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Feng Yao,1,* Chenguang Wang,2,* Jie Ding,1 Qian Zhang,1 Liang Zheng,1 Qin Zhang,1 Tianshu Yang,2 Xunmin Zhang,2 Yong Shan,2 Sheng Hou,2 Hao Wang,2 Renpeng Zhou,1 Wei Hu1 1Department of Clinical Pharmacology, The Second Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Taizhou Mabtech Pharmaceutical Co., Ltd, Taizhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Hu; Renpeng Zhou, Department of Clinical Pharmacology, The Second Affiliated Hospital of Anhui Medical University, No. 678 Furong Road, Hefei, Anhui, 230601, People’s Republic of China, Tel/Fax + 86 0551 65997164, Email huwei@ahmu.edu.cn; zhourenpeng@ahmu.edu.cnPurpose: Secukinumab, a monoclonal antibody targeting interleukin (IL)-17A, is approved for the treatment of psoriasis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, enthesitis-related arthritis, and hidradenitis suppurativa. This study compared the pharmacokinetics (PK), safety, and immunogenicity of CMAB015, a candidate secukinumab biosimilar, with the reference product secukinumab (Cosentyx®) in healthy Chinese male subjects.Patients and methods: This double-blind, parallel-group study randomized healthy Chinese male subjects (N=130) to receive either a single dose of 150 mg CMAB015 or secukinumab subcutaneously. Primary study endpoints were PK parameters such as the maximum concentration (Cmax) and area under the curve from zero to infinity (AUC0-inf), while safety and immunogenicity were secondary endpoints.Results: The 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) of Cmax and AUC0-inf for CMAB015 to secukinumab were all within the bioequivalence limits (80.00– 125.00%). Other PK parameters were comparable between the groups. The safety profile of CMAB015 was similar to that of secukinumab, with no serious adverse events related to treatment. The incidence of TEAEs was slightly higher in the CMAB015 group, but these events were mild to moderate in severity and did not lead to any withdrawals from the study. Immunogenicity analysis revealed low rates of anti-drug antibody (ADA) positivity, with similar rates between CMAB015 and secukinumab.Conclusion: This study demonstrated equivalent PK, comparable safety, and immunogenicity of CMAB015 to secukinumab in healthy Chinese male subjects. These findings support further clinical evaluation of CMAB015 as a secukinumab biosimilar.Trial Registration: The trial was registered on Clinicaltrials.gov (Identifier No. NCT05734482) and Chinadrugtrials.org.cn (Identifier No. CTR20230105).Keywords: CMAB015, secukinumab, biosimilar, pharmacokinetics, safety, immunogenicity

Yifan Wang,1,2,* Fen Yao,2,* Shenglong Chen,3 Xin Ouyang,4 Jinhua Lan,5 Zheng Wu,2 Yirong Wang,2 Jingchun Chen,2 Xipei Wang,6,7 Chunbo Chen1 1Department of Critical Care Medicine, Shenzhen People’s Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518020, People’s Republic of China; 2School of Biology and Biological Engineering, South China University of Technology, Guangzhou, 510006, People’s Republic of China; 3Department of Critical Care Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 4Department of Intensive Care Unit of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 5Department of Pharmacy, General Hospital of Southern Theatre Command, Guangzhou, 510010, People’s Republic of China; 6Research Center of Medical Sciences, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 7Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunbo Chen, Department of Critical Care Medicine, Shenzhen People’s Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518020, People’s Republic of China, Email gghccm@163.com Xipei Wang, Research Center of Medical Sciences, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China, Email xipei_wang@163.comPurpose: To develop a population pharmacokinetic model describing teicoplanin concentrations in patients hospitalized in intensive care unit (ICU) and to perform Monte Carlo simulations to provide detailed dosing regimens of teicoplanin.Methods: This single-center, prospective, observational study was conducted on 151 patients in ICU with 347 plasma samples. The population pharmacokinetics model was established and various covariates were evaluated. The probability of target attainment (PTA) of various proposal dosing regimens was calculated by Monte Carlo simulations.Results: The two-compartment model adequately described teicoplanin concentration-time data. The estimated glomerular filtration rate (eGFR) associated with systemic clearance (CL) was the only covariate included in the final model. The estimate of CL was 0.838 L/h, with the eGFR adjustment factor of 0.00823. The volume of the central compartment (Vc), inter-compartmental clearance (Q) and volumes of the peripheral compartments (Vp) were 14.4 L, 3.08 L/h and 51.6 L, respectively. The simulations revealed that the standard dosage regimen was only sufficient for the patients with severe renal dysfunction (eGFR ≤ 30 mL/min/1.73 m2) to attain target trough concentration (Cmin, PTA 52.8%). When eGFR > 30 mL/min/1.73 m2, increasing dose and the administration times of loading doses were the preferred options to achieve target Cmin based on the renal function and types of infection.Conclusion: The most commonly used standard dosage regimen was insufficient for all ICU patients. Our study provided detailed dosing regimens of teicoplanin stratified by eGFR and types of infection for ICU patients.Keywords: teicoplanin, pharmacokinetics, Monte Carlo simulation, intensive care unit, renal function

