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Yaqing Lin,1,* Xuemei Ling,2,3,* Linghua Li,2,* Ruolei Xin,4 Fengyu Hu,1 Junbin Li,3 Jiaojiao Li,1 Feng Li,1,5 Yun Lan1 1Institute of Infectious Diseases, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Guangzhou Institute of Clinical Infectious Diseases, Infectious Disease Center, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China; 3Guangdong Center for Diagnosis and Treatment of AIDS, Guangzhou, People’s Republic of China; 4Institute of AIDS/STD Prevention and Control, Beijing Center for Disease Prevention and Control, Beijing, People’s Republic of China; 5Scientifc Research Center, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feng Li; Yun Lan, Email gz8h_lifeng@126.com; lanyun.vip@126.comBackground: The capsid inhibitor (CAI) lenacapavir (LEN) was approved for use in 2022, yet there are few reports about its drug resistance mutations (DRMs) and sensitivity.Purpose: To delineate the prevalence of CAI DRMs and drug susceptibility among HIV-1 infected individuals living in Guangdong, China.Patients and Methods: A total of 1035 individuals with HIV-1 infection, including 660 highly Active Anti-Retroviral Therapy (HAART) naive individuals and 375 hAART experienced individuals whose protease (PR)/ reverse transcriptase (RT) fragments were amplified successfully during drug resistance surveillance between October 2021 and December 2023, were randomly included in this study. The entire HIV-1 gag gene was amplified from plasma in LEN-naive individuals with or without antiretroviral therapy. The epidemiological and demographic information of the enrolled individuals were collected. The Stanford HIV Drug Resistance Database HIVdb program for Capsid was used to interpret the CAI DRMs and the LEN susceptibility.Results: Among 1035 samples, 805 gag sequences were amplified, sequenced and assembled successfully from 518 hAART drugs naive individuals and 287 hAART drugs experienced individuals. Among them, 0.50% (4/805) carried at least one CAI DRM, of which 0.19% (1/518) from HAART naive individuals and 1.05% (3/287) from HAART experienced individuals. Among the individuals with CAI DRMs, two patients carried CAI major mutations (Q67H) conferring intermediate resistance to LEN and two patients carried CAI accessory mutation (T107A) conferring low level resistance to LEN.Conclusion: Extremely low prevalence of CAI DRMs was detected among people living with HIV (PLWH) in Guangdong, China. Our observations indicate that LEN application may be promising when used in clinical practice in China. Before the administration of LEN, there is no need to consider detecting CAI mutations in PLWH through DRM examination for the time being.Keywords: HIV-1, capsid inhibitor, lenacapavir, drug resistance mutation, Guangdong

Zhaoyong Li,1,* Yanping Lin,1,* Ting Qiu,2,* Junsheng Liang,1 Yintao Lan,3 Fan Meng,4 Chaohao Liang,4 Yiqing Zhang,4 Qingyun Wang,1 Da Shi,1 Changli Zhang,1 Yanan Shi,1 Liujun Liu,1 Yanlan Yang,1 Jian Zhang4,5 1Department of Radiology, DongGuan Tungwah Hospital, Dongguan Key Laboratory of Radiology and Molecular Imaging, DongGuan, Guangdong, 523000, People’s Republic of China; 2Department of Radiology, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, Guangdong, 519000, People’s Republic of China; 3Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, Guangdong, 510030, People’s Republic of China; 4School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, 511436, People’s Republic of China; 5Department of Oncology, the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, Guangdong, 511500, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian Zhang; Zhaoyong Li, Email jianzhang@gzhmu.edu.cn; lizhaoyong2003@163.comBackground: Photothermal therapy (PTT) guided by photoacoustic imaging (PAI) using nanoplatforms has emerged as a promising strategy for cancer treatment due to its efficiency and accuracy. This study aimed to develop and synthesize novel second near-infrared region (NIR-II) absorption-conjugated polymer acceptor acrylate-substituted thiadiazoloquinoxaline-diketopyrrolopyrrole polymers (PATQ-DPP) designed specifically as photothermal and imaging contrast agents for nasopharyngeal carcinoma (NPC).Methods: The PATQ-DPP nanoparticles were synthesized and characterized for their optical properties, including low optical band gaps. Their potential as PTT agents and imaging contrast agents for NPC was evaluated both in vitro and in vivo. The accumulation of nanoparticles at tumor sites was assessed post-injection, and the efficacy of PTT under near-infrared laser irradiation was investigated in a mouse model of NPC.Results: Experimental results indicated that the PATQ-DPP nanoparticles exhibited significant photoacoustic contrast enhancement and favorable PTT performance. Safety and non-toxicity evaluations confirmed the biocompatibility of these nanoparticles. In vivo studies showed that PATQ-DPP nanoparticles effectively accumulated at NPC tumor sites and demonstrated excellent tumor growth inhibition upon exposure to near-infrared laser irradiation. Notably, complete elimination of nasopharyngeal tumors was observed within 18 days following PTT.Discussion: The findings suggest that PATQ-DPP nanoparticles are a promising theranostic agent for NIR-II PAI and PTT of tumors. This innovative approach utilizing PATQ-DPP nanoparticles provides a powerful tool for the early diagnosis and precise treatment of NPC, offering a new avenue in the management of this challenging malignancy.Keywords: nasopharyngeal carcinoma, photoacoustic imaging, photothermal therapy, PATQ-DPP nanoparticles

Ying Lan,1 Die Hu,1 Shijing Huang,1 Qing Ma,1 Li Chen,2,3 Min Xu,1 Qin He1 1Department of Pharmacy, Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu, Sichuan, 610031, People’s Republic of China; 2Department of Pharmacology, Faculty of Medicine, University of the Basque Country, UPV/EHU, Leioa, Spain; 3Department of Pharmacy and Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Ying Lan; Li Chen, Email lanying0212@126.com; chenl_hxey@scu.edu.cnPurpose: This study conducted a pharmacovigilance analysis based on the FDA Adverse Event Reporting System (FAERS) database to compare the infection risk of inhaled or nasal Beclomethasone, Fluticasone, Budesonide, Ciclesonide, Mometasone, and Triamcinolone Acetonide.Methods: We used proportional imbalance analysis to evaluate the correlation between ICS /INCs and infection events. The data was extracted from the FAERS database from April 2015 to September 2023. Further analysis was conducted on the clinical characteristics, site of infection, and pathogenic bacteria of ICS and INCs infection adverse events (AEs). We used bubble charts to display their top 5 infection adverse events.Results: We analyzed 21,837 reports of infection AEs related to ICS and INCs, with an average age of 62.12 years. Among them, 61.14% of infection reports were related to females. One-third of infections reported to occur in the lower respiratory tract with Fluticasone, Budesonide, Ciclesonidec, and Mometasone; over 40% of infections reported by Triamcinolone Acetonide were eye infections; the rate of oral infections caused by Beclomethasone were 7.39%. The reported rates of fungal and viral infections caused by beclomethasone were 21.15% and 19.2%, respectively. The mycobacterial infections caused by Budesonide and Ciclesonidec account for 3.29% and 2.03%, respectively. Bubble plots showed that the ICS group had more fungal infections, oral infections, pneumonia, tracheitis, etc. The INCs group had more eye symptoms, rhinitis, sinusitis, nasopharyngitis, etc.Conclusion: Women who use ICS and INCs are more prone to infection events. Compared to Budesonide, Fluticasone seemed to have a higher risk of pneumonia and oral candidiasis. Mometasone might lead to more upper respiratory tract infections. The risk of oral infection was higher with Beclomethasone. Beclomethasone causes more fungal and viral infections, while Ciclesonide and Budesonide are more susceptible to mycobacterial infections.Keywords: data mining, FAERS, ICS, INCs, pharmacovigilance, infections

Xiao-Bei Si,1,2 Ling-Yun Zhang,2 Shuo Yang,3 Xiao-Lu Chen,2 Yan-Yan Shi,4 Yu Lan,2 Shi-Gang Ding1 1Department of Gastroenterology, Peking University Third Hospital, Beijing, People’s Republic of China; 2Department of Gastroenterology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Pharmacy, Beijing Jishuitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, People’s Republic of ChinaCorrespondence: Shi-Gang Ding, Department of Gastroenterology, Peking University Third Hospital, Beijing, People’s Republic of China, Email dingshigang222@163.com Yu Lan, Department of Gastroenterology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, People’s Republic of China, Email lany_2022@163.comBackground: Minocycline, a derivative of tetracycline, has anti-Helicobacter pylori (H. pylori) properties and can be used to treat H. pylori infection. However, only a few randomized controlled trials (RCTs) have investigated the efficacy of minocycline-containing quadruple therapy (MCQT) in treating H. pylori infection. This study aimed to determine the efficacy and safety of MCQT and investigate the factors influencing both aspects.Methods: This was a retrospective cohort study. Patients diagnosed with H. pylori infection between January 1, 2022, and July 31, 2023 at. The primary outcome was the eradication rate of H. pylori, and the secondary outcome was the number and type of adverse events.Results: A total of 828 patients were included in this study. The overall H. pylori eradication rate among the included patients at 95% confidence interval (CI) (Range 0.864 to 0.907) was 88.53%. The H. pylori eradication rate for patients who received MCQT regimen as the primary therapy was 92.28% (95% CI: 0.901– 0.945), significantly higher than that of patients who received MCQT as rescue therapy (80.81%; 95% CI: 0.761– 0.855, P= 0.003). Adverse events, including dizziness, abdominal distension, diarrhea, nausea, abdominal discomfort, constipation, headache, rash, sleep disorder, palpitation, backache, and anorexia, occurred in 185 (22.34%) patients, with dizziness being the most common (75/828, 9.06%). Compliance with MCQT therapy was an independent factor influencing H. pylori eradication in patients receiving MCQT as a primary therapy. Compliance and presence or absence of H. pylori infection symptoms at the time of screening were independent factors influencing H. Pylori eradication in patients receiving MCQT as rescue therapy. Factors that influenced the occurrence of adverse events included reasons for H. pylori infection screening, residence, treatment compliance, and the use of acid-suppressant regimens.Conclusion: MCQT regimens were effective in H. pylori infection eradication, and the treatment resulted only in fewer adverse events when used as primary or rescue therapies for H. pylori infection treatment. Future prospective studies with larger sample sizes and more comprehensive data are needed to validate our findings.Keywords: Helicobacter pylori, minocycline, cohort study

Shiqiong Yan,1 Wenzhuo Fan,2 Yonghong Ma,3 Sijia Xie,4 Rong Li,5 Yao Lan,1 Linli Xie,5 Jie Jing5 1College of Nursing, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of China; 2Department of Nursing, Chengdu Women and Children’s Central Hospital, Chengdu, Sichuan Province, People’s Republic of China; 3State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 4School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan Province, People’s Republic of China; 5Department of Nursing, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan Province, People’s Republic of ChinaCorrespondence: Jie Jing, Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, 610072, People’s Republic of China, Tel +028-87393247, Email jingjie_1130@163.comBackground: The problem of maternal mental health is a priority issue of global concern. Dyadic coping refers to the co-managing and making decisions between two parties in response to a joint stressful event. At present, china has limited focus on dyadic coping for pregnant women during pregnancy. This study aimed to investigate different categories and characteristics of dyadic coping in pregnant women throughout pregnancy and to analyze the factors that influence these categories.Methods: This study was a cross-sectional, and 376 pregnant women who visited the obstetric clinic at a tertiary hospital in Sichuan province from June to September 2023 were interviewed face-to-face using convenience sampling. Data were collected using a sociodemographic questionnaire, dyadic coping scale, and family adaptability and cohesion evaluation scale. The data were imported into excel and exported to spss 27.0 to analyze the potential characteristics of pregnant women’s dyadic coping during pregnancy and to explore the effects of this using univariate analysis and multifactorial logistic regression.Results: A total of 376 valid questionnaires were collected. The results of the potential profile analysis showed that the dyadic coping of pregnant women during pregnancy could be categorized into three different groups: the “low coping group” (21.3%), the “general coping group” (67.5%), and the “high coping group” (11.2%). Multiple logistic regression analyses revealed that low monthly family income, early pregnancy, primipara, family adaptability and cohesion were the factors influencing the dyadic coping of pregnant women during pregnancy.Conclusion: During pregnancy, pregnant women exhibit moderate levels of dyadic coping. Three different categories of dyadic coping patterns were exhibited: low coping group, general coping group, and high coping group, with significant heterogeneity. Therefore, there is a need to focus on the dyadic coping status of various categories of pregnant women and implement targeted couple and family-wide interventions.Keywords: pregnancy period, pregnant women, dyadic coping, family adaptability and cohesion, latent profile analysis

