[Efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage â ¡-â ¢ melanoma].

Objective: To explore the efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage Ⅱ-Ⅲ melanoma. Methods: A total of 296 patients who underwent radical surgery for stage Ⅱ-Ⅲ cutaneous orlimb melanoma at Fudan University Shanghai Cancer Center and Shanghai Electric Power Hospital between 2017 and 2021 and received adjuvant PD-1 monoclonal antibody immunotherapy, low-dose interferon (IFN), or observational follow-up were enrolled in this study. Patients were divided into the PD-1 monoclonal antibody group (164 cases) and the IFN or observation group (IFN/OBS group, 132 cases) based on postoperative adjuvant treatment methods. Patients' disease recurrence and survival were observed. Results: Among the 296 patients, 77 had cutaneous melanoma and 219 had limb melanoma; 110 were stage Ⅱ and 186 were stage Ⅲ. Among stage Ⅱ patients, the median recurrence-free survival (RFS) in the PD-1 monoclonal antibody group (46 cases) did not reach, while the median RFS in the IFN/OBS group (64 cases) was 36 months. The 1-year RFS rates were 85.3% and 92.1% and the 2-year RFS rates were 71.9% and 63.7% in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with no statistically significant difference (P=0.394). Among stage Ⅲ patients, the median RFS rates in the PD-1 monoclonal antibody group (118 cases) and the IFN/OBS group (68 cases) were 23 and 13 months, respectively. The 1-year RFS rates were 70.0% and 51.8% and the 2-year RFS rates were 51.8% and 35.1%in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with a statistically significant difference (P=0.010). Stratified analysis showed that the advantage of PD-1 monoclonal antibody adjuvant therapy in improving RFS persisted in the subgroups of primary ulceration (HR=0.558, 95% CI: 0.348-0.893), lymph node macroscopic metastasis (HR=0.486, 95% CI: 0.285-0.828), stage ⅢC (HR=0.389, 95% CI: 0.24-0.63), and the subgroup without BRAF/c-Kit/NRAS gene mutations (HR=0.347, 95% CI: 0.171-0.706). In terms of recurrence patterns, in stage Ⅱ patients, the recurrence and metastasis rate was 15.2% (7/46) in the PD-1 monoclonal antibody group, significantly lower than the IFN/OBS group [43.8% (28/64), P=0.002]. In stage Ⅲ melanoma patients, the recurrence and metastasis rate was 42.4% (50/118) in the PD-1 monoclonal antibody group, also lower than the IFN/OBS group [63.2% (43/68), P=0.006]. Conclusions: In real-world settings, compared with patients receiving low-dose IFN adjuvant therapy or observational follow-up, PD-1 monoclonal antibody immunotherapy can reduce the recurrence and metastasis rate of cutaneous and limb melanoma, and prolong the postoperative RFS of stage Ⅲ cutaneous and limb melanoma patients. Patients with a heavier tumor burden benefit more from immunotherapy.

[Significance of IgA isotype of anti-v-raf murine sarcoma viral oncogene homologue B1 antibody in rheumatoid arthritis].

OBJECTIVE: To detect serum IgA isotype of anti-v-raf murine sarcoma viral oncogene homologue B1 (BRAF) antibody levels in the rheumatoid arthritis (RA) patients in order to investigate their clinical significance in RA. METHODS: Serum samples were obtained from 61 RA patients, 21 osteoarthritis (OA) patients, 16 systemic lupus erythematosus (SLE) patients, 16 gout patients, 16 Sjögren's syndrome (SS) patients and 22 healthy controls. IgA isotype of anti-BRAF antibody levels in the sera were examined by enzyme-linked immunosorbent assay (ELISA). The associations between IgA isotype of anti-BRAF antibody levels and the clinical features including age, disease duration and laboratory parameters including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), disease activity score in 28 joints (DAS28), anti-cyclic citrullinated peptide (anti-CCP) antibody, immunoglobulin and BRAF protein levels in the RA patients were evaluated. Data analyses were performed by using SPSS 19.0 program. RESULTS: The serum IgA isotype of anti-BRAF antibody levels in the RA patients were significantly higher than in the SLE, gout, OA patients and healthy controls, the P value was 0.011, < 0.001, < 0.001 and < 0.001, respectively. The serum IgA isotype of anti-BRAF antibody levels in the SS patients were also significantly higher than in the SLE, gout, OA patients and healthy controls, the P value was 0.029, 0.004, 0.001 and < 0.001, respectively. However, there was no difference between the RA and SS patients (P=0.762). IgA isotype of anti-BRAF antibody was measurable in the RA patients without RF, anti-CCP antibody or anti-keratin antibody (AKA) antibodies. The levels of IgA isotype of anti-BRAF antibody in the RA patients did not show any correlation with clinical features such as age and disease duration or laboratory parameters including ESR, CRP, RF, DAS28, anti-CCP antibody, immunoglobulin and BRAF protein levels. Compared with the clinical features and laboratory indexes of normal and elevated levels of IgA isotype of anti-BRAF antibody groups in the RA patients, there was no significant differences between the two groups in age, disease duration, ESR, CRP, RF, DAS28, anti-CCP antibody, immunoglobulin or BRAF protein levels. CONCLUSION: The elevated level of IgA isotype of anti-BRAF antibody in the RA patients showed that IgA isotype of anti-BRAF antibody might play a role in the pathogenesis of RA. Furthermore, detection of IgA isotype of anti-BRAF antibody in the serum negative RA patients showed that it might be helpful for the diagnosis of the serum negative RA patients.

