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Abstract Rationale Warthin tumor (WT) is the second most common benign tumor in salivary gland. It has a slow growth rate and most frequently occurs in the parotid gland. Most patients present with an incidental finding of a painless mass inferior/anterior to the ear. Besides the epithelial component of the tumor, WT is characteristically associated with lymphoid stroma that is considered benign. While there have been a few reports of malignant transformation of the lymphoid components in WT, cases of WT concomitant with mantle cell lymphoma (MCL) are extremely rare. To the best of our knowledge, two cases have been described in the English literature. Herein, we report a case of WT concomitant with MCL in a 70-year-old female patient, and emphasize the importance of careful examination of lymphoid stroma in WT so that concurrent lymphoma is not missed. Patient concerns A 70-year-old Chinese woman with a 40-year history of cigarette smoking presented with a one year history of a right submaxillary mass with recent enlargement. Diagnosis Cervical ultrasound (US) and computed tomography (CT) scans of the neck revealed a well-circumscribed mass in the right parotid with a maximum diameter of 3.1 cm. Surgical resection of the mass was performed. Histopathological examination revealed a characteristic double-layer of neoplastic epithelium with prominent lymphoid stroma, suggesting WT. In addition, morphology and immunohistochemistry studies confirmed the coexistence of MCL. Thereafter, the final diagnosis of this case was WT concomitant with MCL. Interventions The patient was staged as stage I after clinical assessment. Due to the slow growth of parotid lesions, close observation was decided with periodic clinical and radiological monitoring. Outcomes Currently, the patient demonstrates a stable disease by clinical evaluation. Lessons To the best of our knowledge, reported cases of WT concomitant with MCL are very rare. This case highlights the importance of a comprehensive assessment of the lymphoid stroma of WT to avoid missed diagnosis of a lymphoma component in a collision tumor.

The Gaoligong Mountains are characterized by large variations in elevation and topography, which support high levels of biodiversity and endemism that remain largely understudied. Herein, based on the integration of morphological comparisons and phylogenetic reconstruction, we describe a new species of Rhacophorus from the northern Gaoligong Mountains, Yunnan Province, China. The new species, Rhacophorus dulongensis sp. nov., is morphologically distinguishable from its congeners based on the differences in body size, head length, tibia length, snout and tongue shape, toe webbing formula and coloration, ventral skin texture and coloration, dorsal pattern and coloration, body macroglands, iris coloration, and pattern of markings on flanks. Phylogenetically, it differs from its congeners by uncorrected p-distances of >4.8% for the 16S rRNA gene fragment. Rhacophorus dulongensis sp. nov. is likely to be found in Myanmar, considering its type locality lies close to the China-Myanmar border. The phylogenetic analysis revealed that the “widespread” species, R. rhodopus, is a species complex and a composite of five distinct lineages. The results revealed that R. napoensis is also found in Vietnam, making it a new country record for Vietnam. Interestingly, R. dulongensis sp. nov. likely breeds in bamboo, a hidden behavioral characteristic that makes them easy to overlook. Given the ongoing habitat loss and degradation in the region, further biological exploration is urgently needed in the Gaoligong Mountains as a biodiversity reservoir.

Abstract Background In recent years, the development of adjunctive therapeutic hyperthermia for cancer therapy has received considerable attention. However, the mechanisms underlying hyperthermia resistance are still poorly understood. In this study, we investigated the roles of cold‑inducible RNA binding protein (Cirbp) in regulating hyperthermia resistance and underlying mechanisms in nasopharyngeal carcinoma (NPC). Methods CCK-8 assay, colony formation assay, tumor sphere formation assay, qRT-PCR, Western blot were employed to examine the effects of hyperthermia (HT), HT + oridonin(Ori) or HT + radiotherapy (RT) on the proliferation and stemness of NPC cells. RNA sequencing was applied to gain differentially expressed genes upon hyperthermia. Gain-of-function and loss-of-function experiments were used to evaluate the effects of RNAi-mediated Cirbp silencing or Cirbp overexpression on the sensitivity or resistance of NPC cells and cancer stem-like cells to hyperthermia by CCK-8 assay, colony formation assay, tumorsphere formation assay and apoptosis assay, and in subcutaneous xenograft animal model. miRNA transient transfection and luciferase reporter assay were used to demonstrate that Cirbp is a direct target of miR-377-3p. The phosphorylation levels of key members in ATM-Chk2 and ATR-Chk1 pathways were detected by Western blot. Results Our results firstly revealed that hyperthermia significantly attenuated the stemness of NPC cells, while combination treatment of hyperthermia and oridonin dramatically increased the killing effect on NPC cells and cancer stem cell (CSC)‑like population. Moreover, hyperthermia substantially improved the sensitivity of radiation‑resistant NPC cells and CSC‑like cells to radiotherapy. Hyperthermia noticeably suppressed Cirbp expression in NPC cells and xenograft tumor tissues. Furthermore, Cirbp inhibition remarkably boosted anti‑tumor‑killing activity of hyperthermia against NPC cells and CSC‑like cells, whereas ectopic expression of Cirbp compromised tumor‑killing effect of hyperthermia on these cells, indicating that Cirbp overexpression induces hyperthermia resistance. ThermomiR-377-3p improved the sensitivity of NPC cells and CSC‑like cells to hyperthermia in vitro by directly suppressing Cirbp expression. More importantly, our results displayed the significantly boosted sensitization of tumor xenografts to hyperthermia by Cirbp silencing in vivo, but ectopic expression of Cirbp almost completely counteracted hyperthermia-mediated tumor cell-killing effect against tumor xenografts in vivo. Mechanistically, Cirbp silencing-induced inhibition of DNA damage repair by inactivating ATM-Chk2 and ATR-Chk1 pathways, decrease in stemness and increase in cell death contributed to hyperthermic sensitization; conversely, Cirbp overexpression-induced promotion of DNA damage repair, increase in stemness and decrease in cell apoptosis contributed to hyperthermia resistance. Conclusion Taken together, these findings reveal a previously unrecognized role for Cirbp in positively regulating hyperthermia resistance and suggest that thermomiR-377-3p and its target gene Cirbp represent promising targets for therapeutic hyperthermia.