Xiaokun Wu,1,&ast; Shu Cai,1,&ast; Ye Zhou,2 Yutao Lan,1 Yan Lin3 1School of Nursing, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 2Department of Nursing, Luzhou Traditional Chinese Medicine Hospital, Luzhou, People’s Republic of China; 3Department of Nursing, Guangzhou Women and Children’s Medical Center, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yutao Lan, Guangdong Pharmaceutical University, 283 Jianghai Avenue, Haizhu Distric, Guangzhou, People’s Republic of China, Tel +86 13710667351, Email lanyutao@gdpu.edu.cnPurpose: This study aimed to develop a medication literacy scale for parents of children with epilepsy (MLSPCE) and to test the reliability and validity of the scale.Patients and Methods: The pilot scale was formulated based on the concept of medication literacy, the knowledge-attitude-practice model, and relevant literature reviews. It was formed through two rounds of expert consultations using the Delphi method. A survey of 657 parents of children with epilepsy, who were admitted to the neurology department or examined in the neuro-electrophysiological outpatient department of Guangzhou Women and Children Medical Center, using the pilot scale was conducted from October 2021 to January 2022 to test the reliability and validity of the scale questionnaire. The content validity of the scale questionnaire was assessed by consulting 20 neurology nursing, neurology clinician, and nursing education experts. Numbers, percentages, t-test, correlation analysis, Cronbach’s alpha reliability coefficient and factor analysis were used for data analysis.Results: The MLSPCE included 34 items in four dimensions. Ten factors were drawn from the explorative factor analysis, with a cumulative variance contribution rate of 62.32%. The content validity index of each item on the 34-item scale was between 0.81 and 1.0, and the scale-content validity index/ average was 0.97. The correlation coefficient between each item and its dimension was between 0.399 and 0.760, the correlation coefficients between dimensions were between 0.150 and 0.382, and the correlation coefficients between each dimension and the total scale were between 0.390 and 0.845. Differences for all comparisons were statistically significant (P < 0.05). Cronbach’s alpha coefficient for the total scale was 0.864, and the split-half reliability of the total scale was 0.923.Conclusion: All the statistical procedures performed in the validity and reliability stages of the study showed that MLSPCE is a valid and reliable tool for measuring medication literacy among Chinese parents of children with epilepsy.Keywords: epilepsy in children, medication literacy, scale development, reliability test, validity test

Yongting Wang,1 Yunxia Lan,2 Tiantian Jia,1 Mengdan Ma,1 Chunxu Liu,1 Hao Tang1 1Cardiac Surgery Intensive Care Unit, The Affiliated Chest Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Nursing, The Affiliated Chest Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Yunxia Lan, Department of Nursing, The Affiliated Chest Hospital of Zhengzhou University, No. 1 Weiwu Road, Zhengzhou, 450008, People’s Republic of China, Tel/Fax +86 371 6566 2695, Email lanyunxia@126.comPurpose: To construct a training program for ICU nurses to manage artificial airway gasbags to prevent ventilator-associated pneumonia (VAP) and explore its application in ICU nurses.Methods: From January to March 2023, 17 experts were consulted using the Delphi method to construct the draft of the training program. 52 ICU nurses were selected from a third-level, first-class hospital in Henan Province. They received training using the program for 4 weeks. The training effects were evaluated by examining the theoretical knowledge, testing operation skills, and the ICU medical staff gasbag management knowledge-attitude-behavior questionnaire before and one week after the training in April 2023.Results: The coefficients of expert authority for the two round inquiries were 0.816 and 0.837, respectively. The coordination coefficient of expert opinions ranges from 0.2 to 0.3. The final training program for ICU nurses on managing artificial airway gasbags to prevent VAP was constructed and included 4 primary indicators, 25 secondary indicators, 47 tertiary indicators. After the training by the program, the scores of the ICU nurses’ theoretical knowledge (before, 73.73 ± 8.54 VS after, 88.31 ± 6.29; t = 11.017, P< 0.001) and technical operation (before, 75.29 ± 7.48 VS after, 86.92 ± 4.72; t = 8.986, P< 0.001) were significantly increased. The total scores of the ICU nurses’ knowledge-attitude-behavior on gasbag management (before, 76.67 ± 10.68 VS after, 109.04 ± 9.87; t = 19.916, P< 0.001) were also significantly increased compared to the performance before training.Conclusion: The training program for ICU nurses on managing artificial airway gasbags to prevent VAP based on the Miller pyramid model is scientific and practical and can enhance the knowledge-attitude-behavior level of ICU nurses. This training program constructed in this study can be recommended and applied after further verification for the ICU nurses to manage the artificial airway gasbags in order to reducing the occurrence of the VAP in the clinical practice.Keywords: nursing management, evaluation and assessment, Miller pyramid model, airway management, intensive care

Lulu Li,1,2 Yan Lan,3 Fuqian Wang,1,2 Tiexiang Gao1 1Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, Hubei, People’s Republic of China; 2Department of Pharmacy, Wuhan NO.1 Hospital, Wuhan, Hubei, People’s Republic of China; 3Department of Pharmacy, Huangshi Central Hospital, Huangshi, Hubei, People’s Republic of ChinaCorrespondence: Tiexiang Gao, Faculty of Pharmacy, Hubei University of Chinese Medicine, No. 16 Huangjiahu West Road, Hongshan District, Wuhan, Hubei, 430065, People’s Republic of China, Email Tiexianggao@163.comBackground: Linarin has been implicated in the inhibition of inflammatory responses and hepatoprotective effects. However, the precise mechanism by which Linarin integrates injury-induced signaling from inflammatory responses and oxidative stress remains unclear.Methods: We evaluated the role of Linarin in a mouse model of carbon tetrachloride (CCl4)-induced acute liver injury. Mice were orally pretreated with Linarin or vehicle for seven consecutive days, followed by intraperitoneal injection with 0.2% (v/v) CCl4. To investigate the mechanism of action on oxidative stress, CCl4-stimulated HepG2 cells were utilized.Results: Our results revealed Linarin remarkably attenuated the loss of hepatic architecture, inflammatory cell infiltration, serum transaminases, and pro-inflammatory cytokines induced by CCl4. Linarin attenuated CCl4-induced oxidative stress by increasing the expression of cytosolic Nrf2 (nuclear factor erythroid 2-related factor 2), inducing nuclear localization of Nrf2, and increasing stress-induced protein heme oxygenase-1 (HO-1). Additionally, Linarin decreased the expression of toll-like receptors (TLR)-4, and its downstream proteins, MyD88, IRAK1, and TRAF6. Furthermore, Linarin reversed CCl4-induced phosphorylation of ERK, p38, and JNK. Importantly, Linarin increased the expression of both LC3II and Beclin 1, which are hallmarks of autophagic flux. Autophagy-mediated hepatoprotective effects in Linarin-treated HepG2 cells were mitigated by the autophagy inhibitor 3-MA. However, combined treatment of Linarin with 3-MA failed to significantly reverse cell apoptosis and the production of transaminases and pro-inflammatory cytokines.Conclusion: Linarin prevents acute liver injury, possibly by alleviating ROS-induced oxidative stress, inhibiting TLR4/MyD88 and JNK/p38/ERK-mediated inflammatory responses, and promoting Beclin 1/LC3II-mediated autophagic flux.Keywords: Linarin, acute liver injury, autophagy, TLR4, MAPK, Nrf2

Wanchun Cheng,1 Mohammad Mofatteh,2 José Fidel Baizabal-Carvallo,3,4 Shaohuan Lu,1 Ping Su,1 Yimin Chen,5,6 Luoming Li,1 Lizhi Qin,1 Xingmei Zuo,1 Yifeng Lan,7 Yue Huang,8 Zhihui Yu,9 Zirui Luo,10,&ast; Gang Chen10,&ast; 1Department of Neurology and National Stroke Center, The 5th People’s Hospital of Foshan City, Foshan, People’s Republic of China; 2School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, UK; 3Parkinson’s Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, Texas, USA; 4Department of Sciences and Engineering, University of Guanajuato, León, Mexico; 5Department of Neurology and Advanced National Stroke Center, Foshan Sanshui District People’s Hospital, Foshan, People’s Republic of China; 6Neuro International Collaboration (NIC), Foshan, People’s Republic of China; 7Department of Radiology, the 5th People’s Hospital of Foshan City, Foshan, People’s Republic of China; 8Department of Emergency, the 5th People’s Hospital of Foshan City, Foshan, People’s Republic of China; 9Department of Laboratory Medicine, the 5th People’s Hospital of Foshan City, Foshan, People’s Republic of China; 10Dean’s Office, the 5th People’s Hospital of Foshan City, Foshan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zirui Luo; Gang Chen, Dean’s Office, the 5th People’s Hospital of Foshan City, Foshan, Guangdong Province, 528211, People’s Republic of China, Email ziruiluo@126.com; vikingsaga@163.comPurpose: Intravenous thrombolysis has emerged as an effective approach to improve the long-term survival and functional status of patients with ischemic stroke. The aim of this study was to assess the impact of a national stroke project on the door-to-needle-time (DNT).Patients and Methods: The patients were divided into pre-construction and construction periods. Construction Measures were performed during the construction period. The DNT and onset-to-needle time (ONT) were compared in two period groups.Results: After participating in the National Stroke Center Project and effective measurements, the thrombolysis treatment metrics were improved significantly. The DNT (IQR) was shortened from 65.0 (54.5,85.0) minutes in the Pre-Construction period to 40.0 (33.0,53.0) minutes in the Construction period (p < 0.001). Similarly, the ONT was reduced from 157.0 (IQR) (115.0,184.0) minutes to 116.0 (87.8,170.0) minutes (p = 0.035).Conclusion: The DNT time and ONT time can be shortened by National Stroke Center Construction projects. More suitable hospitals should be encouraged to participate as the National Stroke Center.Keywords: acute ischemic stroke, intravenous thrombolysis, door-to-needle time, onset-to-needle time

Mingjuan Liu,1– 3 Meiyi Tong,1,2 Jia Zhou,1,2 Yining Lan,1,2 Mengyin Wu,1,2 Hanlin Zhang,1,2 Ling Leng,2 Heyi Zheng,1,2 Yanfeng Li,4 Mingli Li,5 Jun Li1,2 1Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of China; 3 4+4 M.D. Program, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, People’s Republic of China; 4Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of China; 5Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of ChinaCorrespondence: Mingli Li; Jun Li, Email limingli@pumch.cn; lijun35@hotmail.comPurpose: General paresis is a common type of neurosyphilis featuring progressive cognitive deterioration. The lack of a golden standard of diagnosis and its nonspecific clinical manifestations resulted in a high rate of misdiagnoses. This study aims to investigate the clinical, laboratory and radiological presentations of general paresis and enrich its knowledge for timely diagnoses.Patients and methods: The study collected hospitalized patients admitted for general paresis from September 2002 to November 2022. Their socio-demographical and medical status, clinical presentations, cognitive assessments, laboratory and radiographical manifestations and treatment information were collected retrospectively.Results: A total of 20 males and 5 females were included. Patients’ ages ranged from 30 to 66 years (average 50.3 years). The average and median time for diagnosing general paresis was 14.1 months and 10.0 months respectively. The most frequent initial symptom is memory deterioration (68.0%). Impaired calculative ability and memory deterioration were the most frequent cognitive anomalies, as found in 50% and 45.4% of subjects during examination. The mean and median scores of MoCA was 16.7 and 17 respectively. Serological tests revealed positive TPPA for all patients and a median RPR titer at 1:64 positive. All CSF samples with TPPA and FTA-ABS results reported positivity. The MRI manifestations of general paresis include patchy or speckled hyperintensities (70.8%) and cerebral atrophy (45.8%). The most common lesioned sites in MRI were the ventricular and paraventricular area (50.0%) and temporal lobes (45.8%). For treatment, penicillin-based anti-syphilitic plans were adopted in 17 patients (68.0%).Conclusion: The clinical features and radiological alternations of general paresis patients often exhibited diverse and nonspecific alternations. However, some specific clinical manifestations and auxiliary examinations can provide meaningful clues for the identification and differential diagnosis of this disease.Keywords: neurosyphilis, general paresis, syphilis, neuropsychiatric symptoms

Yan Lan,1,2,&ast; Yu-Kun Zheng,3,&ast; Liu-Yi Wu,3 Zi-Jun Zhou,3 Ruo-Xin Guan,3 Heng Xu,3 Ji-Yuan Tu,3 Xin Gu,3 Rui Wang,3 Nan Jiang,3 Yuan Wu,4 Cheng-Ren Shu,1,2 Zhong-Shi Zhou3 1Department of Pharmacy, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Huangshi, Hubei, People’s Republic of China; 2Hubei Key Laboratory of Kidney Disease Pathogenesis and Intervention, Hubei, People’s Republic of China; 3College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, Hubei, People’s Republic of China; 4Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cheng-Ren Shu, Department of Pharmacy, Huangshi Central Hospital, NO. 141, Tianjin Road, Huangshi, Hubei, People’s Republic of China, Tel +86-27-13986590438, Email 397112615@qq.com Zhong-Shi Zhou, College of Pharmacy, Hubei University of Chinese Medicine, No. 1, Huangjiahu West Road, Hongshan District, Wuhan City, Hubei Province, People’s Republic of China, Tel +86-27-15871745189, Email monkeyzzs@126.comObjective: Traditional Chinese medicine Polygonum cuspidatum (PC) has significant effects on reducing pain. In this study, we investigated the analgesic effects of the alcohol extract of PC on three types of inflammatory pain and explored its mechanism.Methods: Potential targets for the analgesic effects of the main active components of PC alcohol extract were screened by network pharmacology and molecular docking. Three different inflammatory pain mouse models (acetic acid twisting, formalin foot swelling, and xylene ear swelling) were used to study the analgesic effects of PC. The expression of latent signaling pathways in L4-6 spinal cord tissues in formalin foot swelling mice was evaluated using real-time qPCR (RT-qPCR), Western blot (WB), and immunohistochemistry (IHC) analyses.Results: Network pharmacology analysis shows that PC analgesic mechanism is related to the MAPK/ERK signaling pathway. The five main active components of PC have good docking ability with JNK and p38. PC alcohol extract significantly reduced the pain behavior and alleviated inflammatory reactions in three mouse models, inhibited the mRNA and protein phosphorylation levels of JNK, ERK, p38, and CREB in spinal cord tissues.Conclusion: PC alcohol extract can inhibit inflammation and alleviate pain, which is related to its inhibition of the MAPK/ERK signaling pathway in spinal cord. Thus, PC alcohol extract is a promising candidate for pain treatment.Keywords: Polygonum cuspidatum, network pharmacology, MAPK/ERK, analgesic

