Prediction of the Risk Distributions for Anopheles sinensis, a Vector for Malaria in Shanghai, China.

Malaria is a parasitic disease caused by Plasmodium, and Anopheles sinensis is a vector of malaria. Although malaria is no longer indigenous to China, a high risk remains for local transmission of imported malaria. This study aimed to identify the risk distribution of vector An. sinensis and malaria transmission. Using data collected from routine monitoring in Shanghai from 2010 to 2020, online databases for An. sinensis and malaria, and environmental variables including climate, geography, vegetation, and hosts, we constructed 10 algorithms and developed ensemble models. The ensemble models combining multiple algorithms (An. sinensis: area under the curve [AUC] = 0.981, kappa = 0.920; malaria: AUC = 0.959, kappa = 0.800), with the best out-of-sample performance, were used to identify important environmental predictors for the risk distributions of An. sinensis and malaria transmission. For An. sinensis, the most important predictor in the ensemble model was moisture index, which reflected degree of wetness; the risk of An. sinensis decreased with higher degrees of wetness. For malaria transmission, the most important predictor in the ensemble model was the normalized differential vegetation index, which reflected vegetation cover; the risk of malaria transmission decreased with more vegetation cover. Risk levels for An. sinensis and malaria transmission for each district of Shanghai were presented; however, there was a mismatch between the risk classification maps of An. sinensis and malaria transmission. Facing the challenge of malaria transmission in Shanghai, in addition to precise An. sinensis monitoring in risk areas of malaria transmission, malaria surveillance should occur even in low-risk areas for An. sinensis.

Chinese patent medicine Aidi injection for cancer care: An overview of systematic reviews and meta-analyses.

ETHNOPHARMACOLOGICAL RELEVANCE: Aidi injection is one of the China Food and Drug Administration approved Chinese herbal injections and the most competitive product in cancer care in China. It is composed of the extracts from Mylabris Phalerata, Astragalus Membranaceus, Panax Ginseng, and Acanthopanax Senticosus. AIM OF THE STUDY: This overview aims to map systematic reviews (SRs) of Aidi injection for cancer and provide a summarized evidence for clinical practice and decision making. MATERIALS AND METHODS: Seven databases were searched for SRs and/or meta-analyses of randomized controlled trials on Aidi injection for cancer care until December 2020. Six authors worked in pairs independently identified studies, collected data, and assessed the quality of included studies according to the revised Assessment of Multiple Systematic Reviews (AMSTAR 2) and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A narrative synthesis was used for the evidence mapping. RESULTS: Fifty-two SRs on Aidi injection as adjuvant therapy were included, involving lung cancer (20 SRs), liver cancer (10), colorectal cancer (7), gastric cancer (6), lymphoma (2), breast cancer (2), esophageal cancer (1), ovary cancer (1), and a mix of different cancers (4). Except for one SR focusing on Aidi injection used alone, other SRs evaluated Aidi injection in combination with chemotherapy (43), radiotherapy (4), or chemo/radiology/targeting therapy (4). Aidi injection showed additional beneficial effects on survival (9), objective response rate (44), quality of life (42), and the reduction of side-effects from chemo/radiotherapy (48). Using AMSTAR 2 tool, two reviews were assessed as low and the rest as critically low methodological quality mainly due to the lack of prospective registration. The reporting quality was insufficient assessed with PRISMA in the reporting of search strategy (26, 50.0%), additional analysis (19, 36.5%), and the summary of evidence (2, 3.8%). CONCLUSION: Aidi injection has been evaluated for its adjuvant beneficial effects on cancer survival, tumor responses, quality of life, and reducing the side effects of chemo/radiotherapy, mainly focusing on lung, liver and colorectal cancer. The methodological and reporting quality are weak and need to be improved in the future.

Smart deworming collar: A novel tool for reducing Echinococcus infection in dogs.

