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Lignocellulosic biomass photoreforming is a promising and alternative strategy for both sustainable H2 production and biomass valorization with infinite solar energy. However, harsh reaction conditions (high alkalinity or toxic organic solvents), with low biomass conversion and selectivity are often reported in literature. In this work, we report glucose photoreforming for coproduction of H2 and arabinose with improved selectivity under neutral condition using carbon quantum dots (CQDs) modified TiO2 composites. We show that the conventional CQDs fabricated by a facile one-step hydrothermal process could be endowed with novel color changing property, due to the particle aggregation under the regulation of incident light. The as-fabricated CQDs/TiO2 composites with certain colored CQDs could greatly improve glucose to arabinose conversion selectivity (~75%) together with efficient hydrogen evolution (up to 2.43 mmolh−1g−1) in water. The arabinose is produced via the direct C1-C2 α-scissions mechanism with reactive oxygen species of O2− and OH, as evidenced by 13C labeled glucose and the electron spin-resonance (ESR) studies, respectively. This work not only sheds new lights on CQDs assisted photobiorefinery for biomass valorization and H2 coproduction, but also opens the door for rationale design of different colored CQDs and their potential applications for solar energy utilization in the noble-metal-free system.

BACKGROUND Sedation with propofol injections is associated with a risk of addiction, but remimazolam benzenesulfonate is a comparable anesthetic with a short elimination half-life and independence from cell P450 enzyme metabolism. Compared to remimazolam, remimazolam benzenesulfonate has a faster effect, is more quickly metabolized, produces inactive metabolites and has weak drug interactions. Thus, remimazolam benzenesulfonate has good effectiveness and safety for diagnostic and operational sedation. AIM To investigate the clinical value of remimazolam benzenesulfonate in cardiac surgery patients under general anesthesia. METHODS A total of 80 patients who underwent surgery in the Department of Cardiothoracic Surgery from August 2020 to April 2021 were included in the study. Using a random number table, patients were divided into two anesthesia induction groups of 40 patients each: remimazolam (0.3 mg/kg remimazolam benzenesulfonate) and propofol (1.5 mg/kg propofol). Hemodynamic parameters, inflammatory stress response indices, respiratory function indices, perioperative indices and adverse reactions in the two groups were monitored over time for comparison. RESULTS At pre-anesthesia induction, the remimazolam and propofol groups did not differ regarding heart rate, mean arterial pressure, cardiac index or volume per wave index. After endotracheal intubation and when the sternum was cut off, mean arterial pressure and volume per wave index were significantly higher in the remimazolam group than in the propofol group (P < 0.05). After endotracheal intubation, the oxygenation index and the respiratory index did not differ between the groups. After endotracheal intubation and when the sternum was cut off, the oxygenation index values were significantly higher in the remimazolam group than in the propofol group (P < 0.05). Serum interleukin-6 and tumor necrosis factor-α levels 12 h after surgery were significantly higher than before surgery in both groups (P < 0.05). The observation indices were re-examined 2 h after surgery, and the epinephrine, cortisol and blood glucose levels were significantly higher in the remimazolam group than in the propofol group (P < 0.05). The recovery and extubation times were significantly lower in the remimazolam group than in the propofol group (P < 0.05); there were significantly fewer adverse reactions in the remimazolam group (10.00%) than in the propofol group (30.00%; P < 0.05). CONCLUSION Compared with propofol, remimazolam benzenesulfonate benefited cardiac surgery patients under general anesthesia by reducing hemodynamic fluctuations. Remimazolam benzenesulfonate influenced the surgical stress response and respiratory function, thereby reducing anesthesia-related adverse reactions.

BACKGROUND Because of their cancer and treatment adverse effects, most pediatric oncology patients will experience 1 or more symptoms at one time that can seriously affect their quality of life. Because these children are attached to parents, their symptom burden directly influences the parental stress level and parental interpretations of their children's quality of life. OBJECTIVE The aim of this study was to examine the association between child-reported symptom burden and the pediatric quality of life reported by children with cancer and their parents, and whether parental perceived stress mediates these relationships. METHODS In a cross-sectional design, convenience sampling was used to recruit 80 parent-child dyads. Advanced statistical methods were adopted to analyze the mediating effects of parental stress between children's symptom burden and their quality of life. RESULTS The results revealed that parental stress was the mediator in the relationship between child-reported symptom burden and children's quality of life reported by parents. The results also showed that parental stress was not a mediator in the relationship between child-reported symptom burden and their quality of life. This underscored the differences in interpretations of quality of life reported by children and their parents. CONCLUSION Children's symptom burden is an important factor in predicting parental stress level and the quality of life reported by the children. Children's voice should be incorporated whenever possible. IMPLICATIONS FOR PRACTICE The knowledge gained from this study will facilitate intervention development to enhance parents' abilities in stress management and symptom management for their children with the support of the nursing profession.

Background Src homology region 2 domain‐containing phosphatase 2 (SHP2) is a novel target for Kirsten rat sarcoma oncogene (KRAS) mutant cancer. We retrospectively studied the significance of SHP2 in KRAS mutant non‐small cell lung cancer (NSCLC) treated with immunotherapy and its relationship with tumor microenvironment (TME). Methods Sixty‐one advanced KRAS mutant NSCLC patients who underwent immunotherapy were enrolled. Next‐generation sequencing (NGS) was used to profile mutation status. The expression of SHP2, phospho‐SHP2 (pSHP2), and programmed death ligand 1 (PD‐L1) were analyzed by immunohistochemistry (IHC). Quantitative multiplexed immunofluorescence cytochemistry (mIFC) analysis was conducted to describe the TME. Results SHP2 was heterogeneously expressed in 32 samples in both tumor cells and immune cells and highly expressed (H‐score >10) in 25 (78.1%) samples. The expression levels of SHP2 and pSHP2 were positively correlated. Stromal SHP2 (s‐SHP2) was higher in tumors with PD‐L1 ≥50% versus PD‐L1

To retrospectively analyze the use of artificial pneumoperitoneum in CT scans, to explore its operation methods and technical points, and to lay the foundation for the widespread application of artificial pneumoperitoneum in CT. A total of 331 patients who underwent artificial pneumoperitoneum with CT angiography from January 1, 2013, to November 1, 2019, were recruited. All patients underwent standardized artificial pneumoperitoneum in the horizontal, left and right lateral, and prone positions during CT thin-layer scans of the abdomen and 3D reconstruction. Taking the surgical results as the gold standard, and using kappa test to verify the consistency of surgical results and imaging results. In all 331 patients, 43 patients had a normal peritoneal space, and 288 patients had an abnormal peritoneal space. And only 22 patients developed complications of subcutaneous emphysema, accounting for 6.6% of all 331 patients. In terms of the postoperative results, 28 were normal, and 303 were abnormal. The sensitivity, specificity and accuracy of CT diagnosis of abdominal adhesions using artificial pneumoperitoneum were 100%, 95.04%, and 95.46%, respectively. According to the Kappa consistency test, the imaging diagnosis from the CT scan with artificial pneumoperitoneum had a high consistency with the surgical results (kappa = 0.796, P

Heterozygous missense mutations in TUBB3 have been implicated in various neurological disorders encompassing either isolated congenital fibrosis of the extraocular muscles type 3 (CFEOM3) or complex cortical dysplasia with other brain malformations 1 (CDCBM1). The description of seizures in patients with TUBB3 mutations is rare. Here, we reported a patient who had febrile seizures before and focal seizure this time, which was diagnosed as epilepsy in combination with an abnormal EEG. MRI showed hypoplastic corpus callosum. Mutation analysis showed a novel de novo heterozygous variant of TUBB3 gene (NM_006086), c.763G>A (p.V255I). He had global developmental delay, photophobia and elliptic pupil, but lacking extraocular muscles involvement and malformations of cortical development, which might be a less severe phenotype of TUBB3 mutations. This was the first report of elliptic pupil in patients with TUBB3 mutations and expanded the spectrum of TUBB3 phenotypes. It indicated that the phenotypic range of TUBB3 mutations might be more continuous than discrete, with a severity ranging from mild to severe. Further studies are needed to elucidate the complete spectrum of TUBB3-related phenotypes.

