[The efficacy of radiotherapy based combined therapy for unresectable locally invasive bladder cancer and its associated factors analysis].

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.

Visualization of Chiral Electronic Structure and Anomalous Optical Response in a Material with Chiral Charge Density Waves.

Chiral materials have attracted significant research interests as they exhibit intriguing physical properties, such as chiral optical response, spin-momentum locking, and chiral induced spin selectivity. Recently, layered transition metal dichalcogenide 1T-TaS_{2} has been found to host a chiral charge density wave (CDW) order. Nevertheless, the physical consequences of the chiral order, for example, in electronic structures and the optical properties, are yet to be explored. Here, we report the spectroscopic visualization of an emergent chiral electronic band structure in the CDW phase, characterized by windmill-shaped Fermi surfaces. We uncover a remarkable chirality-dependent circularly polarized Raman response due to the salient in-plane chiral symmetry of CDW, although the ordinary circular dichroism vanishes. Chiral Fermi surfaces and anomalous Raman responses coincide with the CDW transition, proving their lattice origin. Our Letter paves a path to manipulate the chiral electronic and optical properties in two-dimensional materials and explore applications in polarization optics and spintronics.

Maintenance of cellular annexin A1 level is essential for PI3K/AKT/mTOR-mediated proliferation of pancreatic beta cells.

Annexin A1 (AnxA1, also known as lipocortin-1), is a calcium-dependent phospholipid binding protein with diverse functions. Previous studies have indicated that AnxA1 is associated with age-related ß-cell dysfunction and aging, which lead to decreased ß-cell proliferation capacity. However, it has been uncertain whether AnxA1 affects the proliferation of pancreatic beta (ß) cells. In the present study, we reduced AnxA1 expression in the MIN6 islet ß-cell line using small interfering RNA (AnxA1-siRNA), then measured cell cycle distribution and cellular proliferation. We also measured the expression levels of cell cycle-related proteins such as cyclin D1, cyclin E, and cyclin-dependent kinase 2 (CDK2) by Western blot analysis. We investigated the phosphatidylinositol 3-kinase (PI3K)/ serine/threonine protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway to explore the potential mechanism underlying the observed effects. Knockdown of AnxA1 expression using siRNA reduced the rates of MIN6 cell proliferation. The proportions of cells in S and G2/M phases also decreased upon inhibition of AnxA1. Moreover, AnxA1 protein expression in MIN6 cells was positively related to the protein levels of cyclin D1, cyclin E, and CDK2. Activation of the PI3K/Akt/mTOR signaling pathway by AnxA1 may be involved in the signaling cascade to regulate cell proliferation. This study identified a positive correlation between AnxA1 protein and pancreatic ß-cell proliferation. AnxA1 protein expression might affect the proliferation of MIN6 cells via regulation of cyclin D1, cyclin E, and CDK2 proteins, as well as the PI3K/Akt/mTOR signaling pathway.

The giant planar Hall effect and anisotropic magnetoresistance in Dirac node arcs semimetal PtSn4.

Topological semimetals (TSMs) present intriguing quantum states and have attracted much attention in recent years because of exhibiting various anomalous magneto-transport phenomena. Theoretical prediction shows that some novel phenomena, such as negative magnetoresistance (MR) and the planar Hall effect (PHE), originate from the chiral anomaly in TSMs. In this work, high-field (33 T) Shubnikov-de Haas (SdH) oscillations are obtained to reveal the topology of PtSn4. Giant PHE and anisotropic magnetoresistance (AMR) are observed in Dirac node arcs of semimetal PtSn4. First, a non-zero transverse voltage can be acquired while tilting the in-plane magnetic field. Moreover, the amplitude of PHE sharply increases at T * ∼ 50 K with decreasing temperature, which is suggested to be related to the Fermi surface reconstruction observed in PtSn4. Subsequently, the field-dependent amplitudes of the PHE show an abnormal behavior around 50 K, which is thought to stem from the complex correlation between the chiral charge and electric one in PtSn4 driving the system into different coupling states due to the complicated band structure. On the other hand, the relative AMR is negative and up to -98% at 8.5 T. Our work proves that the PHE measurements are a convincing transport fingerprint feature to confirm the chiral anomaly in TSMs.

Effects of dietary supplementation with grape seed procyanidins on nutrient utilisation and gut function in weaned piglets.

