were treated with paclitaxel liposome combined with trastuzumab ± pertuzumab (TH±P). The median PFS of first-line and second-line patients (5.5 and 5.5 months, respectively) were longer than that of patients treated with third line and above (4.9 months, P<0.05); The ORR of the first line, second line, third line and above patients were 46.7%, 36.8% and 28.2%, respectively. Multivariate analysis showed that event-free survival (EFS) and the number of treatment lines were independent prognostic factors for PFS. The common adverse events were myelosuppression, gastrointestinal reactions, hand foot syndrome and abnormal liver function. Conclusion: Paclitaxel liposomes is widely used and has promising efficacy in multi-subtype advanced breast cancer.

Research Progress of Fibroblast Growth Factor Receptor Signaling Pathway in Breast Cancer / 中国医学科学院学报

Breast cancer,one of the common malignant tumors in women,has shown rising incidence in recent years,posing a serious threat to women's health.The advancement of molecular biology facilitates the revealing of the relationships between signaling pathways and breast cancer.Fibroblast growth factor receptor (FGFR) signaling pathway plays an important role in the proliferation,survival,differentiation,migration,and apoptosis of breast cancer cells.Strategies targeting the FGFR signaling pathway thus exhibit a promising prospect in breast cancer treatment.

BRCA1 Reversion Mutation Confers Resistance to Olaparib and Camrelizumab in a Patient with Breast Cancer Liver Metastasis / 한국유방암학회지

Reversion mutations are associated with clinical resistance to poly(ADP-ribose) polymerase inhibitors (PARPi). Here, we describe the detection of a BRCA1 reversion mutation in a 39-year-old woman with metastatic breast cancer harboring a heterozygous germline BRCA1 exons 7–8 deletion who received PARPi olaparib combined with immune checkpoint inhibitor camrelizumab as third-line therapy. During progression from the olaparib and camrelizumab combination therapy, we identified via genomic sequencing a novel 7-base pair somatic deletion in BRCA1 (c.617_623delACAAATC). Sequence analyses indicated that this mutation realigned the reading frame of BRCA1, which potentially led to the reversal of its normal function and conferred resistance to PARPi.

Astragalus mongholicus Bunge and Panax Notoginseng Formula (A&P) Combined With Bifidobacterium Contribute a Renoprotective Effect in Chronic Kidney Disease Through Inhibiting Macrophage Inflammatory Response in Kidney and Intestine.

There is increasing evidence that Chronic Kidney Disease (CKD) can cause intestinal dysfunction, which in turn aggravates the progression of kidney disease. Studies have shown that the immune response of macrophage plays an important role in promoting inflammation in kidney and intestine of CKD. Astragalus mongholicus Bunge and Panax notoginseng formula (A&P) is a widely used traditional medicine for the treatment of CKD in China, however, the underlying mechanism is largely unclear. In this study, we aimed to explore the role of A&P and Bifidobacterium combination treatment in regulation of inflammatory response of macrophage in kidney and intestine of CKD mouse, as well as the potential molecular mechanism. We established a CKD mouse model with 5/6 nephrectomy and a macrophage inflammatory cellular model with LPS and urotoxin in vivo and in vitro. The results showed that A&P combined with Bifidobacterium significantly reduced the expression and secretion of IL-1ß, IL-6, TNFα, and MCP-1 in kidney and blood, as well as in inflammatory macrophage. Interestingly, A&P combined with Bifidobacterium strongly improved the intestinal flora and protected the intestinal barrier. Notably, the maintainer of macrophage polarization, Mincle, was activated in kidney and intestine of CKD mouse as well as in urotoxin stimulated macrophage, that was effectively inhibited by the treatment of A&P and Bifidobacterium combination. Overexpression of Mincle by genetic modification can abolish the inhibitory effects of A&P combined with Bifidobacterium on inflammation in urotoxin stimulated RAW264.7 cells. In summary, these findings demonstrated that A&P combined with Bifidobacterium can protect kidney against CKD by down-regulating macrophage inflammatory response in kidney and intestine via suppressing Mincle signaling, which provides a new insight in the treatment of CKD with traditional medicine.

Clinical outcomes of percutaneous or surgical closure of ruptured sinus of Valsalva aneurysm.

