Search

He Ma,1 Zhenxiang Pan,1 Bingjie Lai,2 Chunfang Zan,3,4 He Liu5 1Department of Anesthesiology, The Second Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Intensive Care Unit, The Second Hospital of Jilin University, Changchun, People’s Republic of China; 3Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 4Collaborative Innovation Center for Molecular Imaging of Precision Medicine, Shanxi Medical University, Taiyuan, People’s Republic of China; 5Department of Orthopedics, The Second Hospital of Jilin University, Changchun, People’s Republic of ChinaCorrespondence: He Liu, Department of Orthopedics, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of China, Email heliu@jlu.edu.cnAbstract: From a clinical perspective, local anesthetics have rather widespread application in regional blockade for surgery, postoperative analgesia, acute/chronic pain control, and even cancer treatments. However, a number of disadvantages are associated with traditional local anesthetic agents as well as routine drug delivery administration ways, such as neurotoxicity, short half-time, and non-sustained release, thereby limiting their application in clinical practice. Successful characterization of drug delivery systems (DDSs) for individual local anesthetic agents can support to achieve more efficient drug release and prolonged duration of action with reduced systemic toxicity. Different types of DDSs involving various carriers have been examined, including micromaterials, nanomaterials, and cyclodextrin. Among them, nanotechnology-based delivery approaches have significantly developed in the last decade due to the low systemic toxicity and the greater efficacy of non-conventional local anesthetics. Multiple nanosized materials, including polymeric, lipid (solid lipid nanoparticles, nanostructured lipid carriers, and nanoemulsions), metallic, inorganic non-metallic, and hybrid nanoparticles, offer a safe, localized, and long-acting solution for pain management and tumor therapy. This review provides a brief synopsis of different nano-based DDSs for local anesthetics with variable sizes and structural morphology, such as nanocapsules and nanospheres. Recent original research utilizing nanotechnology-based delivery systems is particularly discussed, and the progress and strengths of these DDSs are highlighted. A specific focus of this review is the comparison of various nano-based DDSs for local anesthetics, which can offer additional indications for their further improvement. All in all, nano-based DDSs with unique advantages provide a novel direction for the development of safer and more effective local anesthetic formulations.Keywords: local anesthetics, pain, drug delivery system, nanotechnology, nanocarriers, nanoparticles

Le Zhuang,1– 6,* Jie Tian,1– 4,7,* Binbin Lai,1– 4,7 Guohong Zhang,1– 4 Hang Li1– 4 1Department of Dermatology, Peking University First Hospital, Beijing, People’s Republic of China; 2National Clinical Research Center for Skin and Immune Diseases, Peking University First Hospital, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Peking University First Hospital, Beijing, People’s Republic of China; 4NMPA Key Laboratory for Quality Control and Evaluation of Cosmetics, Peking University First Hospital, Beijing, People’s Republic of China; 5Dermatology Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 6Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province, People’s Republic of China; 7Institute of Medical Technology, Peking University Health Science Center, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hang Li, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, People’s Republic of China, Tel +8613693058190, Fax +861083572350, Email drlihang@126.comBackground: Anti-programmed cell death ligand-1 (anti-PD-L1) immunotherapy is often used for advanced urothelial carcinoma and melanoma, including amelanotic melanoma, a relatively rare subtype with little to no pigment in the tumor cells. However, cellular heterogeneity of amelanotic melanoma during or after anti-PD-L1 immunotherapy treatments has not been described.Purpose: To investigate cellular heterogeneity in acral amelanotic melanoma after immunotherapy exposure.Methods: We evaluated subtle visual changes of the melanoma by dermoscopy and performed a pathological examination to analyze the heterogeneity of microscopic morphological and immunohistochemistry changes. The cellular transcriptional heterogeneity and corresponding biological function profiles of the melanoma were determined by single-cell RNA sequencing (scRNA-seq).Results: The dermoscopic examination revealed black globules and scar-like depigmentation areas against a homogeneous red background. Pigmented and amelanotic melanoma cells were observed microscopically. The pigmented cells were large and contained melanin granules expressing Melan-A and HMB45; the amelanotic cells were small and did not express HMB45. Ki-67 immunohistochemical staining revealed that the pigmented melanoma cells had a higher proliferative ability than the amelanotic cells. scRNA-seq identified three cell clusters: amelanotic cell cluster 1, amelanotic cell cluster 2, and pigmented cell cluster. Furthermore, a pseudo-time trajectory analysis showed that amelanotic cell cluster 2 originated from amelanotic cell cluster 1 and transformed into the pigmented melanoma cell cluster. The expression pattern of melanin synthesis-related and lysosome-endosome-related genes in different cell clusters supported the cell cluster transformation results. Also, upregulated expression of cell cycle genes indicated that the pigmented melanoma cells had a high proliferative ability.Conclusion: Coexisting amelanotic and pigmented melanoma cells indicated cellular heterogeneity in an acral amelanotic melanoma from a patient who underwent immunotherapy treatment. Additionally, the pigmented melanoma cells acquired a higher proliferative ability than the amelanotic melanoma cells.Keywords: amelanotic, acral melanoma, cellular heterogeneity, immunotherapy, drug resistance