Ying Lan,1 Nan Yang,2 Yirong Wang,1 Yan Yang,1 Min Xu,1 Qin He1 1Department of Pharmacy, Affiliated Hospital of Southwest Jiaotong University, the Third People’s Hospital of Chengdu, Chengdu, Sichuan, 610031, People’s Republic of China; 2West China School of Pharmacy, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Ying Lan, Email lanying0212@126.comPurpose: Tiotropium/olodaterol (TIO/OLO) fixed-dose combination (FDC) can improve lung function and quality of life for patients with chronic obstructive pulmonary disease (COPD), and is not inferior to other LAMA/LABAs. The aim of this study was to assess the cost-effectiveness of TIO/OLO FDC in patients with moderate to very severe COPD in China.Methods: A Markov model was developed to estimate the cost-effectiveness of TIO/OLO FDC versus TIO in the treatment of COPD from Chinese health system perspective. Four health states were based on 2021 Global Initiative for Chronic Obstructive Lung Disease (GOLD 2021), which included moderate (GOLD II, 50% ≤ FEV1 ≤ 80% of predicted), severe (GOLD III, 30% ≤ FEV1 ≤ 50% of predicted) and very severe (GOLD IV, FEV1 > 30% of predicted) COPD and death. The model simulated in cycles yearly. The indicators of total costs, number of COPD exacerbations, life years (LYs) and quality-adjusted life-years (QALYs) were used as the model output. Costs and outcomes were discounted at a 5% annual rate. A cost-effectiveness analysis was conducted over a 10-year time horizon. The threshold of incremental total cost per unit effectiveness gained (ICER) was 1.5 times of GDP per capita. Uncertainty was assessed by one-way and probabilistic sensitivity analysis.Results: TIO/OLO was 0.007 QALYs more than TIO but 0.012 LYs lower, which increased the total cost by &dollar;2268.17 per patient, but the total exacerbations number was less. Incremental cost effectiveness analysis had shown that the ICER exceeded the willingness to pay threshold. Results were robust under most parameter variation, except the parameters of total drug cost of TIO/OLO FDC in univariate sensitivity analyses.Conclusion: Although TIO/OLO FDC could reduce the exacerbation risk, it was not cost-effective, and needed to be repriced.Keywords: tiotropium, olodaterol, cost-effectiveness, chronic obstructive pulmonary disease, COPD, Markov

Mingjuan Liu,1– 3 Jia Zhou,1,2 Yining Lan,1,2 Hanlin Zhang,1,2 Mengyin Wu,1,2 Xinyi Zhang,4 Ling Leng,1,2 Xia Mi,5 Jun Li1,2 1Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 3 4+4 M.D. Program, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 4Departments of Internal Medicine and Cellular & Molecular Physiology, Yale School of Medicine, New Haven, CT, USA; 5Department of Dermatology, Strategic Support Force Medical Center, Beijing, People’s Republic of ChinaCorrespondence: Xia Mi; Jun Li, Tel +86-69156699, Email mixia501@163.com; lijun35@hotmail.comAbstract: The COVID-19 pandemic has profoundly changed our lives. While healthcare resources were redistributed and mobilized to focus on dealing with the COVID-19 crisis, there have been unmet medical needs of patients with other diseases such as syphilis, weaving an integral but neglected component of the pandemic story. In different countries, the epidemiology of newly reported syphilis underwent diverse changes during the COVID-19 pandemic. Asymptomatic cases experienced the largest decline in number. From the perspective of transmission, on one hand, the implementation of lockdown measures led to a higher degree of abstinence and sex distancing in many countries, thereby reducing the transmission of syphilis. On the other hand, vertical transmission was reported to have increased significantly during COVID-19. Meanwhile, the volume of STI clinic capacity declined, and STI staff were redeployed to facilitate the contact tracing of COVID-19. As a result, many STI centers converted traditional in-person clinical services to telemedicine and self-testing. However, syphilis testing and clinical treatment cannot fully adapt to this conversion. In syphilis diagnosis, COVID-19 infection and vaccination were reported to cause false positivity in syphilis serological tests. Diverse cutaneous manifestations of COVID-19 could resemble the skin lesions in syphilis patients, requiring differential diagnosis from clinicians. As for the post-pandemic years, consequent to service interruptions and diagnosis delays, a surge in the number of confirmed cases of syphilis is expected. The COVID-19 pandemic has also been a meaningful lesson for the control and prevention of infectious diseases. The experience in combating COVID-19 has underscored the importance of maintaining a robust and well-supported medical system for the provision of sexual health services and better healthcare equality even during eras of crisis, not least for syphilis patients.Keywords: COVID-19, syphilis, sexual behavior, STD prevention

Yun Lan,1,&ast; Xuemei Ling,1,2,&ast; Xizi Deng,1,&ast; Yaqing Lin,1 Junbin Li,1,2 Liya Li,1 Ruiying He,1 Weiping Cai,1 Feng Li,1,&ast; Linghua Li,1 Fengyu Hu1 1Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, 510440, People’s Republic of China; 2Guangdong Center for Diagnosis and Treatment of AIDS, Guangzhou, 510060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fengyu Hu; Linghua Li, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, No. 8 Huaying Road, Baiyun District, Guangzhou, 510440, People’s Republic of China, Email gz8hhfy@126.com; llheliza@126.comBackground: Antiretroviral therapy (ART) efficiently reduces the morbidities and mortalities caused by HIV-1 infection and prevents the HIV epidemic. However, virologic failure (VF) occurs in some patients receiving ART experience, especially increases in those patients with intermittent or persistent low-level viremia (LLV). The presence of drug resistance mutations (DRMs) in LLV was a strong predictor of subsequent VF. The data on drug resistance (DR) or DRMs for HIV-1 infections at low-level viral load (LLVL) are limited in China.Objective: To monitor the prevalence of HIV-1 drug resistance and to evaluate the risk factors associated with drug resistance in LLVL HIV-1 infections during ART in Guangdong, China.Methods: Plasma samples with LLVL during ART in Guangdong Province between Jan 2011 and Dec 2022 were subjected to a modified reverse-transcription PCR with a pre-step of virus concentration by ultracentrifugation before extraction and the Sanger sequencing. Then, the genotypic resistance test was performed and DR was analyzed by the Stanford HIVDB program. Finally, DR-associated factors were identified by logistic regression analysis.Results: We found that CRF01_AE (53.57%) and CRF07_BC (25.07%) were the dominant HIV-1 genotypes in LLVL in Guangdong between 2011 and 2022 but that the percentage of CRF01_AE showed a trend of decrease over time. M46 (1.49%), M184 (30.91%), and K103 (21.46%) were the dominant PI-, NRTI-, and NNRTI-associated mutations, respectively. The total DR rate was 47.06%. Specifically, PI (3.71%) showed a significantly lower DR rate than NNRTI (40.74%) and NRTI (34.14%). Duration of ART, initial ART regimen, ethnicity, and WHO clinical stages were associated with DR.Conclusion: The drug resistance rate among the LLVL during ART in Guangdong, China is high. The risk factors associated with HIV drug resistance should be seriously considered for better control.Keywords: HIV, low-level viral load, drug resistance mutation, drug resistance

Kaichen Zhang,&ast; Yihua Fan,&ast; Kunlan Long, Ying Lan, Peiyang Gao Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peiyang Gao, Email gaopy930@126.comBackground: Interest in the application of deep learning (DL) in critical care medicine (CCM) is growing rapidly. However, comprehensive bibliometric research that analyze and measure the global literature is still lacking.Objective: The present study aimed to systematically evaluate the research hotspots and trends of DL in CCM worldwide based on the output of publications, cooperative relationships of research, citations, and the co-occurrence of keywords.Methods: A total of 1708 articles in all were obtained from Web of Science. Bibliometric analysis was performed by Bibliometrix package in R software (4.2.2), Microsoft Excel 2019, VOSviewer (1.6.18), and CiteSpace (5.8.R3).Results: The annual publications increased steeply in the past five years, accounting for 95.67% (1634/1708) of all the included literature. China and USA contributed to approximately 71.66% (1244/1708) of all publications. Seven of the top ten most productive organizations rank in the top 100 universities globally. Hot spots in research on the application of DL in CCM have focused on classifying disease phenotypes, predicting early signs of clinical deterioration, and forecasting disease progression, prognosis, and death. Convolutional neural networks, long and short-term memory networks, recurrent neural networks, transformer models, and attention mechanisms were all commonly used DL technologies.Conclusion: Hot spots in research on the application of DL in CCM have focused on classifying disease phenotypes, predicting early signs of clinical deterioration, and forecasting disease progression, prognosis, and death. Extensive collaborative research to improve the maturity and robustness of the model remains necessary to make DL-based model applications sufficiently compelling for conventional CCM practice.Keywords: hotspots, trends, deep learning, critical care medicine

Fengbing He,1,&ast; Wenzhong Hou,1,&ast; Yintao Lan,1,2 Weijian Gao,1 Mengyu Zhou,1 Jinghang Li,1 Shutong Liu,1 Bin Yang,1 Jian Zhang1 1Qingyuan People’s Hospital, The Sixth Affiliated Hospital of Guangzhou Medical University, School of Biomedical Engineering, Guangzhou Medical University, Guangdong, People’s Republic of China; 2Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Zhang, Email jianzhang@gzhmu.edu.cnBackground: Carotid artery thrombosis is the leading cause of stroke. Since there are no apparent symptoms in the early stages of carotid atherosclerosis onset, it causes a more significant clinical diagnosis. Photoacoustic (PA) imaging provides high contrast and good depth information, which has been used for the early detection and diagnosis of many diseases.Methods: We investigated thrombus formation by using 20% ferric chloride (FeCl3) in the carotid arteries of KM mice for the thrombosis model. The near-infrared selenium/polypyrrole (Se@PPy) nanomaterials are easy to synthesize and have excellent optical absorption in vivo, which can be used as PA contrast agents to obtain thrombosis information.Results: In vitro experiments showed that Se@PPy nanocomposites have fulfilling PA ability in the 700 nm to 900 nm wavelength range. In the carotid atherosclerosis model, maximum PA signal enhancement up to 3.44, 4.04, and 5.07 times was observed by injection of Se@PPy nanomaterials, which helped to diagnose the severity of carotid atherosclerosis.Conclusion: The superior PA signal of Se@PPy nanomaterials can identify the extent of atherosclerotic carotid lesions, demonstrating the feasibility of PA imaging technology in diagnosing carotid thrombosis lesion formation. This study demonstrates nanocomposites and PA techniques for imaging and diagnosing carotid thrombosis in vivo.Keywords: photoacoustic contrast agent, molecular imaging, Se@PPy nanocomposites, carotid artery thrombus

Objective: To evaluate hepatitis B virus (HBV) vaccine coverage and its associated factors among health science students in Vietnam. Methods: This cross-sectional study involving 459 health science students at Tra Vinh University was conducted between April and June 2022. Data were collected using a structured questionnaire with items on sociodemographic characteristics, knowledge and attitude about HBV, and vaccination status. A multivariable logistic regression model was used to explore the factors associated with vaccination status. Results: The majority of participants were female (65.8%) and enrolled at the medical school (56.2%). A total of 30.3% participants received the full dose of the HBV vaccine. The percentages of participants with sufficient knowledge and positive attitudes toward HBV infection were 75.2% and 43.4%, respectively. Vaccination was 11.8 times higher in sixth-year medical students than any healthcare student in their first-year [adjusted odds ratio (aOR) 11.8, 95% CI 3.1-45.1, P

Chenglin Wang,1 Shilin Li,1 Yuzhou Shen,1 Yang Li,1 Muhu Chen,1 Youqiang Wang,2 Youyu Lan,3 Yingchun Hu1 1Department of Emergency Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2Department of Laboratory Medicine, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 3Department of Rheumatology and Immunology, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of ChinaCorrespondence: Yingchun Hu, Department of Emergency Medicine, The Affiliated Hospital of Southwest Medical University, 25 Taiping Street, Jiangyang District, Luzhou, Sichuan, People’s Republic of China, Tel +86-15228232720, Fax +86-0830-3165120, Email huyingchun913@swmu.edu.cn Youyu Lan, Department of Rheumatology and Immunology, The Affiliated Hospital of Southwest Medical University, 25 Taiping Street, Jiangyang District, Luzhou, Sichuan, People’s Republic of China, Tel +86-18090861701, Fax +86-0830-3165120, Email 494077025@qq.comPurpose: To explore the potential active targets and mechanisms of Panax Ginseng in the treatment of sepsis using network pharmacology and RNA-seq technology.Patients and Methods: Patients with sepsis and healthy volunteers were collected according to SEPSIS 3.0, and their peripheral blood was used for RNA-seq analysis. The active ingredients and targets of Panax Ginseng were obtained using the TCMSP database, PPI and GO analysis were performed for disease-drug intersection targets. Then, we used Meta-analysis to screen core genes. Finally, single-cell RNA-seq was used to perform cell localization analysis on core genes.Results: RNA-seq analysis collected 4521 sepsis-related genes, TCMSP database obtained 86 Panax Ginseng active ingredients and their 294 active targets. PPI and GO analysis showed intersection targets were closely linked, and mainly involved in cellular response to chemical stress, response to drug and molecule of bacterial origin, etc. Then, core targets, IL1B, ALOX5, BCL2 and IL4R, were sorted by Meta-analysis, and all four genes have high expression in the sepsis survivor group compared to the sepsis non-survivor group; single-cell RNA-seq revealed that IL1B was mainly localized in macrophages, ALOX5 was mainly localized in macrophages and B cells, BCL2 was mainly localized in natural killer cells, T cells and B cells, IL4R was widely distributed in immune cells. Finally, according to the correspondence between the active ingredients and targets of Panax Ginseng in TCMSP database, we found that Ginsenoside rh2 regulates the expression of IL1B, Ginsenoside rf regulates the expression of IL1B and IL4R, Kaempferol regulates the expression of ALOX5 and BCL2, and β-sitosterol regulates the expression of BCL2.Conclusion: Ginsenoside rh2, Ginsenoside rf, Kaempferol and β-sitosterol may produce anti-sepsis effects by regulating the expression of IL1B, ALOX5, BCL2 and IL4R, thus improving the survival rate of sepsis patients.Keywords: Panax Ginseng, sepsis, RNA-seq, single-cell RNA-seq, network pharmacology