[Potential transmission risk of key parasitic diseases and responses to the risk during the construction of an ecological city in Shanghai Municipality].

A blueprint on Shanghai's ecological space design between 2021 and 2035 was released in 2021, aiming to build an ecological city and improve the development of ecological civilization. The transmission of parasitic diseases is strongly associated with climate and ecological environments. Currently, the prevalence of parasitic diseases has been maintained at extremely low-transmission levels, and there are almost no local cases; however, the alteration of ecological environments may results in a potential transmission risk of parasitic diseases. Hereby, the current status of key parasitic diseases in Shanghai Municipality was described, and the potential transmission risk of parasitic diseases and responses to this risk were analyzed during the construction of an ecological city in Shanghai Municipality. In addition, the suggestions pertaining to surveillance and management of parasitic diseases were proposed during the mid- and long-term construction of an ecological city in Shanghai Municipality.

[Cross-sectional study on quality of life and disease activity of rheumatoid arthritis patients].

OBJECTIVE: To analyze health related quality of life (HR-QoL) and physical function of outpatient department patients with rheumatoid arthritis (RA), and to analyze disease activity influence in HR-QoL and functional capacity as well as the divergences between different disease activity standards. METHODS: The demographic and clinical data of 207 RA cases from Department of Rheumatology and Immunology, Peking University Third Hospital from Jan 2021 to Jul 2021 were collected. RA-specific quality of life (RA-QoL) and the medical outcome 36-item short form health survey (SF-36)were collected to estimate the quality of life. The t test was used for the quantitative data in accordance with normal distribution. RESULTS: A total of 207 cases were included, with RA-QoL score of 7.8±7.1, physical component summary (PCS) score of 63.8±23.8, and mental component summary (MCS) score of 71.7±21.0. According to disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR), there were 119 patients (59.5%) with remission and low disease activity, and 125 patients (62.5%) with simplified disease activity index (SDAI). The HR-QoL of the patients with remission or low disease activity was significantly better than that of the patients with moderate or high disease activity. The physical function (76.7±17.2 vs. 86.4±15.0, t=2.855, P < 0.01), bodily pain (67.8±8.5 vs. 77.7±15.6, t=4.277, P < 0.01) and health transition (52.8±22.3 vs. 63.9±24.1, t=2.134, P < 0.05) in the low disease activity (LDA) group were lower than those in the complete remission (REM) group according to DAS28-ESR. Other domains of SF-36 and RA-QoL had no differences between these two groups. PCS in the LDA group was lower than that in the REM group (68.3±15.2 vs. 77.3±15.2, t=2.716, P < 0.01), but MCS was not different between the two groups. Determined by SDAI, the RA-QoL score in the LDA group was significantly higher than that in the REM group (9.4±7.1 vs. 6.0±4.8, t=-2.260, P < 0.05), the various dimensions of physical function in the SF-36 score and the PCS score (69.9±16.4 vs. 81.4±15.1, t=3.879, P < 0.05) were lower than that in the REM group, and the MCS score was lower than that in the REM group (67.9±19.3 vs. 74.5±18.8, t=2.721, P < 0.01). CONCLUSION: The RA-QoL and SF-36 scores of RA patients in outpatient clinics were better, and the MCS was higher than the PCS. Treat-to-target is essential to improve HR-QoL. SDAI can better indicate the HR-QoL of each domain in REM and LDA RA patients.

[Prevalence and risk factors of coronary artery calcification on lung cancer screening with low-dose CT].

