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Lili Wang,1 Le Cheng,1 Chenhui Lv,1 Jie Kou,1 Wenjuan Feng,1 Haoran Xie,1 Ruolin Yan,1 Xi Wang,1 Shuangzhi Chen,1 Xin Song,1 Lushan Xue,1 Cheng Zhang,1 Xuemin Li,2 Haifeng Zhao1,3 1Department of Nutrition and Food Hygiene, School of Public Health, Shanxi Medical University, Taiyuan, People’s Republic of China; 2Center for Disease Control and Prevention in Shanxi Province, Taiyuan, People’s Republic of China; 3MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention (Shanxi Medical University), Ministry of Education, Taiyuan, People’s Republic of ChinaCorrespondence: Haifeng Zhao, Department of Nutrition & Food Hygiene, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, 030001, People’s Republic of China, Tel/Fax +86-351-4135046, Email haifengzao75@163.comBackground: The present study aimed to explore the association between the inflammatory potential of diet, assessed by energy-adjusted dietary inflammatory index (E-DII) and reduced rank regression (RRR)-derived inflammatory dietary pattern, and the risk for cognitive impairment (CI) in community-dwelling older adults, especially in older adults with chronic diseases and multimorbidity.Methods: A total of 549 older adults from Taiyuan city were included in the present cross-sectional study. The Chinese Version of the Mini-Mental State Examination (CMMSE) was used for the evaluation of cognitive function. E-DII score was calculated based on semi-quantitative food frequency questionnaire (FFQ). Blood samples, including interleukin (IL)-1β, interleukin (IL)-18, tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP), were tested for calculating RRR-derived inflammatory dietary pattern. Logistic regression was used to assess the association between inflammatory dietary pattern and risk of CI. In addition, patients with diabetes, hypertension, hyperlipidemia and multimorbidity were screened for further analysis among 549 older adults.Results: In those 549 older adults, adjusting for demographic characteristics and chronic disease status, there was no association between E-DII score tertile (ORT3VST1: 1.357, 95%CI:0.813~2.265, Ptrend = 0.267), RRR-derived inflammatory dietary pattern score tertile (ORT3VST1: 1.092, 95%CI:0.679~ 1.758, Ptrend = 0.737) and risk of CI. However, in older adults with diabetes and multimorbidity, the score tertile of E-DII and RRR-derived inflammatory dietary pattern were positively correlated with risk of CI in a dose-responsive manner (All Ptrend < 0.05). There is insufficient evidence to reach similar conclusion in patients with hypertension and hyperlipidemia (All Ptrend > 0.05).Conclusion: In the present study, pro-inflammatory diet contributed to the increased risk of CI in older adults with diabetes and multimorbidity. These results supplemented vital evidence for the prevention and treatment of CI in older adults with chronic diseases.Keywords: chronic diseases, multimorbidity, cognitive impairment, inflammatory dietary pattern, dietary inflammatory index, reduced rank regression

Xia Zhou,1 Wei Feng,1 Xiaolong Wang,2 Zejun Niu,1 Peng Wang,1 Li Yuan,1 Pei Wang1 1Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province,People’s Republic of China; 2Department of Emergency Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People’s Republic of ChinaCorrespondence: Pei Wang, Email wangpei@qdu.edu.cnPurpose: Anesthesia for metabolic–bariatric surgery is challenging due to the increased risk of opioid-related adverse events. The purpose of the investigation was to assess the feasibility and efficacy of multimodal opioid-free general anesthesia with transversus abdominis plane (TAP) block for laparoscopic sleeve gastrectomy in contrast with conventional opioid-based general anesthesia.Patients and Methods: Eighty patients who underwent laparoscopic sleeve gastrectomy and eventually 71 patients included in the analysis. They were randomly divided into an opioid-based anesthesia group (control group) with sufentanil or opioid-free anesthesia (OFA) group. Esketamine, dexmedetomidine, and TAP were as part of the OFA. Sevoflurane, dexamethasone, and muscle relaxants were administered intraoperatively to all patients. The primary outcome was antiemetic rescue within 24 hours after surgery. The secondary outcomes included pain scores, analgesic needs, extubation time, complications, the hemodynamic changes, and duration of hospital stay.Results: In contrast with the control group, the need for antiemetic rescue was significantly reduced (p= 0.035). Furthermore, the visual Analog Scale (VAS) for postoperative pain was considerably lower in the OFA group (p < 0.01) than it was in the control group. There was no significant difference in