Yunming Tian,1 Wei-Zeng Huang,2 Lei Zeng,3 Li Bai,1 Fei Han,4,* Yuhong Lan1,* 1Department of Radiation Oncology, Huizhou Central People’s Hospital, Huizhou, Guangdong Province, People’s Republic of China; 2Department of Medical Oncology, Huizhou First Hospital, Huizhou, Guangdong Province, People’s Republic of China; 3Department of Medical Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jixiang Province, People’s Republic of China; 4Department of Radiation Oncology, Sun Yat-Sen University Cancer Centre, State Key Laboratory of Oncology in South China, Guangzhou, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fei Han, Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong Province, People’s Republic of China, Email hanfeisysucc@126.com Yuhong Lan, Department of Radiation Oncology, Hui Zhou Municipal Central Hostpital, Huizhou, Guangdong Province, People’s Republic of China, Email lanyuhonghzyy@126.comObjective: To investigate the treatment outcomes, failure patterns and surveillance strategy in patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT).Methods: A cohort of patients with NPC who had received the full course of IMRT between 2008 and 2012 were retrospectively analyzed. The failure patterns, time to recurrence, and detection methods were recorded. The survival was calculated using the Kaplan–Meier method. Multivariate proportional hazard regression models were used to test the prognostic factors.Results: In total, 2607 patients with NPC treated with IMRT were recruited. After the median follow-up of 112 months, 402 (15.4%) patients experienced distant metastasis, 225 (8.6%) patients had local recurrence, and 77 (3.0%) patients had regional recurrences. The 10-year overall survival (OS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) rates were 74.5%, 90.1%, and 79.3%, respectively. The factors of male sex, age > 50 years, lactate dehydrogenase > 245 IU/L, advanced T classification, and advanced N classification were associated with poor OS. The N disease classification was the most important factor in predicting distant metastasis, and advanced T disease classification for high risk of local recurrence. For patients with T1 disease, the incidence of local recurrence was less than 2%, and the incidence of distant metastasis was less than 5% for patients with N0 disease. About 83% of the recurrence occurred in the first 5 years, and 20% of the recurrences showed no symptoms.Conclusion: High rate of local-regional control can be achieved for patients with NPC after IMRT, while distant metastasis remains as the major cause of failures. Patients with advanced N classification has high risk to develop distant metastasis, and most occurred within 5 years. Developing rational and individualized surveillance strategies based on the high risk factors of recurrence is helpful to balance the survival benefit and medical cost.Keywords: failure patterns, intensity-modulated radiotherapy, nasopharyngeal carcinoma, surveillance

Caihua Wu,1 Yongmin Liu,2 Kexing Wan,2 Yuye Lan,2 Min Jia,3 Lixue Lin,4 Shan Gao,1 Ke Chen,1 Jinmei Yang,1 Hui-Lin Pan,5 Man Li,2 Hongrong Mao1 1Department of Acupuncture, Wuhan First Hospital, Wuhan, Hubei Province, 430030, People’s Republic of China; 2Department of Neurobiology, School of Basic medicine, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei Province, 430030, People’s Republic of China; 3Clinical Laboratories, Wuhan First Hospital, Wuhan, Hubei Province, 430030, People’s Republic of China; 4Department of Rehabilitation, Wuhan First Hospital, Wuhan, Hubei Province, 430030, People’s Republic of China; 5Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USACorrespondence: Hongrong Mao, Department of Acupuncture, Wuhan First Hospital, 215 Zhongshan Avenue, Wuhan, Hubei Province, 430030, People’s Republic of China, Tel +86-13277912052, Email 1838269751@qq.comPurpose: The ultrapotent transient receptor potential vanilloid 1 (TRPV1) agonist resiniferatoxin (RTX) induces small-fiber sensory neuropathy, which has been widely used model of postherpetic neuralgia to study mechanisms of neuropathic pain and new analgesics. The long non-coding RNA (lncRNA) and mRNA expression profiles in spinal dorsal horn tissues of rats six weeks after RTX injection to identify new RNAs related to neuropathic pain.Methods: Microarray technology was applied to determine lncRNA expressions in spinal dorsal horn samples of adult rats 6 weeks after treatment with RTX or vehicle. The lncNA/mRNA co-expression network was constructed, and differential expression patterns of lncRNA and mRNA in RTX-treated rats were identified. Differential expressions of lncRNAs and mRNAs between RTX-treated samples and control samples were examined by RT-qPCR.Results: Microarray analyses showed that 745 mRNA and 139 lncRNAs were upregulated, whereas 590 mRNA and 140 lncRNAs were downregulated in spinal dorsal horn tissues after RTX exposure. TargetScan was used to predict mRNA targets for these lncRNAs, which showed that the transcripts with multiple predicted target sites were related to neurologically important pathways. In addition, differential expressions of lncRNA (ENSRNOG00000022535, ENSRNOG00000042027, NR_027478, NR_030675) and Apobec3b mRNA in spinal cord tissue samples were validated, which confirmed the microarray data. The association between NR_030675 and Apobec3b levels was confirmed, which may be related to neuropathic pain.Conclusion: Our study reveals lncRNA and mRNA of molecule targets that are enriched in the spinal cord dorsal horn and provides new information for further investigation on the mechanisms and therapeutics of neuropathic pain.Keywords: postherpetic neuralgia, lncRNAs, microarray, spinal dorsal horn

Yanping Lin,1,&ast; Ting Qiu,2,&ast; Yintao Lan,3,&ast; Zhaoyong Li,1 Xin Wang,4 Mengyu Zhou,3 Qiuyu Li,1 Yao Li,1 Junsheng Liang,1 Jian Zhang3,4 1Department of Radiology, DongGuan Tungwah Hospital, DongGuan, Guangdong, 523000, People’s Republic of China; 2Department of Radiology, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, Guangdong, 519000, People’s Republic of China; 3Department of Biomedical Engineering, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, 511436, People’s Republic of China; 4Department of Oncology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, Guangdong, 511500, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Zhang; Junsheng Liang, Email jianzhang@gzhmu.edu.cn; 2581892622@qq.comAbstract: Nasopharyngeal carcinoma (NPC) is a common malignant tumor of the head and neck with a high incidence rate worldwide, especially in southern China. Phototheranostics in combination with nanoparticles is an integrated strategy for enabling simultaneous diagnosis, real-time monitoring, and administration of precision therapy for nasopharyngeal carcinoma (NPC). It has shown great potential in the field of cancer diagnosis and treatment owing to its unique noninvasive advantages. Many Chinese and international research teams have applied nano-targeted drugs to optical diagnosis and treatment technology to conduct multimodal imaging and collaborative treatment of NPC, which has become a hot research topic. In this review, we aimed to introduce the recent developments in phototheranostics of NPC based on a nanoplatform. This study aimed to elaborate on the applications of nanoplatform-based optical imaging strategies and treatment modalities, including fluorescence imaging, photoacoustic imaging, Raman spectroscopy imaging, photodynamic therapy, and photothermal therapy. This study is expected to provide a scientific basis for further research and development of NPC diagnosis and treatment.Keywords: nasopharyngeal carcinoma, optical imaging, phototherapy, nanoparticle

Yan Lan, Chensheng Pan, Xiuli Qiu, Jinfeng Miao, Wenzhe Sun, Guo Li, Xin Zhao, Zhou Zhu, Suiqiang Zhu Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Zhou Zhu; Suiqiang Zhu, Tel +86-18171081029 ; +86-13035101141, Email zhouzhu@hust.edu.cn; zhusuiqiang@163.comPurpose: Previous studies have shown that persistent post-stroke depression (PSD) was associated with unfavorable prognosis. The aim of this multicenter prospective study was to investigate the predictors associated with persistent PSD, develop a nomogram and validate its clinical usefulness by decision curve analysis (DCA).Patients and Methods: A total of 875 acute ischemic stroke patients from four hospitals were consecutively recruited and completed 1-year follow-ups. Sociodemographic indicators, vascular risk factors, clinical information, serum biochemical indicators and cytokines were collected on admission. The functional outcome was assessed at 1 year after stroke. Persistent depression was defined as having a presentation of depression at each follow-up points and the depressive symptoms occurring persistently since the diagnosis of depression.Results: There were 513 patients who experienced PSD during the 1-year follow-up, the cumulative incidence of PSD within 1 year was 58.6%. Persistent PSD was recorded in 289 patients, of which 59 (20.4%) result in unfavorable outcomes. The risk factors of persistent PSD in 1 year after stroke were the Hamilton Depression Scale-17 items (HAMD-17) score at admission, serum direct bilirubin and free serum thyroxine (FT4) level and activated partial thromboplastin time (APTT). Nomogram conducted based on these factors has a C-index (± standard deviation) of 0.655 ± 0.039, and the DCA demonstrated that the nomogram had a favorable clinical utility.Conclusion: We found that persistent depression after stroke in the first-year time course after stroke was associated with HAMD-17 score at admission, lower serum direct bilirubin and FT4 level, and APTT. A nomogram was developed with advisable clinical usefulness in our study.Keywords: persistent post-stroke depression, nomogram, decision curve analysis

Yanyan Wang,1 He Wang,2 Wenzhe Sun,1 Jinfeng Miao,1 Wenwen Liang,1 Xiuli Qiu,1 Yan Lan,1 Chensheng Pan,1 Guo Li,1 Xin Zhao,1 Zhou Zhu,1 Suiqiang Zhu1 1Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 2Department of Medical Affairs, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of ChinaCorrespondence: Zhou Zhu; Suiqiang Zhu, Tel +86 18171081029 ; +86 13035101141, Fax +86 27-83663337, Email zhouzhu@hust.edu.cn; zhusuiqiang@163.comBackground: Post-stroke depression (PSD) is the most common neuropsychiatric complication after stroke, seriously affecting the quality of survivors’ life. As one of the important causes of PSD, neuroendocrine mechanism has been widely studied in recent years. The main objective of this study was to investigate the relationship between adrenocorticotropic hormone (ACTH) on admission and PSD at 3 months.Methods: This is a hospital-based prospective cohort study, which was conducted at three independent hospitals (Tongji Hospital, Wuhan First Hospital and Wuhan Central Hospital) between August 2018 and June 2019. A total of 768 ischemic stroke patients were finally eligible for analysis and categorized into equal tertiles according to the distribution of ACTH and the number of patients. The χ2-test, Mann–Whitney U-test and Kruskal–Wallis test were used to check for statistical significance. And restricted cubic spline (RCS) regression model was used to explore the non-linear relationship between continuous ACTH levels and PSD at 3 months.Results: The optimal cut-off points of ACTH were as follows: (T1) 0.32– 20.55 pg/mL, (T2) 20.56– 39.79 pg/mL, (T3) 39.80– 143.40 pg/mL. A total of 305 patients (39.7%) were diagnosed as PSD at 3 months follow-up. Significant differences were found between the PSD and non-PSD groups in ACTH concentration (P = 0.001). After adjustment for all conventional confounders, the odds ratios of PSD were 1.735 (95% CI = 1.176– 2.560, P = 0.005) for the highest tertile of ACTH and 1.496 (95% CI = 1.019– 2.194, P = 0.040) for the middle tertile of ACTH, as compared with the lowest tertile. In multiple-adjusted RCS regression, continuous ACTH showed saturation effect relation with PSD risk after 31.02 pg/mL (P for nonlinear = 0.0143).Conclusion: Higher ACTH level on admission is a significant and independent biomarker to predict the development of PSD at 3 months follow-up. Besides, saturation effect was revealed even if the underlying mechanism is unclear. For stroke patients, doctors should pay attention to the baseline ACTH for screening high-risk PSD in clinical practice.Keywords: neuroendocrinology, HPA axis, adrenocorticotropic hormone, post-stroke depression, restricted cubic spline, saturation effect

