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Ya-Hong Zheng,1,* Chong-Yang Ren,2,* Ying Shen,3 Jia-Bin Li,1,4– 6 Ming-Wei Chen7 1Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, People’s Republic of China; 2Department of Neurology (Sleep Disorder), The Affiliated Chaohu Hospital of Anhui Medical University, Chaohu 238000, People’s Republic of China; 3Department of Endocrinology, Nanjing Tongren Hospital, Nanjing 211102, People’s Republic of China; 4Department of Infectious Diseases, The Affiliated Chaohu Hospital of Anhui Medical University, Chaohu 238000, People’s Republic of China; 5Anhui Center for Surveillance of Bacterial Resistance, Hefei 230022, People’s Republic of China; 6Institute of Bacterial Resistance, Anhui Medical University, Hefei 230022, People’s Republic of China; 7Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ming-Wei ChenDepartment of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of ChinaEmail chmw1@163.comJia-Bin LiDepartment of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of ChinaEmail lijiabin@ahmu.edu.cnObjective: This study explored the changes in the levels of IL-6, IL-17, TNF-α, and TNF-β, whether such changes were associated with anxiety and depression in diabetic peripheral neuropathy (DPN), and what factors associated with the occurrence of DPN.Methods: Forty-four patients diagnosed with DPN comprised the DPN group, including DPN1 (mild diabetic peripheral neuropathy, 29 cases) and DPN2 groups (moderate-severe diabetic peripheral neuropathy, 15 cases). Thirty-seven individuals with type 2 diabetes mellitus constituted the diabetes mellitus with no neuropathy (NDPN) group. Electromyography was applied to confirm DPN, and the Toronto clinical scoring system (TCSS) score was used to assess the severity of DPN. All subjects’ emotions were evaluated using the self-rating anxiety scale (SAS) and self-rating depression scale (SDS). Triiodothyronine (T3), tetraiodothyronine (T4), and thyroid-stimulating hormone (TSH) levels were measured using chemiluminescent immunoassay. The relevant biochemical indicators were detected using an automatic biochemical analyzer. The plasma levels of cytokines were detected using quantitative sandwich enzyme-linked immunosorbent assay.Results: Patients with DPN had elevated levels of anxiety, IL-6, IL-17, and TNF-α. There were some positive associations between negative emotions and cytokines. The TCSS score positively correlated with IL-17, SAS score, and T3. DPN independently correlated with age, disease duration, fasting plasma glucose (FPG), and IL-17. The combination of IL-17 and TNF-α had higher diagnostic value for DPN than any single cytokine.Conclusion: Patients with DPN had elevated levels of inflammatory cytokines, which were associated with negative emotion, and IL-17 had independent correlation with DPN.Keywords: diabetic peripheral neuropathy, emotions, cytokines

BackgroundThe third generation Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) osimertinib has been initially approved for T790M positive lung adenocarcinoma patients and more recently for first-line treatment of EGFR-mutant T790M negative lung adenocarcinoma, Similarly to previous generation TKIs, despite the high response rate, disease progression eventually occurs and current clinical research is focused on novel strategies to delay the emergence of osimertinib resistance.In this study,we investigated a the combination of osimertinib/ gefitinib/ erlotinib with cytotoxic chemotherapy for EGFR-mutated positive lung adenocarcinoma patients in long-term survival outcomes. Method We enrolled Ⅲb-IV stage lung adenocarcinoma patients with an EGFR mutation，Patients receiving standard Osimertinib,Gefitinib,Erlotinip alone treatment and Osimertinib,Gefitinib and Erlotinip with cytotoxic chemotherapy treatment were retrospectively reviewed.The performance status were collected,The response rate, progression-free survival (PFS) and overall survival (OS) and toxicity profile were analyzed.ResultBetween January 2014 to Dec 2020,240 patients with Ⅲb-Ⅳstages lung adenocarcinoma were enrolled from a institution.All patients who received different standard treatment respectively,were divided into four groups,64 who received（gefitinib or Erlotinb)with cytotoxic chemotherapy, 60 who received single gefitinib or erlotinib.58 who received (Osimertinib) with cytotoxic chemotherapy,58 who received single (Osimertinib) were eligible for this study.First generation Chemical-TKItherapy group PFS vs First generation TKI therapy alone PFS.Pp p (HR = 0.56 [0.35–0.89], p ConclusionFirst-Third generation EGFR inhibitor combined with cytotoxic chemotherapy represents a suitable palliative treatment option in further therapy lines for elderly patients with advanced lung adenocarcinoma.The results obtained under real-life conditions add to our understanding of the benefits and risks of First-Third generation EGFR inhibitor combined with cytotoxic chemotherapy in routine clinical practice.