the need for analgesic rescue in both groups (p= 0.155). Extubation time and post-anesthesia care unit (PACU) stay duration were equal between the two groups (p =0.328 and p =0.54). At the end of the surgery and after extubation, hemodynamic changes was more pronounced in the OFA group (p =0.027) than the control group. The length of the hospital stay was significantly shorter compared with the control group (p =0.002).Conclusion: OFA with TAP results in a significant decrease in the need for antiemetic rescue, a lower level of pain after the surgery, and a shorter hospital stay in contrast with anesthesia based on opioids.Keywords: opioid-free, nerve block, esketamine, post-operative nausea and vomiting, bariatric surgery

Ziyu Li,1,&ast; Qiuyan Zhang,2,&ast; Yuhe Gao,3,&ast; Fang Wan,3 Yincang Wang,3 Bin Hou,2 Wenwen Cui,4,5 Yanan Wang,2 Wei Feng,2 Yunlong Hou4,5 1Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, People’s Republic of China; 2New Drug Evaluation Center, Shijiazhuang Yiling Pharmaceutical Co., Ltd, Shijiazhuang, People’s Republic of China; 3Graduate School, Heilongjiang University of Chinese Medicine, Harbin, People’s Republic of China; 4National Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang Yiling Pharmaceutical Co., Ltd, Shijiazhuang, People’s Republic of China; 5Key Laboratory of State Administration of TCM (Cardio-Cerebral VesselCollateral Disease), Shijiazhuang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunlong Hou, Email houyunlonghrb@Hotmail.comBackground: The LuoBiTong (LBT) capsule, a novel traditional Chinese medicine formulation, is currently in Phase III clinical trials. Preliminary preclinical and Phase II clinical studies suggest its efficacy and safety in treating rheumatoid arthritis (RA). However, the underlying mechanisms of its action remain to be elucidated.This research aims to explore the effects and mechanisms of LBT in conjunction with a maintenance dose of methotrexate (M-MTX) on RA.Methods: A Collagen-Induced Arthritis (CIA) mouse model was used to evaluate the anti-RA effects of LBT combined with M-MTX. Assessments included foot swelling, arthritis scoring, serum inflammatory factor analysis, and histopathological examination of the foot. These effects were compared with those of high-dose MTX (H-MTX). Network pharmacology was employed to construct a compound-target network for RA, based on drug composition, to predict its potential mechanism of action. Flow cytometry, Western Blot, and immunohistochemical analyses in animal models identified multiple inflammatory pathways targeted by LBT to augment the anti-RA effects of MTX.Results: The study revealed that LBT combined with M-MTX significantly alleviated CIA-induced arthritis without adverse effects. The combination of LBT and M-MTX showed similar or superior efficacy in regulating macrophage polarization, NF-κB, MAPK signaling pathways, and in the suppression of TH-17 expression in proinflammatory cells. These findings suggest that LBT may exert a multi-pathway therapeutic effect in RA treatment. The predicted pharmacological targets and mechanisms align well with this hypothesis.Conclusion: LBT, when combined with MTX, enhances the anti-RA effect by targeting multiple inflammatory pathways, demonstrating significant therapeutic potential.Keywords: rheumatoid arthritis, traditional Chinese medicine, methotrexate, network pharmacology

Yunhan Zhang,1,&ast; Yuyun Chen,2,&ast; Jilin Lv,1 Xiao Xiang,1 Peiyao Wang,1 Wei Feng,1 Zhenhua Guo1 1Department of Neonatal Surgery, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development, Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Chongqing, People’s Republic of China; 2Fujian Children’s Hospital, Fujian Branch of Shanghai Children’s Medical Center, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China&ast;These authors have contributed equally to this workCorrespondence: Zhenhua Guo, Department of neonatal surgery, Children’s Hospital of Chongqing Medical University, 20 Jinyu Road, Yubei District, Chongqing, 400025, People’s Republic of China, Tel +86-23-68370286, Email zhguo@cqmu.edu.cnBackground: This study aims to investigate the potential significance of mean platelet volume (MPV) and platelet distribution width (PDW) in predicting surgical neonatal necrotizing enterocolitis (NEC) and establish the correlation between MPV/PDW levels and the severity/prognosis of NEC.Methods: A retrospective study was conducted on a cohort of 372 patients diagnosed with NEC. The patients were categorized into two groups based on whether they underwent surgical therapy. Univariate /multivariate analysis were employed to compare the MPV and PDW between the two groups. Moreover, patients in surgical group