In Taiwan, hospice nurses often take family members of terminally ill patients on hospice ward tours and provide information on transfers. We conducted a study to investigate the tour’s effectiveness in encouraging family members to transfer their loved ones to hospice. We conceptualized our study framework based on the Andersen healthcare utilization model. The hospice nurses invited family members who participated in the tour to complete the survey to investigate the tour and hospice facilities’ influence on their willingness to transfer. A total of 87 participants responded to the study, with an average age of 48.84 ± 12.08 years. Most participants were women (78.16%) and the children of patients (55.17%). The results showed that the tour significantly increased willingness scores (before 4.46 ± 0.73, after 4.74 ± 0.58, p = .0036). Practical and activity-related facilities had the highest influence scores. However, binary logistic regression revealed that patients aged ≥65 years (odds ratio [OR]: 0.281, 95% confidence interval [CI] [0.099, 0.797]) and higher influence scores for psychospiritual care features (OR: 0.182, 95% CI [0.040, 0.821]) negatively affected the change in willingness score, possibly due to family members’ anticipatory grief. Hospice tour guides should be able to identify, assess, and deal with this issue. Overall, hospice tours can effectively encourage transfer to the hospice ward, but addressing psychological barriers such as anticipatory grief is crucial for success.

The majority of myxosporean species (Cnidaria: Myxozoa) of the genera Myxobolus (35 species), Henneguya (8 species), and Myxidium (9 species) from freshwater or brackish fish in Japan were recorded more than 30 years ago (accumulatively 81.1% [43/53]). The re-discovery and molecular–genetic characterization of these species is a current research priority. During our myxosporean survey in Japanese freshwater fish, we detected three species that had never been recorded in Japan, but in the Russian Far East (Sakhalin Island, and Maritime Province): Myxobolus tribolodonus sp. n., forming cysts in the gills of Tribolodon sachalinensis (syn. M. marinus sensu Aseeva, 2000; M. marinus sensu Sokolov et Frolova, 2015, recorded from the gills of Pseudaspius (syn. Tribolodon) spp.); Henneguya pungitii Achmerov, 1953, forming cysts in the subcutis of external skin and buccal submucosa of Pungitius sinensis; and Myxidium salvelini Konovalov et Shulman, 1966, in the urinary bladder of Oncorhynchus masou ishikawae. These new isolates were characterized by integrated taxonomic approaches, i.e., myxospore morphology and molecular–genetic characterization of the small subunit ribosomal RNA gene (SSU rDNA). These new isolates were phylogenetically differentiated from any species whose SSU rDNA sequences were deposited in the DNA databases, and concurrently compared with recorded species based on classical morphological criteria. All three species were differentiated from myxosporeans previously recorded in Japan, indicating new distribution records out of the Russian Far East. For reliable species identification, accumulation of at least SSU rDNA sequences of known species worldwide is critically important.