Objective: To investigate the prevalence and risk factors of coronary artery calcification (CAC) on lung cancer screening with low-dose computed tomography (LDCT). Methods: A total of 4 989 asymptomatic subjects (2 542 males and 2 447 females) who underwent LDCT lung cancer screening were recruited at Cancer Hospital, Chinese Academy of Medical Sciences from 2014 to 2017. The visual scoring method was used to assess coronary artery calcification score. χ(2) test or independent t-test was used to compare the difference of CAC positive rate among different groups. Multivariate logistic regression was used to analyze risk factors associated with CAC in the study. Results: Of the 4 989 asymptomatic subjects, CAC occurred in 1 018 cases. The positive rate was 20.4%, of which mild, moderate and severe calcification accounted for 86.3%, 11.4% and 2.3%, respectively. Gender, age, BMI, education level, occupation, smoking history, diabetes, hypertension and hyperlipidemia had statistically significant differences in CAC positive rates among groups. Multivariate logistic regression analysis showed that gender, age, diabetes, hypertension, hyperlipidemia and smoking history were risk factors for CAC. Age, diabetes, hypertension and smoking history were statistically significant risk factors between the mild and moderate CAC group. A total of 1 730 coronary arteries in 1 018 CAC positive cases had calcification, CAC positive rate of left anterior descending was the highest(51.3%); 568 cases (55.8%) were single vessel calcification, 450 cases (44.2%) were multiple vessel calcification. Conclusions: LDCT can be used for the 'one-stop' early detection of lung cancer and coronary atherosclerosis. Gender, age, diabetes, hypertension, hyperlipidemia and smoking are related risk factors for coronary atherosclerosis.

[Prediction of trends for fine-scale spread of Oncomelania hupensis in Shanghai Municipality based on supervised machine learning models].

OBJECTIVE: To predict the trends for fine-scale spread of Oncomelania hupensis based on supervised machine learning models in Shanghai Municipality, so as to provide insights into precision O. hupensis snail control. METHODS: Based on 2016 O. hupensis snail survey data in Shanghai Municipality and climatic, geographical, vegetation and socioeconomic data relating to O. hupensis snail distribution, seven supervised machine learning models were created to predict the risk of snail spread in Shanghai, including decision tree, random forest, generalized boosted model, support vector machine, naive Bayes, k-nearest neighbor and C5.0. The performance of seven models for predicting snail spread was evaluated with the area under the receiver operating characteristic curve (AUC), F1-score and accuracy, and optimal models were selected to identify the environmental variables affecting snail spread and predict the areas at risk of snail spread in Shanghai Municipality. RESULTS: Seven supervised machine learning models were successfully created to predict the risk of snail spread in Shanghai Municipality, and random forest (AUC = 0.901, F1-score = 0.840, ACC = 0.797) and generalized boosted model (AUC= 0.889, F1-score = 0.869, ACC = 0.835) showed higher predictive performance than other models. Random forest analysis showed that the three most important climatic variables contributing to snail spread in Shanghai included aridity (11.87%), ≥ 0 °C annual accumulated temperature (10.19%), moisture index (10.18%) and average annual precipitation (9.86%), the two most important vegetation variables included the vegetation index of the first quarter (8.30%) and vegetation index of the second quarter (7.69%). Snails were more likely to spread at aridity of < 0.87, ≥ 0 °C annual accumulated temperature of 5 550 to 5 675 °C, moisture index of > 39% and average annual precipitation of > 1 180 mm, and with the vegetation index of the first quarter of > 0.4 and the vegetation index of the first quarter of > 0.6. According to the water resource developments and township administrative maps, the areas at risk of snail spread were mainly predicted in 10 townships/subdistricts, covering the Xipian, Dongpian and Tainan sections of southern Shanghai. CONCLUSIONS: Supervised machine learning models are effective to predict the risk of fine-scale O. hupensis snail spread and identify the environmental determinants relating to snail spread. The areas at risk of O. hupensis snail spread are mainly located in southwestern Songjiang District, northwestern Jinshan District and southeastern Qingpu District of Shanghai Municipality.

Three-Dimensional Dirac Phonons with Inversion Symmetry.

Dirac semimetals associated with bulk Dirac fermions are well known in topological electronic systems. In sharp contrast, three-dimensional (3D) Dirac phonons in crystalline solids are still unavailable. Here we perform symmetry arguments and first-principles calculations to systematically investigate 3D Dirac phonons in all space groups with inversion symmetry. The results show that there are two categories of 3D Dirac phonons depending on their protection mechanisms and positions in momentum space. The first category originates from the four-dimensional irreducible representations at the high symmetry points. The second category arises from the phonon branch inversion, and the symmetry guarantees Dirac points to be located along the high symmetry lines. Furthermore, we reveal that nonsymmorphic symmetries and the combination of inversion and time-reversal symmetries play essential roles in the emergence of 3D Dirac phonons. Our work not only offers a comprehensive understanding of 3D Dirac phonons but also provides significant guidance for exploring Dirac bosons in both phononic and photonic systems.