were categorized into multiple subgroups based on intraoperative findings and postoperative prognosis, and the levels of MPV and PDW were compared among these subgroups.Results: Of the 372 patients, the operative group exhibited significantly higher levels of MPV and PDW than the nonoperative group (P < 0.05). Logistic regression analysis revealed that MPV (OR = 4.895, P < 0.001) and PDW (OR = 1.476, P < 0.001) independently associated with surgical NEC. The analysis of the receiver operating characteristic (ROC) curve revealed that the area under the curve (AUC) was 0.706 for MPV alone, with a cut-off value of 11.8 fL. Similarly, the AUC was 0.728 for PDW alone, with a cut-off value of 16%. However, when MPV and PDW were combined, the AUC increased to 0.906 for predicting surgical NEC. In accordance with the intraoperative findings, the levels of MPV and PDW were found to be higher in the large area necrosis group than in the partial or mild necrosis group (P < 0.01). Furthermore, the MPV and PDW values in the death group were significantly greater than those in the survival group (P =0.040, P =0.008).Conclusion: MPV and PDW may serve as potentially valuable indicators for determining the need for surgical intervention and predicting the prognosis of patients with NEC.Keywords: mean platelet volume, platelet distribution width, necrotizing enterocolitis, neonatal

Tao Xue,1,&ast; Hongbin Yu,2,&ast; Wenming Feng,2 Yao Wang,2 Shiyong Wu,3 Lili Wang,4 Peiqin Zhu,5 Jianming Guan,6,7 Quan Sun8 1Clinical Research Center, First People’s Hospital Affiliated to Huzhou University, Huzhou, People’s Republic of China; 2Department of Hepatobiliary Surgery, First People’s Hospital Affiliated to Huzhou University, Huzhou, People’s Republic of China; 3Department of Radiology, First People’s Hospital Affiliated to Huzhou University, Huzhou, People’s Republic of China; 4Department of Nursing, Physical Examination Center of Aishan, Huzhou, People’s Republic of China; 5Department of Internal Medicine, Huzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Huzhou, People’s Republic of China; 6Department of Ultrasound, First People’s Hospital Affiliated to Huzhou University, Huzhou, People’s Republic of China; 7Department of Ultrasound, Mingzhou Hospital, Huzhou, People’s Republic of China; 8Laboratory of Blood Transfusion Research, Huzhou Center Blood Station, Huzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Quan Sun, Laboratory of Blood Transfusion Research, Huzhou Center Blood Station, Fenghuang Road 577&num;, Huzhou, 313000, People’s Republic of China, Email sunquanhz@163.com Jianming Guan, Department of Ultrasound, First People’s Hospital Affiliated to Huzhou University, Guangchanghou Road 158&num;, Huzhou, 313000, People’s Republic of China, Email guan9300@126.comBackground: The presence of macrovascular invasion (MVI) is associated with poor prognosis in advanced hepatocellular carcinoma (HCC). This study aims to evaluate the efficacy and safety of Cinobufacini therapy via hepatic arterial infusion (HAI) in advanced HCC patients with MVI.Methods: The clinical records of 130 consecutive patients with unresectable advanced HCC and MVI who had received Cinobufacini or cisplatin plus 5-fluorouracil (CF) treatment via HAI were retrospectively analyzed. The therapeutic efficacy, overall survival (OS), progression-free survival (PFS), and adverse events were compared between the two treatment groups.Results: The Cinobufacini group demonstrated significant curative effects on treatment via HAI compared with the CF group, including the objective response rate (44.9% vs 27.9%, P=0.048), the median OS (14.8 months vs 11.1 months, P=0.010), and the median PFS (10.3 months vs 6.0 months, P=0.006). Result in subgroup analysis of portal vein invasion grade supported the efficacy in Cinobufacini treatment, especially in the median OS of Vp1-2 (18.3 months vs 14.3 months, P=0.043) and Vp3 (15.0 months vs 11.4 months, P=0.046), as well as the median PFS of Vp1-2 (14.8 months vs 10.2 months, P=0.028) and Vp3 (10.8 months vs 6.6 months, P=0.033) compared with CF treatment. Cox proportional hazards model and forest plot analysis of factors confirmed the survival benefit from HAI with Cinobufacini over CF (hazard ratio [HR], 0.61; 95% CI: 0.40– 0.91; P=0.010). Multivariable analysis identified portal vein invasion grade (Vp4; HR, 1.78; 95% CI: 1.03– 2.16; P=0.032) and AFP (> 1000; HR, 1.61; 95% CI: 1.08– 1.91; P=0.039) as the independent factors for prognosis. Moreover, the total incidence of adverse events in the Cinobufacini group was significantly lower than in the CF group (60.9% vs 82.0%, P=0.009).Conclusion: Cinobufacini therapy via HAI is a viable strategy for curing advanced HCC with MVI, due to prolonged survival and a superior safety profile.Keywords: hepatocellular carcinoma, macrovascular invasion, cinobufacini, hepatic arterial infusion, efficacy

