Photothermal-Controllable Microneedles with Antitumor, Antioxidant, Angiogenic, and Chondrogenic Activities to Sequential Eliminate Tracheal Neoplasm and Reconstruct Tracheal Cartilage.

The optimal treatment for tracheal tumors necessitates sequential tumor elimination and tracheal cartilage reconstruction. This study introduces an innovative inorganic nanosheet, MnO2 /PDA@Cu, comprising manganese dioxide (MnO2 ) loaded with copper ions (Cu) through in situ polymerization using polydopamine (PDA) as an intermediary. Additionally, a specialized methacrylic anhydride modified decellularized cartilage matrix (MDC) hydrogel with chondrogenic effects is developed by modifying a decellularized cartilage matrix with methacrylic anhydride. The MnO2 /PDA@Cu nanosheet is encapsulated within MDC-derived microneedles, creating a photothermal-controllable MnO2 /PDA@Cu-MDC microneedle. Effectiveness evaluation involved deep insertion of the MnO2 /PDA@Cu-MDC microneedle into tracheal orthotopic tumor in a murine model. Under 808 nm near-infrared irradiation, facilitated by PDA, the microneedle exhibited rapid overheating, efficiently eliminating tumors. PDA's photothermal effects triggered controlled MnO2 and Cu release. The MnO2 nanosheet acted as a potent inorganic nanoenzyme, scavenging reactive oxygen species for an antioxidant effect, while Cu facilitated angiogenesis. This intervention enhanced blood supply at the tumor excision site, promoting stem cell enrichment and nutrient provision. The MDC hydrogel played a pivotal role in creating a chondrogenic niche, fostering stem cells to secrete cartilaginous matrix. In conclusion, the MnO2 /PDA@Cu-MDC microneedle is a versatile platform with photothermal control, sequentially combining antitumor, antioxidant, pro-angiogenic, and chondrogenic activities to orchestrate precise tracheal tumor eradication and cartilage regeneration.

[Topological properties of white matter network in first untreated children and adolescents with obsessive-compulsive disorder].

Objective: To investigate the topological properties of the white matter network in the drug-naive first-episode children and adolescent with obsessive-compulsive disorder (OCD). Methods: This study was a case-control study. First-episode OCD childhren and adolescents(OCD group) who were treated in the outpatient or inpatient department of the Second Affiliated Hospital of Xinxiang Medical University from July 2018 to October 2023 were collected as the research subjects. Healthy controls (control group)matched by gender, age and education level were used as controls. Deterministic tractography technique was used to construct the whole brain white matter structural network, and graph theory analysis method was used to analyze the topological attributes of the whole brain white matter structure network in OCD children and adolescents. A network-based statistical method was used to examine the inter-group differences in the functional connectivity strength of the whole brain network. Results: Finally, 31 cases were included in the obsessive-compulsive disorder group, including 22 males and 9 females, with an age of (13.5±1.6) years; There were 34 cases in the control group, including 22 males and 12 females, with an age of (12.7±1.4) years. The global efficiency and local efficiency of the OCD group (0.62±0.03, 0.70±0.07) were significantly higher than those of the control group (0.50±0.06, 0.54±0.21) [both P<0.01, false discovery rate(FDR)correction]; while the characteristic path length (1.77±0.08) was significantly smaller than that of the control group (2.10±0.23) (P<0.01, FDR correction).The centrality comparison of nodal betweenness centrality showed that in the OCD group, the connections were enhanced in the left lateral orbitofrontal gyrus, right dorsal agranular insula, left dorsal granular insula, right granular insula, right posterior central gyrus main area of parietal lobe, left ventral granular insula, granular insula, left ventral granulosa, left granular insula, and left dorsal agranular insula [all P<0.001, family wise error (FWE) correction], while the connection of right thalamic was weakened (P<0.001, FWE correction), There were sub-networks characterized by significantly enhanced connection strength of relevant nodes in subcortical, visual network, and default mode network (P<0.05, permutation test 5 000 times). Conclusions: The topological properties of the brain's functional network in children and adolescents with OCD exhibit abnormalities, indicating an immature state of brain functional connectivity.

[Clinicopathological and molecular genetic features of confined placental mosaicism].