Huan Tang, Wenjuan Di, Hanmei Qi, Juan Liu, Jing Yu, Jinmei Cai, Bing Lai, Guoxian Ding, Peng Cheng Department of Gerontology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Peng Cheng, Department of Gerontology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, Jiangsu, People’s Republic of China, Tel +86-25-68305171, Fax +86-25-83724440, Email cphh@sohu.comPurpose: This study was designed to explore age-related changes in trabecular bone score (TBS) and bone mineral density (BMD) in Chinese men through cross-sectional and longitudinal studies.Patients and Methods: We included adult men who had at least twice TBS and BMD examinations in our hospital between January 2013 and December 2020. All men were divided into an age subgroup per 10 years, comparing differences in baseline lumbar spine (LS) TBS and BMD at various parts between each age group and analyzing age-related changes in TBS and BMD during follow-up.Results: Baseline data showed that in men aged 36 to 85 years, BMD in the hip region showed a decreasing trend with age (P for trend < 0.01). However, TBS reached a high value around the age of 50, after which it decreased with age (P for trend = 0.03). During a mean follow-up of 3 years, the average annual change rate at TBS was − 0.17% in men aged 36 to 85 years, with the fastest decrease rate − 1.08% at 66 to 75 years (P < 0.05). The mean annual rate of change in LS BMD in different age subgroups increased with age (P for trend = 0.001). There was no significant decrease in mean annual change in BMD in hip regions.Conclusion: In men aged 36∼ 85 years, the trend of TBS was inconsistent with BMD. Men experience a high value of LS TBS around age 50, later than the commonly believed age of peak BMD, which may reflect developmental differences between bone microstructure and bone minerals. The TBS may be used as a better indicator of changes in bone strength than BMD in adult men at short-term follow-up. The rapid loss of TBS at age 66 to 75 may have implications for the prevention and medication of osteoporosis in men.Keywords: age-related, bone loss, bone mineral density, men, osteoporosis, trabecular bone score

He Ma,1 Bingjie Lai,2 Chunfang Zan,3 Xin Di,4 Xinran Zhu,1 Ke Wang4 1Department of Anesthesiology, The Second Hospital of Jilin University, Changchun, 130042, People’s Republic of China; 2Department of Intensive Care Unit, The Second Hospital of Jilin University, Changchun, 130042, People’s Republic of China; 3Division of Vascular Biology, Institute for Stroke and Dementia Research (ISD), LMU Klinikum, Ludwig-Maximilians-University (LMU), Munich, 81377, Germany; 4Department of Respiratory Medicine, The Second Hospital of Jilin University, Changchun, 130042, People’s Republic of ChinaCorrespondence: Ke Wang, Department of Respiratory Medicine, The Second Hospital of Jilin University, Changchun, 130042, People’s Republic of China, Email kewangm1@hotmail.comBackground: Escherichia coli-associated antimicrobial resistance (AMR) issue so far needs urgent considerations. This study aims to screen the potent genes associated with extended-spectrum β-lactamases (ESBLs) in drug-resistant Escherichia coli and elucidate the specific drug-resistant mechanism.Methods: Clinical ESBLs-EC samples were obtained based on the microbial identification, and the whole genome was sequenced. In combination with the significantly enriched pathways, several differently expressed genes were screened and verified by RT-PCR. Furthermore, through knocking out glyoxalase 1 (GLO1) gene and transfecting overexpressed plasmids, the potential relationship between GLO1 and ESBLs was then investigated. Lastly, the concentrations of β-lactamases in bacteria and supernatant from different groups were examined by enzyme-linked immunosorbent assay (ELISA).Results: After successful isolation and identification of ESBLs-EC, the whole genome and eighteen differential metabolic pathways were analyzed to select differently expressed genes, including add, deoD, guaD, speG, GLO1, VNN1, etc. RT-PCR results showed that there were no differences in these genes between the standard bacteria and susceptible Escherichia coli. Remarkably, the relative levels of four genes including speG, Hdac10, GLO1 and Ppcdc were significantly increased in ESBLs-EC in comparison with susceptible strains, whereas other gene expression was decreased. Further experiments utilizing gene knockout and overexpression strains confirmed the role of GLO1. At last, a total of 10 subtypes of β-lactamases were studied using ELISA, including BES-, CTX-M1-, CTX-M2-, OXA1-, OXA2-, OXA10-, PER-, SHV-, TEM-, and VEB-ESBLs, and results demonstrated that GLO1 gene expression only affected PER-β-lactamases but had no effects on other β-lactamases.Conclusion: SpeG, Hdac10, GLO1 and Ppcdc might be associated with the drug-resistant mechanism of Escherichia coli. Of note, this study firstly addressed the role of GLO1 in the drug resistance of ESBLs-EC, and this effect may be mediated by increasing PER-β-lactamases.Keywords: GLO1, bacterial drug resistance, extended-spectrum β-lactamases, Escherichia coli, PER type