Ting Gui,1,* Fengxia Yao,2,* Xinzhuang Yang,2 Xi Wang,3 Min Nie,3 Xueyan Wu,3 Qinjie Tian1 1Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric and Gynecologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Medical Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Endocrinology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qinjie Tian, Department of obstetrics and gynecology, Peking Union Medical College Hospital, No. 1, Shuaifuyuan Road, Dongcheng District, Beijing, 100730, People’s Republic of China, Tel +86 010-69158335, Email tqj_tianqinjie@163.comObjective: The 5α-reductase type 2 deficiency is mainly caused by mutations in the SRD5A2 gene. Our study aims to investigate the SRD5A2 gene mutations and their corresponding manifestations.Methods: Four unrelated Chinese patients with 46, XY ambiguous genitalia were studied. Molecular genetic alterations and clinical presentations were analyzed.Results: Five variants in the SRD5A2 gene were identified, all highly conserved in vertebrate orthologs. The p.P251A was a novel variant, predicted to “Affect protein function” and to be “probably damaging”. Combining patients’ gene mutations with their external genitalia and male sexual characteristics, we found that three variants, p.Q6X, p.N193S, and p.H90Y, were associated with severe undervirilization of external genitalia, and the other two, p.G203S and p.P251A, probably retained part of the enzyme activity.Conclusion: Mutation analysis of SRD5A2 gene is crucial for differential diagnosis in patients with 5α-reductase type 2 deficiency. Patients’ variable manifestations depend on the mutation type and residual enzyme activity. The novel variant p.P251A enlarges the spectrum of SRD5A2 mutations.Keywords: 5α-reductase type 2 deficiency, SRD5A2 gene mutation, androgen receptor insensitivity, disorders of sex development, differential diagnosis

Pomacea canaliculata is a pest species of freshwater neotropical gastropod that has colonized the coastal regions of southern China since the 1980s and has expanded its range into temperate regions of the Yangtze River Basin. The breeding and overwintering populations of P. canaliculata have increased during its gradual northward expansion over the past 40 years. There is a high likelihood that P. canaliculata can overwinter in areas conducive to breeding due to the impacts of a changing climate. Yet, the potential future changes in the range of P. canaliculata and associated climatic determinants remain unclear. This study examined the relationship between the limits of geographic distribution and key climate variables determining suitability for P. canaliculata breeding and wintering periods using the ensemble species distribution models from the R package BIOMOD2. Future climate suitability and changes were assessed under two representative concentration pathways (RCP 4.5 and RCP 8.5). The predictions indicated that P. canaliculata is most sensitive to monthly minimum temperature and that this species will extend its breeding range towards northern latitudes and will establish increased wintering locations in China. The predictions for both breeding and overwintering populations suggest a northward shift in the most suitable habitat, a reduction of highly suitable areas in the south, and an increase in suitable areas along the center and east of the Yangtze River Basin extending further northwards. Within the context of an overall expansion in P. canaliculata and climate warming, there should be a focus on the center of the Yangtze River Basin in which this species can overwinter for breeding only. Early monitoring and proactive measures to effectively prevent further spread of this species should be prioritized in this region characterized by abundant rice cultivation and fish breeding. [ABSTRACT FROM AUTHOR]

A fibre laser was used to weld Q345D/20Mn2 dissimilar steel with and without a Ni60 powder filler. Finite element (FE) simulation of the temperature and stress fields in the laser beam welding (LBW) was conducted COMSOL. Experimental investigation determined the effect of Ni-based powder filled welding on the microstructure, morphology, element content, microhardness and fracture morphology of the weld cross-section. The results show that when the laser power was 2700 W, the scanning speed was 1 mm/s and the out-of-focus amount was 0 mm, the tensile properties of Q345D/20Mn2 steel welds were optimal and deformation was minimal. Under such conditions the depth of the weld pool can reach 2.7 mm and the width 2.8 mm. After the Ni-based powder melts and penetrates the bottom of the base material (BM) along the weld seam, small cytosolic, equiaxed and columnar crystal grains can be observed near the fusion line, and the Ni-based filler powder can achieve a good metallurgical bond with the BM. The location of tensile fracture is at the weld and small tough nests can be observed in the cross-section leading to judgment that the fracture mode is ductile. [ABSTRACT FROM AUTHOR]

Through simulation based on the Workbench platform in ANSYS the optimal laser remelting process parameters were identified to achieve the maximum performance of a Ni60 coating laser clad onto a H13 steel surface. Laser remelting with a fibre laser was conducted according to the optimal process parameters obtained and the coating morphology, microstructure and microhardness after remelting were analysed. The results show that when the laser power was 1200 W and the scanning speed was 4 mm/s the remelted coating has the smallest residual stress value, pores in the coating were basically eliminated, the organization was dense, the hardness improved and the coating quality was the best. When the laser power was 900 W and the scanning speed was 2 mm/s the maximum residual stress value of the remelted coating was slightly smaller than that of the un-remelted coating, the coating morphology quality was better, and there were very few bubbles. [ABSTRACT FROM AUTHOR]