Objective: To investigate the clinicopathological and genetic features of confined placental mosaicism (CPM) and its effect on fetal intrauterine growth. Methods: Fourteen CPM cases of Haidian Maternal and Children Health Hospital were collected from May 2018 to March 2022. Clinicopathological examination on placental specimens and molecular genetic analysis were performed. Results: The age of the parturient women ranged from 27 to 34 years, with an average age of (30.0±3.54) years. The gestational weeks ranged from 35+1 to 41+2 weeks. There were 4 premature births and 10 term births, among which 6 were female and 8 were male fetuses. Nine cases (9/14) had adverse pregnancy outcomes, including 7 cases of fetal growth restriction. The weight of CPM placenta decreased, with 6 cases below the 10th percentile of weight standards and 5 cases between the 10th and 25th percentile. All 14 CPM placental specimens showed morphological changes of perfusion dysfunction to varying degrees, with mainly placental-maternal vascular malperfusion followed by placental-fetal vascular malperfusion. The mosaic chromosomes in different CPM cases varied, with 16-trisomy/monosomy mosaicism being the most common followed by 7-trisomy and 21-trisomy/monosomy mosaicism. The mosaic proportion was unequal in different parts of the same CPM placenta, with the mosaic proportion of umbilical cord, fetal membranes, fetal surface, maternal surface, and edge ranging from 1% to 70%. Conclusions: The mosaic chromosomes in different CPM cases vary, and the mosaic proportion is unequal in different parts of the same CPM placenta. The pathological morphology is mainly manifested as perfusion dysfunction, which can lead to adverse pregnancy outcomes such as fetal growth restriction and preterm birth.

[Analysis of the efficacy and safety of CT-guided radiofrequency ablation of posterior root of the spinal nerve in the treatment of postherpetic neuralgia].

Objective: To investigate the efficacy and safety of CT-guided radiofrequency ablation of posterior root of spinal nerve in the treatment of postherpetic neuralgia (PHN). Methods: A total of 102 PHN patients (42 males and 60 females) aged (69.7±9.4) years who underwent CT-guided radiofrequency ablation of posterior root of spinal nerve in the Department of Pain Medicine of the Affiliated Hospital of Jiaxing University from January 2017 to April 2020 were retrospectively included. Patients were followed up, and numerical rating scale (NRS) score, Pittsburgh sleep quality index (PSQI), satisfaction score and complications before surgery (T0) and at 1 d (T1), 3 months (T2), 6 months (T3), 9 months (T4) and 12 months (T5) after surgery were recorded. Results: The NRS score of PHN patients at T0, T1, T2, T3, T4, and T5 [M(Q1, Q3)] was 6(6, 7), 2(2, 3), 3(2, 4), 3(2, 4), 2(1, 4), 2(1, 4), respectively. Likewise, the PSQI score [M(Q1, Q3)] at aforementioned time points was 14(13, 16), 4(3, 6), 6(4, 8), 5(4, 6), 4(2, 8), 4(2, 9), respectively. Compared with T0, the NRS and PSQI scores at all time points from T1 to T5 were lower, with statistically significant differences (all P<0.001). The overall effective rate of surgery at 1 year postoperatively was 71.6% (73/102) with a satisfaction score of 8(5, 9), and the recurrence rate was 14.7% (15/102) with a recurrence time of (7.5±0.8) months. The main postoperative complication was numbness, with an incidence of 86.0% (88/102), and the degree of numbness gradually decreased with time. Conclusion: CT-guided radiofrequency ablation of posterior root of spinal nerve for PHN has a high effective rate and a low recurrence rate, with high safety profile, and may be a feasible surgical option for the treatment of PHN.

[A nested case-control study on the relationship between red blood cell folate and the prognosis of low-grade cervical intraepithelial neoplasia].

Objective: To evaluate the relationship between red blood cell folate (RBC folate) and the prognosis of low-grade cervical intraepithelial neoplasia (CIN 1). Methods: In the married women cohort established in 2014, 564 women with CIN 1 diagnosed by pathology were recruited. The demographic characteristics and factors of cervical intraepithelial neoplasia were collected. Meanwhile, the infection status of human papillomavirus (HPV) was detected by molecular diversion hybridization, and the level of RBC folate was measured by chemical photoimmunoassay. After 24 months of follow-up, pathological examination was performed again to observe the prognosis of participants. The women with reversal were taken as the control group,and those with continuous and progressive CIN 1 were taken as the case group respectively. The relationship between RBC folate and CIN 1 outcome was evaluated by logistic regression model. Results: 453 women completed the follow-up, aged (49.72±6.84) years old. CIN 1 was reversed in 342 women, continued in 58 cases and progressed in 53 cases. The RBC folate level M (Q1,Q3) were 399.01 (307.10, 538.97) ng/ml, 316.98 (184.74, 428.49) ng/ml and 247.14 (170.54, 348.97) ng/ml, respectively. With the decrease of RBC folate, the risk of continuous and progressive CIN 1 increased (all P<0.001), while the risk of reversal CIN 1 decreased gradually (P<0.001). Combined with high-risk human papillomavirus (HR-HPV) infection status, low level of RBC folate could increase the risk of CIN 1 progression regardless of HR-HPV infection (HR-HPV infection: OR=21.34, 95%CI: 3.98-114.54; HR-HPV uninfection: OR=11.15, 95%CI: 2.34-53.13). Conclusion: Low level of RBC folate could increase the risk of CIN 1 persistence and progression regardless of HR-HPV infection.