Grape seed procyanidins (GSPs), widely known for their beneficial health properties, fail to bring about the expected improvement in piglets' growth performance. The effects of dietary supplementation with GSPs on nutrient utilisation may be a critical influencing factor. Hence, the purpose of this study was to investigate the effects of dietary supplementation with GSPs on nutrient utilisation and gut function in weaned piglets. One hundred and twenty crossbred piglets were allocated randomly to four treatment groups, with three replicate pens per treatment and 10 piglets per pen. Each group was given one of the four dietary treatments: the basal diet (control group) or the basal diet with the addition of 50-, 100- or 150-mg/kg GSPs. The trial lasted 28 days. Faeces were collected from d 12 to 14 and from d 26 to 28 for measuring the coefficient of total tract apparent digestibility (CTTAD) of the nutrients. Blood samples were collected on d 14 and 28 for detecting the blood biochemical parameters. Two piglets per pen were slaughtered to collect the pancreas and intestinal digesta for evaluating the digestive enzyme activity and the coefficient of ileal apparent digestibility (CIAD) of the nutrients. On d 14 and 28, supplementation with 150-mg/kg GSPs significantly decreased the CTTAD of DM and CP in piglets. On d 14, GSPs supplementation at a concentration of 150 mg/kg led to a remarkable decrease in the CIAD of CP and gross energy (GE). On d 28, GSPs supplementation at a dose of 150 mg/kg generated a marked decline in the CIAD of DM, GE, CP and ether extract. Grape seed procyanidins supplementation at concentrations of 100 or 150 mg/kg inhibited the activities of lipase and amylase. In contrast, the jejunum mucosa maltase and sucrase activities increased due to the inclusion of GSPs at a concentration of 100 mg/kg in the piglet diet. Compared with the levels of the control group, the serum glucose and total protein levels were enhanced significantly by supplementation with GSPs at 100 mg/kg and reduced dramatically at 150 mg/kg. The serum diamine oxidase activity and endotoxin levels were decreased by GSPs supplementation in piglet diets. In conclusion, higher concentrations of GSPs in weaned piglet diets attenuated nutrient digestion and inhibited digestive enzyme activity; however, suitable concentrations of GSPs could promote brush-border enzyme activity, enhance serum glucose and total protein concentrations and decrease epithelial permeability.

[A study on alterations in mitochondrial biological characteristics during cellular senescence of human embryonic lung fibroblasts].

Objective: To study the alterations of mitochondrial biological characteristics during both cellular replicative and premature senescence induced by hydrogen peroxide in human embryonic lung fibroblasts (HEFs). Methods: The premature senescence was induced by 400 µmol/L H(2)O(2) once a day at the same time and with 2 hours each time, after four consecutive days the premature senescence models were classified into premature senescence initiation group (PSi) and premature senescence persistence group (PSp). Based on the life span of HEFs, the cell replicative senescence was divided into five groups included young-age (22 PDL), middle-age (35 PDL), replicative senescence (49 PDL), PSi and PSp. The mitochondrial distribution, relative content, adenosine triphosphate (ATP) contents, 8-hydroxydeoxyguanosine (8-OHdG) levels, the relative mitochondrial transcription factor A (TFAM) as well as mitochondrial DNA methyltransferase 1 (mtDNMT1) mRNA levels, mtDNA copy number, the relative TFAM protein level and the total enzyme activity of mitochondrial DNA methyltransferases (mtDNMTs) were detected in five senescence groups. Results: The mtDNA copy number, 8-OHdG contents, level of mtDNMT1 mRNA and mtDNMTs activity in 49 PDL group were higher than those in 22 PDL group (all P values <0.05); The level of 8-OHdG in PSi was higher than that in 22 PDL group (P<0.05); The ATP contents, mtDNA copy number, the mRNA and protein expression levels of TFAM and mtDNMTs activity of PSp were higher than those in 22 PDL group (all P values<0.05). Conclusion: During the cellular senescence of HEFs, the higher mtDNA copy number and mtDNMTs activity were common features regardless of replicative or premature senescence, with possibility that oxidative stress was involved in modifying the occurrence of premature senescence.

[Time series analysis on the effect of ambient fine particulate matters and temperature interactions on schizophrenia admission in Tongling City of Anhui Province, 2014-2017].