Developing anatase/rutile phase-junction in TiO2 to construct Z-scheme system is quite effective to improve its photoelectrochemical activity. In this work, the anatase/rutile phase-junction Ag/TiO2 nanocomposites are developed as photocathodes for hydrogen production. The optimized Ag/TiO2 nanocomposite achieves a high current density of 1.28 mA cm−2, an incident photon-to-current conversion efficiency (IPCE) of 10.8 %, an applied bias photon-to-current efficiency (ABPE) of 0.32 at 390 nm and a charge carriers’ lifetime up to 2000s. Such enhancement on photoelectrochemical activity can be attributed to: (i) the generated Z-scheme system in the anatase/rutile phase-junction Ag/TiO2 photocathode enhances the separation, diffusion and transformation of electron/hole pairs inside the structure, (ii) Ag nanodots modification in the anatase/rutile phases leading to the tuned band gap with enhanced light absorption and (iii) the formed Schottky barrier after Ag nanodots surface modification provides enough electron traps to avoid the recombination of photogenerated electrons and holes. Our results here suggest that developing phase-junction nanocomposite as photocathode will provide a new vision for their enhanced photoelectrochemical generation of hydrogen.

Purpose The purpose of this study is to characterize niraparib pharmacokinetics (PK) and safety in patients with normal hepatic function (NHF) versus moderate hepatic impairment (MHI). Methods Patients with advanced solid tumors were stratified by NHF or MHI (National Cancer Institute-Organ Dysfunction Working Group criteria [bilirubin > 1.5–3 × upper limit of normal and any aspartate aminotransferase elevation]). In the PK phase, all patients received one 300 mg dose of niraparib. In the extension phase, patients with MHI received niraparib 200 mg daily; patients with NHF received 200 or 300 mg based on weight (max), area under the curve to last measured concentration (AUClast) and extrapolated to infinity (AUCinf). Safety was assessed in both phases. Exposure–response (E–R) modeling was used to predict MHI effects on exposure and safety of niraparib doses ≤ 200 mg or 300/200 mg or 200/100 mg weight/platelet regimens. Results In the PK phase (NHF, n = 9; MHI, n = 8), mean niraparib Cmax was 7% lower in patients with MHI versus NHF. Mean exposure (AUClast, AUCinf) was increased by 45% and 56%, respectively, in patients with MHI without impacting tolerability. In the extension phase (NHF, n = 8; MHI, n = 7), the overall safety profile was consistent with previous trials. In patients with MHI, E–R modeling predicted niraparib 200 mg reduced Grade ≥ 3 thrombocytopenia incidence, whereas a 200/100 mg regimen yielded exposures below efficacy-associated levels in 15% of patients. Conclusion These findings support adjusting the 300 mg niraparib starting dose to 200 mg QD in patients with MHI. Trial registration NCT03359850; registered December 2, 2017

Objective to observe whether electro-acupuncture (EA) is better in improving hormone levels among women with diminished ovarian reserve (DOR) compared with oral medicine [Chinese herbs with or without hormone replacement therapy (HRT)] that is often used in gynecology clinics in China. Methods eligible participants entered the EA group or medication group according to their preferences. Participants in the EA group received EA treatment, and participants the medication group received herbal decoction alone or combined with HRT. Reproductive hormone levels of the participants were tested before and during treatment in both groups. Results a total of 80 women with DOR were screened and 57 cases were included (29 in the EA group and 28 in the medication group) in the final analysis. The differences in the change from baseline between the EA and medication group in mean follicle-stimulating hormone (FSH) levels were -6.6 (95% CI, -17.03 to 3.72), (P = 0.848) and -7.09 (95% CI, -15.86 to 1.66), (P = 0.539) at weeks 12 and 24, respectively. The proportion of women with regular FSH levels in the EA and medication group was 51.3% vs 32.1% at week 12 (P = 0.134) and 51.3% vs 25.0% at week 24 (P = 0.038). Conclusion EA might influence regulating the levels of FSH, luteinizing hormone (LH), estrogen and the FSH/LH ratio, and no difference was found between the effects of EA and oral medicine in changes of reproductive hormone levels.

Background/Purpose: Recent study suggested that type 2 diabetes (T2DM) attributed to body mass index (BMI) could be influenced by liver aminotransferase. We aim to ascertain the cut-off point of BMI associated with T2DM and the influence of both elevated aminotransferase (AST) and alanine aminotransferase (ALT). Materials and Methods: In our retrospective cohort study, T2DM was diagnosed when FBS ≥ 7.0 mmol/L, BMI of participants with baseline fasting (FBS) < 7.0 mmol/L was divided by percentiles and by aminotransferanse (ALT and AST ≥ 20 U/L, ALT or AST < 20 U/L). Hazard ratios and the turning point of BMI of high T2DM risk was estimated in totality and different aminotransferanse groups. Results: During an average follow-up time of 3.71 years of 33346 participants, 1486 developed T2DM, and the average baseline BMI of participants who developed T2DM was 26.22 kg/m2. Cumulative incidence of T2DM was more than 5% when ALT and AST ≥ 20U/L, age over 44, male sex or BMI over 25.39 kg/m2; The risk of T2DM incidence increased as the BMI grow. The turning point of BMI at high risk of T2DM was 25.0 kg/m2 in totality, 25.1 kg/m2 when ALT or AST < 20 U/L and 26.1 kg/m2 when ALT and AST ≥ 20U/L. Conclusions: BMI of 25.0 kg/m2 was the cutoff point for T2DM development, and there is greater association between BMI and T2DM when ALT or AST < 20 U/L.

Introduction Metastasis is the primary cause of lung cancer-related death. Nevertheless, the underlying molecular mechanisms and evolutionary patterns of lung cancer metastases are still elusive. Methods We performed whole-exome sequencing for 40 primary tumors (PTs) and 61 metastases from 47 patients with lung cancer, of which 40 patients had paired PTs and metastases. The PT-metastasis genomic divergence, metastatic drivers, timing of metastatic dissemination, and evolutionary origins were analyzed using appropriate statistical tools and mathematical models. Results There were various degrees of genomic heterogeneity when comparing the paired primary and metastatic lesions or comparing metastases of different sites. Multiple metastasis-selected/enriched genetic alterations were found, such as MYC amplification, NKX2-1 amplification, RICTOR amplification, arm 20p gain, and arm 11p loss, and these results were were also featured in a meta-analysis cross-validated using an independent cohort from Memorial Sloan-Kettering Cancer Center database. To elucidate the metastatic seeding time, we applied a metastatic model and found 61.1% of the tumors were late dissemination, in which the metastatic seeding happened approximately 2.74 years before clinical detection. One exception was lymph node metastases whose dissemination time was relatively early. By analyzing the evolutionary origins, we reported that nonlymph node metastases were mainly seeded by the PT (87.5%) rather than the earlier colonized lymph node metastases. Conclusions Our results shed light on the molecular features that potentially drive lung cancer metastases. The distinct temporospatial pattern of disease progression revealed that lung cancer was susceptible to either late dissemination or indolent early lymph node metastases, leaving a potential time window to minimize metastases by early cancer detection.

Li Dong,1 Yu-Min Zheng,2 Xiao-Guang Luo,3 Zhi-Yi He2 1Department of Neurology, The Fourth Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China; 3Department of Neurology, The First Affiliated Hospital of South University of Science and Technology, The Second Clinical College of Jinan University, Shenzhen People’s Hospital, Shenzhen, People’s Republic of ChinaCorrespondence: Xiao-Guang LuoDepartment of Neurology, The First Affiliated Hospital of South University of Science and Technology, The Second Clinical College of Jinan University, Shenzhen People’s Hospital, Shenzhen, People’s Republic of ChinaEmail guanche537@126.comZhi-Yi HeDepartment of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of ChinaEmail yizizhan40559@163.comBackground: Parkinson’s disease is a common neurodegenerative disease in the elderly. The incidence of various cancers in Parkinson’s disease patients is significantly lower than in healthy people. Parkinson’s disease patients are individuals with a high tendency for inflammation, whose peripheral immune system is represented in an activated state. We hypothesized that the hyperinflammatory predisposition of Parkinson’s disease patients is pathogenic.Methods: DBA/1 mice were used to simulate “highly inflammatory individuals”, and the carcinogen DEN was used to induce malignancy. Hematoxylin & eosin (H&E) staining was used to observe the formation of lung tumors. Apoptosis of neurons was observed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Immunohistochemistry and flow cytometry were used to observe CD4, CD28, major histocompatibility complex II (MHCII), cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), and programmed death 1 (PD-1). The ionized calcium binding adaptor molecule-1 (IBA-1) + inducible nitric oxide synthase (iNOS) was used to label M1 microglia, and IBA-1 + arginase 1 (Arg1) was used to label M2 microglia by immunofluorescence. The expression of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and anti-inflammatory cytokines IL-10 and IL-4 was detected by ELISA.Results: DBA/1 mice with high inflammatory tendency showed a continuous increase of peripheral inflammation, promoting intracranial inflammation, decreasing the tumor incidence and increasing the neurodegeneration under induction of malignant change. CD28 and CTLA-4/PD-1 reduced the T-cell-dominated inflammatory response, reduced the intracerebral inflammatory response, protected from neurodegeneration, and increased the incidence of tumor. Combination of CTLA-4 and PD-1 blocker can overactivate T cells, worsen peripheral and intracranial inflammation, reduce the incidence of tumor, cause damage to dopamine neurons, and promote the occurrence of neurodegeneration.Conclusion: High inflammatory tendency induced by malignant stimulation through the imbalance of CD28 and CTLA-4/PD-1 leads to dopamine neuron injury.Keywords: high inflammatory tendency, malignant stimulation, CD28, CTLA-4/PD-1, dopamine neuron injury