[The role of STAT-6/KLF-4/PPAR-γ activation in alveolar macrophage polarization changes in silica-induced pulmonary fibrosis].

Objective: To observe the effect of silicon dioxide (SiO(2)) on the polarization of alveolar macrophages (AMs) , and to explore the expressions and the significance of signal transducer and activator of transcription-6 (STAT-6) /Krüppel-like factor-4 (KLF-4) /peroxisome proliferators-activated receptors-γ (PPAR-γ) signaling molecules in AMs. Methods: In November 2020, C57BL/6 mice were randomly divided into crystalline SiO(2) group and normal saline (NS) group, and 12 mice in each group. Mice were intratracheally instillated with 100 µl crystalline SiO(2) suspension (20 mg/ml) or 100 µl NS, and were sacrificed after 28 days. Masson staining was used to observe the degree of pulmonary fibrosis of mice and hydroxyproline (HYP) level were assessed. The proportions of M1-typed and M2-typed AMs in bronchoalveolar lavage fluid (BLAF) were analyzed by flow cytometry. The mRNA relative expression levels of inducible nitric oxide synthase (iNOS) , arginidase-1 (Arg-1) , interleukin (IL) -1ß, tumor necrosis factor-α (TNF-α) , IL-6, IL-10, transforming growth factor-ß (TGF-ß) , STAT-6, KLF-4 and PPAR-γ were detected by real-time fluorescence quantitative PCR. Activities of iNOS and Arg-1, as well as contents of IL-1ß, TNF-α, IL-6, IL-10 and TGF-ß were assessed by the enzyme-linked immunosorbent. The protein relative expression levels of phosphorylation-signal transducer and activator of transcription-6 (p-STAT-6) , KLF-4 and PPAR-γ were evaluated by immunofluorescence. Results: After 28 days of treatment, the structure of the lung tissue of the mice was destroyed, and the deposition of collagen was significantly increased in the crystalline SiO(2) group. Compared with NS group, HYP level of lung tissue in crystalline SiO(2) group were increased, the proportion of M2-typed AMs in crystalline SiO(2) group was increased, the proportion of M1-typed AMs in crystalline SiO(2) group was decreased, the mRNA relative expressions and contents of Arg-1, IL-10, TGF-ß in crystalline SiO(2) group were significantly increased, the mRNA relative expressions and contents of iNOS, IL-1ß, TNF-α, IL-6 in crystalline SiO(2) group were significantly decreased, the mRNA of STAT-6, KLF-4, PPAR-γ and the protein relative expression levels of p-STAT-6, KLF-4, PPAR-γ were significantly increased in crystalline SiO(2) group, and the the differences were statistically significant (P<0.05) . Conclusion: Crystalline SiO(2) may mediate the process of pulmonary fibrosis through promote AMs polarization toward M2-typed by activating the STAT-6/KLF-4/PPAR-γ signaling pathway.

Early-phenotype CAR-T cells for the treatment of pediatric cancers.

Chimeric antigen receptor (CAR)-T-cell therapy is a promising approach for the treatment of childhood cancers, particularly high-risk tumors that fail to respond to standard therapies. CAR-T cells have been highly successful in treating some types of hematological malignancies. However, CAR-T cells targeting solid cancers have had limited success so far for multiple reasons, including their poor long-term persistence and proliferation. Evidence is emerging to show that maintaining CAR-T cells in an early, less-differentiated state in vitro results in superior persistence, proliferation, and antitumor effects in vivo. Children are ideal candidates for receiving less-differentiated CAR-T cells, because their peripheral T-cell pool primarily comprises naïve cells that could readily be harvested in large numbers to generate early-phenotype CAR-T cells. Although several studies have reported different approaches to successfully generate early CAR-T cells, there are only a few clinical trials testing these in adult patients. No trials are currently testing early CAR-T cells in children. Here, we summarize the different strategies used to maintain CAR-T cells in an early phenotypic stage and present evidence suggesting that this approach may be particularly relevant to treating childhood cancers.

[The possible mechanisms of simvastatin on apoptosis of lung adenocarcinoma cells].