Exploiting geothermal resources, especially hot dry rock (HDR), is essential to reduce carbon emissions to build an acceptable energy structure. The enhanced geothermal system (EGS) for mining HDR has experienced more than 50 years since it was proposed in 1970, obtaining rich research results and construction experience. It is of great significance to review the EGS history, which includes discussing the project site selection and thermal storage stimulations, summarizing the reasons for the shutdown of demonstration projects, and indicating the key factors restricting EGS development. Based on this, the future development direction of EGS is clarified, which can help explore deep geothermal energy and construct associated demonstration projects in China. The overall development of EGS is divided into two stages, namely, the research and development stage before 2000 (a total of 14 EGS projects) and the demonstration and quasi-commercialization stage since 2000 with a rapid development speed (a total of 27 EGS projects). By the end of 2021, the cumulative number of EGS worldwide has increased to 41. However, the cumulative installed capacity of power generation only reaches 37.41 MW. EGS is still on the learning curve, resulting in a long way to go to realize the large-scale commercialization of HDR geothermal energy. The factors restricting the commercialization of EGS are the lack of policy support and capital investment, the limitations of technical difficulty, and the unpredictability of the geological condition of the thermal reservoir, which weakens EGS development and even causes its suspension or termination. Because of the complex geological environment of thermal reservoirs, the fracture network and associated reservoir quality induced by hydraulic stimulations are uncontrollable, causing the fractured quality of the thermal reservoir to be lower than its critical value. It results in numerous adverse problems in most EGS projects, including insufficient thermal reservoir volume, an unstable fracture network, associated heat exchange area, severe fluid loss, and induced unacceptable earthquakes. Thus, the fundamental reason for EGS’s inability to commercialize is that it is challenging to form a reproducible thermal reservoir stimulation model induced by the difference in thermal reservoir geological conditions and the dependence of the existing stimulation technologies on the in situ reservoir geological environment. Establishing the database of HDR and EGS plays an urgent role in EGS development by forming an accurate quantitative system of reservoir geological conditions to explore the relationship between geological conditions and reservoir reconstruction and then build a replicable thermal reservoir reconstruction technology. Focusing on new and demonstration stimulations for the thermal reservoir, such as the enhanced geothermal system based on caving technology (EGS-E), FORGE, and DEEPEGS projects, may provide an acceptable way to break through the dependence of thermal reservoir stimulation on in-situ geological conditions and form the “reproducible” deep-geothermal resource mining system to realize the large-scale commercialization of deep-geothermal resources.

Geothermal energy has recently attracted substantial attention due to its abundant reserve, cleanness, and sustainability. Geothermal reservoirs can be stimulated via different approaches/techniques that lead to different heat extraction efficiencies and production through heat transfer between the working fluid and the reservoir network. Typical reservoir stimulation strategies include hydraulic fracturing, which is employed in conventional geothermal systems based on drilling, namely, EGS-D; indirect heat exchange using U-shaped pipes, namely, EGS-P; and block caving, which is based on the well-developed mining excavation framework, namely, EGS-E. Although the above three reservoir stimulation modes have been made available, their heat extraction performances for a certain reservoir over the operation lifespan have been unexplored. Selecting the appropriate reservoir stimulation approach and assessing the corresponding heat extraction performance are crucial for the design and subsequent operation of geothermal systems. Here, we systematically compared the heat extraction efficiencies of different stimulated reservoir networks under four typical stimulation modes, including a high-permeability reservoir (representing a reservoir stimulated by EGS-E), a connected fracture (representing a reservoir stimulated by EGS-P) reservoir, a reservoir with randomly distributed fractures (representing a reservoir simulated by EGS-D), and a reservoir with randomly distributed fractures and connected fractures (representing a reservoir simulated by the combination of EGS-D and EGS-P). The mechanical, hydraulic, and thermal coupling among the rock matrix, fracture network, and working fluid was realized in COMSOL Multiphysics. We found that the heat extraction efficiency of the high-permeability reservoir was the highest and that of the reservoir with randomly distributed fractures and connected fractures was the lowest. Crack aperture evolution was modulated by the competition between matrix contraction and hydraulic enhancement. The total crack aperture can be increased by increasing the matrix contraction and the hydraulic pressure of the working flow. Injection capability improved when the matrix contraction (thermal effect) prevailed but decreased when the working flow pressure (hydraulic effect) dominated. We also found that the smaller the matrix spacing, the larger the thermal effect-induced crack aperture and thus the total aperture. When the matrix spacing was reduced to 50 m, the thermal effect-induced crack aperture was nearly five times the hydraulic effect-induced crack aperture. The above findings have the following implications for EGS-E: first, the reservoir should be caved into fractured blocks that are as small as possible to increase permeability. Heat extraction efficiency and heat production can thus be highly promoted. Second, for the EGS-E with multiple reservoir slices, the slice spacing should be appropriately optimized to ensure high crack apertures and thus commensurate heat extraction efficiency.