A deep understanding of the fine structure at the atomic scale of halide perovskite materials has been limited by their sensitivity to the electron beam that is widely used for structural characterization. The sensitivity of a gamma-CsPbIBr2 perovskite thin film under electron beam irradiation is revealed by scanning transmission electron microscopy (STEM) through a universal large-range electron dose measurement, which is based on discrete single-electron events in the STEM mode. Our research indicates that the gamma-CsPbIBr2 thin film undergoes structural changes with increasing electron overall dose (e(-).A(-2)) rather than dose rate (e(-).A(-2).s(-1)), which suggests that overall dose is the key operative parameter. The electron beam-induced structural evolution of gamma-CsPbIBr2 is monitored by fine control of the electron beam dose, together with the analysis of high-resolution (S)TEM, diffraction, and energy-dispersive X-ray spectroscopy. Our results show that the gamma-CsPbIBr2 phase first forms an intermediate phase [e.g., CsPb(1-x)(IBr)((3-y))] with a superstructure of ordered vacancies in the pristine unit cell, while a fraction of Pb2+ is reduced to Pb-0. As the electron dose increases, Pb nanoparticles precipitate, while the remaining framework forms the Cs2IBr phase, accompanied by some amorphization. This work provides guidelines to minimize electron beam irradiation artifacts for atomic-resolution imaging on CsPbIBr2 thin films.

Background The global incidence and mortality rates of liver cancer, which is the second leading cause of cancer-related deaths worldwide, are increasing. However, information on its epidemiology and clinical prognosis is limited. This study aimed to characterize the epidemiology and prognostic factors of secondary liver cancer to aid in the pretreatment evaluation of the disease. Methods Patients diagnosed with secondary liver cancer between 2010 and 2014 in the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively included. Kaplan-Meier analysis and Multivariate Cox regression analysis were performed to screen for significant factors associated with secondary liver cancer. Results A total of 85,738 secondary liver cancer patients were identified; in this population, the first primary site was the lung (25.9%), followed by the colorectum, pancreas, stomach, breast, and cecum. Patients with primary tumors of the colorectum, cecum and breast had longer median survival time. Advanced age, male gender, black race, poor differentiation or lack of differentiation, regional lymph node metastases, and presence of distant metastasis were associated with poor prognosis. Conclusions In this study, novel findings on the role of the primary site and synchronous distant metastasis to specific organs in patients with secondary liver cancer were described. These findings have significant implications in clinical diagnosis and treatment, and provide a better understanding of secondary liver cancer in the general population.

Non-communicable diseases (NCDs) are an increasing problem worldwide, including in Malaysia. National surveys have been performed by the government but had poor coverage in east Malaysia, particularly in rural regions. This study aimed to describe the achievement of target therapeutic outcomes in the control of diabetes mellitus (DM), hypertension (HPT), and dyslipidemia (DLP) among diabetic patients in rural east Malaysia. A cross-sectional study was conducted among DM patients who visited the NCDs clinic in Lundu Hospital, Sarawak, Malaysia, from Jan to March 2016. In total, 214 patients (male, 37.9%; female, 62.1%) were recruited using a systemic sampling method. Multiple logistic regression models were applied to estimate the adjusted odds ratio (AOR) and confidence interval (CI) for the target therapeutic achievement in the control of DM, HPT, and DLP. Compared to the national average, therapeutic target achievement in Lundu was higher for DM (43.0% vs. 23.8%), equal for DLP (35.8% vs. 37.8%) but lower for HPT (30.9% vs. 47.9%). DM patients who had at least yearly HbA1c monitoring (AOR 2.30, 95% CI 1.04–5.06, P = 0.039), and those 58.7 years or older (AOR 2.50, 95% CI 1.32–4.74, P = 0.005) were more likely to achieve the therapeutic target for DM. Health promotion and public education regarding HPT needs to be emphasized in rural Malaysia. HbA1c monitoring at least once a year was one of the important factors associated with achieving DM control in rural east Malaysia. Accessibility to HbA1c tests and monitoring should be ensured for diabetic patients.

Bacterial therapy is an emerging method of tumor treatment. By utilizing wild-type bacteria or engineered bacteria to treat solid tumors, bacterial therapy has recently attracted attention due to its high therapeutic specificity. Although many bacterial strains have been tested in animal models or have even advanced to clinical trials, the efficacy of bacterial therapy remains undesirable. The lack of efficient control methods could cause side effects as well as insufficient therapeutic efficiency, both of which are urgent problems for bacterial therapy. Therefore, some studies have constructed bacteria with inducible plasmid or adsorption with responsive nanoparticles, which improved controllability and specificity during bacterial therapy. Herein, we introduce the unique advantages of bacteria in cancer treatment and highlight the issues associated with the application of bacterial therapy, focusing on the incorporation of various methodologies in the advancement of some controllable strategies in bacterial therapy.

To evaluate the prevalence of Helicobacter pylori infection and risk factors and to serotype the strains in Wuwei, located in north-western China, which has a high incidence of gastric cancer.Helicobacter pylori infection was analysed in 21 291 adults byThe infection rate of H. pylori was 53.0%, and 90.1% of strains were type I strains. The H. pylori infection rate was higher among farmers (OR = 1.34, 95% CI: 1.19-1.50) and individuals who had a junior high school or higher education level (OR = 1.10, 95% CI: 1.06-1.15), and was lower in older individuals (OR = 0.86, 95% CI: 0.83-0.90), individuals with high income (OR = 0.93, 95% CI: 0.90-0.95), individuals with a habit of eating quickly (OR = 0.93, 95% CI: 0.87-0.99) and individuals who consumed more fruit and vegetables (OR = 0.90, 95% CI: 0.85-0.95). Individuals with history of cholecystitis/cholecystolithiasis, hypertension and asthma were negatively correlated with H. pylori infection (P 0.05).The prevalence of H. pylori infection is high in Wuwei. The major prevalent strain is type I strain. Age, education, occupation, household income, consumption of fruit and vegetables, and habit of eating quickly are independent risk factors for H. pylori infection, which is also associated with individuals with a history of extragastric diseases.Evaluer la prévalence de l'infection à Helicobacter pylori et les facteurs de risque et déterminer le sérotype des souches à Wuwei, situé dans le nord-ouest de la Chine, où l'incidence du cancer gastrique est élevée. MÉTHODES: L'infection à H. pylori a été analysée chez 21.291 adultes par un test respiratoire à l'urée auLa prévalence de l'infection à H. pylori est élevée à Wuwei. La principale souche répandue est du type I. L'âge, l'éducation, la profession, le revenu du ménage, la consommation de fruits et de légumes et l'habitude de manger rapidement sont des facteurs de risque indépendants d'infection à H. pylori, qui est également associée à des personnes ayant des antécédents de maladies extra-gastriques.