[Expert consensus on the strategy and measures to interrupt the transmission of schistosomiasis in China].

Since 2015 when the transmission of schistosomiasis was controlled in China, the country has been moving towards elimination of schistosomiasis, with the surveillance-response as the main interventions for schistosomiasis control. During the period of the 13th Five-Year Plan, the transmission of schistosomiasis had been interrupted in four provinces of Sichuan, Jiangsu, Yunnan and Hubei and the prevalence of schistosomiasis has been at the historically lowest level in China. As a consequence, the goal set in The 13th Five-Year National Schistosomiasis Control Program in China is almost achieved. However, there are multiple challenges during the stage moving towards elimination of schistosomiasis in China, including the widespread distribution of intermediate host snails and complicated snail habitats, many types of sources of Schistosoma japonicum infections and difficulty in management of bovines and sheep, unmet requirements for the current schistosomiasis control program with the currently available tools, and vulnerable control achievements. During the 14th Five-Year period, it is crucial to consolidate the schistosomiasis control achievements and gradually solve the above difficulties, and critical to provide the basis for achieving the ultimate goal of elimination of schistosomiasis in China. Based on the past experiences from the national schistosomiasis control program and the challenges for schistosomiasis elimination in China, an expert consensus has been reached pertaining to the objectives, control strategy and measures for The 14th Five-Year National Schistosomiasis Control Program in China, so as to provide insights in to the development of The 14th Five-Year National Schistosomiasis Control Program in China.

[Prevalence of Clonorchis sinensis infections in freshwater fish in mainland China: A meta-analysis].

OBJECTIVE: To understand the real prevalence of Clonorchis sinensis infections in the freshwater fish in mainland China, so as to provide insights into clonorchiasis control and detection of freshwater fish. METHODS: All literatures reporting the prevalence of C. sinensis infections in the freshwater fish, the second intermediate host of the parasite, were jointly retrieved in Chinese and English electronic databases from January 1, 2010 to December 31, 2020, including Wanfang Data, CNKI, PubMed, Web of Science, Embase and Cochrane Library. All studies were screened based on inclusion and exclusion criteria, and the quality of all enrolled literatures was evaluated. The pooled prevalence of C. sinensis infections in freshwater fish and its 95% confidence interval (CI) were estimated using the software Stata version 15.0, and subgroup analyses were performed to investigate the region-, season- and sample source-specific pooled prevalence of C. sinensis infections in freshwater fish. In addition, the sensitivity and publication bias of all included studies were analyzed. RESULTS: A total of 40 eligible literatures were included in this study, including 37 Chinese literatures and 3 English literatures, and there were 10 high-quality literatures, 27 moderate-quality literatures and 3 low-quality literatures. A total of 53 species containing 37 959 freshwater fish were reported in these 40 studies, and 73.58% (39/53) of freshwater fish species were identified with C. sinensis infections. Meta-analysis showed 23.5% [95% CI: (0.19, 0.28)] pooled prevalence of C. sinensis infections in freshwater fish in mainland China, and subgroup analyses higher prevalence of C. sinensis infections in freshwater fish in northeastern China [35.7%, 95% CI: (0.22, 0.50)] than in central [25.9%, 95% CI: (0.04, 0.48)] and southern China [20.6%, 95% CI: (0.09, 0.32)], higher prevalence of C. sinensis infections in freshwater fish sampled in spring [44.1%, 95% CI: (0.35, 0.53)] than in autumn [6.7%, 95% CI: (0.05, 0.08)] and summer [3.3%, 95% CI: (-0.01, 0.07)], and higher prevalence of C. sinensis infections in freshwater fish sampled from natural water [25.2%, 95% CI: (0.17, 0.33)] than from retail trades [22.2%, 95% CI: (0.17, 0.28)] and breeding chain [12.3%, 95% CI: (0.03, 0.22)]. However, all included studies had a publication bias with a low sensitivity. CONCLUSIONS: The prevalence of C. sinensis infections is high in freshwater fish in mainland China, and there are still challenges for clonorchiasis control. Reinforcement of health education, diagnostics development and food safety supervision is recommended in future clonorchiasis control programs.

Two-Dimensional Dirac Semimetals without Inversion Symmetry.