Jian Shen,1 Bimeng Zhang,2 Jianjie Chen,3 Jiazheng Cheng,1 Jiali Wang,1 Xianhui Zheng,1 Yu Lan,1 Xiaowen Zhang1 1Department of Pediatrics, Shuguang Hospital Affiliated to Shanghai Traditional Chinese Medical University, Shanghai, 201203, People’s Republic of China; 2Department of Acupuncture and Moxibustion, Shanghai General Hospital (The First People’s Hospital Affiliated to Shanghai Jiaotong University), Shanghai, 200080, People’s Republic of China; 3Department of Internal Medicine, Shuguang Hospital Affiliated to Shanghai Traditional Chinese Medical University, Shanghai, 201203, People’s Republic of ChinaCorrespondence: Jian Shen Department of Pediatrics, Shuguang Hospital Affiliated to Shanghai Traditional Chinese Medical University, Shanghai, 201203, People’s Republic of China Tel +86-21-53821650 Email shenjian_78@shutcm.edu.cnObjective: Irritable bowel syndrome (IBS) is characterized by abdominal pain, bloating, and stool irregularity. However, its pathophysiological mechanisms, which trigger intestinal motility disorders and diarrhea leading to diarrhea-predominant IBS (D-IBS), remain largely unknown.Methods: In the present study, we established a D-IBS rat model by mother–infant separation combined with restraint stress. Then we exposed the modelled rats to suberoylanilide hydroxamic acid (SAHA) treatment, followed by determination of their visceral sensitivity. Toluidine blue staining served to reveal the effects of SAHA treatment on mast cells of D-IBS model rats. Then we measured the expression of serotonin (5-hydroxytryptamine; 5-HT) and its receptors by ELISA.Results: Construction of short hairpin RNA (sh)-serotonin transporter (SERT) lentivirus vectors verified the regulation of the 5-HT signaling pathway by phosphorylated (p)-STAT/SERT. SAHA treatment of D-IBS model rats reduced the fecal water content, electromyography integral change rate, abdominal withdrawal reflex score, and number of mast cells, as well as the expression of 5-HT type 3A (5-HT3AR), 3B receptor (5-HT3BR), and 4 receptor (5-HT4R) receptors. The treatment also elevated the expression of signal transducer and activator for transcription 3 (STAT3) and SERT. Activation of p-STAT3 may reverse the inhibitory effect of SAHA on the elevated visceral sensitivity of D-IBS model rats. Moreover, SAHA promoted the transcription of SERT through repression of the p-STAT3/5-HT signaling, thereby inhibiting the visceral sensitivity of D-IBS model rats.Conclusion: This study highlights that SAHA treatment can alleviate D-IBS through regulation of the p-STAT3/SERT/5-HT signaling pathway.Keywords: diarrhea type irritable bowel syndrome, SAHA, p-STAT3, SERT, 5-HT

Ying Lan,1 Nan Yang,2 Yirong Wang,1 Yujie Yang,1 Min Xu,1 Qin He1 1Department of Pharmacy, The Third People’s Hospital of Chengdu, Chengdu, People’s Republic of China; 2West China School of Pharmacy, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Ying Lan, Email lanying0212@126.comBackground: Fixed dose dual bronchodilators such as long-acting muscarinic antagonists (LAMAs) plus long-acting β 2-agonists (LABAs) are a new and important inhaled preparation for COPD treatment in China. Among these, umeclidinium/vilanterol (UMEC/VIL) is increasingly being used in China, especially among the elderly.Purpose: This study aimed to assess the cost-effectiveness of maintenance treatment with UMEC/VIL compared with salmeterol/fluticasone (FSC) as one of the main therapeutic drugs for moderate to very severe COPD in China.Methods: A Markov model was developed to estimate the costs and outcomes from a societal perspective in a 10-year time horizon. Patients with moderate-to-very severe COPD were treated with UMEC/VIL (62.5/25μg) or FSC (50/500ug). Data concerning clinical efficacy, costs, utilities, transition probability, exacerbation rate, and mortality were obtained from the published literature and official government datasets. The costs were presented in US dollars based on 2021 prices. The indicators of total costs, life years (LYs), quality-adjusted life-years (QALYs), and mortality were used as the model output. Costs and outcomes were discounted at a 5% annual rate. Incremental cost-effectiveness ratios were calculated considering the threshold recommended by WHO. One-way and probabilistic sensitivity analyses were conducted to assess the stability of results.Results: Compared with FSC, treatment with UMEC/VIL could save $1947.18, with a gain of 0.12 life-years and 0.05 QALYs. Further, 28.0% patients treated with UMEC/VIL and 29.2% patients treated with FSC were predicted to die after 10 years. Incremental cost effectiveness analysis showed that UMEC/VIL was dominant to FSC. Sensitivity analyses confirmed that the results were robust.Conclusion: UMEC/VIL is a cost-effective treatment option compared with FSC among patients with moderate-to-very severe COPD.Keywords: umeclidinium, vilanterol, salmeterol, fluticasone, cost-effectiveness, COPD, Markov

You Lan, Mao Zhou, Xin Li, Xuan Liu, Jun Li, Wenen Liu Department of Clinical Laboratory, Xiangya Hospital Central South University, Changsha, Hunan, 410008, People’s Republic of ChinaCorrespondence: Wenen LiuDepartment of Clinical Laboratory, Xiangya Hospital Central South University, No. 87 Xiangya Road, Changsha, Hunan, 410008, People’s Republic of China, Tel +86 731 8432 7437, Fax +86 731 8432 7332, Email wenenliu@163.comObjective: To investigate the role of outer membrane vesicles (OMVs) and related proteins in iron acquisition of hypervirulent Klebsiella pneumoniae (HVKP) and classic Klebsiella pneumoniae (cKP).Methods: The OMVs of HVKP and cKP under iron-deficient and iron-sufficient media were extracted and purified by ultracentrifugation. Transmission electron microscopy (TEM) was used to identify OMVs. The quantitative proteomics were performed based on mass spectrometry.Results: Four OMVs samples secreted by HVKP and cKP under iron-deficient and iron-sufficient environment were isolated and collected (HVKP OMVs under iron-deficient environment (A1), HVKP OMVs under iron-sufficient environment (A2), cKP OMVs under iron-deficient environment (B1), cKP OMVs under iron-sufficient environment (B2)). The amount of OMVs released by HVKP in iron-deficient medium was significantly larger than that in iron-sufficient medium (P < 0.05). HVKP secreted more OMVs than cKP in iron-deficient medium (P < 0.05). A total of 1074 kinds of proteins were identified in four samples. A comparison between the iron-deficient vs iron-sufficient environment showed that 61 proteins in HVKP OMVs were identified with a significant change in abundance under iron-deficient environment. Among them, 17 proteins were related to iron acquisition and transportation systems. While in cKP OMVs, 62 proteins significantly changed under iron-deficient environment in which 5 proteins were related to iron acquisition and transportation systems. Upon comparison of the HVKP vs cKP OMVs under iron deficiency, 81 proteins were detected with a significant change in which 8 proteins were related to iron acquisition and transportation systems.Conclusion: Above all, the results of this study suggest a potential role for OMVs in iron acquisition of HVKP and provide evidence of potential connections between OMVs and strong iron-acquisition ability of HVKP during iron limitation.Keywords: hypervirulent Klebsiella pneumoniae, iron acquisition, proteomics

This study determines factors related to the intention to vaccinate against COVID-19 for health science students in Ho Chi Minh City (HCMC), using both the Health Belief Model (HBM) and the Theory of Planned Behavior (TPB) model. A cross-sectional survey was considered in April 2021, using a self-administered questionnaire to all health sciences students of the University of Medicine and Pharmacy in Ho Chi Minh City (UMP), Vietnam. The multiple regression was performed to specify the predictable factors of willingness to get a future COVID-19 vaccination. A total of 854 students completed the survey, whose vaccination acceptance was 77.1%. Predictors of intention to receive a COVID-19 vaccination included year of education, knowledge, and the HBM and TPB variables including the perceived benefits, cues to action, perceived behavioral control, and positive attitudes toward the vaccine (all p

Cong Su,1,&ast; Ting Wu,2,&ast; Bao Meng,2 Chengcheng Yue,2 Yating Sun,2 Lingling He,2 Tingting Bian,2 Yanyan Liu,3,4 Ying Huang,5 Yanhu Lan,4 Jiabin Li2– 4,6 1Department of Infection Management, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 3Anhui Center for Surveillance of Bacterial Resistance, Hefei, People’s Republic of China; 4Institute of Bacterial Resistance, Anhui Medical University, Hefei, People’s Republic of China; 5Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 6Department of Infectious Diseases, The Chaohu Hospital of Anhui Medical University, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiabin LiDepartment of Infectious Diseases, The First Affiliated Hospital and the Chaohu Hospital of Anhui Medical University, Jixi Road 218, Hefei, 230022, People’s Republic of ChinaEmail lijiabin@ahmu.edu.cnYanhu LanInstitute of Bacterial Resistance, Anhui Medical University, Jixi Road 218, Hefei, 230022, People’s Republic of ChinaEmail zixinhu@163.comBackground: Klebsiella pneumoniae (K. pneumoniae) causes community-acquired and hospital-acquired pneumonia. The mortality rates of invasive infections caused by hypervirulent K. pneumoniae (HvKP) are extremely high. However, the microbiological characteristics and clinical manifestations of K. pneumoniae in AnHui province still remain unclear.Purpose: To show the high prevalence of HvKP infections regarding clinical characteristics and antimicrobial resistance in Anhui province.Patients and Methods: A retrospective analysis was conducted to study the clinical data of 115 strains of K. pneumoniae from July 2019 to March 2020 in The First Affiliated Hospital of AnHui Medical University. The virulence genes, capsular types, carbapenemase genes, and molecular subtypes of these hypervirulent isolates were detected.Results: Overall, 59.1% (68/115) cases were HvKP infections, mainly from the department of intensive care unit (ICU, n=14, 20.6%) and the department of respiratory and critical care (n=13, 19.1%). K2 was the most prevalent capsular serotype (n=26), followed by K1 (n=21). The results of MLST identification of 68 strains showed that ST23 (n=15, 22.1%) was the most common type of ST, followed by ST11 and ST65 (n=12, 17.6%), ST86 (n=9, 13.2%), and ST412 (n=6, 8.8%). Among 68 hvKP strains, 12 isolates were carbapenem resistant, and all except two harboured KPC.Conclusion: The high incidence of carbapenemase producing HvKP in the Anhui province, especially the higher mortality of HvKP, should be paid more attention. Meanwhile, epidemiological surveillance and clinical treatment strategies should be continuously determined and implemented.Keywords: Klebsiella pneumoniae, virulence genes, capsular types, antimicrobial resistance

Guo Li,1 Jinfeng Miao,1 Chensheng Pan,1 Ping Jing,2 Guohua Chen,3 Junhua Mei,3 Wenzhe Sun,1 Yan Lan,1 Xin Zhao,1 Xiuli Qiu,1 Yanyan Wang,1 Zhou Zhu,1 Suiqiang Zhu,1 Lifei Lian1 1Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 2Department of Neurology, Wuhan Central Hospital, Wuhan, Hubei, 430014, People’s Republic of China; 3Department of Neurology, Wuhan First Hospital, Wuhan, Hubei, 430022, People’s Republic of ChinaCorrespondence: Lifei Lian Tel +86-151 7150 7263Email 47009189@qq.comPurpose: Post-stroke depression (PSD) is one of the most common and severe psychological sequelae after stroke, negatively affecting the patient’s functional outcome and quality of life. Rapidly measurable biomarkers to predict PSD are pivotal for the optimized care and allocation of healthcare resources. Lactic dehydrogenase (LDH) levels are increased in patients with central nervous system (CNS) disorders such as cerebral infarction and hypoxic–ischemic encephalopathy, which may be related to the occurrence of PSD in acute ischemic stroke (AIS) patients. This study aimed to investigate whether LDH levels on admission are associated with PSD at discharge.Patients and Methods: A multicenter prospective cohort study was conducted, including all consecutive AIS patients within 7 days after symptom onset from May 2018 to October 2019. According to the distribution of LDH and the number of patients, patients were divided into equal tertiles. PSD was evaluated by DSM-V criteria and the 17-item Hamilton Rating Scale for Depression (HRSD-17) at discharge.Results: A total of 518 AIS patients were included. The optimal cut-off points of LDH were: lowest tertile (T1) 102– 159/L, middle tertile (T2) 160– 189 U/L, and upper tertile (T3) 190– 520 U/L. A total of 249 patients (48.07%) were diagnosed with PSD at discharge. After adjusting for potential confounding factors, the odds ratio of T3 PSD was 1.698 (95% CI, 1.070– 2.694, P=0.025), compared with T1.Conclusion: In summary, LDH serum levels on admission are associated with PSD at discharge. Clinicians should pay more attention to the baseline LDH level in screening for PSD at discharge.Keywords: post-stroke depression, lactic dehydrogenase, screen, cohort study

