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Hongwei Huang,1 Jiacheng Mo,2 Gui Jiang,2 Zheng Lu1 1Intensive Care Unit, Guangxi Hospital Division of the First Affiliated Hospital, Sun Yat-Sen University, Nanning, Guangxi, 530022, People’s Republic of China; 2Intensive care unit, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of ChinaCorrespondence: Zheng Lu, Intensive Care Unit, Guangxi Hospital Division of the First Affiliated Hospital, Sun Yat-sen University, Nanning, Guangxi, 530022, People’s Republic of China, Email iculuzheng@163.comPurpose: To evaluate the long-term efficacy and cost-efficiency of blood purification (BP) in severe acute pancreatitis (SAP) through single-center data.Patients and Methods: A total of 155 SAP patients were collected and followed up for 6 months. The participants were divided into control (49 cases) and BP group (106 cases) according to whether they received BP treatment or not. The primary outcomes were 6-month mortality, length of hospital stay, and hospitalization costs. Propensity score matching (PSM) analysis was performed based on various factors such as gender, age, etiology, SOFA score, JSS score, and creatinine value on day 1.Results: There were significant differences in all baseline data between BP and control groups (p< 0.05). However, there was a significant difference in the mortality, length of hospital stay, hospital costs and infection aggravation rate the in outcome data for 6-months (all p< 0.05). BP was not considered a death factor in any adjusted models, with p-values ranging from 0.81 to 0.93. The results of subgroup analysis after PSM showed that BP mode had no significant impact on prognostic indicators, but the length of ICU stay and total costs were significantly increased (all p< 0.001). There was no significant difference in mortality among the cases that did not require early intervention after 6 months (p=0.487). However, the patients in BP group had longer ICU stays (p=0.001) and higher hospitalization costs (p< 0.001) compared to the control group.Conclusion: The utilization of BP therapy did not decrease the 6-month mortality in SAP patients. Additionally, BP therapy has a significant impact on the duration of ICU stay or hospitalization expenses. However, the effectiveness and cost-efficiency of this therapy are unsatisfactory, and early intervention does not enhance survival benefits. Furthermore, there was no substantial variation in survival benefits between continuous veno-venous hemofiltration (CVVH) alone and compound BP.Keywords: severe acute pancreatitis, blood purification, long-term efficacy, cost-efficiency

Yueying Niu,1 Mengqing Cao,1 Shumin Li,1 Juanfen Mo,2 Ziyi Zhu,1 Haiqin Wang1 1Department of Respiratory Medicine, The Second Hospital of Jiaxing, Jiaxing, Zhejiang, People’s Republic of China; 2The Key Laboratory, The Second Hospital of Jiaxing, Jiaxing, Zhejiang, People’s Republic of ChinaCorrespondence: Haiqin Wang; Ziyi Zhu, Department of Respiratory Medicine, The Second Hospital of Jiaxing, 1518 Huanchen North Road, Jiaxing, Zhejiang, 314000, People’s Republic of China, Email w_haiqin@163.com; zhuziyi1986@163.comObjective: To retrospectively study the effects of budesonide inhalation combined with conventional symptomatic treatment on serum inflammatory factor expression levels and pulmonary function in patients with cough variant asthma (CVA) and to evaluate treatment efficacy.Methods: This retrospective cohort study included 200 patients diagnosed with CVA at the Second Hospital of Jiaxing between January 2022 and June 2023 and given conventional symptomatic treatment plus budesonide inhalation were included in this study. Patients were divided into a no remission group, a partial remission group and a complete remission group based on treatment effect. The expression levels of serum inflammatory factors, cough symptom scores, and small airway function indicators in the three groups of patients at different time points were compared.Results: In the three groups of CVA patients, after receiving budesonide inhalation combined with conventional symptomatic treatment, the expression levels of serum IL-5, IL-6, IL-8, TNF-α, TGF-β 1, and IgE and number of eosinophils significantly decreased (P < 0.05). There were statistically significant differences in the IL-6 and TGF-β 1 levels among the three groups of CVA patients at T1, T2 and T3. There were statistically significant differences in IgE levels, number of eosinophils, cough symptom scores, and small airway function indicators between T2 and T3 (P< 0.05). The receiver operating characteristic (ROC) curve prediction analysis revealed significant differences in the expression of IL-6 and TGF-β 1 at T1, T2, and T3.Conclusion: Budesonide inhalation combined with conventional symptomatic treatment can significantly reduce the levels of serum inflammatory factors in patients with CVA to reduce inflammation and the allergic response, thereby reducing the cough symptom score, improving pulmonary function, and improving therapeutic efficacy. In addition, IL-6 and TGF-β 1 can be used as early predictors of budesonide inhalation efficacy.Keywords: budesonide, cough variant asthma, cytokines, IL-6, TGF-β 1