BACKGROUND The misuse and abuse of alcohol is a major public health issue. However, available treatments are limited with variable efficacy. Recently, preclinical studies show that glucagon-like-peptide-1 (GLP-1) and its analogue Exendin-4 (Ex4) potently reduce a range of alcohol intake behaviors, thus highlighting its potential as a treatment for alcohol use disorders. However, the neural mechanisms and sites of action mediating the effects of Ex4 on alcohol intake behaviors remain to be characterized. This study examined the ventral tegmental area (VTA) as a site of action for the effects of GLP-1 on alcohol intake. METHODS Male Long-Evans rats were given intermittent access to 20% alcohol and trained to nose poke for 20% alcohol. Rats received intra-VTA injections of Ex4 (vehicle, 0.01, 0.05 μg), and the effects of VTA Ex4 on alcohol self-administration, motivation, and relapse were assessed. RESULTS When compared to vehicle treatment, intra-VTA Ex4 (0.01, 0.05 μg) delivery significantly reduced alcohol self-administration, an effect that was particularly prominent in high alcohol drinkers. However, VTA Ex4 did not reduce reacquisition of alcohol self-administration after extinction nor the motivation to obtain alcohol. Importantly, the lower dose of Ex4 (0.01 μg) used had no effect on food intake or locomotor activity, suggesting that the reduction in alcohol self-administration observed was not secondary to caloric intake or motor deficits. CONCLUSIONS Together, these findings provide support for the VTA as a key site of action for GLP-1 on alcohol self-administration but not the reacquisition of alcohol self-administration or motivation to work for alcohol.

Background This study aimed to explore the potentially predictive role and dynamic changes of immune checkpoints on T cell subsets in patients with breast cancer receiving neoadjuvant chemotherapies. Methods Fluorescent multiplex immunohistochemistry (mIHC) was used to stain CD4, CD8, PD1, TIM3, and cytokeratins simultaneously in paired breast cancer samples before and after neoadjuvant therapies (NAT) in a prospective cohort (n = 50). Singleplex IHC was conducted to stain for CD3 in 100 cases with inclusion of extra retrospective 50 cases. Cell levels were correlated with clinicopathological parameters and pathological complete response (pCR). Results In pretreatment tumors, the percentages of infiltrating CD8+ , PD1+ , PD1+ CD8+ , and the ratio of PD1+ CD8+ /CD8+ cells, were higher in pCR than non-pCR patients in either the stromal or intratumoral area, but PD1+ CD4+ , TIM3+ CD4+ , TIM3+ CD8+ cells and CD4+ /CD8+ ratio was not. Multivariate analyses showed that the percentage of intratumoral CD8+ cells (OR, 1.712; 95% CI: 1.052-2.786; P = 0.030) and stromal PD1+ CD8+ /CD8+ ratio (OR, 1.109; 95% CI: 1.009-1.218; P = 0.032) were significantly associated with pCR. Dynamically, reduction in the percentages of PD1+ , CD8+ and PD1+ CD8+ cells after therapy strongly correlated with pCR. Notably, incremental percentages of PD1+ CD8+ cells, rather than TIM3+ CD8+ , were shown in tumors from non-pCR patients after NAT. CD3 staining confirmed the percentage of T cells were associated with pCR. Conclusions PD1+ CD8+ rather than TIM3+ CD8+ cells are main predictive components within tumor-infiltrating T cells in NAT breast cancer patients. Dynamically incremental levels of PD1+ CD8+ cells occurred in non-pCR cases after NAT, suggesting the combination of chemotherapy with PD1 inhibition might benefit these patients. Key points SIGNIFICANT FINDINGS OF THE STUDY: PD1+ CD8+ , rather than TIM3+ CD8+ , T cells are the main component to predict the response of neoadjuvant therapies in breast cancer. What this study adds Incremental levels of PD1+ CD8+ T cells in non-pCR post-NAT tumors suggest PD1 inhibition might benefit in the neoadjuvant setting.

To investigate the effects of multidisciplinary and comprehensive Chinese medicine (CM) treatments on progression-free survival (PFS) and median survival time (MST) in patients with advanced non-small cell lung cancer (NSCLC) and identify factors that influence progression and prognosis. Clinical data of 855 patients with advanced NSCLC who received multidisciplinary and comprehensive CM treatments at Longhua Hospital from January 2009 to December 2018 were retrospectively analyzed. Univariate analysis was performed by the Kaplan-Meier method and log-rank sequential inspection. Multivariate analysis of significant variables from the univariate analysis was performed with Cox regression modeling. Key factors correlated to progression and prognosis were screened out, and a Cox proportional hazard model was established to calculate the prognostic index. The PFS and MST of 855 advanced NSCLC patients were 9.0 and 26.0 months, respectively. The 1-, 2-, 3-, and 5-year survival rates were 79.2%, 54%, 36.2%, and 17.1%, respectively. Gender, pathologic type, and clinical stage were independent prognostic risk factors; surgical history, radiotherapy, treatment course of Chinese patent medicine, intravenous drip of Chinese herbal preparation, duration of oral administration of Chinese herbal decoction (CHD), and intervention measures were independent prognostic protective factors. Gender was an independent risk factor for progression, while operation history and oral CHD administration duration were independent protective factors (all P

Background The effect of modest alcohol intake on prevalence of significant hepatic steatosis and severity of liver disease in patients with type 2 diabetes mellitus (T2DM) is unclear. Methods This is a cross-sectional study on T2DM patients. Modest alcohol intake was defined as alcohol intake ≤ 21 units/week in men and ≤ 14 units/week in women. Significant hepatic steatosis was diagnosed on the basis of controlled attenuation parameter > 263 dB/m, while advanced fibrosis was diagnosed on the basis of liver stiffness measurement ≥ 9.6 kPa using M probe or ≥ 9.3 kPa using XL probe. Patients with liver stiffness measurement ≥ 8.0 kPa were offered liver biopsy. Results Five hundred fifty-seven patients underwent transient elastography, and 71 patients underwent liver biopsy. The prevalence of modest drinking was 16.5%. Modest drinking was equally prevalent among ethnic Indians and Chinese at 22.9% and 23.3%, respectively, but uncommon among ethnic Malays at 1.7%. Modest drinkers were more likely to be male, smoked, and had significantly lower glycated hemoglobin, total cholesterol, low-density lipoprotein cholesterol, alkaline phosphatase, and platelet count. There was no significant difference in the prevalence of significant hepatic steatosis or advanced fibrosis based on transient elastography and steatohepatitis or advanced fibrosis between modest drinkers and nondrinkers. The prevalence of significant hepatic steatosis was higher among ethnic Malays and Indians compared with ethnic Chinese, but the Chinese did not have a lower prevalence of more severe liver disease. Conclusion Modest alcohol intake is not associated with higher prevalence of significant hepatic steatosis or more severe liver disease among patients with T2DM.

Background MED13L-related intellectual disability is a new syndrome that is characterized by intellectual disability (ID), motor developmental delay, speech impairment, hypotonia and facial dysmorphism. Both the MED13L haploinsufficiency mutation and missense mutation were reported to be causative. It has also been reported that patients carrying missense mutations have more frequent epilepsy and show a more severe phenotype. Case presentation We report a child with ID, speech impairment, severe motor developmental delay, facial deformity, hypotonia, muscular atrophy, scoliosis, odontoprisis, abnormal electroencephalogram (EEG), and congenital ureteropelvic junction obstruction (UPJO) combined with high ureter attachment. We used whole-exome sequencing (WES) to detect the genetic aberration of the child and found a de novo mutation, c.2605C > T (p.Pro869Ser), in the MED13L gene. Neither of her parents carried the mutation. Additionally, we review the literature and summarize the phenotypes and features of reported missense mutations. After reviewing the literature, approximately 17 missense mutations in 20 patients have been reported thus far. For 18 patients (including our case) whose clinical manifestations were provided, 100% of the patients had ID or developmental delay (DD). A total of 88.9, 83.3 and 66.7% of the patients had speech impairment, delayed milestones and hypotonia, respectively. A total of 83.3% of the patients exhibited craniofacial deformity or other dysmorphic features. Behavioral difficulties and autistic features were observed in 55.6% of the patients. Cardiac anomalies were seen in only 27.8% of the patients. Of these patients, 44.4% had epileptic seizures. Of the 17 mutations, 2 were located in the N-terminal domain, 8 were located in the C-terminal domain, and 1 was located in an α-helical sequence stretch. One of them was located in the MID domain of the MedPIWI module. Conclusions We report a new patient with a reported missense mutation, c.2605C > T (p.Pro869Ser), who exhibited some infrequent manifestations except common phenotypes, which may broaden the known clinical spectrum. Additionally, by reviewing the literature, we also found that patients with missense mutations have a higher incidence of seizures, MRI abnormalities, autistic features and cardiac anomalies. They also have more severe ID and hypotonia. Our case further demonstrates that Pro869Ser is a hotspot mutation of the MED13L gene.