OBJECTIVE: To evaluate the clinical efficacy, safety, and long-term outcomes of percutaneous closure (PC) and surgical repair of ruptured sinus of Valsalva aneurysm (RSVA). METHODS: Eighty-five consecutive patients with RSVA were included in this study. Patients were considered candidates for PC if they met the criterion, surgical repair was performed on patients who were unsuitable or failed PC. Of them, 30 patients underwent PC, while the other 55 patients had surgical repair. RESULTS: RSVA was successfully occluded in 29 of 30 patients who were treated by PC. The mean narrowest diameter at the ruptured site was 6.45 ± 1.60 mm measured by aortography. One patient developed serious occluder-related aortic regurgitation and underwent surgery. The success rate of the interventional approach was 96.7%. In the surgical group, 23 patients underwent repair of combined RSVA and ventricular septal defect. The hospital mortality rate of the surgical approach was 3.57%. During a median follow-up of 83 months (8-152 months), the improvement in NYHA functional class in the PC group was significantly greater than those in the surgical group (P < .01). One patient died of infective endocarditis in the surgical group. There were no further serious complications. CONCLUSIONS: PC is a safe alternative to surgical repair for patients with isolated RSVA. Surgical repair is more suitable for those who have multiple cardiac lesions requiring surgical treatment or failed PC.

Acute effects of Rho-kinase inhibitor fasudil on pulmonary arterial hypertension in patients with congenital heart defects.

BACKGROUND: We investigated the acute vasodilator effects of i.v. fasudil, a specific Rho-kinase inhibitor, on pulmonary circulation in patients with congenital heart defects (CHD) and severe pulmonary arterial hypertension (PAH). METHODS AND RESULTS: Thirty-five patients (34.23±12.10 years old) with CHD and severe PAH were consecutively enrolled. All patients underwent heart catheterization. At baseline and 30 min after initiation of i.v. fasudil, the following hemodynamic parameters were measured and calculated: right atrial pressure, pulmonary and systemic artery pressure (PAP and SAP), pulmonary and systemic vascular resistance, pulmonary-to-systemic blood pressure ratio (Pp/Ps), pulmonary-to-systemic blood flow ratio (Qp/Qs), cardiac index (CI) and artery oxygen saturation (SaO2). After fasudil treatment, marked decrease in mean PAP (mPAP), pulmonary vascular resistance (PVR), total pulmonary resistance, pulmonary-to-systemic vascular resistance ratio (Rp/Rs) and mean Pp/Ps (mPp/Ps) was found, while Qp/Qs increased significantly without affecting CI and SAP. mPAP, PVR, Rp/Rs and Qp/Qs tended to be improved more significantly in the post-tricuspid shunt group compared with the pre-tricuspid shunt group. CONCLUSIONS: Fasudil was well tolerated in patients with CHD and severe PAH, and significantly reduced PAP and PVR without affecting CI, SAP or SaO2.

Safety and efficacy of first-line bevacizumab combined with taxane therapy in Chinese patients with HER2-negative locally recurrent or metastatic breast cancer: findings from the ATHENA study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Three randomised trials have demonstrated that combining bevacizumab with first-line chemotherapy significantly improves progression-free survival versus chemotherapy alone in HER2-negative locally recurrent/metastatic breast cancer (LR/mBC). However, data from Chinese populations are limited and possible differences between ethnic and geographic populations are unknown. This study was conducted to determine whether there are differences in safety and efficacy in patients with HER2-negative LR/mRC between Chinese and Western populations after they receive first-line bevacizumab combined with taxane-based therapy.</p><p><b>METHODS</b>In the single-arm, open-label, Avastin Therapy for Advanced Breast Cancer (ATHENA) study (NCT00448591), patients with HER2-negative LR/mBC received first-line bevacizumab (investigator's choice of 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) combined with taxane-based therapy. The primary endpoint was safety profile and the secondary is time to progression (TTP). A subpopulation analysis was conducted to assess safety and efficacy in Chinese patients.</p><p><b>RESULTS</b>Of 2264 patients treated in ATHENA, 202 were enrolled in China. Bevacizumab was combined with docetaxel in 90% of Chinese patients and paclitaxel in 10%. The most common grade 3/4 adverse events were diarrhoea (in 5.0% of patients) and hypertension (in 2.5% of patients). Grade 3/4 proteinuria occurred in 0.5%. After median follow-up of 17.6 months and events in 56% of patients, median TTP was 9.0 months (95%CI, 8.4-11.1). Overall survival data were immature.</p><p><b>CONCLUSIONS</b>We found no evidence of increased bevacizumab-related toxicity or reduced efficacy in Chinese LR/mBC patients receiving first-line bevacizumab-taxane therapy compared with predominantly Western populations. The safety profile was generally similar to previously reported LR/mBC trials. Subtle differences may be attributable to different lifestyle and cardiovascular risk factors in Chinese patients compared with the overall population. It appears reasonable to extrapolate findings from bevacizumab-based randomised trials to Chinese populations.</p>