Objective: To explore the possible mechanisms of simvastatin-induced apoptosis in lung adenocarcinoma cells. Methods: The experiment was divided into control group (vehicle treated A549 cells), different concentrations (10, 20, 40, 80 mg/L) simvastatin group (simvastatin treated with different concentrations of A549 cells), aspartate specific proteinase (caspase) inhibitor (Z-VAD-FMK) group (50 µmol/L Z-VAD-FMK treated A549 cells), 40 mg/L simvastatin combined with Z-VAD-FMK group (40 mg/L simvastatin combined with 50 µmol/L Z-VAD-FMK co-treated A549 cells), interleukin-6 (IL-6) group (IL-6 acts on A549 cells) and different concentrations (10, 20, 40 mg/L) simvastatin combined with IL-6 group (simvastatin combined with IL-6 act on A549 cells). Cell counting kit-8 (CCK8) method was used to detect the effect on survival rate of lung adenocarcinoma A549 cells; Flow cytometry was used to detect the effect of simvastatin on A549 cell cycle; Mitochondrial membrane potential-1 (JC-1) fluorescent probe was wsed to detect the effect of simvastatin on mitochondrial membrane potential (MMP); Flow-type phosphatidl serine protein antibody Annexin V/propidium iodide (Annexin V-FITC/PI) double staining method was used to detect the effect of simvastatin on A549 cell apoptosis; CCK8 method was used to detect the effect of Z-VAD-FMK on the survival rate of A549 cells; TdT-mediated 2'-deoxyuridine 5'-triphosphate (dUTP) nick end labeling (TUNEL) method was used to detect the effect of Z-VAD-FMK on simvastatin-induced apoptosis in A549 cells; Western blot method was used to detect the effect of simvastatin on the expression levels of Janus kinase 2 and activation of signal transducers and activators of transcription 3 (JAK2/STAT3) pathway-related proteins phosphorylated JAK2 (p-JAK2), JAK2, phosphorylated STAT3 (p-STAT3), and STAT3 before and after the activator IL-6 of JAK2/STAT3 pathway acted on A549 cells. Results: The survival rates of A549 cells in the 20-80 mg/L simvastatin-treated groups were significantly lower than that in the control group (all P<0.05), and gradually decreased with the increase of the concentration of the simvastatin and the extension of the action time. The cells in the G(0)/G(1) phase of the simvastatin group were significantly higher than those in the control group, and the cells in the G(2)/M phase were significantly lower than those in the control group (all P<0.01). The MMP of the treatment group with different concentrations of simvastatin was significantly lower than that of the control group (all P<0.05). The apoptosis rate of the 20 mg/L and 40 mg/L simvastatin-treated group was significantly higher than that of the control group (both P<0.01). The cell survival rate of the 40 mg/L simvastatin group and the 40 mg/L simvastatin combined with Z-VAD-FMK group were (52.2±2.7)% and (57.5±3.8)%, respectively, were lower than that of the control group (100.0±2.7)% (both P<0.01). But the difference between 40 mg/L simvastatin group and the simvastatin combined with Z-VAD-FMK group was not statistically significant (P>0.05). The cell numbers with positive fluorescent staining in the 40 mg/L simvastatin group were significantly more than those in the control group, but the cell numbers with positive fluorescent staining in the 40 mg/L simvastatin combined with Z-VAD-FMK group had no statistical significance compared with the simvastatin group (P>0.05). The specific value of p-JAK2/JAK2 and p-STAT3/STAT3 protein relative expressions in the simvastatin-treated group (20, 40 mg/L) were significantly lower than that in the control group, respectively (both P<0.05). The specific value of p-JAK2/JAK2 and p-STAT3/STAT3 protein relative expressions in IL-6 group were significantly higher than those in control group (both P<0.05), the specific value of p-JAK2/JAK2 and p-STAT3/STAT3 protein relative expressions in simvastatin (20, 40 mg/L) combined with IL-6 groups were lower than those in IL-6 group (all P<0.05), respectively. Conclusion: Simvastatin can induce the apoptosis of A549 cells through a non-caspase-dependent mitochondrial apoptosis pathway, which may be achieved by inhibiting the JAK2/STAT3 pathway.

[The expression and significance of chromobox protein homolog 2 in breast cancer].

Objective: To study the relationship between the expression of Chromobox protein homolog (CBX) mRNA and the clinicopathological prognosis of breast cancer, and to investigate the possibility of Chromobox protein homolog 2 as a therapeutic target for breast cancer. Methods: First, we analyzed the mRNA expression of 8 CBX family genes by METABRIC database, and investigated the relationship between the expression of CBX2 mRNA and the clinicopathological parameters of breast cancer. Then we explored its relationship with prognosis. CBX2 siRNA was used to treat breast cancer cell lines with high expression of CBX2(SUM159 and SUM1315). The effects of knockdown of CBX20 on mRNA and protein expression and cell proliferation were observed. Results: According to the analysis of METABRIC database, among the 8 CBX genes, the most obvious increase in mRNA expression was CBX2, and 22.47% (445/1 980) of the patients showed high mRNA expression. The high expression of CBX2 was closely related to tumor histological grade and the molecular type of breast cancer (P<0.001). Compared with the low-expression group of CBX2 mRNA, the proportion of HER2 breast cancer (28.1% vs 7.5%) and Basal-like (44.5% vs 8.5%) in the high-expression group were both higher. Patients with high CBX2 expression had significantly shorter disease-free survival (DFS) and overall survival (OS). The knockdown of CBX2 by siRNA inhibited the proliferation of breast cancer cells. Conclusion: CBX2 is closely related to the prognosis of breast cancer and may be a target for breast cancer treatment.