Echinococcosis is a serious zoonotic parasitic disease transmitted from canines to humans and livestock. Periodic deworming is recommended by the WHO/OIE as a highly effective measure against echinococcosis. However, manual deworming involves significant challenges, particularly in remote areas with scarce resources. The insufficient awareness delivering praziquantel (PZQ) baits for dogs leads to low compliance rate. The aim of this study was therefore to develop a novel smart collar for dogs to address these challenges. We developed a smart Internet of Things (IoT)-based deworming collar which can deliver PZQ baits for dogs automatically, regularly, quantitatively with predominant characteristics of being waterproof, anti-collision, cold-proof and long life battery. Its performance was tested in two remote locations on the Tibetan Plateau. A cross-sectional survey was conducted to evaluate the compliance of the dog owners. Further, a randomized controlled study was performed to evaluate the difference between smart-collar deworming and manual deworming. The collar's effectiveness was further assessed on the basis of Generalized Estimation Equations (GEE). The testing and evaluation was done for 10 smart deworming collars in factory laboratory, 18 collars attached for 18 dogs in Seni district, Tibet Autonomous Region, China, and 523 collars attached for 523 dogs in Hezuo city, Gansu province, China. The anti-collision, waterproof, and coldproof proportion of the smart collars were 100.0%, 99.5%, and 100.0%, respectively. When compared to manual deworming, the dogs' risk of infection with Echinococcus on smart-collar deworming is down to 0.182 times (95% CI: 0.049, 0.684) in Seni district and 0.355 (95%CI: 0.178, 0.706) in Hezuo city, the smart collar has a significant protective effect. The owners' overall compliance rate to attach the smart collars for their dogs was 89%. The smart deworming collar could effectively reduce the dogs' risk of infection with Echinococcus in dogs, significantly increase the deworming frequency and coverage and rapidly remove worm biomass in dogs. Thus, it may be a promising alternative to manual deworming, particularly in remote areas on the Tibetan Plateau.

The precision of epidemiological investigation of COVID-19 transmission in Shanghai, China.

BACKGROUND: Shanghai had a local outbreak of COVID-19 from January 21 to 24. Timely and precise strategies were taken to prevent further spread of the disease. We discussed and shared the experience of COVID-19 containment in Shanghai. PROCESS: The first two patients worked at two hospitals but no staff from the two hospitals were infected. The suspected case and his two close contacts were confirmed to be infected within 12 h. The testing rate of individuals was low. The scope of screening was minimized to two related districts and the close contact tracing was completed within 12 h, which were precise and cost-effective. CONCLUSIONS: Active monitoring, precise epidemiological investigation and timely nucleic acid testing help discover new cases, minimize the scope of screening, and interrupt the transmission.

Neisseria meningitidis carriage and risk factors among teenagers in Suizhou city in China.

Teenagers are important carriers of Neisseria meningitidis, which is a leading cause of invasive meningococcal disease. In China, the carriage rate and risk factors among teenagers are unclear. The present study presents a retrospective analysis of epidemiological data for N. meningitidis carriage from 2013 to 2017 in Suizhou city, China. The carriage rates were 3.26%, 2.22%, 3.33%, 3.53% and 9.88% for 2013, 2014, 2015, 2016 and 2017, respectively. From 2014 to 2017, the carriage rate in the 15- to 19-year-old age group (teenagers) was the highest and significantly higher than that in remain age groups. Subsequently, a larger scale survey (December 2017) for carriage rate and relative risk factors (population density, time spent in the classroom, gender and antibiotics use) were investigated on the teenagers (15- to 19-year-old age) at the same school. The carriage rate was still high at 33.48% (223/663) and varied greatly from 6.56% to 52.94% in a different class. Population density of the classroom was found to be a significant risk factor for carriage, and 1.4 persons/m2 is recommended as the maximum classroom density. Further, higher male gender ratio and more time spent in the classroom were also significantly associated with higher carriage. Finally, antibiotic use was associated with a significantly lower carriage rate. All the results imply that attention should be paid to the teenagers and various measures can be taken to reduce the N. meningitidis carriage, to prevent and control the outbreak of IMD.

Clinicopathological characteristics and survival outcomes in Paget disease: a SEER population-based study.

The objective of this study was to investigate the clinicopathological characteristics and survival outcomes of Paget disease (PD), Paget disease concomitant infiltrating duct carcinoma (PD-IDC), and Paget disease concomitant intraductal carcinoma (PD-DCIS). We identified 501,631 female patients from 2000 to 2013 in the Surveillance, Epidemiology, and End Results (SEER) database. These identified patients included patients with PD (n = 469), patients with PD-IDC (n = 1832), and patients with PD-DCIS (n = 1130) and infiltrating ductal carcinoma (IDC) (n = 498,076). Then, we compared the clinical characteristics of these patients with those who were diagnosed with IDC during the same period. The outcomes of these subtypes of breast carcinoma were different. Based on the overall survival, the patients with PD-IDC had the worst prognosis (5-year survival rate = 84.1%). The PD-DCIS had the best prognosis (5-year survival rate = 97.5%). Besides, among patients with Paget disease, the one who was married had a better prognosis than who were not. And, according to our research, the marital status was associated with the hormone receptor status in patients with PD-IDC. Among three subtypes of Paget disease, patients with PD-IDC had the worst prognosis. Besides, patients who were unmarried had worse outcomes. And the marital status of patients with PD-IDC is associated with hormone status. The observation underscores the importance of individualized treatment.