Abstract Objective Much of our knowledge of patient autonomy of DNR (do-not-resuscitate) is derived from the cross-sectional questionnaire surveys. Using signatures on statutory documents and medical records, we analyzed longitudinal data to understand the fact of terminal cancer patients’ autonomous DNR decision-making in Taiwan. Methods Using the medical information system database of one public medical center in Taiwan, we identified hospitalized cancer patients who died between Jan. 2017 and Dec. 2018, collected their demographic and clinical course data and records of their statutory DNR document types, letter of intent (DNR-LOI) signed by the patient personally and the consent form signed by their close relatives. Results We identified 1,338 signed DNR documents, 754 (56.35%) being DNR-LOI. Many patients had the first DNR order within their last week of life (40.81%). Signing the DNR-LOI was positively associated with being under the care of a family medicine physician prior to death at last hospitalization and having hospice palliative care and negatively associated with patient age ≥ 65 years, no formal education, having ≥ 3 children, having the first DNR order to death ≤ 29 days, and the last admission in an intensive care unit. Conclusions A substantial proportion of terminal cancer patients did not sign DNR documents by themselves. It indicates they may not know their actual terminal conditions and lose the last chance to grasp time to express their life values and wishes. Medical staff involving cancer patient care may need further education on the legal and ethical issues revolving around patient autonomy and training on communicating end-of-life options with the patients. We suggest proactively discussing DNR decision issues with terminal cancer patients no later than when their estimated survival is close to 1 month.

With the rising popularity of the concept of “carbon neutralization”, low-carbon products are likely to gain more advantages. Related to this, green tea— an important beverage that is widely consumed in China—along with emissions from planting, processing, and use phase should be given attention. Meanwhile, quantifying the carbon footprint (CF) of green tea is an essential task in developing the pathway to carbon neutrality. In this study, we quantified the CF and mitigation potential of green tea through life cycle assessment, after which we investigated the pathway toward carbon neutrality in 16 major tea-producing regions (except Hainan and Taiwan) in China. The system boundary was divided into six subsystems from cradle to grave: cultivation, processing, transport, packaging, consumption, and disposal. The results showed that the total carbon emissions of green tea reached 44.13 Mt CO2eq in 2019, of which 43% came from consumption and 28% from cultivation. There were 18.78 Mt CO2eq emissions from fertilizer production and application, while there was a 7.71 Mt CO2eq carbon sink of tea trees. The average carbon intensity was 24.30 kg CO2eq kg−1 tea, while Shandong and Guizhou ranked as the top two provinces. Sichuan, Hubei, and Yunnan Provinces had the largest amounts of carbon emissions at 6.79, 6.14, and 5.96 Mt CO2eq, respectively. By 2030, 2050 and 2060, total carbon emissions would be reduced by 46%, 63%, and 86%, respectively, under carbon neutrality assumption. A small amount of 6.14 Mt CO2eq carbon emissions was retained to be offset by carbon trading or zero-carbon cultivation. Finally, the results indicate that adopting low-carbon fertilizers and clean energies will be a key entry point for carbon-neutral green tea.

BackgroundIn 2012, the American Board of Internal Medicine Foundation launched the Choosing Wisely campaign to reduce unnecessary care. However, it is unclear how much emergency physicians in Taiwan understand about Choosing Wisely. The purpose of this study was to explore the knowledge, attitude, and behaviour of emergency physicians in Taiwan regarding Choosing Wisely and its related factors; the intention was to identify the baseline knowledge on the basis of which to promote Choosing Wisely in Taiwan.MethodsThis was a cross-sectional study including emergency physicians in Taiwan as research subjects who answered online questionnaires. A 42-item questionnaire was designed according to the Knowledge, Attitude, and Behaviour model (KAB). The questionnaire linkages were delivered to emergency physicians through social media (eg., Line, Facebook) and received assistance from different hospital directors. A total of 162 valid questionnaires were collected. Data analyses include t-test, analysis of variance, chi-square test, Pearson's correlation, and multivariate linear regression model.ResultsThe study determined that although only 38.9% of emergency physicians had heard of Choosing Wisely, the mean correct rate of knowledge score among emergency physicians was 70.1%. Attitude and the behaviour related to Choosing Wisely were positively associated, which means that the more positive the attitude towards Choosing Wisely is, the more positive the behaviour towards Choosing Wisely is. In multiple linear regression analyses, having served as a supervisor, belonging to divisions of health insurance service, and having heard of Choosing Wisely (P < 0.05) positively affect the knowledge of Choosing Wisely, but age presented a negative association.ConclusionThis study found that physicians' knowledge does not influence their attitudes and behaviours, which may be related to barriers of practicing Choosing Wisely activities. To effectively promote Choosing Wisely campaign, it is recommended to focus on the significant factors associated with emergency physicians' perceptions regarding knowledge, attitude, and behavior of Choosing Wisely. Based on these factors, appropriate practice guidelines for Choosing Wisely can be formulated and promoted.