[Observation on the efficacy of CT-guided lumbar sympathetic chemical destructive block in the treatment of cold sensation of limbs].

Objective: To observe the clinical effects of CT-guided chemical destructive block of lumbar sympathetic nerve in the treatment of cold sensation of limbs. Methods: In this retrospective analysis, clinical data of 43 patients with cold sensation of limbs treated by lumbar sympathetic chemical destructive block in the Affiliated Hospital of Jiaxing University from January 2015 to January 2018 were collected. The changes of heart rate, non-invasive blood pressure (NIBP), oxygen saturation (SpO(2)), plantar temperature and peripheral perfusion index (PI) of patients were recorded and analyzed before treatment and 5 min after injection of anhydrous ethanol. The patients were followed up at postoperative 1 day, 1 week, 1 month, 3 months, 6 months, 1 year and 2 years. Results: Fourty-three patients underwent bilateral lumbar sympathetic nerve chemical destructive block under the CT-guided, and all patients were punctured to the target successfully. The PI of patients before and after treatment were 1.2±0.6, 7.2±3.0 respectively, which was significantly increased after treatment compared with before treatment, and the difference was statistically significant (t=12.386, P<0.05). The plantar temperature of patients before and after treatment respectively were (29.6±1.7)℃, (34.6±1.1)℃, which was significantly increased after treatment compared with before treatment, and the difference was statistically significant (t=15.057, P<0.05). There were no significant differences in heart rate, NIBP and SpO(2) between before and after treatment (all P>0.05). Lumbar sympathetic chemical destructive block was clinically effective in 39 patients (90.7%) and ineffective in 4 patients (9.3%). Among the 39 clinically effective patients, the curative effects were excellent in 29 cases and improved in 10 cases. Postoperative recurrence occurred in 10 cases (25.6%). The satisfaction rates of patients at 1 day, 1 week, 1 month, 3 months, 6 months, 1 year and 2 years after operation were 93.0%, 90.7%, 86.0%, 76.7%, 69.7%, 65.1% and 53.4%, respectively. Conclusion: Lumbar sympathetic chemical destructive block is a safe and effective way for the treatment of cold sensation of limbs, which can improve the symptoms of cold sensation of limbs to some extent.

[Pharmacological effects of site specific conjugated anti-human epidermal growth factor receptor 2-antibody drug conjugate using unnatural amino acid technology].

OBJECTIVE: To investigate inhibitory activities of a homogenous anti-human epidermal growth factor receptor 2 (HER2)-antibody drug conjugate (ADC) on the proliferation of nine tumor cell lines with different levels of HER2 expressions, and its activities on the tumor growth of five xenograft mouse models. METHODS: The HER2 expression levels of BT-474, Calu-3, MCF-7, MDA-MB-231, MDA-MB-468, SK-BR-3, SK-OV-3, HCC1954, NCI-N87 tumor cell lines were measured using QIFI KIT. For the in vitro anti-proliferation assay, serial diluted anti-HER2-ADC, ado-trastuzumab emtansine, AS269, pAF-AS269 and paclitaxel were added to the seeded cells, and after 72 or 96 hours of incubation, the cell proliferation was analyzed. For the in vivo activity, 5-6 weeks old mice were inoculated with four HER2 positive tumor cell lines HCC1954, BT-474, SK-OV-3, NCI-N87 or one HER2 negative tumor cell line MDA-MB-468. Different amounts of anti-HER2-ADC, ado-trastuzumab emtansine, trastuzumab, paclitaxel and phosphate buffered saline control were injected after the tumor volume reached a certain size, then the tumor growth inhibition was analyzed. RESULTS: The expression levels of the six high HER2-expression cell lines SK-OV-3, NCI-N87, SK-BR-3, Calu-3, HCC1954, BT-474 were between 430 000 to 800 000 receptors per cell, which were 50 times higher than those of the other three low HER2 expression tumor cell lines MDA-MB-231, MCF-7, MDA-MB-468. Anti-HER2-ADC had inhibition effects on cell lines with high level of HER2 expression in the in vitro anti-proliferation assay. The half maximal inhibitory concentrations of anti-HER2-ADC on SK-OV-3, NCI-N87, SK-BR-3, Calu-3, HCC1954, BT-474 tumor cell lines were 46 pmol/L, 17 pmol/L, 17 pmol/L, 161 pmol/L, 125 pmol/L, 50 pmol/L, respectively. Anti-HER2-ADC had a dose dependent antitumor activity in vivo in all the HER2 positive xenograft mouse models. In NCI-N87 xenograft tumor model, the same dose of anti-HER2-ADC showed better anti-tumor activity compared with trastuzumab and ado-trastuzumab emtansine, and its relative tumor proliferation rates were about 1/30 to 1/20 of the two. In HCC1954 xenograft tumor model, the complete regression of the tumor was observed. As expected, anti-HER2-ADC had no tumor inhibitory effects on MDA-MB-468 xenograft models with low HER2 expression. The antitumor activities of anti-HER2-ADC in HER2 positive xenograft tumor models were the same as or better than the activities of ado-trastuzumab emtansine. CONCLUSION: The homogenous site-specific anti-HER2-ADC obtained using unnatural amino acid technology can inhibit the growth of high HER2-expression tumor cells with high potency both in vivo and in vitro.