Realizing stable two-dimensional (2D) Dirac points against spin-orbit coupling (SOC) has attracted much attention because it provides a platform to study the unique transport properties. In previous work, Young and Kane [Phys. Rev. Lett. 115, 126803 (2015)PRLTAO0031-900710.1103/PhysRevLett.115.126803 proposed stable 2D Dirac points with SOC, in which the Berry curvature and edge states vanish due to the coexistence of inversion and time-reversal symmetries. Herein, using the tight-binding model and k·p effective Hamiltonian, we present that 2D Dirac points can survive in the presence of SOC without inversion symmetry. Such 2D Dirac semimetals possess nonzero Berry curvature near the crossing nodes, and two edge states are terminated at one pair of Dirac points. In addition, according to symmetry arguments and high-throughput first-principles calculations, we identify a family of ideal 2D Dirac semimetals, which has nonzero Berry curvature in the vicinity of Dirac points and visible edge states, thus facilitating the experimental observations. Our work shows that 2D Dirac points can emerge without inversion symmetry, which not only enriches the classification of 2D topological semimetals but also provides a promising avenue to observe exotic transport phenomena beyond graphene, e.g., nonlinear Hall effect.

[Risk factors for lung cancer based on low-dose computed tomography screening].

Objective: To analyze the risk factors related to lung cancer in participants with low-dose computed tomography (LDCT) screening, to provide data support for identifying high-risk groups of lung cancer and to improve the effectiveness of LDCT lung cancer screening. Methods: A total of 5 366 asymptomatic subjects (2 762 males and 2 604 females) who underwent LDCT lung cancer screening were recruited at Cancer Hospital, Chinese Academy of Medical Sciences from 2014 to 2017. The result of LDCT and the risk factors of participants were analyzed. The LDCT positive results were defined as solid or part-solid nodules≥5 mm and non-solid nodule≥8 mm. A total of 12 factors were included and multivariate logistic regression was used to analyze the risk factors associated with lung cancer in the study. Results: Of the 5 366 asymptomatic subjects, 389 were positive and 4 977 were negative for LDCT screening. Among them, 26 of 389 positive cases were confirmed as lung cancers pathologically, and the detection rate of stage I lung cancer was 92.3% (24/26). Multivariate logistic regression showed that age, smoking, low level of education were the relevant risk factors for lung cancer and positive nodules. A stratified analysis of age showed that no risk factors were detected in the 40-49 years old group, while age, smoking, low level of education (primary school and below) were recognized as risk factors in the ≥50 years old group. No statistically significant risk factor was detected between the lung cancer group and the positive nodules group. Conclusions: Age, smoking, and low level of education (primary school and below) are related risk factors for lung cancer and positive nodules. People aged 50 years or older, smoking, and low level of education may be a high risk group for lung cancer. LDCT can effectively detect early lung cancer.

Robust Twin Pairs of Weyl Fermions in Ferromagnetic Oxides.

The ferromagnetic Weyl semimetals with inversion symmetry usually possess odd pairs of Weyl fermions. Here, we present an inversion eigenvalue argument to dictate the existence of even pairs of ferromagnetic Weyl fermions. We show, by a combination of first-principles calculations and symmetry analyses, that this exotic topological feature can be verified in ferromagnetic oxides in different space groups. In particular, a realistic candidate, i.e., hollandite RbCr_{4}O_{8} with a high Curie temperature (∼295 K), hosts intriguing twin pairs of Weyl fermions, which are robustly stable against perturbations. Moreover, our effective model and symmetry analysis show that the twin pairs of Weyl fermions originate from a mirrored nodal ring pair. The nontrivial surface states and Fermi arcs of RbCr_{4}O_{8} are clearly visible, further revealing the topological features. This work strengthens the understanding of the parity analysis in exploring ferromagnetic topological materials with unconventional fermionic excitations.

HOXA11-AS regulates diabetic arteriosclerosis-related inflammation via PI3K/AKT pathway.