Xiuxian Huang,1,&ast; Zhengming Li,1,&ast; Zhenwei Zhai,1,&ast; Qiu Wang,1 Rongyan Wei,1 Jiacheng Mo,2 Jianhao Huang,1 Wensheng Lu1,&ast; 1Department of Endocrinology and Metabolism of Guangxi Academy of Medical Sciences, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China; 2Information Network Center of Guangxi Academy of Medical Sciences, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wensheng Lu, Email lwswxqz@163.comAim: Metabolic dysfunction-related fatty liver disease (MAFLD) is closely related to metabolic disorders. However, the relationship between MAFLD and the prognosis in diabetic foot ulcers (DFUs) remains unclear. This study aimed to explore the association between MAFLD and the risk of major adverse cardiac and cerebral events (MACCEs) in patients with DFUs.Methods: 889 inpatients with DFUs (PEDIS/TEXAS mild and above) were included in this study from 2013 to 2023. All participants were placed into non-MAFLD (n = 643) and MAFLD (n = 246) groups and followed up every 6 months for 10.9 years with a median of 63 months through in-person outpatient interviews and family fixed-line telephone visits. The association between MAFLD and the risk of MACCEs was evaluated through Multivariate Cox regression analyses, Stratified analyses and Kaplan-Meier survival analyses.Results: Of the 889 subjects, 214 (24.07%) experienced MACCEs. Multivariate Cox regression analysis showed that MAFLD was independently associated with MACCEs (P < 0.001), of which with non-fatal myocardial infarction (P = 0.04), non-fatal stroke (P = 0.047), coronary artery revascularization (P = 0.002), heart failure (P = 0.029), and all-cause mortality (P = 0.021), respectively. The stratified analysis revealed that compared with non-MAFLD (HR=1), DFUs with MAFLD had a 2.64-fold increased risk for MACCEs (P < 0.001; P for interaction = 0.001) in peripheral arterial disease (PAD) subgroup. Kaplan-Meier analysis evidenced that the MAFLD group had a higher cumulative incidence of MACCEs (log-rank, all P < 0.05).Conclusion: MAFLD is a high-risk factor for MACCEs in patients with DFUs. The findings will remind clinicians to pay more attention to MAFLD in patients with DFUs, especially in patients with DFUs combined with PAD as early as possible in clinical practice and adopt timely effective intervention strategies to prevent the occurrence of MACCEs to improve the clinical prognosis in patients with DFUs.Keywords: diabetic foot ulcers, peripheral arterial disease, metabolic dysfunction-associated fatty liver disease, major adverse cardiac and cerebral events

Jiangmei Pan,1,2,&ast; Xiuxian Huang,1,&ast; Qiu Wang,1,&ast; Jingxia Sun,1,&ast; Zhenwei Zhai,1,&ast; Jiacheng Mo,3 Jianhao Huang,1 Wensheng Lu1 1Department of Endocrinology and Metabolism, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China; 2Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, People’s Republic of China; 3Information Network Center of Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wensheng Lu, Email Lwswxqz@163.comPurpose: The triglyceride glucose (TyG) index serves as an indicator of insulin resistance (IR), which is also associated with bone metabolism. However, research on the relationship between the TyG index and a fragility fracture in individuals with type 2 diabetes mellitus (T2DM) or osteoporosis (OP) remains sparse. This study aims to explore the association between the TyG index and fragility fracture risk in postmenopausal elderly females with T2DM combined with OP based on an ambispective cohort study.Patients and Methods: A total of 220 postmenopausal women hospitalized with T2DM combined with OP between January 2015 and December 2020 were eligible for inclusion in this study. All participants were followed up every 6 months for 6 years with a median of 42 months. According to the tertiles of the TyG index, participants were divided into three groups: low-level (≤ 8.79, n =73), moderate-level (8.80– 9.32, n=73), and high-level (≥ 9.33, n=74). The association between the TyG index and fragility fracture risk was then assessed.Results: Out of 220 patients, 46 experienced fragility fracture events (20.9%). Multivariate Cox regression analysis showed that the TyG index was positively associated with a fragility fracture in postmenopausal women with T2DM combined with OP. Furthermore, compared to the low-level group, with the TyG index level increase by 1.0, the risk for fragility fracture increased 1.293-fold in the high-level group (HR=2.293, 95% CI=1.007– 5.221, P < 0.05). Kaplan-Meier survival analysis indicated that fragility fractures were more likely to occur in patients with high levels of TyG index (log-rank, all P < 0.05).Conclusion: Our study showed that the TyG index was strongly associated with a fragility fracture in postmenopausal women with T2DM combined with OP. Therefore, special attention should be paid to postmenopausal elderly females with T2DM combined with OP in routine clinical practice.Keywords: type 2 diabetes mellitus, osteoporosis, triglyceride glucose index, fragility fracture

Xiuxian Huang,1,&ast; Licai Deng,1,&ast; Jianhao Huang,1,&ast; Jingxia Sun,1 Qiu Wang,1 Jiacheng Mo,2 Zhenwei Zhai,1 Yuechou Nong,1 Wensheng Lu1,&ast; 1Department of Endocrinology and Metabolism, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China; 2Information Network Center of Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wensheng Lu, Email Lws2613676@sohu.comAim: To clarify the relationship between serum uric acid (UA) and glycosylated hemoglobin (UA/HbA1c) ratio and all-cause mortality in patients with diabetic foot ulcers (DFUs).Methods: A total of 172 inpatients with DFUs (PEDIS grades 2– 4) were eligible for inclusion in this study from 2018 to 2023. This was a retrospective, longitudinal cohort study. All subjects were followed up every 6 months for a median of 60 months. According to the cutoff value of the UA/HbA1c ratio of 39.07 obtained from ROC analysis, the participants were divided into two groups: low-level (≤ 39.07, n = 107) and high-level (> 39.07, n = 65) groups. The correlation between UA/HbA1c ratio and all-cause mortality was also evaluated by Cox regression analysis TheKaplan-Meier survival curve analysis and Log rank tests were used to assess the incidence rates of all-cause mortality. The contribution rate of risk factors was estimated by the population-attributable risk percentage (PAR%) analysis.Results: ROC analysis showed that the optimal cutoff values for UA and the UA/HbA1c ratio were 372 μmol/L and 39.07, respectively. Multivariate Cox regression analysis indicated that a high UA/HbA1c ratio (HR =4.63; 95% CI = 2.004– 10.7, P < 0.001) was independently associated with a high risk of all-cause mortality in patients with DFUs. Stratified analysis indicated that subjects aged ≥ 60 years had a greater risk of all-cause mortality associated with a high UA/HbA1c ratio (HR = 4.450; 95% CI = 1.711– 11.574, P = 0.002). Kaplan-Meier survival analysis showed that all-cause mortality had a significant positive association with a high UA/HbA1c ratio (log-rank, P < 0.001) and a significant negative correlation with the lowered HbA1c level (< 6.5%) after a follow-up of 32 months (log-rank, P < 0.001). The population attributable risk percentage (PAR%) analysis suggested that the contribution rate of the high-level UA/HbA1c ratio to all-cause mortality was 33.7%, which was much greater than the 19.69% of UA.Conclusion: In brief, our study showed that for every 1.0% increase in the UA/HbA1c ratio, the all-cause mortality rate in elderly patients with DFUs aged ≥ 60 years increased by 3.45-fold. For elderly patients with DFUs, a safe and effective strategy to reduce all-cause mortality is to strictly control serum UA levels to < 372 μmol/L and appropriately loosen the control goal of HbA1c to ≥ 6.5%.Keywords: diabetic foot ulcer, uric acid to glycosylated hemoglobin ratio, all-cause mortality