[The influence factors of pathologic complete response of the ipsilateral supraclavicular lymph node of breast cancer after neoadjuvant chemotherapy].

Objective: To investigate the factors affecting the pathologic complete response (PCR) of the ipsilateral supraclavicular lymph node (ISLN) of breast cancer after neoadjuvant chemotherapy (NAC). Methods: A total of 178 patients with breast cancer who had primary ipsilateral supraclavicular lymph node metastasis (ISLNM), receiving NAC and subsequent ISLN dissection, were retrospectively reviewed. The single factor and multi factor analysis were carried out by the chi square test and the Logistic regression model. Results: The enrolled patients were all female, 28 to 74 years old. The rate of PCR on the ISLN was 52.2%. Single factor analysis showed that KI67 expression level (χ(2)=7.717,P=0.005), breast PCR (bPCR) (χ(2)=33.564,P<0.001), and axillary PCR (aPCR) (χ(2)=31.750, P<0.001) were associated with the ISLN PCR. Multifactor analysis showed that KI67 expression level (OR=4.096, 95%CI: 1.176-14.263, P=0.027), bPCR (OR=4.452, 95%CI: 1.894-10.461, P<0.001) and aPCR (OR=5.183, 95%CI: 1.974-13.605, P<0.001) were independent predictors of ISLN PCR. The rate of PCR on the ISLN was 90.9% in the patients with KI67>30% and simultaneous breast and axilla PCR. Conclusions: The PCR rate of the ISLN after neoadjuvant chemotherapy is higher than that of the breast and axillary PCR. The expression level of KI67, the bPCR and the aPCR are independent predictors of the PCR on the ISLN.

Systemic mastocytosis identified in two women developing fragility fractures during lactation.

Two women presenting with fragility fractures during lactation had bone mineral density (BMD) reduced more greatly than usually associated with lactation. The first woman was 29 years old with a BMD T-score of - 3.2 SD at the spine and- 2.0 SD at the femoral neck. The second woman was 35 years old with a BMD T-score of - 4.5 SD at the spine and - 2.8 SD at the femoral neck. Both women had increased cortical porosity and reduced trabecular density. Investigation identified an elevated serum tryptase, and marrow biopsy confirmed the diagnosis of mastocytosis. Lactation causes bone loss, but the occurrence of fractures in the setting of severe deficits in BMD and microstructural deterioration signals the need to consider additional causes of bone loss.

Characterization of transcriptional complexity during pre-implantation development of the yak (Bos grunniens) using RNA-Seq.

The objective of this study was to investigate the mechanism that regulates pre-implantation development of the yak (Bos grunniens). We determined the transcriptomes of in vitro-produced yak embryos at two-cell, four-cell, eight-cell stages, and morula and blastocyst using the Illumina RNA-seq for the first time. We obtained 47.36-50.86 million clean reads for each stage, of which, 85.65%-90.02% reads were covered in the reference genome. A total of 17,368 genes were expressed during the two-cell stage to blastocyst of the yak, of which 7,236 genes were co-expressed at all stages, whereas 10,132 genes were stage-specific expression. Transcripts from 9,827 to 14,893 different genes were detected in various developmental stages. When |log2 ratio| ≥ 1 and q-value <0.05 were set as thresholds for identifying differentially expressed genes (DEGs), we detected a total of 6,922-10,555 DEGs between any two consecutive stages. The GO distributions of these DEGs were classified into three categories: biological processes (23 terms), cellular components (22 terms) and molecular functions (22 terms). Pathway analysis revealed 310 pathways of the DEGs that were operative in early pre-implantation yak development, of which 32 were the significantly enriched pathways. In conclusion, this is the first report to investigate the mechanism that regulates yak embryonic development using high-throughput sequencing, which provides a comprehensive framework of transcriptome landscapes of yak pre-implantation embryos.

[The influence of lumpectomy on the axillary lymph node status of breast cancer patients].