OBJECTIVE: This study aims to explore whether homeobox A11 antisense RNA (HOXA11-AS) could regulate inflammation induced by diabetic arteriosclerosis (DAA) via PI3K/AKT pathway. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect expressions of HOXA11-AS and proinflammatory genes in carotid endarterectomy samples of symptomatic and asymptomatic atherosclerosis (AS) patients, diabetes mellitus (DM), and non-DM patients. The above-mentioned genes in DM animal model and non-DM animal model were also detected. We detected the expression of HOXA11-AS in vascular smooth muscle cells (VSMCs) treated with platelet-derived growth factor (PDGF) or PDGF inhibitor imatinib, respectively. Subsequently, we applied cell transfection technology to interfere with the expression of HOXA11-AS in VSMCs. In vascular endothelial cells (VECs) and VSMCs, we detected the effect of HOXA11-AS on the expressions of genes related to the proliferation, migration, and cell cycle. Then, VSMCs were treated with tumor necrosis factor-α (TNF-α), and the expression of HOXA11-AS was examined in VSMCs. The effect of HOXA11-AS on TNF-α-induced inflammation in VSMCs was detected as well. Finally, we analyzed the effect of HOXA11-AS on PDGF-induced activation of PI3K/AKT pathway in VSMCs and VECs. RESULTS: HOXA11-AS expression was markedly increased in carotid endarterectomy specimens of symptomatic AS patients compared to that of asymptomatic AS patients. Expression levels of HOXA11-AS and pro-inflammatory genes were significantly elevated in carotid endarterectomy specimens of DM patients. Similarly, HOXA11-AS expression was also significantly increased in carotid arteries of DM mice compared with that of non-DM mice. PDGF could upregulate HOXA11-AS expression in VSMCs, which was reversed by PDGF inhibitor imatinib. HOXA11-AS knockdown could reduce the expressions of the proliferation-associated gene (PCNA) and the cycle-related genes (p21, p53), and also inhibited the proliferation and migration of VSMCs induced by PDGF. HOXA11-AS was upregulated by TNF-α. HOXA11-AS knockdown remarkably downregulated expressions of inflammation-related genes in VSMCs induced by TNF-α. In VECs, low expression of HOXA11-AS can inhibit the expression of TNF-α-induced pro-inflammatory genes and PDGF-induced vascular inflammation-related genes. Low expression of HOXA11-AS inhibited PDGF-induced activation of PI3K/AKT pathway in VSMCs and VECs. CONCLUSIONS: HOXA11-AS may participate in DAA by activating the PI3K/AKT pathway to regulate inflammation in VSMCs and VECs.

Excessive Oxidative Stress in the Synergistic Effects of Shikonin on the Hyperthermia-Induced Apoptosis.

BACKGROUND: Hyperthermia (HT) has been used widely for cancer therapy, and the development of modern devices has made it more efficient. Shikonin (SHK) is a natural naphthoquinone derivative from a Chinese herb. Although the anticancer properties of SHK are evident, the underlying molecular mechanisms are not fully understood. OBJECTIVE: In this study, the effects of combining low doses of SHK with mild HT were investigated in the U937 cell line. METHODS: The cells were subjected to HT at 44°C for 10 min with or without SHK pretreatment, and parameters reflecting apoptosis, ROS generation and intracellular calcium elevation were evaluated by using DNA fragmentation, flow cytometry, and western blot analyses. RESULTS: SHK 0.5 µM significantly enhanced HT-induced apoptosis as indicated by DNA fragmentation and caspase-3 activation with increased generation of ROS and elevation of intracellular calcium. The combined treatment also synergistically activated proapoptotic proteins and inactivated anti-apoptotic proteins. Furthermore, the phosphorylation of JNK and PKC- δ and the dephosphorylation of ERK and AKT were the upstream effects that may have compounded the induction of apoptosis. The modulatory effects of HT and SHK were abrogated with the employment of NAC and JNK-IN-8 by inactivating the MAPK pathway and cleavage of caspase-3. Intracellular calcium was also elevated and was found to be responsible for the induction of cell death evident by the DNA fragmentation with or without the employment of BAPTA-AM. CONCLUSION: Conclusively, this study provides persuasive evidence that SHK in combination with HT is a propitious therapeutic way for augmentation of apoptosis and hence suggest a novel strategy for treating cancers.

[The effect of human islet amyloid polypeptide on autophagy in murine INS-1 cells and potential mechanisms].

Objective: The aims of the study were to investigate the effects of human islet amyloid polypeptide (hIAPP) on autophagy in INS-1 cells and its underlying mechanism, and to explore the role of autophagy in hIAPP-induced cytotoxicity and oxidative stress. Methods: INS-1 cells were treated with hIAPP (10 µmol/L) for 24 h in the presence or absence of N-acetyl-L-cysteine (NAC), compound C, 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside (AICAR) and 3-methyladenine (3-MA), respectively. Transmission electron microscopy was used to observe the number of autophagosome in cells. Cell viability was determined by methyl thiazolyl tetrazolium (MTT) test. 2',7'-dichlorofluorescin diacetate (DCFH-DA) assay was used to measure the relative levels of reactive oxygen species (ROS). Western blot was used to detect expression of adenosine monophosphate-activated protein kinase (AMPK) and autophagic markers p62 and microtubule associated protein 1 light chain3 (LC3). Results: Treatment of INS-1 cells with hIAPP resulted in a significant increase in the number of autophagosomes and the expression of LC3-Ⅱ/LC3-Ⅰ (both P<0.05). Meanwhile, treatment of INS-1 cells with hIAPP enhanced the level of ROS to 1.76 times of control cells (P<0.01). Co-treatment with NAC, an antioxidant, inhibited hIAPP-induced ROS generation, and the expression of LC3-Ⅱ/LC3-Ⅰ and p-AMPK in the INS-1 cells (all P<0.05). Pretreatment of INS-1 cells with AMPK inhibitor compound C suppressed hIAPP and AICAR, an activator of AMPK, induced expression of LC3-Ⅱ/LC3-Ⅰ and p-AMPK (all P<0.05). Autophagic inhibitor 3-MA and compound C aggravated the hIAPP-induced cell death and ROS generation in INS-1 cells (All P<0.05). The cytotoxic effects of hIAPP were significantly attenuated by co-treatment with AICAR (P<0.05). Conclusion: Autophagy may act as an adaptive mechanism to alleviate hIAPP-induced oxidative damage and toxicity in INS-1 cells.