Lapatinib plus capecitabine in treating HER2-positive advanced breast cancer: efficacy, safety, and biomarker results from Chinese patients / 癌症

Overexpression of human epidermal growth factor receptor-2 (HER2) in metastatic breast cancer (MBC) is associated with poor prognosis. This single-arm open-label trial (EGF109491; NCT00508274) was designed to confirm the efficacy and safety of lapatinib in combination with capecitabine in 52 heavily pretreated Chinese patients with HER2-positive MBC. The primary endpoint was clinical benefit rate (CBR). Secondary endpoints included progression-free survival (PFS), time to response (TTR), duration of response (DoR), central nervous system (CNS) as first site of relapse, and safety. The results showed that there were 23 patients with partial responses and 7 patients with stable disease, resulting in a CBR of 57.7%. The median PFS was 6.34 months (95% confidence interval, 4.93-9.82 months). The median TTR and DoR were 4.07 months (range, 0.03-14.78 months) and 6.93 months (range, 1.45-9.72 months), respectively. Thirteen (25.0%) patients had new lesions as disease progression. Among them, 2 (3.8%) patients had CNS disease reported as the first relapse. The most common toxicities were palmar-plantar erythrodysesthesia (59.6%), diarrhea (48.1%), rash (48.1%), hyperbilirubinemia (34.6%), and fatigue (30.8%). Exploratory analyses of oncogenic mutations of PIK3CA suggested that of 38 patients providing a tumor sample, baseline PIK3CA mutation status was not associated with CBR (P = 0.639) or PFS (P = 0.989). These data confirm that the lapatinib plus capecitabine combination is an effective and well-tolerated treatment option for Chinese women with heavily pretreated MBC, irrespective of PIK3CA status.

Construction of eukaryotic expression plasmids containing green fluorescent protein gene and CYP19 WT or its variants / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To construct eukaryotic expression plasmids containing green fluorescent protein gene and CYP19 wild-type or its variants (W39R, R264C, W39R-R264C) and to observe its expression in MCF-7 and Bcap-37 cells.</p><p><b>METHODS</b>The aromatase WT cDNA sequence was obtained by RT-PCR amplification and cloned into the eukaryotic expression vector pcDNA3.1(+). pcDNA3.1(+)-CYP19-GFP plasmid was then used as the template for site-directed mutation to create variant constructs (W39R, R264C, W39R-R264C). pcDNA3.1(+)-CYP19-GFP was transfected and expressed in MCF-7 and Bcap-37 cells.</p><p><b>RESULT</b>The construction of pcDNA3.1(+)-CYP19-GFP plasmid was confirmed by enzyme digestion and DNA sequencing. pcDNA3.1(+)-CYP19(W39R)-GFP, pcDNA3.1(+)-CYP19(R264C)-GFP, pcDNA3.1(+)- CYP19(W39R-R264C)-GFP plasmids were confirmed by DNA sequencing. The MCF-7 and Bcap-37 cells transfected with the pcDNA3.1(+)-CYP19-GFP plasmid expressed reporter gene of GFP.</p><p><b>CONCLUSION</b>The eukaryotic expression plasmids have been constructed and expressed in MCF-7 and Bcap-37 cells successfully, which lays the foundation for the research of biological activities of CYP19 variant allozymes.</p>