BackgroundThe presence of minimal residual disease (MRD) is an independent risk factor for poor prognosis in patients with acute lymphoblastic leukemia (ALL). Moreover, the role of chimeric antigen receptor T-cell (CAR-T) therapy in patients with MRD is currently unclear.MethodsWe conducted a prospective study to investigate the role of CAR-T therapy in patients with persistent/recurrent MRD-positive ALL in first remission.ResultsA total of 77 patients who had persistent/recurrent MRD were included. Of these patients, 43 were enrolled in the CAR-T group, 20 received chemotherapy as a bridge to allogeneic hematopoietic cell transplantation (allo-HSCT), and 14 patients received intensified chemotherapy. MRD negativity was achieved in 90.7% of the patients after CAR-T infusion. Patients who received CAR-T therapy had a higher 3-year leukemia-free survival (LFS) than patients who did not (77.8% vs. 51.1%, P = 0.033). Furthermore, patients in the CAR-T group had a higher 3-year LFS than those in the chemotherapy bridge-to-allo-HSCT group [77.8% (95% CI, 64.8–90.7%) vs. 68.7% (95% CI, 47.7–89.6%), P = 0.575] and had a significantly higher 3-year LFS than those in the intensified chemotherapy group [77.8% (95% CI, 64.8–90.7%) vs. 28.6% (95% CI, 4.9–52.3%), P = 0.001]. Among the patients who received CAR-T therapy, eight were not bridged to allo-HSCT, and six (75%) remained in remission with a median follow-up of 23.0 months after CAR-T infusion.ConclusionsOur findings show that CAR-T therapy can effectively eliminate MRD and improve survival in patients with a suboptimal MRD response.

Abstract Background We examined the utilization of rehabilitation resources among children with autism spectrum condition (ASC), a neurodevelopmental condition, in Taiwan. Methods We derived from the National Health Insurance Research Database of Taiwan data pertaining to 3- to 12-year-old children for the period 2008–2010. Based on diagnoses executed in accordance with the International Classification of Diseases, Ninth Revision, Clinical Modification, we classified these data into the ASC and non-ASC groups and analyzed them through multiple linear regression model, negative binomial model, independent sample t testing, and χ2 testing. Results Compared with the non-ASC group, the ASC group exhibited higher utilization of rehabilitation resources. Because hospitals are constrained by overall expenditure limits, expenditure on rehabilitation resources has plateaued, preventing any increase in the utilization of rehabilitation resources. In our ASC group, preschool-aged children significantly outnumbered (p

Ovarian and breast cancer are prevalent female malignancies with increasing occurrence incidence and metastasis, significantly affecting the health and life quality of women globally. Anesthetic lidocaine has presented anti-tumor activities in the experimental conditions. However, the effect of lidocaine on ovarian and breast cancer remains elusive. We identified the important function of lidocaine in enhancing ferroptosis and repressing progression of ovarian and breast cancer. Our data showed that lidocaine further repressed erastin-inhibited ovarian and breast cancer cell viabilities. The treatment of lidocaine induced accumulation of Fe2+, iron and lipid reactive oxygen species (ROS) in ovarian and breast cancer cells. The ovarian and breast cancer cell proliferation was suppressed while cell apoptosis was induced by lidocaine in vitro. Lidocaine attenuated invasion and migration of ovarian and breast cancer cells as well. Regarding the mechanism, we found that lidocaine downregulated solute carrier family 7 member 11 (SLC7A11) expression by enhancing microRNA-382-5p (miR-382-5p) in the cells. The inhibition of miR-382-5p blocked lidocaine-induced ferroptosis of ovarian and breast cancer cells. MiR-382-5p/SLC7A11 axis was involved in lidocaine-mediated inhibition of ovarian and breast cancer cell proliferation in vitro. The miR-382-5p expression was down-regulated but SLC7A11 expression was up-regulated in clinical ovarian and breast cancer samples. Furthermore, the treatment of lidocaine repressed tumor growth of ovarian cancer cells in vivo, in which the miR-382-5p expression was increased while SLC7A11 expression was decreased. Consequently, we concluded that the lidocaine promoted ferroptosis by miR-382-5p/SLC7A11 axis in ovarian and breast cancer cells. The clinical value of lidocaine in the treatment of ovarian and breast cancer deserves to be proved in detail.

In 2010, Taiwan included the fecal occult blood test (FOBT) under preventive health insurance services. For patients whose test positive, receiving follow-ups is paramount. This study investigated factors affecting the follow-up time of these patients. This retrospective study used data from the colorectal cancer screening archives. The study period was from 2010 to 2013, and the subjects were 50-75-year-old persons who tested positive for FOBT. The t test, one-way ANOVA, and multiple regression were performed to address the differences in the mean tracking period between variables such as the population's demographic characteristics. The mean follow-up time for the 98,482 participants whose screening results were positive exhibited significant differences (p < 0.001) according to medical unit region and classification, age, screening location, family history, examination method, and diagnosis. The model predicting the mean follow-up time predicted a period of 10.079 days longer for those whose hospital was on an offshore island than that of those whose hospital was in the eastern regions. The follow-up time was 1.257 days shorter for people who were inpatients than those who were outpatients and was 8.902 days longer for people who underwent double contrast barium enema plus flexible sigmoidoscopy than those who underwent other examination methods. Patients with a family history of colorectal cancer and those whose examination results indicated cancer had a follow-up time of 2.562 and 2.476 days shorter than those who did not know their family history and those with other results, respectively. Factors affecting the follow-up time of people whose FOBT results were positive consisted of the location and classification of the follow-up institution, age, screening location, family history, examination method, and diagnosis. This provides valuable references for improving the cancer screening program.