Middle East Respiratory Syndrome (MERS) is a respiratory disease caused by a coronavirus (MERS-CoV). Since its emergence in 2012, nosocomial amplifications have led to its high epidemic potential and mortality rate of 34.5%. To date, there is an unmet need for vaccines and specific therapeutics for this disease. Available treatments are either supportive medications in use for other diseases or those lacking specificity requiring higher doses. The viral infection mode is initiated by the attachment of the viral spike glycoprotein to the human Dipeptidyl Peptidase IV (DPP4). Our attempts to screen antivirals against MERS led us to identify montelukast sodium hydrate (MSH), an FDA-approved anti-asthma drug, as an agent attenuating MERS-CoV infection. We showed that MSH directly binds to MERS-CoV-Receptor-Binding Domain (RBD) and inhibits its molecular interaction with DPP4 in a dose-dependent manner. Our cell-based inhibition assays using MERS pseudovirions demonstrated that viral infection was significantly inhibited by MSH and was further validated using infectious MERS-CoV culture. Thus, we propose MSH as a potential candidate for therapeutic developments against MERS-CoV infections., Highlights • Montelukast (MSH) directly binds to MERS-CoV-Receptor-Binding Domain (RBD). • MSH inhibits MERS-Spike pseudovirion (PV) entry. • MSH attenuates live MERS-CoV infection in host cells.

The importance of uplink resource allocation in ensuring the Quality of Service (QoS) of guaranteed bit rate (GBR) bearers has led to the development of numerous resource allocation schemes. The criteria used in the development of such schemes include maximizing system throughput or fairness and the ability to take transmission power or user priority into account. After accepting a GBR bearer, the eNodeB (eNB) must allocate sufficient resource blocks (RBs) to guarantee the requested QoS. In order to achieve high utilization of radio resource, eNB also must allocate remaining RBs to non-GBR bearers. The QoS is generally specified by the data rate (throughput) or packet delay; however, the 3rd Generation Partnership Project (3GPP) has not specified the means by which data rates for a GBR bearer are to be measured. In this paper, we define the measurement of data rates based on the exponentially weighted moving average (EWMA), thereby enabling the eNB to perform scheduling tasks with greater accuracy. We also present an AAG-2 (Allocate As Granted-version 2) scheme capable of supporting the QoS for GBR bearers, while enabling the efficient allocation of RBs to non-GBR bearers. The existence of parties seeking superior levels of service makes it necessary for telecommunications operators to provide options with regard to QoS. This study proposes a revision of the AAG-2 scheme referred to as AAG-D to accommodate such demands. Simulation results demonstrate the efficacy of the new scheme in achieving goals related to throughput and average packet delay.

The aim of the present study was to investigate the correlation of enhancer of Zeste homolog 2 (EZH2) and SET and MYND domain containing 3 (SMYD3) gene polymorphisms with breast cancer susceptibility and prognosis. A total of 712 patients with breast cancer and 783 healthy individuals were selected. Normal breast epithelial cells MCF-10A and breast cancer cells MCF-7, MDA-MB-231, T47D, and Bcap-37 were cultured. Polymerase chain reaction (PCR)-restriction fragment length polymorphism method was applied for genotyping. Reverse-transcription quantitative PCR (RT-qPCR) and Western blotting were used to examine EZH2 and SMYD3 expression in breast cancer tissues and cells. The risk factors and prognostic factors for breast cancer were estimated. The C allele of EZH2 rs12670401 (odds ratio (OR) =1.255, 95% confidence interval (95% CI): 1.085–1.452), T allele of EZH2 rs6464926 (OR =1.240, 95% CI: 1.071–1.435), and three alleles of SMYD3 variable number of tandem repeats (VNTRs) (OR =1.305, 95% CI: 1.097–1.552) could increase susceptibility to breast cancer. Combined genotypes of EZH2 rs12670401 (TC + CC) and EZH2 rs6464926 (CT + TT) were associated with breast cancer susceptibility. Breast cancer tissues had higher EZH2 and SMYD3 expression. EZH2 rs12670401, EZH2 rs6464926, age of menarche, and menopausal status were associated with breast cancer susceptibility. Patients with TT genotype of EZH2 rs12670401 or with CC genotype of EZH2 rs6464926 had higher overall survival (OS). EZH2 rs12670401, EZH2 rs6464926, and clinical staging were independent prognostic factors for breast cancer. SMYD3 VNTR polymorphism exhibited no association with susceptibility and prognosis. EZH2 rs12670401 and rs6464926 polymorphisms, EZH2 and SMYD3 expression, clinical staging, lymph node metastasis, human epidermal growth factor receptor-2 (HER2) status, and metastasis may be correlated with breast cancer susceptibility and prognosis.