Feifei Yao,1 Jing Zhao,2 Yong Cui,3 Dandan Yu,4 Xiangyu Tang5 1Accreditation Department, Shekou People’s Hospital, Shenzhen City, Guangdong Province, 518067, People’s Republic of China; 2Department of Preventive Health, Daqing People’s Hospital, Daqing City, Heilongjiang Province, People’s Republic of China; 3Department of Oncology, Shekou People’s Hospital, Shenzhen City, Guangdong Province, 518067, People’s Republic of China; 4Jiangsu Center for Adverse Drug Reaction Monitoring, Nanjing, 210002, People’s Republic of China; 5Gastroenterology Department, Shekou People’s Hospital, Shenzhen City, Guangdong Province, 518067, People’s Republic of ChinaCorrespondence: Xiangyu TangGastroenterology Department, Shekou People’s Hospital, Shenzhen City, Guangdong Province, 518067, People’s Republic of ChinaEmail 347535969@qq.comPurpose: The role of sleep duration in the development of hypertension remains controversial. Little is known about the combined effects of nocturnal and daytime sleep. We assessed the association between total sleep duration and the development of hypertension in middle-aged and elderly Chinese adults.Patients and Methods: Data were obtained from 3 waves of China Health and Retirement Longitudinal Study surveys. Middle-aged and elderly Chinese initially without hypertension were followed biennially from 2011 to 2015. Sleep duration was self-reported. Hypertension was defined as a systolic and/or diastolic blood pressure ≥ 140/90 (mmHg), the current use of anti-hypertensive medications or self-reported hypertension.Results: Over 31,392 person-years of follow-up, 2682 of 10,176 participants developed hypertension. The multivariable adjusted hazard ratios (HR) (95% confidence intervals, 95% CI) for the development of hypertension between those with 0– 30 minutes and ≥ 30 minutes daytime sleep vs those without daytime sleep were 0.67 (0.58, 0.77), and 0.73 (0.59, 0.92), respectively. The protective role of longer periods of daytime sleep (> 30 minutes) varied between different subgroups. Compared with moderate nocturnal sleepers, long nocturnal sleepers (HR: 1.66, 95% CI=1.25– 2.21) had an increased risk of hypertension. Compared with moderate nocturnal sleepers without daytime sleep, HRs (95% CI) for hypertension were 0.52 (0.45, 0.59) for short nocturnal sleep plus short daytime sleep and 0.55 (0.49, 0.62) for short nocturnal sleep plus long daytime sleep. People with extremely short (HR: 1.34, 95% CI=1.22– 1.48) and long (HR: 1.28, 95% CI=1.13– 1.44) combined sleep periods had an increased risk of hypertension. Consistent results were also found in subgroups stratified by age and gender.Conclusion: Both extremely long and short total sleep periods were associated with an increased risk of hypertension. People with short or moderate nocturnal sleep durations, especially short nocturnal sleep duration, can benefit from habitual daytime sleep to prevent hypertension.Keywords: sleep duration, daytime sleep, hypertension, middle-aged and elderly

Xipei Wang,1,* Yifan Wang,2,3,* Fen Yao,2,3,* Shenglong Chen,2,* Yating Hou,4 Zhijie Zheng,1 Jinbiao Luo,5 Binghui Qiu,6 Zhanfu Li,7 Yirong Wang,2 Zheng Wu,2 Jinhua Lan,2 Chunbo Chen8,9 1Department of Medical Sciences, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangdong Cardiovascular Institute, Guangzhou, 510080, People’s Republic of China; 2Department of Critical Care Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong, People’s Republic of China; 3School of Biology and Biological Engineering, South China University of Technology, Guangzhou, Guangdong, 510080, People’s Republic of China; 4Department of Oncology, Maoming People’s Hospital, Maoming, 525000, Guangdong, People’s Republic of China; 5Department of Neurosurgery, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, People’s Republic of China; 6Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, People’s Republic of China; 7Department of Intensive Care Unit, Guangdong 999 Brain Hospital, Guangzhou, 510510, Guangdong, People’s Republic of China; 8Department of Intensive Care Unit of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Laboratory of South China Structural Heart Disease, Guangzhou, 510080, Guangdong, People’s Republic of China; 9The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510000, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunbo ChenDepartment of Intensive Care Unit of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Laboratory of South China Structural Heart Disease, 96 Dongchuan Road, Guangzhou, 510080, Guangdong, People’s Republic of ChinaEmail gghccm@163.comPurpose: The aim of this study is to use a population pharmacokinetic (PK) approach to evaluate the optimal dosing strategy for linezolid (LNZ) in critically ill patients.Methods: This multicenter, prospective, open-label, observational study was conducted in 152 patients, and 117 of them were included in the PK model, whereas the rest were in the validation group. The percentage of therapeutic target attainment (PTTA) comprising two pharmacodynamic indices and one toxicity index was used to evaluate dosing regimens based on Monte Carlo simulations stratified by low, normal, and high renal clearance for MICs of 0.25– 4 mg/L.Results: A single-compartment model with a covariate creatinine clearance (CrCL) was chosen as the final model. The PK parameter estimates were clearance of 5.60 L/h, with CrCL adjustment factor of 0.386, and a distribution volume of 43.4 L. For MIC ≤ 2 mg/L, the standard dosing regimen (600 mg q12h) for patients with severe renal impairment (CrCL, 40 mL/min) and standard dosing or 900 mg q12h for patients with normal renal functions (CrCL, 80 mL/min) could achieve PTTA ≥ 74%. The dose of 2400 mg per 24-h continuous infusion was ideal for augmented renal clearance (ARC) with MIC ≤ 1 mg/L. For MICs > 2 mg/L, rare optimal dose regimens were found regardless of renal function.Conclusion: In critically ill patients, the standard dose of 600 mg q12h was sufficient for MIC ≤ 2 mg/L in patients without ARC. Moreover, a 2400 mg/day 24-h continuous infusion was recommended for ARC patients.Keywords: critically ill patients, linezolid, population pharmacokinetic