Significance of multidrug resistance gene-associated proteins in the postoperative adjuvant chemotherapy for gastric carcinoma and the prognosis / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the expression of multidrug resistance (MDR) gene-associated proteins (MRP) in gastric carcinoma, and their effects on the postoperative adjuvant chemotherapy and the prognosis of patients.</p><p><b>METHODS</b>The expressions of ToPo II, MRP, GST-pi in 99 patients with gastric carcinoma were detected by immunohistochemistry. The expression and its relationship to the pathological data were analyzed. The positive expression of MRP and GST-pi, and the negative expression of ToPo II were considered as risk factors. Patients were divided into two groups: a high risk drug-resistant group (2-3 risk factors) and the low risk drug-resistant group (0-1 risk factors). Postoperative recurrence, survival rate, and efficacy of adjuvant chemotherapy were compared between two groups.</p><p><b>RESULTS</b>The positive rate of ToPo II was 74.7%, and the expression was associated with types and differentiation of the tumor. The positive rate of GST-pi was 49.5%, and the expression was related to the gender and the differentiation. The positive rate of MRP was 40.4%, and there was no relationship between the MRP expression and the pathological finding. There were no significant differences in the recurrence, time to recurrence, and the 5-year survival rate between the positive and negative group of the three proteins (P>0.05). Recurrence was found in 25 cases(55.6%) in the high risk drug-resistant group and the mean time to recurrence was (15.2+/-8.1) months. The time to recurrence was shorter in the low risk drug-resistant group [(21.3+/-11.1) months, P<0.05] , but there was no significant difference in the recurrence rate between two groups (P>0.05). The 5-year survival rate of the high risk drug-resistant group and the low risk drug-resistant group was 44.4% and 55.6% (P>0.05). The 5-year survival rates of patients with or without chemotherapy in the high risk drug-resistant group were 45.8% and 42.9% (P>0.05). The 5-year survival rates of patients with or without chemotherapy in the low risk drug-resistant group were 70.4% and 40.7%. The survival rate of patients with chemotherapy was higher than that of the patients without chemotherapy (P<0.05).</p><p><b>CONCLUSIONS</b>The expression of ToPo II, MRP and GST-pi is associated with the efficacy of postoperative adjuvant chemotherapy. Chemotherapy appears to be more beneficial to patients with low risk drug-resistance.</p>

The repair of acute spinal cord injury in rats by olfactory ensheathing cells graft modified by glia cell line-derived neurotrophic factor gene in combination with the injection of monoclonal antibody IN-1 / 中华外科杂志

<p><b>OBJECTIVE</b>To research the repair effect of transplantation of glial cell line-derived neurotrophic factor (GDNF) modified olfactory ensheathing cells (OECs) combination with injecting axonal growth inhibiting protein antibody (IN-1) in vivo.</p><p><b>METHODS</b>To construct lentivirus vector with GDNF gene and infect OECs in vitro, use the immunoblotting (Western Blot) to observe the expression of GDNF was detected through Western Blot. Fifty adult female SD rats which to establish thoracic spinal cord transection injury model were randomly divided into A (control group), B (IN-1 antibody group), C (OECs group), D (GDNF-OECs group), and E (GDNF-OECs+IN-1 group) 5 groups of each 10 rats. To observe regeneration of the impaired nerve axon by NF200 immunohistochemistry, Biotinylated dextran amine (BDA) anterograde tracing corticospinal tract. Basso, Beattie and Bresnahan (BBB) score was used to evaluating hindlimb motor function recovery.</p><p><b>RESULTS</b>Add up to 13 rats died post operation. OECs labeled by hoechst still survived and migrated in spinal cord 8 weeks post operation. Lots of confused and disorderly regenerated axons which crossing the injured region of spinal cord were displayed between spinal cord stumps in GDNF-OECs+IN-1 group and GDNF-OECs group; some of axons existed in OECs group, but there is no obviously continue nerve fibers crossing the injured region of spinal cord;in contrast to IN-1 and control groups, few of regenerated axons and atrophy of spinal cord stumps were observed. The results of BBB hindlimb motor rating scale were 7.70+/-0.24, 7.89+/-0.15, 10.50+/-0.25, 11.43+/-0.23 and 12.81+/-0.40 for the control group, IN-1 group, OECs group, GDNF-OECs group and the allied treatment group respectively.</p><p><b>CONCLUSIONS</b>The transplantation of GDNF-OECs combination with IN-1 antibody may benefit the survival and regeneration of the injured axons, and accelerate the repair of the injured spinal cord and functional recover of hindlimb locomotor in rats in a more efficient way than that with OECs or IN-1 alone.</p>

Clinical observation of erythropoietin in treating the anemia induced by chemotherapy / 肿瘤研究与临床

Objective Observe the response and adverse effects of impact dose recombination human erythropoietin(rhEPO)in the breast cancer patients with anemia induced by chemotherapy.Methods 43 breast cancer patients with anemia induced by chemotherapy were randomly divided into two groups,treatment group(23 patients)and the control(20 patients).The treatment group received rhEPO for 10 days and oral iron therapy,while the control group was oral iron therapy only.Results After 4 weeks,the hemoglobin level, hematocrit,reticulocyte and quality of life be revaluated,the treatment group was significantly better than the control.The adverse effects was tolerable.Conclusion The impact dose rhEPO is effective and tolerable in the breast cancer patients with anemia induced by chemotherapy.