[The volume and mass growth of persisted pulmonary nodules detected in low-dose CT screening and its influence factors].

Objective: To evaluate the changes of volume and mass of pulmonary nodules which were detected in low-dose computed tomography (LDCT) screening, and to analyze the influencing factors. Methods: This retrospective study analyzed the CT images of the participants who underwent at least two chest LDCT scanning from March 2009 to December 2015 in National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. The inclusion criteria was the nodule diameter ≥6 mm; the volume growth was defined as ≥20%. Fifty-one pulmonary nodules (PNs) were selected among 51 enrolled participants (26 men and 25 women). According to characteristic of nodule and risk stratification of participant, the nodules were classified into different groups (10 non-solid nodules, 17 part-solid nodules and 24 solid nodules; 14 PNs in high-risk group, 12 PNs in moderate-risk group and 25 PNs in low-risk group). The Lung-VCAR software was used to measure the diameter and volume of the PNs, and all nodules were calculated for the volume doubling time (VDT) and mass doubling time (MDT). Results: Among the 51 PNs, the diameter of 33 nodules increased more than 1.5 mm while 18 nodules increased less than 1.5 mm. The median VDT of part-solid nodules was 364 days, which was shorter than that of non-solid nodules and solid nodules (761 and 819 days, respectively), the differences were statistically significant (both P<0.05). The median MDT of part-solid nodules was 351 days, which was lower than that of non-solid nodules and solid nodules (772 days and 840 days, respectively). The difference was statistically significant (P<0.05). The median VDT and MDT of the pulmonary nodules in the high-risk group were 181 days and 256 days, respectively, which were lower than those in the low risk group (1 037 days and 1 035 days, respectively). VDT has good correlation with MDT (r=0.909, P<0.001). Conclusions: Both the characteristic of PNs and the risk status of the participants could affect the growth of nodules in LDCT screening. The part-solid nodules and high-risk group nodules grew relatively faster, which should be closely focused on. Compared with the two-dimensional diameter, the three-dimensional quantitative indicators (VDT and MDT) were more sensitive for nodule growth. The mass changes of part-solid nodules were earlier than that of volume.

Development and evaluation of the automated risk assessment system for multidrug-resistant organisms (autoRAS-MDRO).

BACKGROUND: A high proportion of infections acquired in hospitals are caused by multidrug-resistant organisms (MDROs). The priority in MDRO prevention is to detect high-risk patients and implement preventive intervention as soon as possible. AIM: To develop an automated risk assessment system for MDROs (autoRAS-MDRO) to screen for patients at MDRO infection risk and evaluate the predictive validity of the autoRAS-MDRO. METHODS: Data for 4200 variables were extracted from the electronic health records (EHRs) for constructing the MDRO risk-scoring algorithm, which was based on a logistic regression model. The autoRAS-MDRO was designed such that the MDRO risk classification (high, moderate, low risk) could be automatically displayed on the nursing Kardex screen in the EHRs system. For the development of the MDRO risk-scoring algorithm, 1000 patients with MDROs and 4000 patients without MDROs were selected; similarly, for the evaluation, 2173 and 8692 patients with and without MDROs, respectively, were selected. FINDINGS: The predictive validity of the autoRAS-MDRO was as follows: (i) at the 6-month evaluation: sensitivity, 81%; specificity, 79%; positive predictive value (PPV), 49%; negative predictive value (NPV), 94%; and Youden index, 0.60; (ii) at the 12-month evaluation: sensitivity 79%, specificity 78%, PPV 47%, NPV 94%, and Youden index, 0.57. CONCLUSION: The autoRAS-MDRO had moderate predictive validity. It could be useful in redirecting nurses' time and efforts required for MDRO risk assessment and implementation of infection control measures, and in reducing the incidence of MDRO infection in hospitals, thereby contributing to patient safety.

Emergence of topological nodal loops in alkaline-earth hexaborides XB6 (X = Ca, Sr, and Ba) under pressure.