Jianhao Huang,1,2,&ast; Jingxia Sun,2,&ast; Qiu Wang,2,&ast; Jianming Mo,2,&ast; Yuechou Nong,2 Zhenwei Zhai,2 Xiuxian Huang,2 Jiacheng Mo,3 Wensheng Lu2 1The Department of Endocrinology and Metabolism, Jinan University, Guangzhou, Guangdong, 510632, People’s Republic of China; 2The Department of Endocrinology and Metabolism, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China; 3Information Network Center of Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wensheng Lu, Email Lwswxqz@163.comAim: To explore the therapeutic efficacy of autologous wound edge-dotted full-thickness skin grafting in improving diabetic foot ulcer healing.Methods: Sixty-three patients were divided into three groups: conventional wound therapy (CWT) (n = 23), platelet-rich plasma (PRP) (n = 20), and graft (n = 20). All participants were followed up for 12 weeks. The therapeutic efficacy of the three different wound treatment modalities was analyzed.Results: After follow-up, 37 (58.7%) patients showed complete wound re-epithelialization, of which 10 (43.5%) occurred in the CWT group, 14 (70.0%) in the PRP group, and 13 (65.0%) in the graft group. Multivariate Cox analysis showed that the independent predictive factors for ulcer healing were different treatment modalities (graft: HR = 3.214, 95% CI=1.300– 7.945, P < 0.05; platelet-rich plasma: HR = 3.075, 95% CI=1.320– 7.161, P < 0.01), ABI (HR = 9.917, 95% CI=2.675– 36.760, P < 0.01), and TcPO2 (HR = 1.040; 95% CI=1.005– 1.076; P < 0.05). Stratified analysis showed that higher ABI in graft group or PRP group had higher wound healing rate (graft group: HR = 3.748, 95% CI=1.210– 11.607, P < 0.05; PRP group: HR = 5.029, 95% CI=1.743– 14.509, P < 0.05); higher TcPO2 in the graft group had higher wound healing rate (HR = 15.805, 95% CI=4.414– 56.594, P < 0.01). Additionally, the wound healing time (P < 0.0167) and cumulative healing rate (P < 0.05) in both the PRP group and graft group were more advantageous. The graft group promotes wound re-epithelialization earlier and faster than in the CWT group and PRP group (P < 0.05). Meanwhile, the graft group had lower medical costs (P < 0.0167).Conclusion: Autologous wound edge dotted full-thickness skin grafting has a higher cost-performance ratio than traditional diabetic foot ulcer wound care and is worthy of further clinical application.Keywords: diabetic foot ulcers, autologous wound edge dotted full-thickness skin graft, platelet-rich plasma

Zeling Huang,&ast; Binjie Lu,&ast; Xianda Zhang,&ast; Jiangping Wang, Xuefeng Cai, Yujiang Liu, Jianxiong Mo, Yuwei Li, Bo Xu, Xiaofeng Shen Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, 215008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Xu; Xiaofeng Shen, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, 215008, People’s Republic of China, Tel +86 18359146790, Email xubo12080@163.com; 29240818@qq.comPurpose: The aim of this study was to investigate the effect of Zhiqiao Gancao decoction (ZQGCD) on hyperalgesia in lumbar disc herniation (LDH) and its mechanism.Methods: The potential mechanism of ZQGCD’s therapeutic effect on LDH was investigated through network pharmacology, which involved screening the targets of eight components that were absorbed into the bloodstream. The effects of CCR2 inhibitors and ZQGCD-containing serum on the excitability of the CCL2/CCR2 signaling pathway and dorsal root ganglion neurons (DRGn) were investigated in vitro. The effects of CCR2 inhibitors and ZQGCD on the expression of the CCL2/CCR2 signaling pathway and ASIC3 in the rat intervertebral disc and dorsal root ganglion (DRG), the degree of disc degeneration, the threshold of foot retreat, and the latency of foot retreat in LDH rats were examined in vivo. The binding affinities and interaction modes between CCR2 and the components absorbed into the blood were analyzed using the AutodockVina 1.2.2 software.Results: Network pharmacology revealed that ZQGCD could treat LDH through a mechanism involving the chemokine signaling pathway. It was observed that the CCR2 inhibitor and ZQGCD-containing serum downregulated CCR2 and ASIC3 expression and decreased cell excitability in DRGn. The CCL2/CCR2 signaling pathway was activated in the degenerated intervertebral disc and DRG of LDH rats, increased the expression of ASIC3, and decreased the mechanical allodynia domain and thermal hyperalgesia domain. However, a CCR2 inhibitor or ZQGCD could ameliorate the above changes in LDH rats. The target proteins, CCL2 and CCR2, exhibited a robust affinity for the eight components that were absorbed into the bloodstream.Conclusion: The CCL2/CCR2 pathway was activated in the intervertebral disc and DRG of LDH rats. This was accompanied by upregulation of ASIC3 expression, increased excitability of DRGn, and the occurrence of hyperalgesia. ZQGCD improves hyperalgesia in LDH rats by inhibiting the CCL2/CCR2 pathway and downregulating ASIC3 expression.Keywords: lumbar disc herniation, dorsal root ganglion neurons, hyperalgesia, traditional Chinese medicine, molecular docking