Objective: To explore the effect of ambient fine particulate matters (PM(2.5)) and temperature interaction on schizophrenia admission. Methods: All admission data were retrieved from the Psychiatric Hospital and Municipal Hospital of TongLing from January 1, 2014 to December 31, 2017. Daily air pollution and meteorological data were collected from the Tongling Environmental Protection Agency and Meteorological Bureau, respectively. A distributed lag non-linear model combined with the generalized additive model were applied to explore the effects of PM(2.5), multi-pollutants, and the interaction between temperature and PM(2.5) on schizophrenia admission. The stratification of temperature was divided by three criteria. The low temperature layer was defined as P(95) or >P(90) or >P(80) was defined as the high temperature layer. Results: From 2014 to 2017, 6 642 patients were admitted for schizophrenia in Tongling, and the median of PM(2.5) and temperature were 47.0 µg/m(3) and 17.5 ℃, respectively. The median concentration of PM(2.5) (P(50)) was taken as a reference. When the exposure concentration of PM(2.5) was P(90), the lagged effect appeared in the first day with RR=1.03 (95%CI: 1.00-1.07) and reached the maximum in the fifth day with RR=1.16 (95%CI: 1.13-1.19). In the multi-pollutant models, it was found that the simultaneous inclusion of PM(2.5) and NO(2) had higher risk of schizophrenia admission, with the RR=1.18 (95%CI: 1.15-1.22), P<0.001. The risk of schizophrenia admission caused by PM(2.5) exposure at high temperature was greatest under the three temperature stratification standards, which were 12.1% (8.5%-15.7%), 9.7% (6.9%-12.6%) and 17.1% (11.6%-22.8%), all P values <0.001. Conclusion: With the increase of PM(2.5) concentration, the risk of schizophrenia admission is increased, and the risk effect of PM(2.5) is stronger at high temperature.

[Prevalence of allergy in children with acute rhinosinusitis].

Objective:To explore the prevalence of allergy in patients with acute rhinosinusitis (ARS) and evaluate the severity of symptoms in ARS children with or without allergy.Method:Two hundred and seven children (4-12 years of age) with ARS and 85 children of control group were included in our research from June, 2016 to January, 2018. We use questionaire to collect the basic information of pediatric patients. The results of skin prick test (SPT) were recorded. Mothers were required to complete the Sinus and Nasal Quality-of-Life Survey (SN-5).All ARS childern were divided into allergic group and non-allergic group according to the result of SPT. We use binomial distribution to evaluate the population rate. t-test, Chi-square test and Wilcoxon rank-sum test were appropriately used to compare the parameters between two groups.Result:Among the 207 ARS participants in this study, 44.4% participants were shown to response to at least one Inhalation allergen and 40.6% participants were shown to response to at least one perennial allergen. Both ratios were significantly higher than those of the control group. Perennial allergy seems to be much more common than seasonal allergy in pediatric patients with ARS. The most troublesome symptoms among the participants with acute rhinosinusitis combined with allergic rhinitis were nasal obstruction (5.28±1.34), nasal discharge (5.07±1.04), post-nasal drip (4.63±1.31) and itchy eyes/nose (4.28±1.51). Four subscale scores of the SN-5 including nasal obstruction, allergy symptoms, emotional distress and activity limitation in the allergic group were obviously higher than those of the non-allergic group.Conclusion:Allergic factors play an important role in the pathogenesis of pediatric acute rhinosinusitis.

[Analysis of the related factors of attention deficit/hyperactivity disorder and allergic rhinitis in children].

Objective:To investigate the association between symptom of attention deficit/hyperactivity disorder (ADHD) and allergic rhinitis (AR) in children with AR at different sexes and different ages. Method:A total of 439 AR children aged 6 to 12 years were enrolled in this study. Basic information (age, gender, medical history, family history and comorbidities) of children with AR was collected. Results of prick tests on children skin were recorded. (TNSS) and Chinese version of the SNAP-Ⅳ scale, children under the guidance of independent completion of children's quality of life of children with nasal conjunctivitis scale (PRQLQ). According to the results of SNAP-Ⅳ, children were divided into AR with ADHD group ï¼»attention deficit and hyperactivity symptom score (IHS) >1.25ï¼½ and AR without ADHD group (IHS≤1.25). The differences between the two groups of children were analyzed using group t-test and χ² test, and the relationship between each parameter and IHS >1.25 was analyzed by binary logistic regression. Result:Using SPSS 22.0 software, among all the included AR children, IHS >1.25 children accounted for 26.4%, IHS >1.25 group AR symptom scores were significantly higher than HIS ≤1.25 groups. Univariate analysis showed that children with age, gender, duration of AR symptoms, skin index and PRQLQ subscales had a correlation with IHS >1.25. After controlling for age and gender, duration of AR symptoms and skin index correlated with IHS >1.25 The estimated OR values are 1.807 (95%CI: 1.350-2.419) and 1.912 (95%CI: 1.320-2.772), respectively. The estimated OR values of PRQLQ subscale and IHS >1.25 were 1.657 (nasal symptom score), 1.324 (eye symptom score), 2.48 (non-eye-nasal symptom score), 1.418 (Behavior problem score) and 2.045 (activity and sleep score). The correlation between IHS>1.25 and the skin index and PRQLQ subscales was mainly found in males with stratification of age and gender, and the association between duration of AR symptoms and HIS >1.25 was statistically significant among all groups reflected. Conclusion:The association between attention deficits and hyperactivity symptoms in AR children was correlated with the severity of AR symptoms, duration, and skin index, and this association was more pronounced in males. In children with AR and ADHD, early management of AR symptoms may improve their ADHD symptoms.