Cancer is a common cause of mortality in the world. For cancer treatment modalities such as chemotherapy, photothermal therapy and immunotherapy, the concentration of therapeutic agents in tumor tissue is the key factor which determines therapeutic efficiency. In view of this, developing targeted drug delivery systems are of great significance in selectively delivering drugs to tumor regions. Various types of nanomaterials have been widely used as drug carriers. However, the low tumor-targeting ability of nanomaterials limits their clinical application. It is difficult for nanomaterials to penetrate the tumor tissue through passive diffusion due to the elevated tumoral interstitial fluid pressure. As a biological carrier, bacteria can specifically colonize and proliferate inside tumors and inhibit tumor growth, making it an ideal candidate as delivery vehicles. In addition, synthetic biology techniques have been applied to enable bacteria to controllably express various functional proteins and achieve targeted delivery of therapeutic agents. Nanobiohybrids constructed by the combination of bacteria and nanomaterials have an abundance of advantages, including tumor targeting ability, genetic modifiability, programmed product synthesis, and multimodal therapy. Nowadays, many different types of bacteria-based nanobiohybrids have been used in multiple targeted tumor therapies. In this review, firstly we summarized the development of nanomaterial-mediated cancer therapy. The mechanism and advantages of the bacteria in tumor therapy are described. Especially, we will focus on introducing different therapeutic strategies of nanobiohybrid systems which combine bacteria with nanomaterials in cancer therapy. It is demonstrated that the bacteria-based nanobiohybrids have the potential to provide a targeted and effective approach for cancer treatment.

A highly efficient photoenergy conversion is strongly dependent on the cumulative cascade efficiency of the photogenerated carriers. Spatial heterojunctions are critical to directed charge transfer and, thus, attractive but still a challenge. Here, a spatially ternary titanium-defected TiO2@carbon quantum dots@reduced graphene oxide (denoted as VTi@CQDs@rGO) in one system is shown to demonstrate a cascade effect of charges and significant performances regarding the photocurrent, the apparent quantum yield, and photocatalysis such as H2 production from water splitting and CO2 reduction. A key aspect in the construction is the technologically irrational junction of Ti-vacancies and nanocarbons for the spatially inside-out heterojunction. The new "spatial heterojunctions" concept, characteristics, mechanism, and extension are proposed at an atomic-/nanoscale to clarify the generation of rational heterojunctions as well as the cascade electron transfer.

Ultrasound (US) can be used to evaluate the brain structure and nervous system damage. Patients with neurologic symptoms need rapid, noninvasive imaging with high spatial resolution and tissue contrast. Magnetic resonance imaging is currently the most sensitive and specific imaging method for evaluating neuropathologic conditions. This approach does present some challenges, such as the need to transport patients who may be seriously ill to the magnetic resonance imaging suite and the need for patients to remain for a considerable time. Cranial US provides a very valuable imaging method for clinicians, which can make a rapid diagnosis and evaluation without ionizing radiation. The main disadvantage of cranial US is its low sensitivity and specificity for subtle/early lesions. In recent years, with the rapid development of anatomic and functional US technology, the practicability of US diagnosis and intervention has been greatly improved. Ultrasound elastography may have the potential to improve the sensitivity and specificity of various cranial nerve conditions. Ultrasound elastography has received considerable critical attention, and an increasing number of studies have recognized its critical role in evaluating brain diseases. At present, US elastography has been applied to the evaluation of traumatic brain injury, ischemic stroke, intraoperative brain tumors, and hypoxic ischemic encephalopathy. The latest animal experiments and human clinical trial developments in the applications of US elastography for brain diseases are summarized in this review.

Background: The eosinophilic chronic obstructive pulmonary disease (COPD) is known to be more sensitive to corticosteroid. The sputum microbiome has been shown to affect COPD prognosis, but its role in acute exacerbations of eosinophilic COPD is unclear. This study aimed to investigate the dynamic changes of the airway microbiome in patients with acute exacerbations of eosinophilic COPD. Methods: Fifty-seven patients with acute exacerbations of COPD from the First Affiliated Hospital of Guangxi Medical University between June 2017 and June 2018 were divided into two groups. Patients with eosinophils ≥300 cells/μL in the peripheral venous blood were assigned to the eosinophilic group (Eos) and the rest to the non-eosinophilic group (Noneos). All patients received similar treatment including inhaled budesonide according to the guidelines. The induced sputum microbiome was analyzed on the 1st and 7th day of treatment using the 16S ribosomal RNA (rRNA) method. The levels of interleukin (IL)-6 and IL-8 were measured in the plasma and the sensitivity to corticosteroids was determined in isolated peripheral blood mononuclear cells. Quantitative data were compared between the two groups using the independent samples t test or Mann-Whitney U test. Categorical data were evaluated using Chi-squared test or Fisher’s exact test. Results: Twenty-six patients were classified into Eos group and 31 patients were classified into Noneos group. Prior to treatment, the alpha diversity (Shannon index) (2.65 ± 0.63 vs. 2.56 ± 0.54, t = 0.328, P = 0.747) and the structure of the sputum microbiome were similar in the Eos group and the Noneos group. After 7 days of treatment, alpha diversity increased in both groups, while the microbiome richness (Ace index) was significantly lower in the Eos group (561.87 ± 109.13 vs. 767.88 ± 148.48, t = -3.535, P = 0.002). At the same time, IL-6 (12.09 ± 2.85 pg/mL vs. 15.54 ± 2.45 pg/mL, t = -4.913, P < 0.001) and IL-8 (63.64 ± 21.69 pg/mL vs. 78.97 ± 17.13 pg/mL, t = -2.981, P = 0.004) decreased more significantly in the Eos group, and the percentages of inhibition of IL-8 at dexamethasone concentrations 10-8 to 10-6 mol/L were significantly higher in the Eos group than those in the Noneos group (all P < 0.05). Conclusions: The induced sputum microbiome richness decreased more significantly following treatment in the Eos patients compared to the Noneos patients. The lower plasma inflammatory factor levels and the higher percentage of inhibition of IL-8 might be due to higher corticosteroid sensitivity in Eos patients. Key words: Acute exacerbations of chronic obstructive pulmonary disease; Sputum; Microbiome; Eosinophilic; Corticosteroid; Interleukin-8 inhibition

Objective: Kashin-Beck disease (KBD) is an endemic deformable bone and joint disease, which seriously affects the quality of life (QOL) of patients. We tried to conduct a cross-sectional study of the QOL of KBD patients by a new KBD quality of life (KBDQOL) questionnaire.Methods: 252 KBD patients came from Northwest China, and 260 healthy people living in the same area as KBD patients served as the control group. KBDQOL questionnaire was used to evaluate the QOL of all objects. Results: The average score of physical functions, activity limitations, support of society, mental health and general health of KBD patients was significantly lower than that in control group. There was no statistical difference in economics between KBD patients and control group. The univariate analysis showed that age, height, weight status, education level and grade of KBD had a statistically significant effect on KBDQOL score. The results of multivariate analysis showed that grade of KBD was the influencing factor of physical function score; sex, age, height, grade of KBD and duration of symptoms were the influencing factors of activity restriction score; grade of KBD was the influencing factor of economic score, age and grade of KBD were influencing factors of general health.Conclusions: The QOL of patients with KBD was significantly lower than that of healthy people living in the same place. The KBDQOL questionnaire may be a promising tool for assessing the QOL of KBD patients.