Kailian He,1,2,&ast; Xiashuang Zhang,1,2,&ast; Dong Yang,3 Xiaofeng Fu,3 Yulu Chen,1,2 Ziqi Chen,1,2 Jinglin Mo,3 Lingmi Zhou,3 Fang Xu,3 Xiuli Jiang,3 Wuxiang Shi,4 Liang Cao,1,5 You Li1,2 1Department of Environmental Health and Occupational Medicine, School of Public Health, Guilin Medical University, Guilin, Guangxi, 541199, People’s Republic of China; 2Guangxi Health Commission Key Laboratory of Entire Lifecycle Health and Care (Guilin Medical University), Guilin, Guangxi, 541199, People’s Republic of China; 3Department of AIDS Control and Prevention, Guilin Center for Disease Control and Prevention, Guilin, Guangxi, 541000, People’s Republic of China; 4Health Management Unit, Faculty of Humanities and Management, Guilin Medical University, Guilin, Guangxi, 541199, People’s Republic of China; 5Department of Experimental Teaching Center, School of Public Health, Guilin Medical University, Guilin, Guangxi, 541199, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: You Li; Liang Cao, Email liyou121300@163.com; caoliang00552@163.comPurpose: The purpose of our study is to understand the current status of depression and medical social support in elderly HIV/AIDS, as well as the role of social support on depression, so as to provide a certain reference for reducing the occurrence of depression in the population.Methods: A total of 115 participants with PLWHA (people living with HIV/AIDS) aged 50 years or older were collected in Guilin from December 2021 to July 2022. Depression and medical social support were assessed using the Center for Streaming Depression Scale (CES-D) and the Medical Social Support Scale (MOS-SSS). The structural equation model was used to examine the relationship between medical social support and depression.Results: Sixty-one of 115 participants developed depressive symptoms with a prevalence of 53.0%. The results of univariate analysis showed that ethnicity, health status, mean monthly income, antiviral treatment status, and medical social support influenced PLWHA depression (P< 0.05). Simple linear regression showed that health status (95% CI: − 9.901~-2.635), and antiviral treatment status (95% CI: − 12.969~-3.394) influent depression (P< 0.05). There were associations between total medical social support, practical support dimension, message and emotional support dimension, social interactive cooperation dimension, emotional support dimension and depression (unadjusted and adjusted for contextual factors) (P < 0.05). Using multiple linear regression analyses, we found that medical-social support was negatively associated with depression with a standardized effect value of − 0.223. PLWHA with higher medical social support had lower prevalence of depression.Conclusion: The results indicate that the prevalence of depression among HIV/AIDS patients in Guilin is high. So the joint efforts of individuals, families, and society are needed to improve the physical and mental health of the PLWHA.Keywords: older people living with HIV/AIDS, medical social support, depression, structural equation model, SEM

Meimei Wang,1,&ast; Zhenzhen Zhang,2,&ast; Ning Sun,3 Baolin Yang,4 Jihao Mo,5 Daping Wang,2 Mingqin Su,1 Jian Hu,1 Miaomiao Wang,6 Lei Wang7,8 1Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China; 2Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, 518055, People’s Republic of China; 3Institute of Clinical Laboratory Science, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu, 210002, People’s Republic of China; 4Institute of Technical Biology & Agriculture Engineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, 230032, People’s Republic of China; 5Department of Medical Laboratory, Luoyang Orthopedic Hospital of Henan Province, Orthopedic Institute of Henan Province, Luoyang, Henan, 459001, People’s Republic of China; 6School of Medical Science, Huang He Science and Technology University, Zhengzhou, Henan, 459001, People’s Republic of China; 7School of Biological Sciences, Nanyang Technological University, Singapore, 639798, Singapore; 8Department of Physiology and Biophysics, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA&ast;These authors contributed equally to this workCorrespondence: Lei Wang, Department of Physiology and Biophysics, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA, Tel +1 786-620-1400, Email lxw561@miami.eduIntroduction: The increasing use of gold nanoparticles (Au NPs) in the medical field has raised concerns about the potential adverse effect of Au NPs exposure. However, it is difficult to assess the health risks of Au NPs exposure at the individual organ level using current measurement techniques.Methods: The physical and chemical properties of Au NPs were characterized by transmission electron microscope (TEM), Fourier transform infrared (FTIR), and zeta sizer. The RNA-seq data of Au NPs-exposed worms were analyzed. The food intake was measured by liquid culture and Pharyngeal pumping rate. The function of the smell and taste neurons was evaluated by the chemotaxis and avoidance assay. The activation of ASE neurons was analyzed by calcium imaging. The gene expression of ins-22 and egl-19 was obtained from the C. elegans single cell RNA-seq databases.Results: Our data analysis indicated that 62.8% of the significantly altered genes were functional in the nervous system. Notably, developmental stage analysis demonstrated that exposure to Au NPs interfered with animal development by regulating foraging behavior. Also, our chemotaxis results showed that exposure to Au NPs reduced the sensation of C. elegans to NaCl, which was consistent with the decrease in calcium transit of ASEL. Further studies confirmed that the reduced calcium transit was dependent on voltage-gated calcium channel EGL-19. The neuropeptide INS-22 was partially involved in Au NPs-induced NaCl sensation defect. Therefore, we proposed that Au NPs reduced the calcium transit in the ASEL neuron through egl-19-dependent calcium channels. It was partially regulated by the DAF-16 targeting neuropeptide INS-22.Discussion: Our results demonstrate that Au NPs affect food sensation by reducing the calcium transit in ASEL neurons, which further leads to reduced pharynx pumping and feeding defects. The toxicology studies of Au NPs from worms have great potential to guide the usage of Au NPs in the medical field such as targeted drug delivery.Graphical Abstract: Keywords: gold nanoparticles, RNA sequencing, ASEL neuron, voltage-gated calcium channel, developmental toxicity, Caenorhabditis elegans