Based on first-principles calculations, we report that external pressure can induce a topological phase transition in alkaline-earth hexaborides, XB6 (X = Ca, Sr, and Ba). It was revealed that XB6 are transformed from trivial semiconductors to topological node-line semimetals under moderate pressure when the spin-orbit coupling (SOC) is ignored. The band inversion between the B p-orbitals at the X point is responsible for the formation of node-line semimetals. Three node-line rings around the X point are protected by the combination of the time-reversal and spatial inversion symmetries, and drumhead surface bands are obtained in the interiors of the projected node-line rings. When the SOC is included, tiny gaps (<4.8 meV) open at the crossing lines and the XB6 become strong topological insulators with Z2 indices (1 : 111). As the SOC-induced gap opening is negligible, our findings thus suggest ideal real systems for experimental exploration of the fundamental physics of topological node-line semimetals.

Polymorphisms of TGFB1, TLE4 and MUC22 are associated with childhood asthma in Chinese population.

OBJECTIVE: To investigate whether the genetic variants of TGFB1, TLE4, MUC22 and IKZF3 are associated with the development of asthma in Chinese children. METHODS: 572 adolescent asthma patients and 590 age-matched healthy controls were included in this study. A total of four SNPs were genotyped, including rs2241715 of TGFB1, rs2378383 of TLE4, rs2523924 of MUC22, and rs907092 of IKZF3. Allele frequencies of the patients and the control group were compared by the Chi-square test. The Student t test was used to analyse the relationship between genotypes and clinical feature of the patients. RESULTS: Patients were found to have significantly different frequencies of allele A of rs2241715, allele G of rs2378383 and allele A of rs2523924 as compared with the controls (40.4% vs. 45.9%, p=0.01 for rs2241715; 17.2% vs. 13.4%, p=0.01 for rs2378383; 15.3% vs. 11.9%, p=0.02 for rs2523924). For patients with severe asthma, those with genotype AA/AG of rs2241715 had remarkably higher FEV1% as compared with those with genotype GG (59.1±4.3% vs. 55.4±3.7%, p<0.001). Moreover, those with genotype GG/GA of rs2378383 had remarkably lower FEV1% as compared with those with genotype AA (54.6±2.9% vs. 58.6±4.1%, p<0.001). CONCLUSIONS: Genes TGFB1, TLE4 and MUC22 are associated with the risk of childhood asthma in Chinese population. Our results associating TGFB1 and TLE4 with clinical features of asthma suggest potential application of these parameters in the management of asthma children.

[Significance of v-raf murine sarcoma viral oncogene homologue B1 in rheumatoid arthritis].

OBJECTIVE: To detect serum v-raf murine sarcoma viral oncogene homologue B1 (BRAF) protein levels and to investigate their clinical significance in rheumatoid arthritis (RA) patients. METHODS: Serum samples were obtained from 78 RA patients, 32 osteoarthritis (OA) patients, 16 systemic lupus erythematosus (SLE) patients, 16 gout patients, 16 ankylosing spondylitis (AS) patients, 16 Sjogren syndrome (SS) patients and 30 healthy controls. BRAF protein in the sera was examined by enzyme-linked immunosorbent assay (ELISA). The associations between BRAF levels and the clinical features including age, sex, disease duration, swelling joints, tenderness joints, duration of moning stiffness, joint deformity, visual assessment scale (VAS) and extra articular manifestations and laboratory parameters including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), disease activity score in 28 joints (DAS28), anti-cyclic citrullinated peptide (CCP) antibody, antikeratin antibody, antnuclear antibody (ANA), immunoglobulin and cytokines, such as TNF-α, IL-1ß, IL-6 and IL-17A in RA patients were evaluated. Data analyses were performed by using SPSS 19.0 program. RESULTS: The serum BRAF protein levels in the RA patients were significantly higher than those of other rheumatic diseases groups including OA, SLE, AS, SS, gout patients and healthy controls, the P value was 0.002, <0.001, <0.001, <0.001, 0.001 and <0.001 respectively. The level of serum BRAF protein in the RA patients showed a positive correlation with the rheumatoid factor (P=0.009) and IgA levels (P=0.006), but no correlation with clinical features, such as age and duration or other laboratory parameters, including CRP, ESR, anti-CCP antibody, IgM, IgG, TNF-α, IL-1ß, IL-6 and IL-17A. The RA patients were further divided into normal levels of BRAF protein group and elevated levels of BRAF protein group. Compared with the clinical features and laboratory indexes of normal and elevated levels of BRAF protein groups in the RA patients, there was no significant difference between the two groups in age, duration, DAS28, CRP, ESR, RF, anti-CCP, IgA, IgG, IgM, TNF-α or IL-6. CONCLUSION: The elevated level of BRAF protein in the RA patients showed that BRAF might play a role in the pathogenesis of RA. Further researches on BRAF gene expression may help to clarify the role of BRAF in RA.