Nitrous oxide (N2O) is a potent greenhouse gas and a strong ozone‐depleting substance. Ocean is an important natural source of atmospheric N2O, which has attracted increasing attention recently as to understand the biogeochemical cycles of nitrogen in marine systems. Nitrification is one of the major N2O production pathways during which N2O is produced as a side product and hydroxylamine (NH2OH) is produced as an obligate intermediate. However, few studies have reported the NH2OH variability in natural seawater and its relationship between N2O remains ambiguous. In summer 2022, spatial distribution and influencing factors of N2O and NH2OH in the northern South China Sea (SCS) were investigated. Dissolved N2O varied from 5.79 to 34.80 nmol L−1 in water column and generally increased with water depth above 800 m. N2O was correlated with dissolved oxygen and nitrate, inferring that N2O was mainly produced via nitrification. NH2OH varied from below detection limit to 3.91 nmol L−1. The adoption of multiple standard additions can largely reduce the bias in NH2OH measurement. Structural equation modeling showed that NH2OH has a potential effect favoring excessive N2O. Surface N2O saturation ranged between 102% and 278%, indicating that the northern SCS was a net source of atmospheric N2O in summer. Plain Language Summary: Hydroxylamine (NH2OH) is an important intermediate product and a precursor of N2O in nitrification, but debates persist regarding NH2OH variability and N2O production. We investigated the distribution, variation and regulatory mechanism of dissolved N2O and NH2OH in the northern SCS, analyzed their potential relationship during nitrification, and provided a new perspective for the greenhouse gas research in the future. We have also proved that a shift in recovery factor can cause large error and thus necessitate the introduction of multiple calibration curves in NH2OH measurement. We have found a weak but positive correlation between NH2OH and ∆N2O, indicating the potential contribution of NH2OH to N2O production during ammonia oxidation. Key Points: A shift in recovery factor from different depths necessitates the introduction of multiple calibration curves in NH2OH measurementA weak correlation between NH2OH and excessive N2O indicated the potential NH2OH oxidation to N2O production via nitrificationThe northern South China Sea (SCS) is a net source of atmospheric N2O [ABSTRACT FROM AUTHOR]

Droplet evaporation coupled with gravity and surface tension on a wall with the radial temperature gradients is numerically studied with the arbitrary Lagrangian-Eulerian method. The influence of the wall temperature distribution on the droplet evaporation process, which is less considered in the existing literature, is mainly discussed. The droplet temperature coefficient of the surface tension and the viscosity on the droplet profile evolution, flow, heat and mass transfer characteristic are also discussed. The results indicate that the droplets become flat first and then retract under the gravity and Marangoni convection during droplet evaporation. There are two high-velocity regions inside the evaporating droplet. One region is at the droplet axis, in which fluid flows to the wall from the droplet top. The other region is near the droplet surface, where fluid flows to the droplet top. There are turning points on the two sides of which the influence of wall temperature distribution on the ratio between the droplet height and the radius of the three-phase contact line (h/Rc), the velocity in the droplet and the surface temperature converts. All of them are larger before the turning point when the wall temperature slope is positive. After the turning point, these are reversed. For both h/Rc and average surface temperature, there is one turning point, which are t*=1.63×10-4 and t*=1.05×10-4, respectively. For maximum velocity and average velocity in droplet, there are two turning points, which are both t*=1.63×10-4 and t*=1.7×10-5. The droplet morphology changes more obviously when it is with a greater temperature coefficient of surface tension. Moreover, the turning point is delayed from t*=6.41×10-5 while a is 8 K/m to t*=7.91×10-5 while a is -8 K/m, which indicates that the negative wall temperature slope is beneficial to inhibit the Marangoni effect on droplet evaporation. [ABSTRACT FROM AUTHOR]

Yang Zhang,1 Fang Yao,1 Xiaohong Kuang,1 Lijuan Li,1 Lihua Huang,1 Qi Zhou,1 Jiazhu Peng,1 Qingyu Chang2 1Department of Nursing, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou 215600, People’s Republic of China; 2Department of Surgery, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou 215600, People’s Republic of ChinaCorrespondence: Xiaohong Kuang Email zjgszyyykxh@aliyun.comPurpose: To evaluate the quality of systematic reviews/meta-analyses (SR/MAs) on alternative exercise traditions in cancer care.Methods: PubMed, Cochrane Library, Web of Science, Ovid, EBSCOhost, WanFang Database, China National Knowledge Infrastructure, and VIP Database were searched from their inception to June 30, 2020. The search used a combination of subject words and free words. The search terms included “Tai Chi,” “Qigong,” “Baduanjin,” “Yoga,” “Pilates,” “Cancer,” “Meta-analysis,” and “Systematic review.” Two researchers independently performed literature screening and data extraction and used AMSTAR scale and PRISMA statement to evaluate the methodology and the quality of the evidence.Results: A total of 26 SR/MAs were included. The AMSTAR scale score was 5– 10 points, with an average of 7.46± 1.33 points. Overall, the methodological quality was considered to be moderate. The PRISMA list score was 13– 24 points, with an average of 19.19± 2.86 points. Among the papers evaluated, eight reports were relatively complete. A total of 15 papers indicated certain defects. A total of three papers showed relatively serious information defects.Conclusion: Relative to the control group, alternative exercise traditions may be effective in improving the quality of life, anxiety, depression, distress, and fatigue of cancer patients. However, they may not necessarily improve patients’ sleep outcome, body mass index, and pain. During convalescence, cancer patients can be encouraged to start engaging in physical exercise, and professionals can develop appropriate exercise alternatives to ensure the expected effect of exercise while ensuring the safety of patients. The methodological quality of the systematic evaluations of the intervention effects of alternative exercise traditions on cancer patients is not satisfactory. Hence, focus should be directed to the improvement of the preliminary design scheme, publication status, literature retrieval, conflict of interest, and other aspects.Keywgords: alternative exercise traditions, cancer care, COVID-19, overview