Jianming Mo,&ast; Chao Zeng,&ast; Wei Li,&ast; Weidong Song, Ping Xu Department of Pulmonary and Critical Care Medicine, Peking University Shenzhen Hospital, Shenzhen, 518034, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ping Xu, Peking University Shenzhen Hospital, 1120 Lianhua Road, Shenzhen, 518036, People’s Republic of China, Email 582233978@qq.comBackground: Obstructive sleep apnea syndrome (OSAS) is a common chronic sleep disorder. OSAS is closely related to cardiovascular disease, metabolic disorders, cancer risk, and sudden death. This association has special significance in young people. Although it is known that OSAS has a great impact on physical health, it is estimated that 70– 80% of patients with moderate-to-severe OSAS remain undiagnosed. Therefore, a new method for early diagnosis of the disease, the therapeutic effect of OSAS and prevention of complications to important.Methods: A total of 110 patients with moderate-to-severe OSAS diagnosed in the Sleep Disorders Diagnosis and Treatment Center of Peking University Shenzhen Hospital were selected. After excluding other diseases, 59 patients were finally selected as the OSAS group. In addition, 60 healthy people were selected as the control group. Serum RNA was then extracted. Eight RNA samples were randomly selected from the two groups for high-throughput miRNA sequencing. The 10 miRNAs with the greatest differences were selected as preselected markers from the results. Then, qRT-PCR was performed on the remaining RNA samples of the two groups to extract and verify the 10 miRNAs, and statistical analysis was performed between groups.Results: A diagnostic panel was constructed by a stepwise logistic regression model combined with the expression data of miRNAs in the validation phase. A four-miRNA panel was identified to better predict OSAS, and the model was calculated using the following formula: Logit (P)= 0.77– 1.65 × miR-486-5p - 4.56 × miR-148a-3p + 1.79 × miR-744-5p + 1.13 × let-7d-3p. The AUC for the four-miRNA panel was 0.955 (95% CI: 0.899 to 0.985; sensitivity = 91.38%, specificity = 91.38%). Gene Ontology (GO) annotation and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis was included in bioinformatic analysis.Conclusion: A 4-miRNAs panel as a diagnostic biomarker for OSAS screening is feasible.Keywords: biomarkers, microRNA, obstructive sleep apnea syndrome, diagnosis, bioinformatics

Jianming Mo,1,2 Liya Zhang3 1Jinan University, Guangzhou, Guangdong, 510632, People’s Republic of China; 2Department of Endocrinology and Metabolism, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China; 3Department of Endocrinology, Shanxi Yingkang Healthcare General Hospital, Yuncheng, Shanxi, 044000, People’s Republic of ChinaCorrespondence: Liya Zhang, Email 15807718691@163.com

Xue Lian,1,2 Dakui Cao,2 Xun Hu,3 Weiqiang Mo,2 Xiujuan Yao,4 Juanfen Mo,5 Haiqin Wang1,2 1Department of Respiratory Medicine, Bengbu Medical College, Bengbu, Anhui, 233000, People’s Republic of China; 2Department of Respiratory Medicine, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, 314000, People’s Republic of China; 3Department of Thoracic Surgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, 314000, People’s Republic of China; 4Department of Pathology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, 314000, People’s Republic of China; 5The Key Laboratory, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, 314000, People’s Republic of ChinaCorrespondence: Haiqin Wang, Department of Respiratory Medicine, The Second Hospital of Jiaxing, 1518 Huanchen North Road, Jiaxing, Zhejiang, 314000, People’s Republic of China, Email w_haiqin@163.comBackground: Lung adenocarcinoma (LUAD) is a life-threatening disease worldwide with a high mortality rate. The early diagnosis of LUAD is crucial for improving subsequent treatment and prognosis. However, biomarkers for early detection remain a clinical challenge in LUAD. Here, we aimed to develop circular RNAs (circRNAs) in circulating plasma from LUAD patients as valuable diagnostic biomarkers in LUAD.Methods: CircRNA expression was determined by circRNA microarray in three pairs of LUAD tumour tissues and patient-matched normal lung tissues. Hsa_circ_101555 and hsa_circ_008068 were selected as potential biomarkers in LUAD tissues and plasma by RT–PCR, respectively. The diagnostic value was analysed by the area under the curve (AUC) and the receiver operating characteristic (ROC) test.Results: Our results showed that 6261 circRNAs were upregulated and 7238 circRNAs were downregulated in LUAD tumour tissues compared with patient-matched normal lung tissues. Hsa_circ_101555 and hsa_circ_008068 were filtered as biomarkers for early-stage LUAD. Q-PCR results showed that hsa_circ_101555 and hsa_circ_008068 were significantly upregulated in both LUAD cancer tissues and circulating plasma. Hsa_circ_101555 and hsa_circ_008068 were positively associated with tumour differentiation, tumour size and CEA (P< 0.05). The ROC analysis showed that hsa_circ_101555 and hsa_circ_008068 had a better diagnostic potential compared to the traditional biomarkers (CEA, SCC, CYFRA21-1) in the detection of early-stage LUAD.Conclusion: The circular RNAs hsa_circ_101555 and hsa_circ_008068 could serve as novel diagnostic biomarkers for early-stage LUAD.Keywords: circRNAs, lung adenocarcinoma, diagnostic biomarker, circ101555