Clinicopathological characteristics and survival outcomes of male breast cancer according to race: A SEER population-based study.

To investigate the clinicopathological characteristics and survival outcomes of breast cancer in the male population, 8,607 cases of patients were identified in the Surveillance, Epidemiology, and End Results (SEER) database, including white males (n = 7122), black males (n = 1111), and other males (American Indian/AK Native, Asian/Pacific Islander) (n = 374). Black male breast cancer patients were more likely to be in stages II-IV and have more advanced tumors. The rate of lymph node (LN) involvement at diagnosis was higher in black men than in whites and others. The ER- and PR-positive rates were lower in black men than in whites and others. The distant metastasis rate was higher in blacks than in whites and others. Furthermore, the overall survival (OR) rates and breast cancer-specific survival rates were significantly poorer in blacks than in whites and others (χ2 = 29.974, P < 0.001; χ2 = 7.285, P = 0.026, respectively). In a multivariate analysis, the results showed that race could also be a prognostic indicator (P < 0.001). Moreover, significant differences were also observed in OS among 1:1:1 matched white, black, and other groups (P < 0.001). Differences in outcomes may be partially explained by differences in tumor grades, LN status, and ER and PR status between the 3 groups. This study might provide insights into a better understanding of male breast cancer.

Comparison of patterns and prognosis among distant metastatic breast cancer patients by age groups: a SEER population-based analysis.

To investigate the effects of age at diagnosis on metastatic breast cancer and patients' prognosis, we collected patient data from the Surveillance, Epidemiology, and End Results (SEER) database. We finally identified 4932 eligible metastatic breast cancer patients diagnosed between 2010-2013, including 850 younger patients (<50 years), 2,540 middle-aged patients (50-69 years) and 1,542 elder patients (>69 years). The results revealed that in stage IV patients, elder patients were more likely to have lung metastasis (P < 0.001) and less likely to have only distant lymphatic spread (P = 0.004). Higher proportion of younger (34.9%) and middle-aged (36.2%) patients had multiple metastatic sites than elder patients (28.3%) (P < 0.001). In survival analysis, younger patients presented the best prognosis, while elder patients had the worst both in overall survival (χ2 = 121.9, P < 0.001) and breast cancer-specific survival (χ2 = 69.8, P < 0.001). Age at diagnosis was an independent prognostic factor for metastatic breast cancer patients. Moreover, patients with bone metastasis only had superior survival compared to other metastatic patients (P < 0.001). Brain metastasis only group and multiple sites metastasis group had the poorest prognosis (P < 0.05). We hope the results will provide insights into a better understanding of distant metastatic breast cancer.

SSBP1 Suppresses TGFß-Driven Epithelial-to-Mesenchymal Transition and Metastasis in Triple-Negative Breast Cancer by Regulating Mitochondrial Retrograde Signaling.

Triple-negative breast cancer (TNBC) is a highly aggressive tumor subtype lacking effective prognostic indicators or therapeutic targets. Mitochondrial function is dysregulated frequently in cancer cells to allow for adaptation to a harsh tumor microenvironment. Targeting mitochondrial biogenesis and bioenergetics is, therefore, an attractive therapeutic strategy. In this study, we performed quantitative proteomic analyses in human parental and metastatic breast cancer cell lines to identify mitochondrial proteins involved in TNBC metastasis. We found that single-strand DNA-binding protein 1 (SSBP1) was downregulated in highly metastatic breast cancer cells. Moreover, SSBP1 downregulation promoted TNBC cell metastasis in vitro and in vivo. Mechanistically, SSBP1 loss decreased mitochondrial DNA copy number, thereby potentiating calcineurin-mediated mitochondrial retrograde signaling that induced c-Rel/p50 nuclear localization, activated TGFß promoter activity, and TGFß-driven epithelial-to-mesenchymal transition. Low SSBP1 expression correlated with tumor progression and poor prognosis in patients. Collectively, our findings identified SSBP1 as a novel metastasis suppressor and elucidated the mechanisms by which dysregulated mitochondrial signaling contributes to metastatic potential, providing potential new prognostic indicators for patients with TNBC.

Loss of TIM50 suppresses proliferation and induces apoptosis in breast cancer.