Chromium (Cr) can degrade silicon wafer-based solar cell efficiencies at concentrations as low as 1010cm-3. In this contribution, we employ synchrotron-based X-ray fluorescence microscopy to study chromium distributions in multicrystalline silicon in as-grown material and after phosphorous diffusion. We complement quantified precipitate size and spatial distribution with interstitial Cr concentration and minority carrier lifetime measurements to provide insight into chromium gettering kinetics and offer suggestions for minimizing the device impacts of chromium. We observe that Cr-rich precipitates in as-grown material are generally smaller than iron-rich precipitates and that Cri point defects account for only one-half of the total Cr in the as-grown material. This observation is consistent with previous hypotheses that Cr transport and CrSi2 growth are more strongly diffusion-limited during ingot cooling. We apply two phosphorous diffusion gettering profiles that both increase minority carrier lifetime by two orders of magnitude and reduce [Cri] by three orders of magnitude to 1010cm-3. Some Cr-rich precipitates persist after both processes, and locally high [Cri] after the high-temperature process indicates that further optimization of the chromium gettering profile is possible.

Siping Zhu,1,* Wei Lin,1,* Shu Chen,1,* Hanmei Qi,1 Siting Wang,2 Aisen Zhang,1 Jinmei Cai,1 Bing Lai,1 Yunlu Sheng,1 Guoxian Ding11Division of Geriatric Endocrinology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Division of Intensive Care Unit, Nanjing Jiangning Hospital, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workBackground: Sarcopenia is typically defined as the loss of muscle mass, strength and low physical performance with aging. Ultrasound is a safe and easy method for evaluating muscle mass and quality by muscle thickness (MT) and pennation angle (PA), respectively. Although the positive correlations between MT and muscle mass and handgrip strength were observed, the relationship between MT, PA and physical performance remains unclear.Purpose: This study aimed to investigate the correlation of aforementioned ultrasound parameters with muscle mass, muscle strength and physical performance and explore the utility of ultrasound in predicting sarcopenia.Patients and methods: A total of 265 elderly Chinese community dwellers were included. MT of both forearm and lower leg as well as PA of gastrocnemius was assessed by ultrasound. Muscle mass was assessed by dual-energy X-ray absorptiometry. Muscle strength was measured by a Jamar hand dynamometer. Physical performance was assessed by the Short Physical Performance Battery (SPPB).Results: Anterior radial MT in men and regional MTs except posterior fibula in women were negatively correlated with the age. No significant correlation was observed between PA and the age in both genders. Posterior tibial MT and posterior fibula MT were positively correlated with the relative appendicular skeletal muscle mass in men and women, respectively. Anterior ulnar MT was positively correlated with grip strength in both genders. Moreover, gastrocnemius medialis PA showed a positive association with gait speed and SPPB in women but not in men.Conclusion: A combination of posterior fibula MT, anterior ulnar MT and gastrocnemius medialis PA measured by muscle ultrasound is helpful for the assessment of sarcopenia in Chinese elderly women. In addition, a combination of posterior tibial MT and anterior ulnar MT measured by muscle ultrasound is helpful for the assessment of sarcopenia in Chinese elderly men.Keywords: B-mode ultrasound, muscle thickness, pennation angle, muscle mass, muscle strength, physical performance