Objective: To investigate the influence of lumpectomy on axillary lymph node status of breast cancer patients. Methods: The clinical data of 738 invasive breast cancer patients with non-palpable axillary lymph node and sentinel lymph node (SLN) biopsy from November 2011 to August 2013 in Henan Provincial Cancer Hospital were collected and retrospectively analyzed. Among them, 136 patients underwent preoperative lumpectomy (lumpectomy group) and 602 patients underwent puncture biopsy only (biopsy group). The difference of axillary lymph node status and positive ratio of SLN detected by color Doppler ultrasound were compared between these two groups. Results: Among the 738 breast cancer patients, the axillary lymph nodes of 444 (60.2%) cases could be detected by ultrasound. Among them, 92 cases belonged to lumpectomy group, significantly less than 352 cases of biopsy group (P=0.048). Among the patients with ultrasound-visible lymph nodes, the proportion of the biggest diameter of axillary lymph node >1 cm of lumpectomy group or biopsy group was 58.7% (54/92) or 52.8% (186/352), respectively, without significant difference (P=0.316). The proportion of patients with the ratio of long diameter to short diameter <2 of lumpectomy group or biopsy group was 37.0% (34/92) or 38.6% (136/352), respectively, with marginal difference (P=0.768). The positive rate of SLN of lumpectomy group or biopsy group was 23.5% (32/136) or 26.9% (162/602), respectively, without significant difference (P=0.419). The incidence rate of the ultrasound visible axillary lymph nodes of patients whose postoperative time ≤ 7 days or > 7days was 71.1% (64/90) or 60.9% (8/46), respectively, without significant difference (P=0.227). However, the positive rate of SLN of these two groups was 28.9% (26/90) and 13.0% (6/46), respectively, with significant difference (P=0.039). The number of ultrasound visible axillary lymph nodes, the biggest diameter of axillary lymph nodes and the ratio of the long diameter to short diameter <2 were substantially correlated with the positive rate of SLN (P<0.05). Conclusions: The incidence rate of ultrasound visible axillary lymph node in the patients with lumpectomy is higher than that of patients with puncture biopsy only. The positive rate of SLN of the patients with a long postoperative time is lower than that of patients with a short postoperative time, even though the axillary lymph nodes are ultrasound visible.

[The significance of different predictive equations for resting energy expenditure in patients receiving invasive mechanical ventilation].

To calculate resting energy expenditure (REE) in patients receiving invasive mechanical ventilation and compare different predictive equations with indirect calorimetry(IC).A total of 60 patients in intensive care unit(ICU) were enrolled. Measure calculating daily REE in the first week included IC, Harris-Benedict formula, Penn State formula and Swinamer formula. Daily REE did not exhibit significant difference in the first week of mechanical ventilation by IC (all P>0.05).All patients' REE values by IC were higher than those by Harris-Benedict formula (all P<0.01). By Penn State formula, REE in day l, 2, and 5 were comparable (all P>0.05) with those by IC, whereas the consistency between the two methods was poor. Similarly, daily REE by Swinamer formula calculation in the first week did not show significant difference (all P>0.05), with acceptable consistency as IC. Resting energy expenditure in patients receiving invasive mechanical ventilation dose not significantly change during the first week. Swinamer formula is more accurate than other equations when IC is considered as the standard method.

[Analysis of predictive effect of Androgen receptor on the response to neoadjuvant chemotherapy in breast cancer patients].

Objective: To explore the expression of androgen receptor (AR) in the tissues as well as its association with the clinicopathological factors of primary breast cancer patients treated with neoadjuvant chemotherapy (NAC), and analyze the effect of AR in the prediction of pathologic complete response (PCR) rate. Method: A total of 668 breast cancer patients treated with NAC in Henan Cancer Hospital between March 2014 and June 2017 were retrospectively reviewed. The relationship of AR expression and clinicopathological characteristics was calculated using chi square test. Multivariate analysis using binary Logistic regression was used to analyze correlations of different factors with PCR. Result: All patients were female, with the age of 20-76 years old. AR was detected in 74.6% of tumors, and significantly correlated with hormone receptor (HR), human epidermalgrowth factor receptor-2 (HER-2), Ki-67, CK5/6, epidermal growth factor receptor (EGFR) and molecular subtypes (all P<0.05). Multivariate analysis showed that AR, HR and HER-2 were independent predictors for PCR (all P<0.05). Conclusions: The expressions of AR were more frequently in HR positive breast cancer tissues (86.7%), and lowest in triple-negative breast cancer (TNBC) group (23.2%). AR was independent predictor for PCR.

[Analysis of factors influencing the axillary lymph node metastasis and breast cancer-specific survival in patients with T1 breast cancer].