Nanoporous FeP nanorods grown on Ti plate as an enhanced binder-free hydrogen evolution cathode.

A porous and interconnected nanorod-like FeP structure on titanium plate has been fabricated by a simple hydrothermal method and followed by a calcination process. The nanorod is assembled by many paralleled FeP nanowires with a porous structure. With the porous surface structure of FeP nanorods and the synergetic effect from the electronic conductive Ti support, this binder-free FeP electrode brings about a desirable electrocatalytic activity for the hydrogen evolution reaction (HER), showing a low onset overpotential of 23 mV and a small Tafel slope of 39 mV dec-1. Meanwhile, its catalytic activity could be maintained almost unchanged for at least 12 h in an acidic solution. This work provides us an effective HER electrocatalyst which can be easily produced on a large scale and at low cost.

Incidence and management of diarrhea in patients with HER2-positive breast cancer treated with pertuzumab.

Background: Pertuzumab disrupts heterodimerization between human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR), HER3, and HER4. Thus, pertuzumab could result in adverse events similar to those observed with EGFR antagonists, such as diarrhea. We report the incidence and severity of diarrhea observed with pertuzumab in the CLEOPATRA, NeoSphere, and TRYPHAENA studies. Patients and methods: Patients (n = 1443) had metastatic [CLEOPATRA (n = 804)] or early-stage breast cancer [NeoSphere (n = 416) and TRYPHAENA (n = 223)]. The incidence and severity of diarrhea were analyzed by treatment received. The incidence of febrile neutropenia concurrent with diarrhea and the effect of pre-existing gastrointestinal comorbidities were also evaluated. Subgroup analyses were carried out using CLEOPATRA data. Results: The incidence of all-grade diarrhea across studies was generally greater for pertuzumab-based treatment, ranging from 28% to 72% (grade 1, 21%-54%; grade 2, 8%-37%; grade 3, 0%-12%; grade 4, 0%). Incidence was highest during the first pertuzumab-containing cycle, decreasing with subsequent cycles. Dose delays or discontinuations due to diarrhea were infrequent, ranging from 0% to 8%. Among pertuzumab-treated patients with diarrhea, 47%-67% received pharmacological intervention, most commonly with loperamide. Overlap between diarrhea and febrile neutropenia was uncommon, ranging from 0% to 11%. No relationship was observed between pre-existing gastrointestinal comorbidities and diarrhea. In CLEOPATRA, patients ≥65 years treated with pertuzumab had a higher incidence of grade 3 diarrhea than patients <65 years (19% versus 8%). All-grade diarrhea occurred at greater frequency among pertuzumab-treated Asian versus white patients with metastatic breast cancer (74% versus 63%); the corresponding rates in the control arm were 53% and 45%, respectively. Conclusions: In both the metastatic and early-stage breast cancer settings, diarrhea was common but manageable for all pertuzumab-containing regimens. Diarrheal episodes were mainly low grade and occurred most often during the first treatment cycle. Diarrheal-related drug delays or discontinuations were uncommon. ClinicalTrials.gov identifiers: NCT00567190 (CLEOPATRA), NCT00545688 (NeoSphere), NCT00976989 (TRYPHAENA).

Enhanced electrochemical supercapacitance of binder-free nanoporous ternary metal oxides/metal electrode.

Free-standing nanoporous Ni-Cu-Mn mixed metal oxides on metal with a high surface area was fabricated by chemically dealloying a Ni8Cu12Mn80 single-phase precursor, followed by electrochemical oxidation in an alkaline solution. Electrochemical analysis shows that first Cu and Mn-based metal oxides formed by the electrochemical oxidation. Ni-based oxides grow later with the increase of electrochemical CV cycles and mix with the Cu/Mn oxides, forming a relatively stable mixed metal oxides thin film on metal ligament network. Due to the different electrochemical properties of each metal and the synergetic effect between them, the mixed ternary metal oxides formed on metal nano-ligament can operate stably between a wide potential window (1.5V) in 1.0M KOH aqueous solution when tested as a free-standing supercapacitor electrode. Due to the high volumetric surface area, wide operating potential window and excellent conductivity, the nanoporous metal oxides@metal composite exhibits a high volumetric capacitance (∼500Fcm(-3)), high energy density (∼38mWhcm(-3)) and good cycling stability.