Qian Zhang,1,2,&ast; Jun Li,3,&ast; Minjie Bian,1,2 Qin He,1,2 Yuxian Shen,1,2 Yue Lan,4 Dongfeng Huang1,2 1Department of Rehabilitation Medicine, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, People’s Republic of China; 2Guangdong Engineering and Technology Research Center for Rehabilitation Medicine and Translation, Guangzhou, People’s Republic of China; 3Department of Urology, Kidney and Urology Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, People’s Republic of China; 4Department of Rehabilitation Medicine, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yue LanDepartment of Rehabilitation Medicine, Guangzhou First People’s Hospital, Guangzhou Medical University, 151 Yanjiang Road, Guangzhou, 510030, People’s Republic of ChinaTel +86-18988991916Email sybluemoon@126.comDongfeng HuangDepartment of Rehabilitation Medicine, The Seventh Affiliated Hospital, Sun Yat-sen University, 628 Zhenyuan Road, Shenzhen, 518107, People’s Republic of ChinaTel +86-13322800919Fax +86-0755-81206511Email huangdf@mail.sysu.edu.cnBackground and Purpose: Mild Cognitive Impairment (MCI) is thought to be the signal of many progressive diseases but is easily ignored. Therefore, a simple and easy screening method for recognizing and predicting MCI is urgently needed. The study aimed to establish machine learning models of retinal vascular features to categorize and predict MCI.Patients and Methods: Subjects enrolled underwent cognitive function assessment and were divided into a normal group, an MCI group, and a dementia group, and fundus photography was performed. MATLAB 2019b was used for fundus image preprocessing and vascular segmentation. Via the Green channel, adaptive histogram equalization (AHE), image binarization, and median filtering, we obtained the original and segmentation retinal vessel images. Afterwards, the histogram of oriented gradient (HOG) was used for image feature extraction. Support vector machine (SVM) and extreme learning machine (ELM) were selected for training models in the fundus original images and fundus vascular segmentation images, respectively. Among the three cognitive groups, sensitivity, specificity, the receiver operating characteristic (ROC) curves, and the area under the curve (AUC) were used to evaluate and compare the predictive performance of the two models in the fundus original and vascular segmentation images, respectively.Results: A total of 86 eligible subjects were enrolled in the study. After a clinical cognitive assessment, the participants were divided into the normal group (N = 38), the MCI group (N = 26), and the dementia group (N = 22). A total of 332 qualified fundus images were adopted after screening. Comparing the models among the three groups showed that the SVM model had more advantages than the ELM model in the fundus original images and vascular segmentation images. Meanwhile, we found that the original images performed better than the segmentation images in the same prediction model. Among the three groups, the SVM model of the fundus original images had the best performance.Conclusion: The establishment of a predictive model based on vascular-related feature extraction from fundus images has high recognition and prediction abilities for cognitive function and can be used as a screening method for MCI.Clinical Trial Registration: ChiCTR.org.cn (ChiCTR1900027404), Registered on Nov 12, 2019.Keywords: retinal imaging techniques, mild cognitive impairment, machine learning, support vector machine, extreme learning machine

Sujuan Zeng,1,&ast; Shiqi Liu,1,2,&ast; Yintao Lan,3 Ting Qiu,3 Mengyu Zhou,3 Weijian Gao,3 Wenyan Huang,1 Lihong Ge,1,4 Jian Zhang1,3 1Department of Pedodontics, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangdong, People’s Republic of China; 2Department of Stomatology, Taihe Hospital, Institute of Oral Diseases, School of Dentistry, Hubei University of Medicine, Hubei, People’s Republic of China; 3Department of Biomedical Engineering, School of Basic Medical Sciences, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Guangzhou Medical University, Guangdong, People’s Republic of China; 4Department of Pediatric Dentistry, Stomatology Hospital of Peking University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Zhang; Lihong Ge Email jianzhang@gzhmu.edu.cn; gelh0919@126.comBackground: Squamous cell carcinoma of the head and neck is the sixth most common cancer worldwide, with 40% occurring in the oral cavity. Although the level of early diagnosis and treatment of OSCC has improved significantly, the five-year survival rate of advanced patients remains unsatisfactory. However, the main challenges before us are how to get an early and accurate diagnosis and how to formulate effective treatment. Nanoparticle-based chemo-photothermal therapy has proven to be a promising non-invasive approach to treating oral squamous cell carcinoma treatment.Methods: In this study, we tried to design and synthesize multifunctional hyaluronic acid (HA) modified gold nanorods/mesoporous silica-based nanoparticles loaded with doxorubicin hydrochloride (DOX) for photoacoustic imaging (PAI) guided cooperative chemo-photothermal therapy.Results: The resultant nanocomposite shows favorable biocompatibility, relatively low cytotoxicity, ideal drug loading capability and strong PAI signals. In addition, they showed an excellent photothermal conversion efficiency of 49.02% for photothermal therapy (PTT). Moreover, in vivo and in vitro experiments have shown that synergistic chemo-photothermal therapy has better therapeutic effects than chemotherapy alone or PTT (P < 0.05). After being injected into the CAL-27 tumor-bearing mice, the DOX-AuNRs@mSiO2-HA nanoparticles could accumulate rapidly at the tumor sites and achieve complete ablation of tumors when combined with near-infrared laser irradiation, without obvious side effects on normal tissues.Conclusion: Our research provides a solid demonstration of the potential of DOX–AuNRs@mSiO2-HA as a multifunctional platform in PAI-guided photothermal chemotherapy for oral squamous cell carcinoma.Keywords: mesoporous silica coated gold nanorods, photoacoustic imaging, chemo-photothermal therapy, oral squamous cell carcinoma

Wentao Huang,1,&ast; Shu Cai,1,&ast; Ye Zhou,1 Jingxin Huang,1 Xibin Sun,2 Yunhui Su,3 Meifen Dai,4 Yutao Lan1 1School of Nursing, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 2School of Public Health, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 3Department of Emergency, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 4Department of Nursing, The Sixth Affiliated Hospital, South China University of Technology (Nanhai District People’s Hospital of Foshan), Foshan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yutao LanSchool of Nursing, Guangdong Pharmaceutical University, Guangzhou, 510310, People’s Republic of ChinaEmail lanyutao@gdpu.edu.cnMeifen DaiDepartment of Nursing, The Sixth Affiliated Hospital, South China University of Technology (Nanhai District People’s Hospital of Foshan), Foshan, 528200, People’s Republic of ChinaEmail 63015911@qq.comBackground: A high prevalence of psychological distress is observed in nurses due to multiple occupational stressors. Personality traits and personal factors are important factors that lead to psychological distress. The personality profile reflects a combination of personality traits; however, the relationship between personality profiles and personal factors that affect psychological distress among nurses has not been defined.Methods: This cross-sectional study was conducted in November 2020 in China. Convenience and snowball sampling were used to recruit participants. Latent profile analysis was used to identify personality profiles of nurses based on the big-five personality traits. Single-factor analysis and multivariate logistic regression were used to determine the factors affecting psychological distress. The structural equation model was used to verify the hypothetical model linking personality profiles, self-efficacy, psychological resilience, and coping style with psychological distress.Results: A total of 953 Chinese nurses (934 female) with a mean (S.D.) age of 32.8 (8.6) years were recruited. Personality profiles identified were negative, normative, and positive. A personality profile may predict psychological distress directly and indirectly through self-efficacy, psychological resilience, and coping style.Limitations: No complex sampling limits the representativeness of Chinese nurses. External factors affecting psychological distress were not investigated.Conclusion: Nurses with anegative personality profile had a higher prevalence of psychological distress. This study establishes the importance of personality profile assessment to identify nurses at higher risk of psychological distress. It suggests that interventions should be based on self-efficacy, psychological resilience, and coping style as potential management strategies.Keywords: psychological distress, personality profile, self-efficacy, psychological resilience, coping style, nurse

Qiuming Wang,1,&ast; Heming Wu,2,&ast; Yongquan Lan,1 Jinhong Zhang,1 Jingna Wu,1 Yunuo Zhang,1 Liang Li,1 Donghua Liu,1 Jinfeng Zhang1 1Department of Medical Oncology, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinfeng ZhangDepartment of Medical Oncology, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Huangtang Road, Meijiang District, Meizhou, Guangdong, 514031, People’s Republic of ChinaTel/Fax +86 753-220-2723Email jfzhang1980@hotmail.comPurpose: Although the burden of breast cancer remains especially high in rural China, data on the clinicopathological characteristics and prevalence of the breast cancer susceptibility gene 1/2 (BRCA1/2) mutations in patients with breast cancer remain limited. We investigated the clinicopathological characteristics, changing patterns, and prevalence of BRCA1/2 mutations in patients with breast cancer.Patients and Methods: The clinicopathological characteristics of 3712 women with pathologically confirmed primary breast cancer treated at Meizhou People’s Hospital between January 2005 and December 2018 were evaluated. The prevalence of BRCA1/2 mutations in 340 patients with breast cancer diagnosed between January 2017 and September 2018 was also evaluated.Results: The median age at diagnosis was 49± 10.5 (range, 20– 94) years. Positivity for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) was observed in 59.0%, 52.5%, and 24.9% of patients, respectively. Time trend analysis revealed that an increasing trend was observed for age at diagnosis (p = 0.001), proportion of patients without a reproductive history (p < 0.001), postmenopausal patients (p = 0.001), invasive pathological cancer type (p = 0.008), ER-positive rate (p < 0.001), PR-positive rate (p = 0.008), and HER2-positive rate (p < 0.001). Compared with patients without BRCA1/2 mutations, those with BRCA1/2 mutations were more likely to have a family history of breast or ovarian cancer (p < 0.001) and have triple-negative breast cancer (TNBC) (p < 0.001). Family history of breast or ovarian cancer (odds ratio [OR], 103.58; 95% confidence interval [CI], 20.58– 521.45; p < 0.001) and TNBC subtype (OR, 5.97; 95% CI, 1.16– 30.90; p = 0.033) were independent predictors for BRCA1/2 mutation.Conclusion: The clinicopathological characteristics of patients with breast cancer in this rural area have changed during the past decade. BRCA1/2 testing should be performed in patients with breast cancer with a family history of breast or ovarian cancer and TNBC.Keywords: BRCA1/2 mutation, breast neoplasm, molecular subtype, stage

Yun Lan,&ast; Xizi Deng,&ast; Linghua Li, Weiping Cai, Junbin Li, Xiaoli Cai, Feng Li, Fengyu Hu, Chunliang Lei, Xiaoping Tang Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, 510030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunliang Lei; Xiaoping TangGuangzhou Eighth People’s Hospital, Guangzhou Medical University, 627 Dongfeng East Road, Yuexiu District, Guangzhou, 510030, People’s Republic of ChinaEmail gz8hlcl@126.com; tangxp@gzhmu.edu.cnBackground: Guangdong, located in South China, is one of the areas heavily affected by HIV-1 in China. The transmission of HIV-1 among men who have sex with men (MSM) has gradually been increasing in Guangdong.Objective: To investigate the characteristics of the HIV-1 drug resistance, and genetic transmission networks in MSM with antiretroviral therapy (ART) failure from 2014 to 2019 in Guangdong.Methods: HIV-1 pol gene sequences were amplified. An online subtyping tool was used to determine the genotype, and a maximum likelihood phylogenetic tree was reconstructed to confirm the genotype results. The Stanford University HIV Drug Resistance Database was used to analyse the sequences of drug resistance mutations (DRMs) and drug resistance profiles. A pairwise Tamura-Nei 93 genetic distance-based method was used to analyse the genetic transmission networks.Results: Of 393 sequences isolated from HIV-infected MSM with ART failure, CRF01_AE (47.3%), CRF07_BC (21.4%) and CRF55_01B (21.4%) were the top three strains. 55.2% individuals harboured NRTI DRMs, whereas 67.4% carried NNRTI DRMs. 96.8% cases harboured mutations resistance to NRTIs or NNRTIs at high-level. The most common DRMs were M184I/V (42.2%), followed by V179D/E (37.9%) and K65R (27.2%). Of the subtype B sequences, no sequence fell into a cluster. Of the CRF01_AE, CRF55_01B, and CRF59_01B sequences, 14.5%, 61.9%, and 33.3% fell into clusters, respectively. Of the CRF07_BC sequences, 39.3% fell into clusters. The majority of MSM in transmission networks were concentrated at age below 35 years old, with multiple links. Moreover, approximately 54.8% of MSM had more than 2 potential transmission partners.Conclusion: Drug resistance mutations more frequently occurred in NNRTIs among MSM with ART failure in Guangdong Province. Transmission network analysis revealed a complex transmission pattern, and more attention should be given to younger HIV-1-infected MSM with multiple links.Keywords: HIV-1, drug resistance, genetic transmission networks, MSM

Xiaocong Jiang,1,&ast; Ting Song,2,&ast; Xiuhua Pan,1 Xinyu Zhang,1 Yuhong Lan,1 Li Bai1 1Department of Radiotherapy Oncology, Huizhou Central People’s Hospital, Huizhou, 516001, Guangdong, People’s Republic of China; 2Department of Hepatology, The Sixth People’s Hospital of Qingdao, Qingdao, 266033, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Bai Email bl_0067@126.comObjective: The occurrence and development of hepatocellular carcinoma (HCC) remain unclear. This study aimed to investigate potential diagnostic or prognostic markers for early HCC by applying bioinformatic analysis.Methods: The gene expression profiles of early HCC and normal tissues from a TCGA dataset were used to identify differentially expressed genes (DEGs) and then analysed by weighted gene coexpression network analysis. The integrated genes were selected to construct the protein–protein interaction (PPI) network and determine the hub genes. The prognostic impact of the hub genes was then analysed.Results: A total of 508 integrated genes were selected from the 615 DEGs and 8956 genes in the turquoise module. A PPI network was constructed, and the top 20 hub genes, including apolipoprotein A-IV (APOA4), fibrinogen gamma chain (FGG), vitamin K-dependent protein Z (PROZ), secreted phosphoprotein 24 (SPP2) and fetuin-B (FETUB), were identified. Only PROZ was significantly associated with the prognosis of early HCC.Conclusion: In this study, we demonstrated that the expression of PROZ was decreased in early HCC compared with normal liver controls, and low PROZ expression might result in poor overall survival of early HCC.Keywords: hepatocellular carcinoma, weighted gene coexpression network analysis, bioinformatics analysis, vitamin K-dependent protein Z