Yueting Tang,1 Yirong Li,1 Jiayu Sun,2 Huaqin Pan,3 Fen Yao,2 Xiaoyang Jiao2 1Department of Clinical Laboratory, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China; 3Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of ChinaCorrespondence: Xiaoyang JiaoShantou University Medical College, Shantou, Guangdong, People’s Republic of ChinaTel +86-754-88900459Fax +86-754-88557562Email xyjiao@stu.edu.cnPurpose: It is difficult to predict the prognosis of COVID-19 patients at the disease onset. This study was designed to add new biomarkers into conventional inflammatory panels to build an optimal combination panel, to better triage patients and predict their outcomes.Patients and Methods: Biochemical parameters representing multi-organ functions, cytokines, acute-phase proteins, and other inflammatory markers were measured in COVID-19 patients on hospital admission. Receiver operating characteristic (ROC) curves, logistic regression, event-free survival (EFS), and Cox analyses were performed to screen and compare the predictive capabilities of the new panel in patients with different illness severity and outcome.Results: This study included 120 patients with COVID-19, consisting of 32 critical, 28 severe, and 60 mild/moderate patients. Initial levels of the selected biomarkers showed a significant difference in the three groups, all of which influenced patient outcome and EFS to varying degrees. Cox proportional hazard model revealed that procalcitonin (PCT) and interleukin 10 (IL-10) were independent risk factors, while superoxide dismutase (SOD) was an independent protective factor influencing EFS. In discriminating the critical and mild patients, a panel combining PCT, IL-6, and neutrophil (NEUT) yielded the best diagnostic performance with an AUC of 0.99, the sensitivity of 90.60% and specificity of 100%. In distinguishing between severe and mild patients, SOD’s AUC of 0.89 was higher than any other single biomarker. In differentiating the critical and severe patients, the combination of white blood cell count (WBC), PCT, IL-6, IL-10, and SOD achieved the highest AUC of 0.95 with a sensitivity of 75.00% and specificity of 100%.Conclusion: The optimal combination panel has a substantial potential to better triage COVID-19 patients on admission. Better triage of patients will benefit the rational use of medical resources.Keywords: COVID-19, diagnostic panel, cytokine, acute-phase protein

Fengjiao Yao, Yacong An, Xundou Li, Zhaoyi Li, Jinhong Duan, Xian-Da Yang Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Xian-Da Yang Email ayangmd@hotmail.comPurpose: Chemotherapy is the primary treatment for advanced colon cancer, but its efficacy is often limited by severe toxicities. Targeted therapy in the form of selectively drug delivery system (SDDS) is an important strategy to reduce adverse effects. Here, we aim to design a novel SDDS with potential for practical application using biocompatible components and scalable production process, for targeted delivery of doxorubicin (Dox) to colon cancer cells.Methods: The SDDS was made of a self-assembled DNA nano-cross (Holliday junction, or HJ) functionalized by four AS1411 aptamers (Apt-HJ) and loaded with Dox.Results: Apt-HJ had an average size of 12.45 nm and a zeta potential of − 11.6 mV. Compared with the monovalent AS1411 aptamer, the quadrivalent Apt-HJ showed stronger binding to target cancer cells (CT26). A complex of Apt-HJ and doxorubicin (Apt-HJ-Dox) was formed by intercalating Dox into the DNA structure of Apt-HJ, with each complex carrying approximately 17 Dox molecules. Confocal microscopy revealed that Apt-HJ-Dox selectively delivered Dox into CT26 colon cancer cells but not the control cells. Moreover, Apt-HJ-Dox achieved targeted killing of CT26 cancer cells in vitro and reduced the damage to control cells. Importantly, compared with free Dox, Apt-HJ-Dox significantly enhanced the antitumor efficacy in vivo without boosting the adverse effects.Conclusion: These results suggest that Apt-HJ-Dox has application potential in targeted treatment of colon cancer.Keywords: colon cancer, targeted therapy, aptamer, holliday junction, doxorubicin