Field return rate prediction is important for manufacturers to assess the product reliability and develop effective warranty management. To get timely predictions, lab reliability tests have been widely used in assessing field performance before the product is introduced to the market. This work concerns warranty prediction for highly reliable products. But, due to the high reliability associated with modern electronic devices, the failure data in lab tests are typically insufficient for each individual product, resulting in less accurate prediction for the field return rate. To overcome this issue, a hierarchical reliability model is suggested to efficiently integrate the information from multiple devices of a similar type in the historical database. Under a Bayesian framework, the warranty prediction for a new product can be inferred and updated as the data collection progresses. The proposed methodology is applied to a case study in the information and communication technology industry for illustration. Bayesian prediction is demonstrated to be very effective compared to other alternatives via a cross-validation study. In particular, the prediction error rate based on our updating prediction scheme is significantly improved as more field data are collected, and achieves a prediction error rate lower than 20% after launching the product for 3 months.

Many resource allocation schemes have been proposed based on different criteria such as system throughput, fairness, transmission power, user priority and others. According to the 3GPP specifications, however, as long as a GBR (guaranteed bit rate) bearer is admitted, eNB has to allocate resource blocks (RBs) for this bearer to ensure its transmission right. At the same time, eNB also must distribute the remaining RBs to non-GBR bearers so as to achieve high radio resource utilization. However, 3GPP has not specified how to measure GBR. In this paper, we use exponentially weighted moving average (EWMA) to define the measurement of data rate and show that it is beneficial to the scheduling on both UE and eNB sides. We also present a scheduling scheme, AAG-2, which aims at ensuring QoS for all in-progress GBR sessions, while at the same time efficiently allocating RBs to non-GBR sessions.

The research is to investigate the association between plasma concentrations of total and high-molecular-weight (HMW) adiponectin and risk of early and advanced colorectal cancer. One hundred and sixty-five male colorectal cancer patients and one hundred and two controls were enrolled; based on the T factor of the TNM system, intraepithelial carcinoma and submucosally invasive carcinoma were defined as early cancer, and invasion into the muscularis propria or deeper was defined as advanced cancer. The plasma levels of glucose, fasting insulin, total cholesterol, triglyceride, and total and HMW adiponectin levels were measured. Each factor level was designated as low or high, and the risk of cancer was estimated by univariate and multivariate logistic regression analyses. In the patients with early cancer, high waist/hip ratio (WHR), high fasting insulin, high HOMA model insulin resistance index (HOMA-IR), low total adiponectin and HMW adiponectin were all associated with a significant increase in the odds ratio (OR) by univariate analysis. In multivariate analysis, WHR, HOMA-IR, total adiponectin and HMW adiponectin were all related to increased cancer risk. However, in the patients with advanced cancer, only low HMW adiponectin was associated with a significant increase in the OR by univariate analysis. In multivariate analysis, a low HMW adiponectin level was still related to increased cancer risk, with an adjusted OR of 3.971 (P = 0.036). In conclusion, a decreased level of adiponectin was a strong risk factor not only for early colorectal cancer but also for advanced colorectal in Chinese male patients. HMW adiponectin might be more closely associated with colorectal cancer risk than total adiponectin.

Students often get a good score in written exams but fail to apply their knowledge when trying to solve real-world problems. This is applies particularly to computer hardware courses in which students are required to learn and memorize many key terms and definitions. Also, teachers often find it difficult to gauge students’ progress when teaching computer hardware fundamentals. These problems are related to the learning process, so it is necessary to find an appropriate instructional model to overcome these problems. This chapter describes a Web-based tool called the assistant tool, which is based on problem-based learning (PBL) theory and not only assists instructors in teaching computer hardware fundamentals but also overcomes the above-mentioned problems.

There is an increasing awareness among the populace of the need for regular health check-up to detect diseases in their early stages and thereby administer treatments in a timely fashion. However, commercially available physiological signal monitoring devices, which may offer clues on the onset of diseases, are time-consuming, far from user friendly and limited in their applications. We design an e-caring chair that combines six modular physiological signal measurement instruments into a single unit, enabling users to simultaneously measure the blood pressure, body temperature, heart rate, height, weight and body fat percentage, and display the results and simple diagnoses in real time. The e-caring chair further allows for easy integration of additional physiological signal measuring devices, speedy measurements and long term monitoring of any trends that may emerge, making it easier for users to be alerted to physiological changes in the body without the need to enlist assistance from medical personnel. In this paper, we describe how this e-caring chair can be placed in several different environments for different purposes.