Xin-lin Li,1,* Hui-juan Cao,1,* Ya-jing Zhang,1 Rui-xue Hu,1 Bao-yong Lai,1 Nan-qi Zhao,1 Hui Hu,2 Zhan-guo Xie,3 Jian-Ping Liu1 1Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Chaoyang District, Beijing 100029, China; 2The Department of Acupuncture and Metabolic Diseases, Eastern Hospital Affiliated to Beijing University of Chinese Medicine, Fengtai District, Beijing, China; 3The Department of Acupuncture and Moxibustion, First People’s Hospital of Dongcheng District, Beijing, China *These authors contributed equally to this work Objective: To explore the influence of patients’ participation in and completing the acupuncture clinical trials through a cross-sectional survey. In addition, we explored potential factors involved in improving patient’s compliance to treatment, thus enhancing the quality of acupuncture clinical studies.Methods: A survey was conducted at outpatient department of acupuncture and metabolic diseases in two hospitals in Beijing. The semi-structured questionnaire was designed based on literature review and Delphi methods. It contains 15 questions related to patients’ experience and attitude. SPSS 22.0 was used for analyses. OR and 95% CI were used for dichotomous outcomes. Logistic regression analysis (LRA) and multi-LRA were used to explore the factors influencing patients’ participation or completion and the relationship between demographic characteristics and potential factors.Results: A survey was conducted from April to September 2016. Five hundred patients were consecutively sampled to fill semi-structured questionnaires regardless of their types of disease. The participants (75.2% were female) were in the age range of 15–85 years and all of them completed the survey. The effect and safety of acupuncture therapy were considered to be the deciding factors by 92% and 96% of the respondents, respectively. Only 40 of the surveyed participants (8.0%) had previously participated in the clinical trials. The LRA showed they paid more attention to treatment regimen (frequency and session of treatment) when deciding whether or not to participate in the trials (OR 1.54, 95% CI 1.02–2.34). Multivariate LRA showed that elder people considered cost (OR 1.36, 95% CI 1.09–1.70) to be an important factor, while the participants having medical insurance (OR 1.45, 95% CI -0.20–0.93) thought informed consent was important. Meanwhile, participants with higher education preferred regular follow-up (OR 1.16, 95% CI 0.02–0.28).Conclusion: After providing adequate information regarding the potential benefits and harms of the acupuncture treatment, completion of the treatment within the specific time regimen was found to be the most important factor affecting patient’s compliance. Other factors, such as cost and regular follow-up, should also be given special consideration. Keywords: patient compliance, acupuncture, clinical trials, cross-sectional study

X-ray fluorescence microscopy (mu-XRF), x-ray beam induced current (XBIC), and x-ray absorption spectromicroscopy (mu-XAS) were performed on fully-processed BaySix cast multicrystalline silicon and aluminum-gettered AstroPower Silicon-Film(TM) sheet material. Over ten iron precipitates--predominantly of iron silicide--were identified at low lifetime regions in both materials, both at grain boundaries and intragranular defects identified by XBIC. In addition, large (micron-sized) particles containing oxidized iron and other impurities (Ca, Cr, Mn) were found in BaySix material. The smaller iron silicide precipitates were more numerous and spatially distributed than their larger oxidized iron counterparts, and thus deemed more detrimental to minority carrier diffusion length.

Li X, Cao H, Zhang Y, Hu R, Lai B, Zhao N, Hu H, Xie Z, Liu JP. Patient Prefer Adherence. 2019;13:53–61.Page 53, Abstract, Results section, the text “Multivariate LRA showed that elder people considered cost (OR 1.36, 95% CI 1.09–1.70) to be an important factor, while the participants having medical insurance (OR 1.45, 95% CI -0.20–0.93) thought informed consent was important. Meanwhile, participants with higher education preferred regular follow-up (OR 1.16, 95% CI 0.02–0.28).” should read “Multivariate LRA showed that elder people considered cost (OR 1.36, 95% CI 1.09–1.70) to be an important factor, while the participants having medical insurance (OR 1.45, 95% CI 0.82–2.54) thought informed consent was important. Meanwhile, participants with higher education preferred regular follow-up (OR 1.16, 95% CI 1.02–1.32). Read the original article

This article discusses a case of infantile neuroaxonal dystrophy (INAD) in a 7-year-old boy. The patient experienced delayed speech and motor development, weakness in his lower limbs, and limited eye contact. Magnetic resonance imaging revealed abnormal signals in the bilateral globus pallidus, iron deposits in the pallid globules, and cerebellar atrophy. INAD is a rare autosomal recessive neurodegenerative disorder that typically presents before the age of 3. The authors of the article are Qinglin Zhong, Qingping Zhong, and Binglin Lai, and the research was conducted at the Department of Medical Imaging, Ganzhou People's Hospital in China. [Extracted from the article]