Qiwen Wang,1,2,* Bingyu Ye,1,2,* Ping Wang,1,2 Fenjie Yao,1,2 Chunyan Zhang,1,2 Guoying Yu1,2 1Henan International Joint Laboratory of Pulmonary Fibrosis, College of Life Science, Henan Normal University, Xinxiang 453007, Henan, People’s Republic of China; 2State Key Laboratory Cell Differentiation and Regulation, College of Life Science, Henan Normal University, Xinxiang 453007, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunyan Zhang; Guoying YuCollege of Life Science, Henan Normal University, 46# East of Construction Road, Xinxiang, Henan 453007, People’s Republic of ChinaTel +86 373 3325654; +86 373 3326001Fax +86 373 3326524Email zcy1119sdc@163.com; guoyingyu@htu.edu.cnAbstract: microRNAs (miRNAs) are a class of endogenous short, non-coding RNAs that regulate a multitude of genes at the post-transcriptional level. miR-199, which is a highly conserved miRNA family, consists of miR-199a and miR-199b. Researchers mainly focused on miR-199a over the past few years. Functional studies have demonstrated that mature miR-199a is a key player in the maintenance of normal homeostasis and in the regulation of disease pathogenesis. Here, we summarize the biological functions of miR-199a and review recent research on its roles in the physiological processes of cancer cells, such as proliferation, migration, invasion, apoptosis, autophagy and glycometabolism.Keywords: microRNA-199a, target genes, carcinoma, biomarker, regulatory mechanisms

Fei Yao,1 Qiang Wang,1 Qingming Wu1,21Department of Public Health and Preventive Medicine, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, People’s Republic of China; 2Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology, Wuhan 430065, People’s Republic of ChinaAbstract: Long noncoding RNAs (lncRNAs), longer than 200 nucleotides in length, play important roles in the development and progression of various cancers. An increasing number of studies have revealed that lncRNAs function as potential oncogenes or tumor suppressors to influence biological processes, such as cell growth, invasion, migration and apoptosis. Urothelial carcinoma associated 1 (UCA1), an oncogenic lncRNA, was first found in bladder cancer and highly expressed in multiple cancers, including gastric cancer, colorectal cancer, lung cancer and breast cancer. UCA1 promotes tumorigenesis mainly via binding to tumor-suppressive microRNAs (miRNAs), activating several pivotal signaling pathways and alteration of epigenetic and transcriptional regulation. In addition, high expression of UCA1 is related to poor clinicopathological features especially for shorter overall survival, suggesting that UCA1 might be regarded as a prognosis biomarker in human cancers. In the present review, we summarized current studies on UCA1 to explore its prognostic value and underlying regulation mechanisms in the development of multiple cancers in order to provide a glimmer of hope for the prevention and treatment of malignant tumors.Keywords: UCA1, lncRNA, cancer, prognostic, mechanism

Dangui Chen,1 Yang Zhan,1 Jun Peng,2 Fusheng Yao11Department of Hematology, Anqing Municipal Hospital, Anqing Hospital Affiliated to Anhui Medical University, Anqing, People’s Republic of China; 2Department of Pathology, Anqing Municipal Hospital, Anqing Hospital Affiliated to Anhui Medical University, Anqing, People’s Republic of ChinaAbstract: Richter’s syndrome, the development of high-grade non-Hodgkin lymphoma in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), may be triggered by viral infections (eg, Epstein–Barr virus infection). Herein, we report an unusual case of CD5-negative CLL/SLL patient with gastrointestinal mantle cell lymphoma (MCL) and hepatitis B virus infection. CLL/SLL was diagnosed based on lymph node immunohistochemistry and bone marrow pathology. This patient was treated with seven cycles of multi-agent chemotherapy. During treatment, the hepatitis B viruses were activated. Then, after 20 months of antiviral treatment with entecavir, he developed abdominal discomfort and abdominal lymphadenopathy and was diagnosed with MCL based on intestinal biopsy. This work indicates that the hepatitis B virus in patients with CLL/SLL may accelerate the progress or transformation to MCL.Keywords: Richter’s syndrome, chronic lymphocytic leukemia/small lymphocytic lymphoma, mantle cell lymphoma, hepatitis B virus infection

OBJECTIVE: A meta-analysis (MA) was carried out to examine the influence of metformin on autosomal dominant polycystic kidney disease (ADPKD) patient prognosis. MATERIALS AND METHODS: We reviewed and examined scientific articles from PubMed, Clinicalkey, Google Scholar, Medline, Embase, and Cochrane from the initiation date till June 2023 to identify investigations that examined metformin performance in managing ADPKD. Among the employed search terminology, we searched for terms such as “metformin” and “ADPKD”. MA was conducted using the Cochrane Collaboration’s RevMan version 5.3.0 (The Cochrane Collaboration, Oxford, UK). RESULTS: We identified 4 investigations, with 164 total subjects who fulfilled our inclusion criteria. The experimental cohort displayed a marked reduction in the decline of estimated glomerular filtration rate (eGFR) relative to controls [mean difference (MD) = 2.31, 95% confidence interval (CI) = 0.82-3.79, p = 0.002]. We observed no obvious difference in the height-adjusted total kidney volume alteration, gastrointestinal side effects, and hypoglycemia between the two cohorts. CONCLUSIONS: Metformin was easily tolerable and safe and substantially reduced the eGFR decline among ADPKD patients. Moreover, although metformin-treated patients were more likely to suffer gastrointestinal adverse events, we observed no discernible difference between the two cohorts. [ABSTRACT FROM AUTHOR]