Objective: To investigate the predictors of axillary lymph node metastasis and the breast cancer-specific survival (BCSS) in patients with T1 breast cancer. Methods: A retrospective analysis of clinical and pathological data of 840 T1 invasive breast cancer cases between January 2009 and January 2014 in Henan Cancer Hospital was conducted.Chi square test and Logistic regression analysis were carried out to identify relevant factors of lymph node metastasis. Analysis of prognostic factors were analyzed by Log-rank test and Cox regression. Results: Among the 840 T1 breast cancer cases, positive axillary lymph nodes were found in 150 (17.9%) cases. Univariate analysis showed that tumor size, histological grade, tumor location, and HER2 status were associated with axillary lymph node status (P<0.05). Multivariate analysis showed that tumor size, histological grade, tumor location, and HER2 status were independent predictive factors of axillary lymph node metastasis (P<0.05). Log-rank test showed that tumor size, histological grade, HER2 status, partial response (PR) status and number of positive lymph nodes were important factors influencing BCSS of the patients with positive axillary lymph nodes (P<0.05). Cox analysis showed that the size of the primary tumors and the number of positive lymph nodes were independent factors affecting the BCSS of the patients(P<0.05). Conclusions: Tumor size, histological grade, tumor location and HER2 status correlated with axillary lymph nodes status of T1 breast cancer. For T1 breast cancer patients with positive axillary lymph node, more positive lymph nodes involved and smaller primary tumor correlated with worse prognosis.

[Analysis of corneal and conjunctival sensitivities and its related factors of premature babies].

Objective: To analyse the corneal and conjunctival sensitivities of premature babies and to study the relevant influencing factors. Methods: Cross-sectional study. One hundred premature infants born at Women's Hospital School of Medicine Zhejiang University between May 2015 and September 2015 were enrolled, among which 51 were male (51%) and 49 were female (49%), the mean gestational age was (30.93±1.75)w, the mean corrected gestational age was (33.65±1.53)w, the mean birth weight was (1 592±336)g. The thresholds of cornea and conjunctiva of infants' left or right eyes were measured with Cochet-Bonnet aesthesiometer at 8-10 o'clock every morning when they naturally woke up, the minimum length of nylon wire that induced three successive times of eye-blink responses was recorded. Paired sample t test was used to compare the corneal and conjunctival sensitivities, the ocular surface sensitivities of preterm infants of different gender were compared using independent samples t-test, Pearson correlation and multiple linear regression analysis was conducted to analyze the correlation of corneal and conjuncitval sensitivities with gestational age, birth weight, age and corrected gestational age. Results: The mean corneal sensitivity was (44.85±5.53) mm and the mean conjunctival sensitivity was (23.50±5.48)mm in premature babies, corneal sensitivity was significantly higher than conjunctival sensitivity (t=25.620, P<0.001). No statistical significance was found between male and female preterm infants in corneal sensitivity [(44.80±5.83) mm vs. (44.90±5.25) mm, t=-0.085, P=0.933] and conjunctival sensitivity[(23.14±5.83) mm vs. (23.88±5.13) mm, t=-0.673, P=0.502]. Pearson correlation analysis showed that corneal sensitivity was significantly associated with conjunctival sensitivity in prematurity(r=0.676, P<0.001). There was significant correlation between corneal sensitivity and age, corrected gestational age (r=0.238, P=0.017; r=0.679, P<0.001), however no significant correlation was found between corneal sensitivity and gestational age, birth weight in preterm infants (r=0.067, P=0.510; r=-0.179, P=0.075). There was significant correlation between conjunctival sensitivity and corrected gestational age (r=0.490, P<0.001), however no significant correlation was found between conjunctival sensitivity and gestational age, birth weight and age in preterm infants (r=0.078, P=0.439; r=-0.096, P=0.344; r=0.151, P=0.133). Multiple linear regression revealed that corneal sensitivity(Y1) was positively correlated with corrected gestational age(X), the regression equation was Y1=2.45X-37.52, the conjunctical sensitivity(Y2) was also positively correlated with corrected gestational age(X), the regression equation was Y2=1.75X-35.41. Conclusions: The corneal sensitivity is higher than conjunctival sensitivity in premature babies.No statistical significance is found between male and female preterm infants in corneal sensitivity and conjunctival sensitivity. The corneal sensitivity and conjunctival sensitivity are correlated with corrected gestational age in preterm infants. The corneal and conjunctival sensitivities of premature babies tend to increase along with the increase of corrected gestational age. (Chin J Ophthalmol, 2018, 54: 115-119).

Performance of InGaN based green laser diodes improved by using an asymmetric InGaN/InGaN multi-quantum well active region.

Series of green laser diodes (LDs) with different (In)GaN barrier layers are investigated. It is found that the optical confinement factor of multi-quantum well (MQW) always increases with increasing indium content of InGaN barrier layer, which results in a decrease of threshold current when indium content of InGaN barrier layer increases from 0 to 5%. However, when a high In content InGaN barrier is used (> 5%), both threshold current and slop efficiency of LDs deteriorate. It may be attributed to the waste of carriers in the potential well at the interface between the last barrier (LB) and the upper waveguide (UWG) layers, which is induced by the piezoelectric polarization effect in high In content InGaN LB layer. Therefore, a new LD structure using a thin thickness of the LB layer to reduce the effect of polarization shows a low threshold current and a high output power even when the In content of barrier layers is as large as 7%.