Abstract Background To investigate the association between primary insomnia and dementia using a Taiwanese population-based database. Methods This case-control study involved a subset of Taiwan’s National Health Insurance Research Database of reimbursement claims. We included 51,734 patients who were diagnosed with primary insomnia from 2002 to 2004 as the test group and 258,715 nonprimary insomnia participants aged 20 years or older as the reference group. We excluded patients under 20 and those with depression, post-traumatic stress disorder, and/or sleep disorders caused by organic lesion(s), drugs, or alcohol. We used a Cox proportional hazards model to assess the primary insomnia on the risk of developing dementia after adjusting for sociodemographic characteristics and comorbidities. Results The primary insomnia cohort had a higher prevalence of diabetes, dyslipidemia, hypertension, coronary heart disease, chronic liver disease, and chronic kidney disease at baseline. After adjusting for select comorbidities, primary insomnia remained a significant predisposing factor for developing dementia, and was associated with a 2.14-fold (95% confidence interval, 2.01–2.29) increase in dementia risk. We also found a higher risk of dementia in younger patients. Conclusions Taiwanese patients with primary insomnia, especially those under 40, had a higher risk of developing dementia than those without primary insomnia.

This retrospective study included COPD patients who attended our medical center between January and October 2018, and analyzed the outcomes of their influenza vaccination, including medical visits, hospitalization, medical expenses, and the incidence of respiratory failure. Airflow limitation was stratified according to GOLD guidelines. Overall, 543 COPD patients were enrolled, including 197, 113, 126, and 107 mild, moderate, severe, and very severe patients, respectively. Of all the participants, 238 received an influenza vaccination (43.8%), which significantly reduced hospital utilization for moderate (odds ratio [OR] 0.22, 95%CI 0.09–0.51), severe (OR 0.19, 95%CI 0.08–0.44), and very severe patients (OR 0.15, 95%CI 0.05–0.5) compared to mild patients (OR 0.51, 95%CI 0.2–1.26); reduced emergency department utilization for moderate (OR 0.33, 95%CI 0.14–0.77), severe (OR 0.22, 95%CI 0.10–0.52), and very severe patients (OR 0.30, 95%CI 0.10–0.88) compared to mild patients (OR 0.64, 95%CI 0.30–1.37); and reduced the occurrence of respiratory failure for moderate (OR 0.20, 95%CI 0.06–0.68), severe (OR 0.40, 95%CI 0.16–0.98), and very severe patients (OR 0.36, 95%CI 0.15–0.82) compared to mild patients (OR 0% CI 0.14–3.20). Influenza vaccination is more effective in COPD patients with moderate, severe, and very severe airflow obstruction than in those with mild obstruction with respect to hospital utilization, emergency department utilization, and respiratory failure.

This study explores whether continuity of care is associated with health care outcomes and medical care use among patients with newly diagnosed diabetes. A retrospective cohort analysis was performed using the Taiwanese National Health Insurance database, and cases were followed up from January 2010 to December 2012. Four thousand and seven patients with newly diagnosed diabetes were followed for 3 years. The continuity of care was measured using the continuity of care index (COCI) and the usual provider continuity score (UPCS) with high and low dichotomous categories. The probabilities of dementia, hospitalization, emergency room visits, and death were used as health care outcomes. Medical care use was defined as the number of hospital admissions, length of hospital stays, and number of emergency room visits. Adjusted odds ratios (ORs) were obtained using multivariate logistic regression; adjusted ORs for the probabilities of dementia, hospital admissions, and emergency room visits in the higher COCI patient group were 0.582 (p < 0.05), 0.623 (p < 0.001), and 0.650 (p < 0.001), respectively. Negative binomial regression models for medical resource use indicated that the group with higher COCI scores used fewer medical resources compared with the group with lower COCI scores. The findings of UPCS analysis showed that those in the high COCI group also fell into the high UPCS group. In this study, continuity of care was associated with favorable health care outcomes and less medical care uses among newly diagnosed diabetic patients. Long-term relationships between patients and health care providers should be enhanced to provide improved continuity of care.