Liwen Fan,1 Haitang Yang,1,2 Feng Yao,1 Yang Zhao,1 Haiyong Gu,1 Ke Han,1 Heng Zhao1 1Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Division of General Thoracic Surgery, Inselspital University Hospital Bern, Bern, Switzerland Purpose: The therapeutic efficacy of targeted therapy for adenosquamous carcinoma (ASC) of the lung remains unclear and the role of epidermal growth factor receptor (EGFR) testing in patients with ASC also remains controversial. We aimed to analyze the efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs) in ASC. Methods: Clinical records of patients with ASC who received treatment with EGFR-TKIs between January 2006 and December 2014 at two institutions were retrospectively reviewed. Results: A total of 27 EGFR mutation-positive patients with ASC who received TKI therapy were enrolled in this study. EGFR mutations included a deletion in exon 19 in 15 cases and a point mutation at codon 858 (L858R) in exon 21 in 12 cases. Among the 27 ASC patients who received treatment with EGFR-TKIs, nine had a partial response and 11 achieved stable disease, accounting for a disease control rate of 74.1% (20/27). The median postoperative overall survival (OS) of the EGFR-mutant patients who received TKI therapy was 39 months (95% confidence interval [CI]: 25.6–52.4). The median progression-free survival for EGFR mutation-positive patients was 15 months (95% CI: 12.9–17.1), and the median relapse OS was 19 months (95% CI: 0.9–37.1). In addition, the 3- and 5-year postoperative survival rate was 51.9% and 15.3%, respectively. Conclusion: ASC patients harboring EGFR mutations had a good response to TKI therapy. Routine EGFR testing for ASCs was recommended. Further studies on TKI therapy versus chemotherapy alone for EGFR-mutant ASCs are required. Keywords: adenosquamous carcinoma of the lung, epidermal growth factor receptor tyrosine kinase inhibitors, mutation, survival

Heng Zhao,1,* Haitang Yang,2–4,* Ke Han,5,* Jianlin Xu,6 Feng Yao,5 Yang Zhao,5 Liwen Fan,5 Haiyong Gu,5 Zhenya Shen1,* 1Department of Cardiovascular Surgery of First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Division of General Thoracic Surgery, Inselspital, Bern University Hospital, 3Graduate School for Cellular and Biomedical Sciences, 4Department of Clinical Research, University of Bern, Bern, Switzerland; 5Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 6Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: The incidence of adenocarcinomas as multiple primary lung cancers (MPLCs) is increasing. How to determine the treatment strategies of MPLCs, especially second primary lung adenocarcinomas (SPLACs), and the prognostic factors associated with it are unclear.Methods: The clinical records of patients undergoing surgery for second adenocarcinomas based on Martini–Melamed criteria between 2001 and 2014 were retrospectively reviewed. Survival rates were calculated by the Kaplan–Meier method and compared using the log-rank test. Multivariate analysis was conducted using the Cox proportional hazards model.Results: A total of 115 patients with SPLACs were identified based on Martini–Melamed criteria. With respect to the second resections, three subgroups with low- (adenocarcinoma in situ, n=6; minimally invasive adenocarcinoma, n=19), intermediate- (lepidic, n=9; acinar, n=40; papillary, n=23), and high-grades (solid, n=9; micropapillary, n=2; invasive mucinous, n=7) were assigned. The 5-year overall survival (OS) rates from the time of the first and the second resections were 86.5% and 69.5%, respectively. Cox multivariate analysis identified computed tomography (CT) morphology of SPLACs (ground glass opacity predominant versus solid predominant; hazard ratio [HR]=0.42; P=0.036), histologic classification (same/similar vs different; HR=0.06; P

A Ni60/WC gradient composite coating was prepared on the surface of H13 steel by the laser cladding in situ generation method using a fibre laser. The phase composition, microstructure, microhardness and wear mechanism of the laser clad Ni60/WC gradient composite coating were analysed to reveal that it possessed few pores and cracks, the delamination phenomenon was obvious, the enhancement phase was small and uniformly distributed, and it formed a good metallurgical bond with the H13 steel substrate. In the laser clad Ni60/WC gradient composite coating the branch reinforcing phases are mainly WC, W2C, WSi2 phases, and a small amount of Cr7C3, FexC and other compounds, and the interbranch structures are mainly A-[Fe,Ni] solid solution and Cr7C3, FexC and other compounds. The Ni60+40% (W+C) and Ni60+20% (W+C) layers gradually decrease in number and size from top to bottom, while the shape gradually changes from irregular tetragonal to petal-shaped. The microhardness of the laser clad Ni60/WC gradient composite coating shows a gradient downward trend from top to bottom, and the maximum hardness can reach 1083.7 HV0.5 and the average hardness was 4.18 times that of the H13 steel substrate. The wear amount of the laser clad Ni60/WC gradient composite coating is 20.3% of the H13 steel substrate. The wear mechanism is mainly adhesive wear, brittle spalling and abrasive wear, which can prolong the service life of the mould and reduce the waste of resources. [ABSTRACT FROM AUTHOR]

WC-enhanced Ni-based coatings were prepared in situ on a H13 steel substrate by laser cladding with a fibre laser. The influence law of the central temperature per unit mass of powder, acting on the morphology, microstructure, microhardness and friction wear properties of the coating was investigated. The results show that the metallurgical bonding between the WC--enhanced Ni-based coating and base metal (BM) was good. The dilution rate of the clad layer increases with the increase of. WC, Cr3C2 reinforcing phases, FeNi3 solid solution, FeC carburized body, Fe3W3C interstitial compound are mainly present in the coating at different values of The microstructure gradually changes from dendritic and cellular to irregular aggregation with increasing. The microhardness of the coating increases first and then decreases with the increase of. The microhardness of the coating is the highest when 1=16483 K/g. A value of a=16483 K/g gave the best wear performance. The wear mechanism of the WC-enhanced Ni-based coating is mainly adhesive wear, brittle spalling and abrasive wear. [ABSTRACT FROM AUTHOR]