Background Intestinal ischemia/reperfusion (I/R) injury commonly occurs during perioperative periods, resulting in high morbidity and mortality on a global scale. Dexmedetomidine (Dex) is a selective α2-agonist that is frequently applied during perioperative periods for its analgesia effect; however, its ability to provide protection against intestinal I/R injury and underlying molecular mechanisms remain unclear. Methods To fill this gap, the protection of Dex against I/R injury was examined in a rat model of intestinal I/R injury and in an inflammation cell model, which was induced by tumor necrosis factor-alpha (TNF-α) plus interferon-gamma (IFN-γ) stimulation. Results Our data demonstrated that Dex had protective effects against intestinal I/R injury in rats. Dex was also found to promote mitophagy and inhibit apoptosis of enteric glial cells (EGCs) in the inflammation cell model. PINK1 downregulated p53 expression by promoting the phosphorylation of HDAC3. Further studies revealed that Dex provided protection against experimentally induced intestinal I/R injury in rats, while enhancing mitophagy, and suppressing apoptosis of EGCs through SIRT3-mediated PINK1/HDAC3/p53 pathway in the inflammation cell model. Conclusion Hence, these findings provide evidence supporting the protective effect of Dex against intestinal I/R injury and its underlying mechanism involving the SIRT3/PINK1/HDAC3/p53 axis.

Introduction: Pulmonary atypical carcinoid (PAC) is a rare subtype of pulmonary neuroendocrine neoplasm. Although EML4-ALK fusion has been detected in PAC, EGFR mutations have not been reported before. Methods: We performed hematoxylin and eosin staining, immunohistochemistry, and next-generation sequencing on tissues at baseline and after surgery. Results: The patient was diagnosed with having advanced PAC harboring the EGFR L858R mutation and then received a combination of icotinib and irinotecan plus cisplatin chemotherapy, achieving a partial response before the operation. Postoperative histology results revealed SCLC harboring the EGFR L858R mutation. Surprisingly, both the KRAS amplification and the RB1 deletion disappeared. Conclusions: EGFR tyrosine inhibitors plus irinotecan plus cisplatin chemotherapy might be a potential treatment option for advanced pulmonary neuroendocrine neoplasms harboring EGFR mutations.

Background: Depression is a stress-related disorder that seriously threatens people’s physical and mental health. Xiaoyaosan is a classical traditional Chinese medicine formula, which has been used to treat mental depression since ancient times. More and more notice has been given to the relationship between the occurrence of necroptosis and the pathogenesis of mental disorders.Objective: The purpose of present study is to explore the potential mechanism of Xiaoyaosan for the treatment of depression using network pharmacology and experimental research, and identify the potential targets of necroptosis underlying the antidepressant mechanism of Xiaoyaosan.Methods: The mice model of depression was induced by chronic unpredictable mild stress (CUMS) for 6 weeks. Adult C57BL/6 mice were randomly divided into five groups, including control group, chronic unpredictable mild stress group, Xiaoyaosan treatment group, necrostatin-1 (Nec-1) group and solvent group. Drug intervention performed from 4th to 6th week of modeling. The mice in Xiaoyaosan treatment group received Xiaoyaosan by intragastric administration (0.254 g/kg/d), and mice in CUMS group received 0.5 ml physiological saline. Meanwhile, the mice in Nec-1 group were injected intraperitoneally (i.p.) with Nec-1 (10 mg/kg/d), and the equivalent volume of DMSO/PBS (8.3%) was injected into solvent group mice. The behavior tests such as sucrose preference test, forced swimming test and novelty-suppressed feeding test were measured to evaluate depressive-like behaviors of model mice. Then, the active ingredients in Xiaoyaosan and the related targets of depression and necroptosis were compiled through appropriate databases, while the “botanical drugs-active ingredients-target genes” network was constructed by network pharmacology analysis. The expressions of RIPK1, RIPK3, MLKL, p-MLKL were detected as critical target genes of necroptosis and the potential therapeutic target compounds of Xiaoyaosan. Furthermore, the levels of neuroinflammation and microglial activation of hippocampus were measured by detecting the expressions of IL-1β, Lipocalin-2 and IBA1, and the hematoxylin and eosin (H&E) stained was used to observe the morphology in hippocampus sections.Results: After 6-weeks of modeling, the behavioral data showed that mice in CUMS group and solvent group had obvious depressive-like behaviors, and the medication of Xiaoyaosan or Nec-1 could improve these behavioral changes. A total of 96 active ingredients in Xiaoyaosan which could regulate the 23 key target genes were selected from databases. Xiaoyaosan could alleviate the core target genes in necroptosis and improve the hippocampal function and neuroinflammation in depressed mice.Conclusion: The activation of necroptosis existed in the hippocampus of CUMS-induced mice, which was closely related to the pathogenesis of depression. The antidepressant mechanism of Xiaoyaosan included the regulation of multiple targets in necroptosis. It also suggested that necroptosis could be a new potential target for the treatment of depression.

Objective Kashin–Beck disease (KBD) is an endemic degenerative joint disease with a high disability rate. We retrospectively evaluated the 18-year clinical follow-up outcomes of adult patients with KBD who underwent arthroscopic debridement for knee osteoarthritis. Methods Thirty-one patients with KBD (31 knees) underwent arthroscopy for knee osteoarthritis. The visual analog scale (VAS) score, walking distance, knee mobility, and patients’ self-evaluated improvement in clinical symptoms were retrospectively evaluated before and 18 years after the operation. Results The patients’ self-evaluated clinical symptoms showed considerable improvement at 2, 6, and 8 years after surgery but deteriorated at 10 and 18 years after surgery. Knee mobility was greater after than before arthroscopy but decreased from 6 to 18 years postoperatively. The VAS score for knee pain was high before the operation, decreased at 2 years postoperatively, increased at 6 years postoperatively, and was significantly lower at 18 years postoperatively than before surgery. The walking distance was significantly longer at 2, 6, and 8 years postoperatively than preoperatively. Conclusions Arthroscopic treatment may be an effective therapy for adult patients with KBD who develop knee osteoarthritis. In this study, arthroscopy had a long-term effect on patients with KBD who had Kellgren–Lawrence grade

This paper presents a wide-bandwidth buffer with adjustable common-mode levels and differential-mode swing. By using an analog common-mode feedback control loop consisted of a rail-to-rail error amplifying OP and complementary current mirrors, the range of output common-mode levels are maximized. By digital tail current source controls, the differential swing was almost independent to the common-mode levels. In 0.18um technology, the buffer test chip occupies an active area of 0.082mm2. Under single 1.8V of supply voltage, the buffer with a 0.3-to-1.5V of controlled common-mode level, a 6-to-21dB of variable gain and a 275MHz of -3dB bandwidth.

Purpose HIV infection is associated with a variety of ocular surface diseases. Understanding the difference of the ocular microbiota between HIV-infected and healthy individuals as well as the influence of antiretroviral therapy will help to investigate the pathogenesis of these conditions. Methods A cross-sectional study was conducted on subjects including HIV-negative individuals, untreated HIV-infected individuals, and HIV-infected individuals with antiretroviral therapy. Conjunctival microbiota was assessed by bacterial 16S rRNA sequencing of the samples obtained from the conjunctival swab. Results The microbial richness in ocular surface was similar in HIV-negative, untreated HIV-positive, and highly active antiretroviral therapy (HAART) subjects. The bacterial compositions were similar in the two HIV infection groups but were significantly different from the HIV-negative group. HAART changed the beta diversity of bacterial community as determined by Shannon index. CD4+ T cell count had no significant influence on the diversity of ocular microbiota in HIV-infected individuals. Conclusions The data revealed the compositional and structural difference in conjunctival microbial community in subjects with and without HIV infection, indicating that HIV infection or its treatment, may contribute to ocular surface dysbiosis.

Background Primary pulmonary lymphoepithelioma‐like carcinoma (PLELC) is a rare and unique subtype of lung cancer. However, the prevalence of driver alterations, such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements, and the response of tyrosine kinase inhibitor (TKIs) in PLELC has not been thoroughly investigated. Method We retrospectively reviewed the genetic profiles and treatment course of 330 PLELC patients at the Guangdong Lung Cancer Institute (GLCI) from 1st January, 2008 to 30th December, 2018. We searched and analyzed related literature published in PubMed and Web of Science from 1st January, 2000 and 31th August, 2019 based on their mention of “driver mutations” and “the response of TKIs to mutant PLELC”. Results Genetic alterations of EGFR/ALK were tested in 203 patients (203/330, 61.5%). Five patients (5/175, 2.9%) had EGFR mutation and three patients (3/140, 2.1%) had ALK alteration. From the total of 15 articles identified from electronic searches, 1071 PLELC cases mentioned the driver mutations. EGFR mutation and ALK rearrangement were detected in 15 patients and one patient, respectively. In total, there were four EGFR/ALK mutant PLELC patients who received targeted therapy as palliative treatment at the GLCI and in the literature. However, there was disease progression in all cases one month after use of TKIs. Conclusion The mutation rates of EGFR and ALK were low in PLELC. EGFR and ALK TKIs showed limited response in EGFR/ALK mutant PLELC. Further studies are needed to explore other molecular targets to optimize the therapeutic strategy for PLELC.