Nitrogen (N) is one of the macronutrients required for plant growth, and reasonable application of N fertilizers can increase crop yields and improve their quality. However, excessive application of N fertilizers will decrease N use efficiency and also lead to increases in N2O emissions from agricultural soils and many other environmental issues. Research on the effects of different N fertilizer management practices on wheat yields and N2O emissions will assist the selection of effective N management measures which enable achieving high wheat yields while reducing N2O emissions. To investigate the effects of different N management practices on wheat yields and soil N2O emissions, we conducted field trials with 5 treatments of no N fertilizer (CK), farmers common N rate (AN), optimal N rate (ON), 20% reduction in optimal rate+dicyandiamide (ON80%+DCD), 20% reduction in optimal rate+nano-carbon (ON80%+NC). The static closed chamber gas chromatography method was used to monitor N2O emissions during the wheat growing season. The results showed that there were obvious seasonal characteristics of N2O emissions under each treatment and N2O emissions were mainly concentrated in the sowing-greening stage, accounting for 54.6–68.2% of the overall emissions. Compared with AN, N2O emissions were decreased by 23.1, 45.4 and 33.7%, respectively, under ON, ON80%+DCD and ON80%+NC, and emission factors were declined by 22.2, 66.7 and 33.3%, respectively. Wheat yield was increased significantly under ON80%+DCD and ON80%+NC by 12.3 and 11.9%, respectively, relative to AN while there was no significant change in yield in the ON treatment. Compared with ON, overall N2O emissions were decreased by 29.1 and 13.9% while wheat yields improved by 18.3 and 17.9% under ON80%+DCD and ON80%+NC, respectively. We therefore recommend that ON80%+DCD and ON80%+NC be referred as effective N management practices increasing yields while mitigating emissions.

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder in children. This study investigated the use of rehabilitation treatment in Taiwan. We selected children aged 3-12 years from the National Health Insurance Research Database from 2008 to 2012 and included them in the analysis. The children who received a diagnosis according to the International Classification of Diseases, Ninth Revision, Clinical Modification were divided into two groups: ADHD and non-ADHD. We used the chi-squared test, independent sample t test, and multiple regression analysis to conduct the analysis. The utilisation of rehabilitation resources was higher in the ADHD group than in the non-ADHD group. The number of school-aged children with ADHD was higher than the number of preschool-aged children (p < 0.001). The highest utilisation of rehabilitation resources was observed in clinics (p < 0.001). In terms of region, Taipei exhibited the highest utilisation of rehabilitation resources, and the East exhibited the lowest resource utilisation (p < 0.001). Prediction of the use of rehabilitation resources, average cost, average frequency of visits, and total annual cost was affected by factors such as the average frequency of rehabilitation use, demographic characteristics, and the hospital characteristics and location (p < 0.001). The number of children with ADHD and rehabilitation use are increasing yearly; however, limitations in payment restrict the growth of rehabilitation resource use in hospitals. Supplementation of rehabilitation resources at clinics accounts for more than 60%, however, the total annual cost is less than what is observed for hospitals (p < 0.001). Policies should be established to aid in the early detection and treatment of children with ADHD to improve treatment outcomes and reduce the family burden and treatment expenditure in the future.

Follicle-stimulating hormone receptor (FSHR), which is expressed only on Sertoli cells and plays a key role in spermatogenesis, has been paid attention for its potential in male contraception vaccine research and development. This study introduces a method for the preparation and purification of human FSHR 57-amino acid protein (FSHR-57aa) as well as determination of its immunogenicity and antifertility effect. A recombinant pET-28a(+)-FSHR-57aa plasmid was constructed and expressed in Escherichia coli strain BL21 Star TM (DE3) and the FSHR-57aa protein was separated and collected by cutting the gel and recovering activity by efficient refolding dialysis. The protein was identified by Western blot and high-performance liquid chromatography analysis with a band of nearly 7 kDa and a purity of 97.4%. Male monkeys were immunized with rhFSHR-57aa protein and a gradual rising of specific serum IgG antibody was found which reached a plateau on day 112 (16 weeks) after the first immunization. After mating of one male with three female monkeys, the pregnancy rate of those mated with males immunized against FSHR-57aa was significantly decreased while the serum hormone levels of testosterone and estradiol were not disturbed in the control or the FSHR-57aa groups. By evaluating pathological changes in testicular histology, we found that the blood-testis barrier remained intact, in spite of some small damage to Sertoli cells. In conclusion, our study demonstrates that the rhFSHR-57aa protein might be a feasible male contraceptive which could affect sperm production without disturbing hormone levels.

AIM:To investigate the clinical effect of intravitreal conbercept on wet age-related macular degeneration(wAMD)and polypoidal choroidal vasculopathy(PCV). METHODS: Sixteen patients(16 eyes)with wAMD and 5 patients(5 eyes)with PCV, both clinical diagnosed, were enrolled. All patients were treated with intravitreous conbercept.Additional treatments were administered if needed. Best corrected visual acuity(BCVA), central retinal thickness(CRT)and choroidal thickness(CT)were measured periodically. RESULTS:The mean injection times at 6mo was 2.93±0.27. The mean BCVAs were 0.87±0.52 at baseline and 0.74±0.43 at 6mo, which the difference was not statistically significant. The mean CRT significantly improved from 352.24±131.82 to 251.73±69.41μm at 6mo(PPCONCLUSION:Intravitreal conbercept can keep the visual acuity stable, reduce the retinal thickness and is safe on treating wAMD and PCV.