Chunyang Du,1,2,* Yonghong Shi,1,2,* Yunzhuo Ren,1,2 Haijiang Wu,1,2 Fang Yao,1,2 Jinying Wei,1,2 Ming Wu,1,2 Yanjuan Hou,1,2 Huijun Duan1,2 1Department of Pathology, Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Hebei Key Laboratory of Kidney Diseases, Shijiazhuang, People’s Republic of China *These authors contributed equally to this work Abstract: The dysregulation of cholesterol metabolism and inflammation plays a significant role in the progression of diabetic nephropathy (DN). Anthocyanins are polyphenols widely distributed in food and exert various biological effects including antioxidative, anti-inflammatory, and antihyperlipidemic effects. However, it remains unclear whether anthocyanins are associated with DN, and the mechanisms involved in the reciprocal regulation of inflammation and cholesterol efflux are yet to be elucidated. In this study, we evaluated the regulation of cholesterol metabolism and the anti-inflammatory effects exerted by anthocyanins (cyanidin-3-O-β-glucoside chloride [C3G] or cyanidin chloride [Cy]) and investigated the underlying molecular mechanism of action using high-glucose (HG)-stimulated HK-2 cells. We found that anthocyanins enhanced cholesterol efflux and ABCA1 expression markedly in HK-2 cells. In addition, they increased peroxisome proliferator-activated receptor alpha (PPARα) and liver X receptor alpha (LXRα) expression and decreased the HG-induced expression of the proinflammatory cytokines intercellular adhesion molecule-1 (ICAM1), monocyte chemoattractant protein-1 (MCP1), and transforming growth factor-β1 (TGFβ1), as well as NFκB activation. Incubation with the PPARα-specific inhibitor GW6471 and LXRα shRNA attenuated the anthocyanin-mediated promotion of ABCA1 expression and cholesterol efflux, suggesting that anthocyanins activated PPARα-LXRα-ABCA1-dependent cholesterol efflux in HK-2 cells. Moreover, the knockout of LXRα abrogated the anti-inflammatory effect of anthocyanins, whereas the PPARα antagonist GW6471 does not have this effect. Further investigations revealed that LXRα might interfere with anthocyanin-induced decreased ICAM1, MCP1, and TGFβ1 expression by reducing the nuclear translocation of NFκB. Collectively, these findings suggest that blocking cholesterol deposition and inhibiting the LXRα pathway-induced inflammatory response might be one of the main mechanisms by which anthocyanins exert their protective effects in DN. Keywords: 3-O-β-glucoside chloride, cyanidin chloride, diabetic nephropathy, inflammation, liver X receptor alpha

Chuang Chen,1 Jing-Ping Yuan,2,3 Wen Wei,1 Yi Tu,1 Feng Yao,1 Xue-Qin Yang,4 Jin-Zhong Sun,1 Sheng-Rong Sun,1 Yan Li2 1Department of Breast and Thyroid Surgery, Wuhan University, Renmin Hospital, Wuhan, 2Department of Oncology, Zhongnan Hospital of Wuhan University and Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, Wuhan, 3Department of Pathology, The Central Hospital of Wuhan, Wuhan, 4Medical School of Jingchu University of Technology, Jingmen, People’s Republic of China Background: Hormone receptors, including the estrogen receptor and progesterone receptor, human epidermal growth factor receptor 2 (HER2), and other biomarkers like Ki67, epidermal growth factor receptor (EGFR, also known as HER1), the androgen receptor, and p53, are key molecules in breast cancer. This study evaluated the relationship between HER2 and hormone receptors and explored the additional prognostic value of Ki67, EGFR, the androgen receptor, and p53. Methods: Quantitative determination of HER2 and EGFR was performed in 240 invasive breast cancer tissue microarray specimens using quantum dot (QD)-based nanotechnology. We identified two subtypes of HER2, ie, high total HER2 load (HTH2) and low total HER2 load (LTH2), and three subtypes of hormone receptor, ie, high hormone receptor (HHR), low hormone receptor (LHR), and no hormone receptor (NHR). Therefore, breast cancer patients could be divided into five subtypes according to HER2 and hormone receptor status. Ki67, p53, and the androgen receptor were determined by traditional immunohistochemistry techniques. The relationship between hormone receptors and HER2 was investigated and the additional value of Ki67, EGFR, the androgen receptor, and p53 for prediction of 5-year disease-free survival was assessed. Results: In all patients, quantitative determination showed a statistically significant (P0.05) between the five subtypes. EGFR and Ki67 had prognostic significance for 5-year disease-free survival in univariate analysis, but the androgen receptor and p53 did not. Multivariate analysis identified that EGFR expression had predictive significance for 5-year disease-free survival in hormone-receptor positive patients and in those with the lymph node-positive breast cancer subtype. Conclusion: Hormone receptor expression was indeed one of the molecular profiles in the subtypes identified by quantitative HER2 and vice versa. EGFR status may provide discriminative prognostic information in addition to HER2 and hormone receptor status, and should be integrated into routine practice to help formulate more specific prediction of the prognosis and appropriate individualized treatment. Keywords: quantum dots, breast cancer, molecular classification, prognosis, prediction