Purpose: To present a relatively uncommon case with a secondary iris cyst in the anterior chamber and its successful management with an anterior chamber mass excision surgery. Case report: A 46-year-old Chinese woman presented with a dark shadow in her left eye for 6 months without any other discomfort. She had a history of blunt ocular trauma by a badminton strike 3 years ago. Slit-lamp examination showed a small, nearly circular, sharply demarcated, and movable mass in the anterior chamber OS, which could change its position with head tilt. The anterior segment optical coherence tomography revealed a well-circumscribed cystic lesion in the anterior chamber with higher reflective outer layer and lower internal reflectivity. An anterior chamber mass removal surgery was performed without recurrence up to 1 year. Conclusion: Secondary free-floating iris cyst following a blunt trauma is rarely reported. It is relatively stable and nonprogressive so it may remain asymptomatic for a long time. Appropriate imaging techniques are necessary for facilitating diagnosis and therapy. Therapeutic management should be considered if visual symptoms arise, especially when complications occur.

Objective. The incidence of superficial organ diseases has increased rapidly in recent years. New methods such as computer-aided diagnosis (CAD) are widely used to improve diagnostic efficiency. Convolutional neural networks (CNNs) are one of the most popular methods, and further improvements of CNNs should be considered. This paper aims to develop a multiorgan CAD system based on CNNs for classifying both thyroid and breast nodules and investigate the impact of this system on the diagnostic efficiency of different preprocessing approaches. Methods. The training and validation sets comprised randomly selected thyroid and breast nodule images. The data were subgrouped into 4 models according to the different preprocessing methods (depending on segmentation and the classification method). A prospective data set was selected to verify the clinical value of the CNN model by comparison with ultrasound guidelines. Diagnostic efficiency was assessed based on receiver operating characteristic (ROC) curves. Results. Among the 4 models, the CNN model using segmented images for classification achieved the best result. For the validation set, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the curve (AUC) of our CNN model were 84.9%, 69.0%, 62.5%, 88.2%, 75.0%, and 0.769, respectively. There was no statistically significant difference between the CNN model and the ultrasound guidelines. The combination of the two methods achieved superior diagnostic efficiency compared with their use individually. Conclusions. The study demonstrates the probability, feasibility, and clinical value of CAD in the ultrasound diagnosis of multiple organs. The use of segmented images and classification by the nature of the disease are the main factors responsible for the improvement of the CNN model. Moreover, the combination of the CNN model and ultrasound guidelines results in better diagnostic performance, which will contribute to the improved diagnostic efficiency of CAD systems.

The oil price is influenced not only by the fundamentals of supply and demand but also by unpredictable political conflicts, climate emergencies, and investor intentions, which cause enormous short-term fluctuations in the oil price. The proposition of the Google index-driven decomposition ensemble model to forecast crude oil price risk uses big data technology and a time series decomposition method. First, by constructing an index of investor attention for the market and emergencies combined with a bivariate empirical mode decomposition, we analyze the impact of investor attention on oil price fluctuations. Second, we establish a vector autoregression model, and the impulse responses define the impact of emergencies on the crude oil price. Finally, with the help of machine learning and historical simulation methods, the risk of crude oil price shocks from unexpected events is predicted. Empirical research demonstrates that concerns related to the oil market and emergencies that appear in Google search data are closely related to changes in oil prices. Based on the Google index, our model’s prediction of crude oil prices is more accurate than other models, and the prediction of value-at-risk is closer to the theoretical value than the historical simulation with the ARMA forecasts method. Considering the impact of emergencies in the prediction of crude oil price risk can help provide technical guidance for investors and risk managers and avoid economic risks caused by climate disasters or political conflicts.

To investigate the effect of compound laser acupuncture-moxibustion on blood glucose, fasting insulin and blood lipids levels in type 2 diabetes mellitus (T2DM) rats.Forty male Wistar rats were randomly divided into 4 groups, including the normal group, model control group, laser group and sham laser group (n=10 per group). The rats in the normal group were fed with a standard diet. Rats in other groups were fed with a high-sugar and high-fat diet for 4 weeks, then intraperitoneally injected with 1% streptozotocin to induce T2DM model. The laser group was irradiated by 10.6 µm and 650 nm compound laser on bilateral Pishu (BL 20), Shenshu (BL 23) and Sanyinjiao (SP 6) for 5 min, 6 times a week for 5 weeks. The sham laser group received the same treatment as the laser group, but without laser output. The model control group and normal group were not treated. Blood glucose levels were measured before and after 1, 2, 3, 4 and 5 weeks of treatment. The serum levels of fasting insulin, total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were analyzed after the last treatment.The blood glucose levels in the model control group increased during the 5 weeks of treatment compared with the normal group (P0.05), while those in the laser group were significantly lower than the model control group after weekly treatment (P0.01 or P0.05). After 1, 2 and 3 weeks of treatment, the blood glucose levels in the laser group decreased obviously compared with the sham laser group (P0.01 or P0.05). Compared with the normal group, the levels of fasting insulin, TC and LDL in the model control group notably increased (P0.01 or P0.05), while their levels in the laser group were significantly lower than the model control group after 5 weeks of treatment (P0.05 or P0.01). However, no statistically significant differences were observed in TG or HDL levels among the 4 groups (P0.05).The compound laser acupuncture-moxibustion of 10.6 µm and 650 nm had positive effects on the regulation of hyperglycemia and insulin resistance in T2DM rats, which may be a potential treatment for T2DM, and also provide an alternative to the traditional acupuncture and moxibustion therapy.

The pursuit of high-performance photodetectors functioning in the solar-blind spectrum is motivated by both scientific and practical applications ranging from secure communication, monitoring, sens...

Background: Cytidine deaminase (CDA) polymorphisms may affect the response to gemcitabine/cisplatin chemotherapy in patients with non-small cell lung cancer (NSCLC). This study is designed to investigate the associations of CDA-79A>C and 208G>A polymorphisms and gemcitabine/cisplatin chemotherapy effectiveness in Xinjiang Uyghur and Han patients. Methods: This prospective cohort study enrolled consecutive patients with stage IIIb/IV NSCLC administered gemcitabine/cisplatin chemotherapy at the First Affiliated Hospital, Medical College of Shihezi University and the First People’s Hospital, Kashgar Region. CDA-A79C and CDA-G208A polymorphisms were detected by direct sequencing. Progression-free survival was analyzed by the Kaplan-Meier method. Associations of A79C and G208A polymorphisms with treatment effectiveness and progression-free survival were analyzed using logistic regression and multivariate Cox regression analyses. Subgroup analyses based on ethnicity were performed. Results: The study enrolled 120 patients. A79C and G208A polymorphisms followed the Hardy-Weinberg equilibrium. The frequencies of the AA, AC, and CC genotypes and the A and C alleles of A79C were 52.2%, 29.9%, 17.9%, 67.2%, and 32.8%, respectively, in Han patients and 75.4%, 18.9%, 5.7%, 84.9%, and 5.1%, respectively, in Uyghur patients. Uyghur patients had lower frequencies of A79C-AC/CC genotypes, A79C-C allele, G208A-GA genotype, and G208A-A allele ( PConclusion: For Uyghur and Han ethnic groups, A79C and G208A polymorphisms can be used as a promising biomarker for the chemotherapy efficacy and prognosis of NSCLC.