In this work, a 24-GHz frequency-modulated continuous-wave (FMCW) radar system with two sectoral horn antennas and one transmitting lens antenna for long-range drone detection is presented. The present work demonstrates the detection of a quadcopter-type drone using the implemented radar system up to a distance of 1 km. Moreover, a 3D subspace-based algorithm is proposed for the joint range-azimuth-Doppler estimation of long-range drone detection. The effectiveness of the long-range drone detection is verified with the implemented radar system through a variety of experiments in outdoor environments. This is the first such demonstration for long-range drone detection with a 24-GHz FMCW radar.

OBJECTIVE In this study, we applied multidrug resistant leukemia cell line expressing mdr1-mRNA to observe changes in mdr1-mRNA, the P-gp, cell cycle and apoptosis before and after bortezomib was used, in order to explore the mechanism of reversal of leukemia multidrug resistance by the proteasome inhibitor bortezomib.METHODS Flow cytometry (FCM) was used to detect the intracellular drug concentration, expression of P-gp, cell apoptosis and cell cycle status of K562/DNR cells before and afer treatment with different concentrations of bortezomib. Fluorescence quantitative PCR was applied to detect the mdr1-mRNA expression in K562/DNR and K562/S cells. RESULTS Bortezomib could increase the intracellular DNR content in K562/DNR cells, but showed no effect in K562/S cells. 5-100 nmol/L bortezomib could significantly reduce the P-gp/mdr1-mRNA expression in K562/DNR cells in vitro, and showed a dose-dependent effect. There was a statistically significant difference (P < 0.05) between different concentration groups and the control group. P-gp/mdr1-mRNA expression was negatively correlated with cell apoptosis (r = -0.912 and P < 0.01). After treatment with different concentrations of bortezomib for 24 h, K562/DNR cells in G2 + M phases were significantly increased, while cells in G0 + G1 phases and S phase were significantlydecreased, accompanied by an increased apoptotic rate.CONCLUSION Bortezomib can induce G0 + G1 phase to G2 + M phase, and thereby enhance the chemosensitivity of leukemia, and may also reverse the multidrug resistance in leukemia mediated by P-gp overexpression encoded by mdr1 gene. This confirms that bortezomib can reverse leukemia multidrug resistance at the levels of nucleic acid and protein molecules.

In this paper, a three-dimensional (3D)-subspace-based azimuth angle, elevation angle, and range estimation method with auto-pairing is proposed for frequency-modulated continuous waveform (FMCW) radar with an L-shaped array. The proposed method is designed to exploit the 3D shift-invariant structure of the stacked Hankel snapshot matrix for auto-paired azimuth angle, elevation angle, and range estimation. The effectiveness of the proposed method is verified through a variety of experiments conducted in a chamber. For the realization of the proposed method, K-band FMCW radar is implemented with an L-shaped antenna.

This article deals with the development of a dual channel S-Band frequency-modulated continuous wave (FMCW) system for a through-the-wall imaging (TWRI) system. Most existing TWRI systems using FMCW were developed for synthetic aperture radar (SAR) which has many drawbacks such as the need for several antenna elements and movement of the system. Our implemented TWRI system comprises a transmitting antenna and two receiving antennas, resulting in a significant reduction of the number of antenna elements. Moreover, a proposed algorithm for range-angle-Doppler 3D estimation based on a 3D shift invariant structure is utilized in our implemented dual channel S-band FMCW TWRI system. Indoor and outdoor experiments were conducted to image the scene beyond a wall for water targets and person targets, respectively. The experimental results demonstrate that high-quality imaging can be achieved under both experimental scenarios.

We introduced a new subclass of univalent harmonic functions defined by the shear construction in the present paper. First, we showed that the convolutions of two special subclass harmonic mappings are convex in the horizontal direction. Secondly, we proved a necessary and sufficient condition for the above subclass of harmonic mappings to be convex in the horizontal direction. We also presented some basic examples of univalent harmonic functions explaining the behavior of the image domains.

AIM: To research the vision changes after phacoemulsification for herpes simplex keratitis(HSK)with cataract, and the clinical effect of antiviral drugs in preventing HSK relapse as well.METHODS:Twenty-two cases(22 eyes)with HSK combined cataract were treated by phacoemulsification and intraocular lens implantation, and then randomly divided into two groups. The patients in treatment group received aciclovir tablets and ganciclovir ophthalmic gel, those in control group received ganciclovir ophthalmic gel only. The vision changes after phacoemulsification were observed and the HSK relapse was analyzed.RESULTS: After follow-up of 6 months, the visions of patients in both groups were improved. No relapse of HSK was found in the treatment group, and only one relapse of HSK was found in the control group after 6 months. There were no significant differences in therapy effects. CONCLUSION: Under the protection of antiviral drug, cataract surgery can be applied to patients with HSK recurrence-free more than 6 months, and improve the visions effectively. Ganciclovir ophthalmic gel can effectively prevent the relapse of HSK after cataract surgery.