Searching for health information on the Internet is a popular and important activity. However, most Chinese medical sites do not have wealthy content to satisfy all searchers. In this paper we propose an approach to meta-search Chinese health information on the Internet. Our system queries several general-purpose search engines and merges the returned search results into one ranked list. A major issue of developing a meta-search engine is how to integrate search results of different search engines. We propose a merging strategy that uses five features to estimate the merging score of a result entity. All result entities reported by source search engines are merged into one ranked list according to their merging scores. We intend to generate a high precision ranked list by raising the ranks of the documents that are in the medical domain. We conduct a search task to evaluate the effectiveness of our system. Experimental results show that our meta-search engine performs better than Google Web search engine. The proposed merging method can provide better search results for health information seekers.

We implement an instructional system, called Internet virtual community (IVC for short), according to the instructional model of the Problem-Based Internet Assisted Learning System (PBIALS for short), a previous research result based on the problem-based learning (PBL for short) theory. In order to achieve the instructional model of the PBIALS, four phases are developed for the instructional process include the phase school I - III and the phase outside school. To ensure the instructional system is work and useful, a teaching unit - Dream Computer - is constructed for the basic computer concept I, the first year course of the information program in Chi-Ping vocational school, Taiwan. A self designed questionnaire is also used for collecting the feedbacks responded from the students and evaluating the instructional model/process/system proposed by us.

Hot spots produced by long-wavelength infrared (LWIR) radiation in an energetic material, crystalline RDX (1,3,5-trinitroperhydro-1,3,5-triazine), were studied by thermal-imaging microscopy. The LWIR source was a CO2 laser operating in the 28-30 THz range. Hot spot generation was studied using relatively low intensity (∼100 W cm−2), long-duration (450 ms) LWIR pulses. The hot spots could be produced repeatedly in individual RDX crystals, to investigate the fundamental mechanisms of hot spot generation by LWIR, since the peak hot-spot temperatures were kept to ∼30 K above ambient. Hot spots were generated preferentially beneath RDX crystal planes making oblique angles with the LWIR beam. Surprisingly, hot spots were more prominent when the LWIR wavelength was tuned to be weakly absorbed (absorption depth ∼30 μm) than when the LWIR wavelength was strongly absorbed (absorption depth ∼5 μm). This unexpected effect was explained using a model that accounts for LWIR refraction and RDX thermal conduction. The weakly absorbed LWIR is slightly focused underneath the oblique crystal planes, and it penetrates the RDX crystals more deeply, increasing the likelihood of irradiating RDX defect inclusions that are able to strongly absorb or internally focus the LWIR beam.

We have observed and characterized hot spot formation and hot-spot ignition of energetic materials (EM), where hot spots were created by ultrasonic or long-wavelength infrared (LWIR) exposure, and were detected by high-speed thermal microscopy. The microscope had 15-20 μm spatial resolution and 8.3 ms temporal resolution. LWIR was generated by a CO2 laser (tunable near 10.6 μm or 28.3 THz) and ultrasound by a 20 kHz acoustic horn. Both methods of energy input created spatially homogeneous energy fields, allowing hot spots to develop spontaneously due to the microstructure of the sample materials. We observed formation of hot spots which grew and caused the EM to ignite. The EM studied here consisted of composite solids with 1,3,5-trinitroperhydro-1,3,5-triazine crystals and polymer binders. EM simulants based on sucrose crystals in binders were also examined. The mechanisms of hot spot generation were different with LWIR and ultrasound. With LWIR, hot spots were most efficiently generated within the EM crystals at LWIR wavelengths having longer absorption depths of ∼25 μm, suggesting that hot spot generation mechanisms involved localized absorbing defects within the crystals, LWIR focusing in the crystals or LWIR interference in the crystals. With ultrasound, hot spots were primarily generated in regions of the polymer binder immediately adjacent to crystal surfaces, rather than inside the EM crystals.

Miniaturization is an on-going effort in many industries, making smaller products that perform better and with more features compared with older generation products, which they subsequently replace. With this trend there is a need for new manufacturing technologies, and laser micro-welding is gradually accepted as a method of choice for metal joining. Furthermore, laser micro-welding can be readily automated using robotics and computer controlled motions. To have a successful, automated laser micro-welding system requires the combination of a reliable laser source; a good definition of how the welding spot addresses the work piece; a sound mechanical design to move the parts; and a user friendly software to facilitate the operation of the system. This paper describes the development of a turnkey, automated laser welding system for welding orthodontic brackets.Miniaturization is an on-going effort in many industries, making smaller products that perform better and with more features compared with older generation products, which they subsequently replace. With this trend there is a need for new manufacturing technologies, and laser micro-welding is gradually accepted as a method of choice for metal joining. Furthermore, laser micro-welding can be readily automated using robotics and computer controlled motions. To have a successful, automated laser micro-welding system requires the combination of a reliable laser source; a good definition of how the welding spot addresses the work piece; a sound mechanical design to move the parts; and a user friendly software to facilitate the operation of the system. This paper describes the development of a turnkey, automated laser welding system for welding orthodontic brackets.