Wentao Huang,1 Dagfinn Aune,2– 4 Gerson Ferrari,5 Lei Zhang,6 Yutao Lan,1 Jing Nie,7 Xiong Chen,8 Dali Xu,9 Yafeng Wang,10 Leandro FM Rezende11 1School of Nursing, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 2Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK; 3Department of Nutrition, Bjørknes University College, Oslo, Norway; 4Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway; 5Universidad de Santiago de Chile (USACH), Escuela de Ciencias de la Actividad Física, el Deporte y la Salud, Santiago, Chile; 6Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital of Fudan University, Shanghai, People’s Republic of China; 7Department of Sociology & Institute for Empirical Social Science Research, School of Humanities and Social Sciences, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 8Department of Endocrinology, Wenzhou Medical University First Affiliated Hospital, Wenzhou, Zhejiang, People’s Republic of China; 9Department of Psychiatry and Neuroimaging Centre, Wenzhou Seventh People’s Hospital, Wenzhou, Zhejiang, People’s Republic of China; 10Department of Epidemiology and Biostatistics, School of Health Sciences, Wuhan University, Wuhan, People’s Republic of China; 11Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Medicina Preventiva, Sao Paulo, BrazilCorrespondence: Dali XuDepartment of Psychiatry and Neuroimaging Centre, Wenzhou Seventh People’s Hospital, Wenzhou, Zhejiang, People’s Republic of ChinaEmail dali0421@163.comWentao HuangSchool of Nursing, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of ChinaEmail huangwentau@outlook.comAim: To examine the association of psychological distress with all-cause, cardiovascular disease (CVD) and cancer mortality in US adults, and verified whether the associations differed between participants with and without diabetes.Methods: A total of 485,864 adults (446,288 without diabetes and 39,576 with diabetes) who participated in the National Health Interview Survey from 1997 to 2013 were linked to the National Death Index through December 31, 2015. Psychological distress was measured by the Kessler 6 distress scale (K6). Multivariable Cox proportional hazards regression models were performed to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the association between psychological distress and mortality.Results: We ascertained 11,746 deaths (mean follow-up, 7. 7 years) among people with diabetes and 51,636 deaths (9.9 years) among those without diabetes. Psychological distress was associated with higher all-cause, CVD, and cancer mortality. Compared to non-diabetic adults without psychological distress, HRs (95% CI) were 1.07 (1.04 to 1.09) for mild, 1.26 (1.22 to 1.30) for moderate and 1.46 (1.38 to 1.55) for severe psychological distress. Compared to the same reference group, in diabetic participants the HRs were 1.39 (1.33 to 1.44) for no psychological distress, 1.59 (1.53 to 1.66) for mild, 1.90 (1.80 to 2.00) for moderate and 1.98 (1.82 to 2.17) for severe psychological distress. Similar associations were also observed for CVD and cancer mortality but with non-statistically significant interaction.Conclusion: Psychological distress was associated with higher mortality, particularly in participants with diabetes. Strategies to ameliorate psychological distress may be important to reduce mortality in this population.Keywords: diabetes mellitus, psychological distress, mortality, cohort

Guo Li,1 Ping Jing,2 Guohua Chen,3 Junhua Mei,3 Jinfeng Miao,1 Wenzhe Sun,1 Yan Lan,1 Xin Zhao,1 Xiuli Qiu,1 Zhou Zhu,1,&ast; Suiqiang Zhu1,&ast; 1Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 2Department of Neurology, Wuhan Central Hospital, Wuhan, Hubei, 430014, People’s Republic of China; 3Department of Neurology, Wuhan First Hospital, Wuhan, Hubei, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhou Zhu Tel +86-18171081029Email zhouzhu@hust.edu.cnSuiqiang Zhu Tel +86-13035101141Email zhusuiqiang@163.comPurpose: The early detection of major post-stroke depression (PSD) is essential to optimize patient care. A major PSD prediction tool needs to be developed and validated for early screening of major PSD patients.Patients and Methods: A total of 639 acute ischemic stroke (AIS) patients from three hospitals were consecutively recruited and completed a 3-month follow-up. Sociodemographic, clinical and laboratory test data were collected on admission. With major depression criteria being met in the DSM-V, 17-item Hamilton Rating Scale For Depression (HRSD) score ≥ 17 at 3 months after stroke onset was regarded as the primary endpoint. Multiple imputation was used to substitute the missing values and multivariable logistic regression model was fitted to determine associated factors with a bootstrap backward selection process. The nomogram was constructed based on the regression coefficients of the associated factors. Performance of the nomogram was assessed by discrimination (C-statistics) and calibration curve.Results: A total of 7.04% (45/639) of patients were diagnosed with major PSD at 3 months. The final logistic regression model included age, baseline NIHSS and mRS scores, educational level, calcium–phosphorus product, history of hypertension and atrial fibrillation. The model had acceptable discrimination, based on a C-statistic of 0.81 (95% CI, 0.791– 0.829), with 71.1% sensitivity and 78.6% specificity. We also transformed the model to a nomogram, an easy-to-use clinical tool which could be used to facilitate the early screening of major PSD patients at 3 months.Conclusion: We identified several associated factors of major PSD at 3 months and constructed a convenient nomogram to guide follow-up and aid accurate prognostic assessment.Keywords: major post-stroke depression, nomogram, calcium–phosphorus product, C-statistic

Wen Li,1,2 Qing Song,2 Yu Lan,2 Jie Li,3 Ying Zhang,2 Lin Yan,2 Yingying Li,2 Yan Zhang,2 Yukun Luo2 1Department of Ultrasound, Medical School of Chinese PLA, Beijing, People’s Republic of China; 2Department of Ultrasound, The First Medical Center Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Pathology, The First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yukun Luo; Yan Zhang No. 28 Fuxing Road, Haidian District, Beijing, 100853, People’s Republic of ChinaTel +8613311373556; +8613581937501Fax +8601055499255Email luoyk301@126.com; zhangyaner301@126.comPurpose: Differentiation between follicular thyroid carcinomas (FTCs) and follicular thyroid adenomas (FTAs) is difficult and the sonographic features of FTC are not yet fully established. The purpose of this study is to explore the sonographic features of FTC and the value of sonography in differentiating FTCs from FTAs.Patients and Methods: A total of 28 pathologically proven FTCs and 53 FTAs in 78 patients who were performed thyroid surgery were included in this retrospective study. The sonographic features of each tumor including an interrupted halo, satellite nodule(s) with or without halo ring, local irregularity of margin and cluster of grapes sign were evaluated. A mode image of FTC halo was built up in our study. The frequencies of the sonographic features were compared by chi-square test or Fisher exact test between FTCs and FTAs. The relative risk of malignancy was assessed by logistic regression analysis.Results: Logistic regression analysis showed that a thick, irregular and/or interrupted halo with or without satellite nodule(s), hypoechoic or marked hypoechoic echogenicity, a predominantly solid pattern, cluster of grapes sign, micro-or macro-calcifications, rim calcifications correlated with significant increases in relative risk for FTCs (odds ratio 11.48 (1.37– 96.56), 6.74 (1.05– 43.30), 17.51 (1.78– 172.53), 9.55 (1.44– 63.46), 9.36 (1.25– 70.15) and 17.45 (1.04– 292.65), respectively, p< 0.05). Two new sonographic features, an interrupted halo and satellite nodule(s) with or without halo ring, can only be found in FTCs.Conclusion: An interrupted halo and satellite nodule(s) with or without halo ring are specific sonographic features for FTCs. Sonography could play a role in differentiating follicular thyroid carcinoma from adenoma.Keywords: follicular thyroid carcinoma, follicular thyroid adenoma, ultrasonography

Ting Qiu,1,* Yintao Lan,1,* Zuwu Wei,2 Yanfen Zhang,3 Yanping Lin,1 Chenggong Tu,1 Guangjuan Mao,1 Lingmin Zhang,3 Bin Yang,1 Jian Zhang1 1The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Department of Biomedical Engineering, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, People’s Republic of China; 2The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fujian, 350025, People’s Republic of China; 3School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian Zhang Email jianzhang@gzhmu.edu.cnBackground: Effective treatment strategy for cervical carcinoma is subject to the limitation of its anatomical location and histological characteristics. Comprehensive imaging before cervical carcinoma treatment is of great significance for the patients. Current imaging methods cannot meet the requirements of high resolution, deep imaging depth and non-invasive imaging at the same time. Fortunately, Photoacoustic imaging (PAI) is a novel imaging method that combines rich optical contrast, high ultrasonic spatial resolution, and deep penetration depth in a single modality. Moreover, PAI-guided photothermal therapy (PTT) by aid of targeting nanoparticles is an emerging and effective cancer treatment in recent years.Methods: Here, strong near-infrared region (NIR) absorption-conjugated polymer PIIGDTS (PD) nanoparticles with folic acid (FA) modification (namely, PD-FA) that targeted at Hela cell were specifically designed as cervical tumor imaging contrast agents and photothermal agents.Results: The obtained PD-FA nanoparticles exhibited admirable photoacoustic contrast-enhancing ability and desirable PTT behavior with the photothermal conversion efficiency as high as 62.6% in vitro. Furthermore, the PAI performance and PTT efficiency were tested in HeLa tumor-bearing nude mice after injection of PD-FA nanoparticles. In vivo multi-scale, PAI provided B-san and 3D dimension imaging for intuitive and comprehensive information of Hela tumor. Moreover, the Hela tumor can be completely eliminated within 18 days after PTT, with no toxicity and side effects.Conclusion: In summary, PD-FA injection combined with PAI and PTT systems provides a novel powerful tool for early diagnosis and precise treatment of cervical cancer.Keywords: cervical cancer, multi-scale photoacoustic imaging, photothermal therapy, PIIGDTS nanoparticle

Yuan Nie,* Xizi Deng,* Yun Lan, Linghua Li, Feng Li, Fengyu Hu Research Institute, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fengyu Hu; Feng LiResearch Institute, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, No. 627, Dongfeng Road, Yuexiu District, Guangzhou, Guangdong 510030, People’s Republic of ChinaEmail gz8hhfy@126.com; gz8h_lifeng@126.comBackground: Human immunodeficiency virus (HIV)/hepatitis B virus (HBV) co-infection can accelerate HBV-induced liver disease. A previous study showed that variation in the HBV pre-S region and quasispecies heterogeneity (Sn, mean genetic distance, dS, dN, and dS/dN) are both related to HBV-induced terminal liver disease in HBV mono-infection. Currently, data are lacking on quasispecies variation of the HBV pre-S region in HIV/HBV co-infection. Investigating the quasispecies variation of the HBV pre-S region and its related factors in HIV/HBV co-infection will help to better explore the pathogenic mechanism of HIV/HBV co-infection.Methods: According to the HIV antibody results obtained before treatment, chronic HBV-infected patients were divided into HIV/HBV co-infected and HBV mono-infected groups. The clinical characteristics of all patients were collected, and DNA was extracted from the serum. The HBV pre-S region was amplified by nested PCR and was further TA cloned. BioEdit software 7.0 was used for sequence alignment with reference to the standard sequence of the matched HBV genotype. We used 1:1 propensity score matching (PSM) to control for baseline confounding factors between the two groups.Results: After 1:1 PSM, we identified 100 patients with similar propensities: 50 HIV/HBV co-infected patients and 50 HBV mono-infected patients. HBV quasispecies indices were lower in the HIV/HBV co-infected group than those in the HBV mono-infected group. A significant correlation was observed between all quasispecies indices and soluble cluster of differentiation 163 (sCD163) and interleukin-18 (IL-18) in the HIV/HBV co-infected group; however, this phenomenon was not found in the HBV mono-infected group.Conclusion: Combined HIV infection reduces quasispecies heterogeneity in the HBV pre-S region, and the quasispecies heterogeneity is related to the sCD163 and IL-18 levels.Keywords: HIV, HBV, quasispecies, pre-S region, inflammation

Yun Lan,1,* Linghua Li,2,* Weilie Chen,1,* Xizi Deng,1 Junbin Li,2 Qinghong Fan,1 Xiaoli Cai,1 Weiping Cai,2 Fengyu Hu1 1Institute of Infectious Disease, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Infectious Disease Center, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weiping CaiInfectious Disease Center, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, 627 Dongfeng East Road, Yuexiu District, Guangzhou 510030, People’s Republic of ChinaTel +86-20-83710825Email gz8hcwp@126.comFengyu HuInstitute of Infectious Disease, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, 627 Dongfeng East Road, Yuexiu District, Guangzhou 510030, People’s Republic of ChinaTel +86-20-83710851Email gz8hhfy@126.comBackground: Antiretroviral therapy (ART) containing an integrase strand transfer inhibitor (INSTI) plus two nucleoside reverse-transcriptase inhibitors has been recommended as a first-line regimen for ART-naïve HIV-1-infected patients in the latest Chinese Guidelines for Diagnosis and Treatment of HIV/AIDS.Objective: To determine the prevalence of INSTI-related mutations among ART-naïve HIV-1-infected adults in Guangdong, China, in 2018.Methods: The entire integrase gene was amplified from blood plasma. Demographic and epidemiological information was collected. INSTI mutations and antiretroviral susceptibility were interpreted using the Stanford University HIV Drug Resistance Database HIVdb program.Results: Of 927 samples, 827 integrase sequences were successfully obtained. Among them, no major resistance mutations to INSTIs were identified, and four accessory mutations, including T97A (0.12%, 1/827), A128T (0.24%, 2/827), E157Q (0.85%, 7/827), and G163R (0.24%, 2/827), were found in twelve individuals. Two patient samples contained the G163R mutation conferring low-level resistance to elvitegravir and raltegravir.Conclusion: The overall prevalence of INSTI mutations remains low. Drug resistance mutation testing for the detection of INSTI drug resistance mutations in HIV treatment-naïve patients should be considered due to the circulation of polymorphisms contributing to INSTI resistance and the expected increasing use of this class of drugs.Keywords: HIV-1, integrase inhibitor, drug resistance mutation, Guangdong