TIM50 is an essential component of TIM23 complex and involved in protein translocating into the inner mitochondrial membrane. Here, we found that TIM50 was increased in breast cancer cells by SILAC. However, its biological functions and molecular mechanisms in breast cancer are poorly understood. To gain insight into the functions of TIM50 in breast cancer, we constructed two stably transfected cell lines and examined TIM50 expression in tissue samples. Our data showed that TIM50 expression was increased in breast cancer. The stable suppression of TIM50 expression through lentivirus-mediated shRNA was shown to inhibit the abilities of cancer cell proliferation and induce apoptosis. What is more, depletion of TIM50 could decrease mitochondrial membrane potential, which may be associated with cell viability. Taken together, our findings reveal a new role for TIM50 in regulating cell proliferation and apoptosis through decreasing mitochondrial membrane potential in breast cancer cell and suggest that TIM50 might be a potential target for controlling breast cancer progression.

Down-Regulation of NDUFB9 Promotes Breast Cancer Cell Proliferation, Metastasis by Mediating Mitochondrial Metabolism.

Despite advances in basic and clinical research, metastasis remains the leading cause of death in breast cancer patients. Genetic abnormalities in mitochondria, including mutations affecting complex I and oxidative phosphorylation, are found in breast cancers and might facilitate metastasis. Genes encoding complex I components have significant breast cancer prognostic value. In this study, we used quantitative proteomic analyses to compare a highly metastatic cancer cell line and a parental breast cancer cell line; and observed that NDUFB9, an accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I), was down-regulated in highly metastatic breast cancer cells. Furthermore, we demonstrated that loss of NDUFB9 promotes MDA-MB-231 cells proliferation, migration, and invasion because of elevated levels of mtROS, disturbance of the NAD+/NADH balance, and depletion of mtDNA. We also showed that, the Akt/mTOR/p70S6K signaling pathway and EMT might be involved in this mechanism. Thus, our findings contribute novel data to support the hypothesis that misregulation of mitochondrial complex I NADH dehydrogenase activity can profoundly enhance the aggressiveness of human breast cancer cells, suggesting that complex I deficiency is a potential and important biomarker for further basic research or clinical application.

Loss of COX5B inhibits proliferation and promotes senescence via mitochondrial dysfunction in breast cancer.

COX5B, a peripheral subunit of the cytochrome c oxidase complex, has previously been reported to maintain the stability of this complex. However, its functions and mechanisms involved in breast cancer progression remain unclear. Here, by performing SILAC assays in breast cancer cell models and detecting COX5B expression in tissues, we found that COX5B expression was elevated in breast cancer. Down-regulation of COX5B in breast cancer cell lines can suppress cell proliferation and induced cell senescence which was accompanied by elevating production of IL-8 and other cytokines. Interestingly, conditioned medium from COX5B knockdown cells could promote breast cancer cell migration. Mechanistic studies reveal that COX5B silence induces an increase in production of ROS, depolarization of MMP and a decrease in ATP. What's more, silence of COX5B leads to metabolic disorders, such as increased glucose uptake and decreased lactate secretion. Collectively, our study shows that loss of COX5B induces mitochondrial dysfunction and subsequently leads to cell growth suppression and cell senescence. Cytokines such as IL-8 secreted by senescent cells may in turn alter the microenvironment which could enhance cell migration. These findings may provide a novel paradigm for the treatment which combined anti-cancer drugs with particular cytokine inhibitors such as IL-8 blockers.

Loss of RAB1B promotes triple-negative breast cancer metastasis by activating TGF-ß/SMAD signaling.

Triple-negative breast cancer (TNBC) is a highly aggressive tumor subtype associated with a poor prognosis. The mechanism involved in TNBC progression remains largely unknown. To date, there are no effective therapeutic targets for this tumor subtype. In this study, by performing quantitative proteomic analyses in highly metastatic and parental breast cancer cell line, we found that RAB1B, a member of the RAS oncogene family, was significantly down-regulated in highly metastatic breast cancer cells. Moreover, down-regulation of RAB1B was also found to promote the proliferation and migration of TNBC cells in vitro and in vivo. Mechanistically, loss of RAB1B resulted in elevated expression of TGF-ß receptor 1 (TßR1) through decreased degradation of ubiquitin, increased levels of phosphorylated SMAD3 and TGF-ß-induced epithelial-mesenchymal transition (EMT). Furthermore, low RAB1B expression correlated with poor prognosis in breast cancer patients. Taken together, our findings reveal that RAB1B acts as a metastasis suppressor in TNBC by regulating the TGF-ß/SMAD signaling pathway and RAB1B may serve as a novel biomarker of prognosis and the response to anti-tumor therapeutics for patients with TNBC.