The chloroform fumigation extraction (CFE) method determines microbial biomass carbon (MBC) or nitrogen (MBN) by calculating the increase in extractable carbon (C) or nitrogen (N) due to microbial lysis during chloroform fumigation. In China, many studies have focused on the impacts of N and phosphorus (P) addition on soil MBC and MBN in forest ecosystems, where substantial atmospheric N deposition has strongly acidified soils. The addition of nutrients may alter the extraction process applied in the CFE method, potentially influencing the MBC and MBN determined by the CFE method independently of the actual microbial biomass. In this study, we tested whether the MBC and MBN determined by the CFE method were biased by the experimental addition of N and P in strongly acidified Chinese forest soils by adding N and P to the soils immediately before chloroform fumigation, which should not affect the actual microbial biomass. P addition significantly elevated the dissolved organic carbon (DOC) content, especially after fumigation, while N addition significantly reduced the dissolved nitrogen (DN) content. The added N was subtracted using blank samples without soil. However, the altered DOC and DN contents did not affect the MBC and MBN contents determined by the CFE method. In conclusion, our study suggests that the CFE is a relatively robust method to test the impacts of nutrient addition on microbial biomass in the strongly acidified soils of Chinese forests. We also suggested that: (i) even if a fertilization experiment results in an elevated DOC content following P addition, it does not necessarily indicate a stimulation of DOC production by microbes; and (ii) the soil adsorption capacity or the strength of microbial N uptake during the extraction procedure applied in the CFE method may affect the determination of MBN by influencing the DN extraction efficiency.

Kunpeng Wang,1 Xiongying Miao,2 Fanhua Kong,2 Siqi Huang,3 Jinggang Mo,1 Chong Jin,1 Yanwen Zheng2 1Department of General Surgery, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, 318000, Zhejiang, People’s Republic of China; 2Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People’s Republic of China; 3Department of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People’s Republic of ChinaCorrespondence: Yanwen ZhengDepartment of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People’s Republic of ChinaEmail zyw.1018@csu.edu.cnBackground and Aim: Pancreatic cancer is one of the most malignant tumors worldwide. Zuojin pills (ZJP), a traditional Chinese medicine (TCM) formula, which can treat a variety of cancers. However, the active compounds present in ZJP and the potential mechanisms through which ZJP acts against pancreatic cancer have not been thoroughly investigated.Methods: Data on pancreatic cancer-related genes, bioactive compounds, and potential targets of ZJP were downloaded from public databases. Bioinformatics analysis, including protein–protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, was conducted to identify important components, potential targets, and signaling pathways through which ZJP affects pancreatic cancer. The results of this analysis were verified by in vitro experiments.Results: The network pharmacology analysis results showed that 41 compounds and 130 putative target genes of ZJP were associated with anti-pancreatic cancer effects. ZJP may exert its inhibitory effects against pancreatic cancer by acting on key targets such as JUN, TP53, and MAPK1. Moreover, KEGG analysis indicated that the anti-pancreatic cancer effect of ZJP was mediated by multiple pathways, such as the PI3K-AKT, IL-17, TNF, HIF-1, and P53 signaling pathways. Among these, the PI3K-AKT signaling pathway, which included the highest number of enriched genes, may play a more important role in treating pancreatic cancer. The in vitro results showed that ZJP significantly inhibits the cell cycle and cell proliferation through the PI3K/AKT/caspase pathway and that it can induce apoptosis of pancreatic cancer cells, consistent with the results predicted by network pharmacological methods.Conclusion: This study preliminarily investigated the pharmacological effects of ZJP, which appear to be mediated by multiple compounds, targets and pathways, and its potential therapeutic effect on pancreatic cancer. Importantly, our work provides a promising approach for the identification of compounds in TCM and the characterization of therapeutic mechanisms.Keywords: pancreatic cancer, Zuojin pill, network pharmacology, traditional Chinese medicine, proliferation, apoptosis

Fengjuan Shi,1,&ast; Tongning Deng,2,&ast; Jian Mo,1 Huiru Wang,1 Jianxun Lu3,4 1Department of Gynaecology and Obstetrics, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530022, People’s Republic of China; 2Department of Gynaecology and Obstetrics, Meiao Gynaecology and Obstetrics Hospital of Guangxi, Nanning, Guangxi, 530000, People’s Republic of China; 3Department of Medical Oncology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530022, People’s Republic of China; 4Department of Medical Oncology, The First People’s Hospital of Nanning, Nanning, Guangxi, 530022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianxun LuThe Fifth Affiliated Hospital of Guangxi Medical University, 89 Qixing Road, Nanning, Guangxi, 530022, People’s Republic of ChinaTel +867712636253Email lujianxun1970@sina.comBackground: Ovarian serous cystadenocarcinoma (OSCC) is a life-threatening malignancy with poor prognosis. Therefore, the identification of immune-related genes associated with OSCC prognosis may reveal new targets of immunotherapy for OSCC.Patients and Methods: The gene expression profiles of overlapped genes were extracted by weighted gene co-expression network analysis (WGCNA) to identify immune-related modules. Significant genes were identified by univariate Cox regression analysis of model genes. Model characteristic genes were obtained by least absolute shrinkage and selection operator (LASSO) analysis and used to calculate a “signature index”. The model’s ability to predict prognosis in OSCC patients was assessed using time-dependent receiver operator characteristic curves. Differences in the biological processes and Kyoto Encyclopedia of Genes and Genomes pathways between groups with high or low signature index were assessed using gene set enrichment analysis (GSEA). The types of immune cells and their abundance in the two index groups were explored by single-sample GSEA.Results: The expression profiles of 3517 overlapped genes were extracted by WGCNA, and nine modules related to the immune system of OSCC were obtained. The expression profiles of 114 hub genes were then subjected to LASSO analysis. Among them, 10 immune-related genes were significant, of which six were identified as model characteristic genes and were used to calculate the signature index. Moreover, 24 types of immune cells were identified in the tumor microenvironment, and their abundance was explored in high- and low-signature index groups of two datasets.Conclusion: ARHGEF18, PLEKHA7, MTOR, VPS45, BRCA1, and HINT2 were identified as characteristic genes and used to develop a new immune-related gene-based signature as a promising prognostic biomarker for OSCC.Keywords: ovarian serous cystadenocarcinoma, prognostic biomarker, signature index, immune-related genes