Jiaying Tan,1,* Wenjin Yu,2,* Gang Wu,1 Jun Shen,1 Yong Fang,1 Hechen Zhu,1 Qianyi Xiao,3 Weixia Peng,3 Yukun Lan,3 Ye Gong1 1Department of Critical Care Medicine, Huashan Hospital, Fudan University, Shanghai 200040, People’s Republic of China; 2Department of Pharmacy , Huashan Hospital, Fudan University, Shanghai 200040, People’s Republic of China; 3Department of Preventive Medicine and Health Education, School of Public Health, Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ye Gong Email gong_ye@fudan.edu.cnBackground: We conducted a real-world analysis of the effectiveness of different antibiotic regimens for bloodstream infections (BSIs) caused by carbapenem-resistant gram-negative bacilli (CR-GNB) in a Chinese population.Methods: A retrospective observational study was conducted between January 2010 and December 2017. Patients with BSIs caused by CR-GNB confirmed by in vitro susceptibility tests were enrolled, and patient medical record data on antimicrobial agents and microbiological and clinical outcomes were extracted.Results: A total of 175 individuals were included; 127 individuals (72.6%) received combination therapy (two or more antibiotics), while 48 individuals (27.4%) received monotherapy (single antibiotic). The all-cause 28-day mortality was 20.0%. Treatment success or presumed success rates were very similar between the monotherapy and combination therapy groups (58.3% versus 59.1%; P = 0.931). Combination therapy had a higher success rate trend than monotherapy in septic shock patients (40.7% versus 18.2%; P = 0.268). Improved therapeutic effects were observed in the active agent-containing group, although the differences were not significant.Conclusion: Combination therapy likely has better therapeutic effects on critical BSIs caused by CR-GNB than monotherapy. Choosing a proper active agent in an antimicrobial regime is relatively crucial to the ultimate treatment outcome.Keywords: bloodstream infection, carbapenem-resistant gram-negative bacilli, antimicrobial regimen, treatment success rate, real-world, Chinese population

Yuan Nie,1,2,* Xi-Zi Deng,1,* Yun Lan,1 Feng Li,1 Feng-Yu Hu1 1Research Institute, Guangzhou Eighth People’s Hospital Affiliated to Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feng-Yu HuResearch Institute,Guangzhou Eighth People’s Hospital Affiliated to Guangzhou Medical University, No. 627, Dongfeng Road, Yuexiu District, Guangzhou 510030, Guangdong, People’s Republic of ChinaEmail gz8hhfy@126.comBackground: Combined HIV infection can accelerate HBV-induced liver disease. It is known that HBV Pre-S deletion is closely related to HBV-associated terminal liver disease in HBV mono-infection. Currently, data on HBV Pre-S quasispecies feature deletion in HIV/HBV co-infected patients are lacking.Methods: The characteristics and blood samples of patients with chronic HBV infection were collected and classified into an HIV/HBV co-infection group and an HBV mono-infection group according to HIV antibody results before treatment. HBV DNA in serum was extracted. The HBV Pre-S region was amplified by nested-PCR and was further T-A cloned. Using the standard sequence of the matched genotype HBV as a reference, BioEdit 7.0 software was employed for sequence alignment.Results: HBV Pre-S regions were successfully amplified from 147 patients, including 71 cases in the HIV/HBV co-infected group and 76 cases in the HBV mono-infected group. The proportion of the HIV/HBV co-infected group with Pre-S quasispecies deletion was lower than that of the HBV mono-infected group. By analyzing the frequency of Pre-S quasispecies in the two groups, the frequency of Pre-S quasispecies in HIV/HBV co-infected patients with Pre-S quasispecies was higher than HBV mono-infected patients. The frequency of Pre-S quasispecies deletion of the S protein promoter region in the HIV/HBV co-infected group was significantly higher than that in the HBV mono-infected group.Conclusion: High-frequency Pre-S quasispecies deletions are predominant in HIV/HBV co-infected patients; however, low-frequency Pre-S deletions are predominant in HBV mono-infected patients, providing a reference for the pathogenesis of the accelerated progression of liver disease in HIV/HBV co-infection.Keywords: human immunodeficiency virus, hepatitis B virus, quasispecies, Pre-S region, deletion

Zhimin Cao,1 Yuanbo Lan,1 Ling Chen,1 Min Xiang,1 Zhiyuan Peng,1 Jianyong Zhang,1 Hong Zhang1,2 1Tuberculosis Division, Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, People’s Republic of China; 2Department of R & D, Z-BioMed, Inc, Rockville, MD, 20855, USACorrespondence: Ling Chen; Hong ZhangTuberculosis Division, Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Zunyi, Guizhou 563003, People’s Republic of ChinaTel +86 851 2860 9237Fax +86 851 2860 8239Email lingjuncd@163.com; hzhang@zbiomed.comBackground: China is one of the high-burden countries for multidrug-resistant tuberculosis (MDR-TB), and pyrazinamide is one of the anti-TB drugs used for the shorter MDR-TB treatment regimen. The aim of this study was to determine the correlation between pncA gene mutations and resistance to four first-line anti-TB drugs as well as treatment history in clinical isolates of Mycobacterium tuberculosis.Patients and methods: M. tuberculosis clinical isolates were collected from 318 in-patients with smear-positive TB between October 2008 and September 2016 at a major hospital in Zunyi, Guizhou Province of China, and used for drug susceptibility testing against four first-line anti-TB drugs. Genomic DNA extracted from clinical isolates was used for PCR amplification and DNA sequencing of the pncA gene.Results: Among 318 clinical isolates, 129 (40.6%), 170 (53.5%), 66 (20.8%) and 109 (34.3%) were resistant to rifampicin, isoniazid, ethambutol and streptomycin respectively. In addition, 124 clinical isolates were MDR-TB and 71.8% of them were previously treated cases. Sequencing results showed that 46.8% of MDR-TB and 2.2% of drug susceptible isolates harbored a pncA mutation, and 52 types of pncA mutations were detected from 64 isolates. The prevalence of pncA mutations in isolates resistant to first-line anti-TB drugs and previously treated TB cases was significantly higher than that in drug-susceptible isolates and new cases of TB.Conclusion: High prevalence of pncA mutations in clinical isolates of M. tuberculosis from Zunyi, Guizhou Province of China, is correlated with resistance to four first-line anti-TB drugs, MDR-TB and previously treated TB cases.Keywords: Mycobacterium tuberculosis, pyrazinamide, drug resistance, pncA mutation

Wenhua Zhang,1,2,* Wenhua Xu,1,* Yu Lan,3 Xuliang He,1 Kaibin Liu,4 Ye Liang21Department of Inspection, Medical Faculty, Qingdao University, Qingdao 266003, People’s Republic of China; 2Key Laboratory, Department of Urology and Andrology, Affiliated Hospital of Qingdao University, Qingdao 266003, People’s Republic of China; 3Department of Inspection, Weihai Central Hospital, Weihai 264400, People’s Republic of China; 4Department of Clinical Medicine, Second Military Medical University, Shanghai 200433, People’s Republic of China*These authors contributed equally to this workPurpose: Nanoparticle (NP)-mediated targeted delivery of therapeutic genes or siRNAs to tumors has potential advantages. In this study, hyaluronic acid (HA)-modified chitosan nanoparticles (CS NPs-HA) loaded with cyanine 3 (Cy3)-labeled siRNA (sCS NPs-HA) were prepared and characterized.Methods: Human non-small cell lung cancer (NSCLC) A549 cells expressing receptor CD44 and tumor-bearing mice were used to evaluate the cytotoxic and antitumor effects of sCS NPs-HA in vitro and in vivo.Results: The results showed that noncytotoxic CS NPs-HA of small size (100–200 nm) effectively delivered the Cy3-labeled siRNA to A549 cells via receptor CD44 and inhibited cell proliferation by downregulating the target gene BCL2. In vivo experiment results revealed that sCS NPs-HA directly delivered greater amounts of Cy3-labeled siRNA to the tumor sites, resulting in the inhibition of tumor growth by downregulating BCL2, as compared to unmodified NPs loaded with siRNA (sCS NPs) and to naked Cy3-labeled siRNA.Conclusion: The HA-modified NPs based on chitosan could serve as a promising carrier for siRNA delivery and targeted therapy for NSCLC expressing CD44.Keywords: nanoparticle, siRNA, CD44, hyaluronic acid, cancer

The biggest Phanerozoic mass extinctionoccurred at the Permian-Triassic boundary and resulted in the loss of about 95% or more of all marine species. For quite some time, many kinds of abnormal environmental events were adopted to explain the abnormal reduction of carbon isotope at the Permian-Triassic boundary, however there still has not been a unified opinion. In this paper, based on the carbon cycle balance model of the earth under a long-period scale, the contributions of possible cataclysm events at the Permian-Triassic boundary to the carbon isotope records in carbonates were quantitatively simulated. The results proved that a single event, such as volcanism, terrestrial ecosystem collapse or another factor, was not strong enough to lead to the negative bias of carbon isotope at the Permian-Triassic boundary. Even though the release of methane hydrate can result in a comparably large negative excursion of inorganic carbon, this explanation becomes unsuitable when both the shifting Permian-Triassic boundary and the fluctuation record of other inorganic carbon isotopes in the early Triassic as a whole are considered. Therefore, it is suggested that the dynamic equilibrium between inorganic carbon reserves and organic carbon reserves was possibly disturbed by a superimposed effect of multiple events.

Abstract Genetically improved farmed tilapia (GIFT, Oreochromis niloticus) are commercially important fish that are cultured in China. GIFT are highly susceptible to diseases when exposed to high temperatures in summer. Better understanding the GIFT regulatory response to heat stress will not only help in determining the relationship between heat stress signalling pathways and adaption mechanisms, but will also contribute to breeding new high-temperature tolerant strains of GIFT. In this study, we built control (28 °C) and heat-treated (37.5 °C) groups, and extracted RNA from the liver tissues for high-throughput next-generation sequencing to study the miRNA and mRNA expression profiles. We identified 28 differentially expressed (DE) miRNAs and 744 DE mRNAs between the control and heat-treated groups and annotated them using the KEGG database. A total of 38 target genes were predicted for 21 of the DE miRNAs, including 64 negative miRNA–mRNA interactions. We verified 15 DE miRNA–mRNA pairs and 16 other DE mRNAs by quantitative real-time PCR. Important regulatory pathways involved in the early response of GIFT to heat stress included organism system, metabolism, and diseases. Our findings will facilitate the understanding of regulatory pathways affected by acute heat stress, which will help to better prevent heat damage to GIFT.

Zhenzhen Liu,1,* Haijun Gong,2,* Rui Zeng,2 Xuan Liang,1 Li-Ming Zhang,1 Liqun Yang,1,* Yuqing Lan2,* 1Institute of Polymer Science, School of Chemistry and Chemical Engineering, Key Laboratory of Designed Synthesis and Application of Polymer Material, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Ophthalmology, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: A hyperbranched cationic polysaccharide derivative-mediated small interfering (si)RNA interference strategy was proposed to inhibit nuclear transcription factor-kappa B (NF-κB) activation in human retinal pigment epithelial (hRPE) cells for the gene therapy of diabetic retinopathy. Two hyperbranched cationic polysaccharide derivatives containing the same amount of cationic residues, but with different branching structures and molecular weights, including 3-(dimethylamino)-1-propylamine-conjugated glycogen (DMAPA-Glyp) and amylopectin (DMAPA-Amp) derivatives, were developed for the efficient delivery of NF-κB siRNA into hRPE cells. The DMAPA-Glyp derivative showed lower toxicity against hRPE cells. Furthermore, the DMAPA-Glyp derivative more readily condensed siRNA and then formed the nanoparticles attributed to its higher branching architecture when compared to the DMAPA-Amp derivative. Both DMAPA-Glyp/siRNA and DMAPA-Amp/siRNA nanoparticles were able to protect siRNA from degradation by nuclease in 25% fetal bovine serum. The particle sizes of the DMAPA-Glyp/siRNA nanoparticles (70–120 nm) were smaller than those of the DMAPA-Amp/siRNA nanoparticles (130–180 nm) due to the higher branching architecture and lower molecular weight of the DMAPA-Glyp derivative. In addition, the zeta potentials of the DMAPA-Glyp/siRNA nanoparticles were higher than those of the DMAPA-Glyp/siRNA nanoparticles. As a result, siRNA was much more efficiently transferred into hRPE cells using the DMAPA-Glyp/siRNA nanoparticles rather than the DMAPA-Amp/siRNA nanoparticles. This led to significantly high levels of suppression on the expression levels of NF-κB p65 messenger RNA and protein in the cells transfected with DMAPA-Glyp/siRNA nanoparticles. This work provides a potential approach to promote hyperbranched polysaccharide derivatives as nonviral siRNA vectors for the inhibition of NF-κB activation in hRPE cells.Keywords: glycogen, amylopectin, siRNA, nuclear transcription factor-kappa B, human retinal pigment epithelial cells