Population pharmacokinetics of rolapitant and its active metabolite M19 were studied in 482 patients receiving this neurokinin-1 receptor antagonist in combination with a 5-hydroxytryptamine-3 receptor antagonist and dexamethasone for prevention of chemotherapy-induced nausea and vomiting (CINV). Patients received a single dose of rolapitant (range, 9-180 mg) before administration of moderately or highly emetogenic chemotherapy. Population pharmacokinetic analysis was performed via nonlinear mixed-effects modeling. Rolapitant pharmacokinetics was best characterized by a 2-compartment model. Population typical values were estimated to be 0.962 L/h for apparent oral clearance and 214 L for central compartment volume of distribution. The intercompartment clearance and peripheral compartment volume of distribution was estimated to be 2.79 L/h and 164 L, respectively. Metabolite M19 pharmacokinetics was described by a 1-compartment model with an apparent metabolite clearance of 1.83 L/h. Intersubject variability was moderate for pharmacokinetics parameters. Weight positively correlated with central compartment volume of distribution and peripheral compartment volume of distribution but not with apparent oral clearance. No other demographic, clinical, or pathophysiologic covariates, including liver and renal function, influenced rolapitant pharmacokinetics. A slight positive trend was observed between rolapitant exposure and efficacy (ie, complete response defined as no emesis and no use of rescue medication) in the delayed phase of CINV (>24-120 hours after chemotherapy). This further supports the 180-mg dose of rolapitant in CINV patients. In summary, this validated population pharmacokinetic model satisfactorily describes pharmacokinetics of rolapitant and M19 in patients with CINV. These results support the recommendation that no dose adjustment for patient variables investigated is necessary.

The voltage fade of Li-rich layered oxide cathode material Li1.2Ni0.13Co0.13Mn0.54O2 (LNCM) heavily hinders its application in Li-ion batteries. Herein, we revisit the origin of the voltage fade of LNCM and propose a solution to suppress this effect. It is demonstrated that the voltage fade of the LNCM cathode comes from the structural change of the crystal from layer structure to spinel structure, involving all the cations rearrangement. Such rearrangement of all the cations in LNCM is due to the high degree of delithiation and oxygen release at high cutoff voltage of 4.8 V. It is also evidenced that nickel and cobalt change from low valence to high valence at the discharged state, which not only inhibits the transport of lithium ions, but also leads to the loss of high voltage platforms. In particular, the cation rearrangement of Li/Mn causes valence change from Mn4+ to Mn3+, resulting in the decrease of discharge voltage platform at the cutoff voltage of 4.8 V much higher than at 4.6 V. The lower charge cutoff voltage can be a solution to suppress the voltage fade of LNCM cathode materials and have a good stability of LNCM cathode materials without compromising the battery performance.

Photocatalytic hydrogen (H 2 )production based on semiconductors is important to utilize solar light for clean energy and environment. Herein, we report a visible light responsive heterostructure, designed and constructed by molybdenum disulfide quantum dots (MoS 2 -QDs)in-situ seeds-directing growth and self-assemble of zinc indium sulfide (ZnIn 2 S 4 )nanosheet to ensure their full contact through a simple one-step solvothermal method for highly improved visible light H 2 production. The MoS 2 -QDs in-situ seeds-directing ZnIn 2 S 4 heterostructure not only builds heterojunctions between MoS 2 and ZnIn 2 S 4 to spatially separate the photogenerated electrons and holes, but also serves as the active sites trapping photogenerated electrons to facilitate H 2 evolution. As a result, MoS 2 -QDs/ZnIn 2 S 4 exhibits high photocatalytic activity for H 2 production, and the optimized 2 wt% MoS 2 -QDs/ZnIn 2 S 4 (2MoS 2 -QDs/ZnIn 2 S 4 )heterostructure exhibits the highest H 2 evolution rate of 7152 umol·h −1 ·g −1 under visible light, ∼9 times of pure ZnIn 2 S 4 . Our strategy here could shed some lights on developing noble-metal free heterostructures for highly efficient photocatalytic H 2 production.

Objective. Ultrasound imaging is well known to play an important role in the detection of thyroid disease, but the management of thyroid ultrasound remains inconsistent. Both standardized diagnostic criteria and new ultrasound technologies are essential for improving the accuracy of thyroid ultrasound. This study reviewed the global guidelines of thyroid ultrasound and analyzed their common characteristics for basic clinical screening. Advances in the application of a combination of thyroid ultrasound and artificial intelligence (AI) were also presented. Data sources. An extensive search of the PubMed database was undertaken, focusing on research published after 2001 with keywords including thyroid ultrasound, guideline, AI, segmentation, image classification, and deep learning. Study selection. Several types of articles, including original studies and literature reviews, were identified and reviewed to summarize the importance of standardization and new technology in thyroid ultrasound diagnosis. Results. Ultrasound has become an important diagnostic technique in thyroid nodules. Both standardized diagnostic criteria and new ultrasound technologies are essential for improving the accuracy of thyroid ultrasound. In the standardization, since there are no global consensus exists, common characteristics such as a multi-feature diagnosis, the performance of lymph nodes, explicit indications of fine needle aspiration, and the diagnosis of special populations should be focused on. Besides, evidence suggests that AI technique has a good effect on the unavoidable limitations of traditional ultrasound, and the combination of diagnostic criteria and AI may lead to a great promotion in thyroid diagnosis. Conclusion. Standardization and development of novel techniques are key factors to improving thyroid ultrasound, and both should be considered in normal clinical use.

Fibroblast growth factor (FGF) family members are important regulators of cell growth, proliferation, differentiation, and regeneration. The abnormal expression of certain FGF family members can cause skeletal diseases, including achondroplasia, craniosynostosis syndrome, osteoarthritis, and Kashin-Beck disease. Accumulating evidence shows that FGFs play a crucial role in the growth and proliferation of bone and in the pathogenesis of certain bone-related diseases. Here, we review the involvement of FGFs in bone-related processes and diseases; FGF1 in the differentiation of human bone marrow mesenchymal stem cells and fracture repair; FGF2, FGF9, and FGF18 in osteoarthritis; FGF6 in bone and muscle injury; FGF8 in osteoarthritis and Kashin-Beck disease; and FGF21 and FGF23 on bone regulation. These findings indicate that FGFs are targets for novel therapeutic interventions for bone-related diseases.

In recent years, non-pharmacological approaches have been introduced for older adults with mild cognitive impairment (MCI) in an attempt to address cognitive decline and improve cognitive functioning. Art therapy is a widely accepted psychosocial treatment known to engage attention and enhance cognition, and improve mood for persons with dementia. However, research assessing the benefits of art therapy in the MCI population is limited. This study used structured art therapy that was introduced as a 9-month randomized control trial of older adults with MCI (N = 68). The trial involved three arms, art therapy (N = 22), music reminiscence activity (N = 24) and a control group (no treatment; N = 22). Both art therapy and music reminiscence activity were conducted weekly for 3 months and then fortnightly for 6 months. Art therapy comprised of two structured components, physical creation of art pieces and the cognitive evaluation of paintings. The primary outcome, cognitive performance on neuropsychological tests, showed significant improvement in memory domains which were sustained at 9 months with art therapy. Additional improvements were noted in visuospatial abilities, attention, working memory, and executive function.

Ternary zinc oxide/bismuth vanadate/three-dimensional ordered macroporous titanium dioxide (ZnO/BiVO4/3DOM TiO2) heterojuncted nanocomposites with cascade electronic band structures were successfully designed and synthesized for visible light photodegradation of two different molecules: Rhodamine B (RhB) and Tartrazine. The photocatalytic active species have been investigated by using electron scavenger (AgNO3) and hole scavenger (Triethanolamine: TEOA). The band edge positions of each component in tenary nanocomposites have been measured by using photoelectrochemical Mott-Schottky method and valence band XPS (VB-XPS) spectroscopy. Within the heterojunction, charges are favorably and spatially separated through the gradient potential at the interfaces. This largely suppresses the recombination of photogenerated electrons and holes. Furthermore, 3DOM inverse opal structure is beneficial for high diffusion efficiency and highly accessible surface area of reactants and light and multiple scattering for light harvesting. Consequently, these heterojuncted nanocomposites exhibit highly enhanced photocatalytic performance compared with pure BiVO4 nanostructure, and binary BiVO4/3DOM TiO2, ZnO/BiVO4 nanocomposites. A detailed mechanism of charge transfer is proposed for these ternary ZnO/BiVO4/3DOM TiO2 nanocomposites on the basis of a large series of spectroscopic and photocatalytic results. Our work demonstrates clearly that coupling multicomponent semiconductors with different energy levels of conduction and valence bands can significantly increase the photogenerated charge carriers through the efficient charge separation across their multiple interfaces. This work gives some new ideas on developing new visible light responsive nanocomposites for highly efficient solar energy utilization.