Chunling Zhao,1,* Jingjia Mo,2,* Xiaowen Zheng,1 Zimeng Wu,1 Qian Li,1 Jihua Feng,1 Jiefeng Luo,1 Junyu Lu,3 Jianfeng Zhang1 1Department of Emergency Medicine, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, People’s Republic of China; 2Department of General Medicine, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, People’s Republic of China; 3Intensive Care Unit, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, People’s Republic of China*These authors contributed equally to this workCorrespondence: Junyu Lu; Jianfeng ZhangThe Second Affiliated Hospital of Guangxi Medical University, No. 166 Daxuedong Road, Nanning, Guangxi, 530007, People’s Republic of ChinaTel +867713277166Fax +867713277285Email junyulu@gxmu.edu.cn; drzhangjf@163.comPurpose: Acute respiratory distress syndrome (ARDS) is a rapidly progressive diffuse lung injury that is characterized by high mortality and acute onset. The pathological mechanisms of ARDS are still unclear. But alveolar macrophages have been shown to play an important role in inflammatory responses during ARDS. We aimed to find the biomarkers for ARDS for early diagnosis, to give ARDS patients timely treatment.Methods: Gene expression profiles were downloaded from Gene Expression Omnibus (GEO) and screened for differentially expressed genes (DEGs). The common upregulated genes in all the datasets were defined as circulating ARDS alveolar macrophage-related genes (cARDSAMGs). We performed a functional enrichment analysis to explore potential biological functions of cARDSAMGs, and we built protein–protein interaction networks. Gene set variation analysis (GSVA) was used to calculate the core gene set variation analysis (CGSVA) score for individual samples. Receiver operating characteristic (ROC) curve analysis was applied on the CGSVA score to evaluate its ability for diagnosis of ARDS.Results: A total of 60 genes were upregulated in all ARDS datasets and were therefore denominated as cARDSAMGs. The cARDSAMGs were significantly involved in multiple inflammation-, immunity- and phagocytosis-related biological processes and pathways. In the protein–protein interaction network associated with host responses to ADRS, eight genes were identified as a core gene set: PTCRA, JAG1, C1QB, ADAM17, C1QA, MMP9, VSIG4 and TNFAIP3. ROC curve analysis showed that the CGSVA score may be considered as a biomarker for ARDS: it was significantly higher in patients with ARDS than those in healthy in both alveolar lavage fluid and whole blood.Conclusion: The ARDS alveolar macrophage-related CGSVA score may be useful as a biomarker for ARDS.Keywords: acute respiratory distress syndrome, lung injury, gene expression omnibus, differentially expressed genes

Junxian Mo,1,2,* Dongni Chen,3,* Changbo Li,2 Mingwu Chen1 1Department of Cardio-Thoracic Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China; 2Department of Cardio-Thoracic Surgery, The Seventh Affiliated Hospital of Guangxi Medical University, Wuzhou, Guangxi 543000, People’s Republic of China; 3Department of Thoracic Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mingwu ChenDepartment of Cardio-Thoracic Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of ChinaEmail chenmingwu535@163.comObjective: The impact of negative lymph nodes (NLNs) count on prognosis in esophageal cancer (EC) was analyzed using two institutions surgical database.Methods: We conducted a retrospective study of 768 EC patients treated by surgical resection between January 2010 and December 2012. The effects of the NLNs count on prognosis was analyzed. Cox regression model was conducted to determine the significant prognostic elements.Results: The number of NLNs was studied as a categorical variable based on the quartiles (Q1: ≤ 15, Q2: 16– 21, Q3: 22– 30, Q4: ≥ 31). And a better overall survival (OS) was observed with increasing number of NLNs (HR= 0.762; 95% CI, 0.596– 0.974 for Q2, HR= 0.666; 95% CI, 0.516– 0.860 for Q3 and HR= 0.588; 95% CI, 0.450– 0.768 for Q4) (all P< 0.05). Multivariate regression analysis revealed that the NLNs count was an independent prognostic factor. Besides, for patients in T2 or T3 stage, a high number of NLNs was found to be significantly associated with a favorable OS (log rank P< 0.001).Conclusion: A higher number of NLNs is independently related to the better OS in EC patients after surgical resection.Keywords: esophageal cancer, negative lymph node, prognostic factor

Dongni Chen,1,* Weidong Wang,1,* Youfang Chen,1 Jia Hu,1 Men Yang,2 Junxian Mo,3 Zhesheng Wen1 1Department of Thoracic Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; 2Department of Cardio-Thoracic Surgery, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong 518000, China; 3Department of Cardio-Thoracic Surgery, The Seventh Affiliated Hospital of Guangxi Medical University, Wuzhou, Guangxi 543000, China *These authors contributed equally to this work Objective: The aim of this study was to construct a risk model to assess overall survival (OS) and disease-free survival (DFS) in patients with esophageal cancer (EC) after surgery.Patients and methods: A total of 872 consecutive EC patients who had undergone surgery between February 2009 and October 2012 were retrospectively analyzed. The cutoff for risk value (RV) was inferred by receiver operating characteristic curves and the Youden index. A log-rank test was used to compare the survival curves, and a Cox regression analysis was performed to clarify the significant prognostic factors.Results: The area under the curve was 0.688 for OS and 0.645 for DFS. The survival rates were 69.4% (259/373) and 39.1% (195/499), and the rates of recurrence were 19.2% (70/364) and 27.6% (132/479), respectively, for RV

Kui Huang,1 Marla B Sultan,2 Duo Zhou,3 Charles S Tressler,4 Jingping Mo1 1Epidemiology, Worldwide Safety and Regulatory, 2Clinical Sciences, Global Innovative Products Business, 3Clinical Statistics, Global Established Pharma Business, 4Safety Surveillance and Risk Management, Worldwide Safety and Regulatory, Pfizer Inc, New York, NY, USA Purpose: This study was performed to understand the practice patterns of ophthalmologists administering intravitreal (IVT) injections in Europe after the procedure became routine.Methods: As part of a prospective, multinational, non-interventional cohort study in 13 countries in Europe between 2006 and 2012, ophthalmologists completed the Baseline Questionnaire and the Follow-up Questionnaire 1 year after baseline.Results and discussion: Of the 125 ophthalmologists who participated in the study, 113 (90.4%) completed the Baseline Questionnaire. Most of these ophthalmologists were medical retina specialists (43.0%). The median number of IVT injections that the ophthalmologists performed per month during the year prior to completing the Baseline Questionnaire was 20.0. The majority of the ophthalmologists had performed their last IVT injection prior to completing the questionnaire in an operating room or theater (68.4%). When performing IVT injections, a majority of the ophthalmologists reported applying povidone–iodine (90.4%) before IVT injections and topical antibiotics right after IVT injections (89.5%). In addition, 81.6% of the ophthalmologists reported using a sterile adhesive eye drape and 80.7% reported using an eyelid speculum. In all, 95 ophthalmologists (76%) completed the Follow-up Questionnaire. The median number of IVT injections performed per month during the year prior to completing the Follow-up Questionnaire by these ophthalmologists was increased to 35. The results of the Follow-up Questionnaire on administering IVT injections were similar to those of the Baseline Questionnaire. A majority of the ophthalmologists reported applying povidone–iodine (87.4%) before IVT injections, topical antibiotics right after IVT injections (89.5%), and an eyelid speculum (85.3%).Conclusion: The results of this study indicated a good adherence to all aspects of the guidelines on IVT injections. It seemed that ophthalmologists were more experienced in IVT injections after they became a routine treatment procedure. Keywords: intravitreal injection, questionnaire, povidone–iodine, topical antibiotics, eyelid speculum

Stromal cells derived from adipose tissue (ASCs) can proliferate as undifferentiated cells with a fibroblast-like morphology in cell culture, or can be induced to differentiate into a variety of cell types including, adipipogenic, myogenic, neurogenic, osteogenic, chondrogenic and hepatic cells. There is increasing interest to understand the factors controlling the proliferation of ASCs since these cells might provide a readily available source of autologous stem/progenitor cells for cell therapy applications. To explore potential genetic factors that modify the properties of ASCs, we tried to identify relevant properties of ASCs that differ between inbred mouse strains. Plating cells in a modified colony forming assay indicates that the percentage of high proliferative cells among ASCs differs more than 2-fold between 129x1/svj and C57Bl/6J mice. The identification of genetic factors affecting the proliferative capacity of stem cell populations could improve the efficacy of cell therapy.

We present high-cadence UV, optical, and near-infrared data on the luminous Type II-P supernova SN 2017gmr from hours after discovery through the first 180 days. SN 2017gmr does not show signs of narrow, high-ionization emission lines in the early optical spectra, yet the optical light-curve evolution suggests that an extra energy source from circumstellar medium (CSM) interaction must be present for at least 2 days after explosion. Modeling of the early light curve indicates a ∼500 R o progenitor radius, consistent with a rather compact red supergiant, and late-time luminosities indicate that up to 0.130 ± 0.026 M o of 56Ni are present, if the light curve is solely powered by radioactive decay, although the 56Ni mass may be lower if CSM interaction contributes to the post-plateau luminosity. Prominent multipeaked emission lines of Hα and [O i] emerge after day 154, as a result of either an asymmetric explosion or asymmetries in the CSM. The lack of narrow lines within the first 2 days of explosion in the likely presence of CSM interaction may be an example of close, dense, asymmetric CSM that is quickly enveloped by the spherical supernova ejecta.

We present an exquisite 30 minute cadence Kepler (K2) light curve of the Type Ia supernova (SN Ia) 2018oh (ASASSN-18bt), starting weeks before explosion, covering the moment of explosion and the subsequent rise, and continuing past peak brightness. These data are supplemented by multi-color Panoramic Survey Telescope (Pan-STARRS1) and Rapid Response System 1 and Cerro Tololo Inter-American Observatory 4 m Dark Energy Camera (CTIO 4-m DECam) observations obtained within hours of explosion. The K2 light curve has an unusual two-component shape, where the flux rises with a steep linear gradient for the first few days, followed by a quadratic rise as seen for typical supernovae (SNe) Ia. This "flux excess" relative to canonical SN Ia behavior is confirmed in our i-band light curve, and furthermore, SN 2018oh is especially blue during the early epochs. The flux excess peaks 2.14 ± 0.04 days after explosion, has a FWHM of 3.12 ± 0.04 days, a blackbody temperature of K, a peak luminosity of , and a total integrated energy of . We compare SN 2018oh to several models that may provide additional heating at early times, including collision with a companion and a shallow concentration of radioactive nickel. While all of these models generally reproduce the early K2 light curve shape, we slightly favor a companion interaction, at a distance of ∼ based on our early color measurements, although the exact distance depends on the uncertain viewing angle. Additional confirmation of a companion interaction in future modeling and observations of SN 2018oh would provide strong support for a single-degenerate progenitor system.