Jing Yang, Yan Ma, Bo Li, Zhiqin Xi, Li Zhang, Yuxi Wang, Wenli Feng Department of Dermatovenereology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030001, People’s Republic of ChinaCorrespondence: Wenli Feng; Jing Yang, Department of Dermatovenereology, The Second Hospital of Shanxi Medical University, No. 382, Wuyi Road, Taiyuan, Shanxi, 030001, People’s Republic of China, Tel +86-351-3365410, Email Wenlifeng2010@163.com; yang_jing@sxmu.edu.cnPurpose: RNA terminal phosphate cyclase like 1 (RCL1) undergoes overexpression during the immune response of Candida albicans following drug treatment. This study aims to investigate the expression levels of RCL1 in C. albicans under various stress conditions.Methods: Fifteen itraconazole (ITR)-resistant strains of clinical C. albicans, and one standard strain were employed for RCL1 sequencing, and mutations in RCL1 were analyzed. Subsequently, 14 out of the 15 ITR-resistant clinical strains and 14 clinical strains sensitive to ITR, fluconazole (FCA) as well as voriconazole (VRC) were cultured under diverse conditions. The expression of RCL1 ITR-resistant and sensitive C. albicans was then assessed using real-time quantitative PCR (RT-qPCR) assays.Results: Compared to the standard strain, three missense mutations (C6A, G10A, and A11T) were identified in the RCL1 gene of ITR-resistant C. albicans through successful forward sequencing. Additionally, using successful reverse sequencing, one synonymous mutation (C1T) and four missense mutations (C1T, A3T, A7G, and T8G) were found in the RCL1 gene of ITR-resistant C. albicans. RCL1 expression was significantly higher in ITR-resistant C. albicans than in sensitive strains under standard conditions (37°C, 0.03% CO2, pH 4.0). Low temperature (25°C) increased RCL1 expression in sensitive C. albicans while decreasing it in ITR-resistant strains. Elevated CO2 concentrations (5% CO2) had a negligible effect on RCL1 expression in sensitive C. albicans, but effectively reduced RCL1 level in ITR-resistant strains. Furthermore, a medium with a pH of 7 decreased the expression of RCL1 in both resistant and sensitive C. albicans.Conclusion: This study demonstrated that RCL1 mutations in ITR-resistant C. albicans, and variations in culture conditions significantly influence RCL1 expression in both ITR-resistant and sensitive C. albicans, thereby inducing alterations in the dimorphism of C. albicans.Keywords: Candida albicans, itraconazole resistance, RCL1, culture conditions

Wenwei Feng,&ast; Jiancong Zhou,&ast; Zhubin Lun, Dianhua Zhou, Peiwen Li, Jianfeng Ye Department of Cardiology, Dongguan Hospital of Guangzhou University of Chinese Medicine, Dongguan, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianfeng Ye, Department of Cardiology, Dongguan Hospital of Guangzhou University of Chinese Medicine, Dongguan, Guangdong, People’s Republic of China, Email yipjf@hotmail.comBackground: Contrast-associated acute kidney injury (CA-AKI) is a prevalent complication following coronary angiography (CAG). However, there is ongoing controversy surrounding its precise definition. Although previous studies have demonstrated the successful application of appropriate definitions in managing high-risk CA-AKI patients, there remains limited research on the association between different definitions and prognosis specifically in patients with chronic kidney disease (CKD).Methods: A total of 4197 CKD patients undergoing coronary angiography (CAG) were included in this study. Two definitions of contrast-associated acute kidney injury (CA-AKI) were used: CA-AKIA, which was defined as an increase of ≥ 0.5 mg/dL or > 25% in serum creatinine (SCr) from baseline within 72 hours after CAG, and CA-AKIB, which was defined as an increase of ≥ 0.3 mg/dL or > 50% in SCr from baseline within 48 hours after CAG. Cox regression analysis was employed to assess the association between these two definitions and long-term mortality. Additionally, population attributable risks (PARs) were calculated to evaluate the impact of CA-AKI definitions on long-term prognosis.Results: During the median follow-up period of 4.70 (2.50– 7.78) years, the overall long-term mortality was 23.6%, and the long-term mortality in patients with CA-AKI according to both CA-AKIA and CA-AKIB criteria were 33.5% and 33.8%, respectively. We found that CA-AKIA (HR: 1.45, 95% CI: 1.23– 1.70, p< 0.001) and CA-AKIB (HR: 1.44, 95% CI: 1.23– 1.69, p< 0.001) were associated with long-term mortality. The PARs were the highest for CA-AKIA (5.87%), followed by CA-AKIB (5.70%).Conclusion: Contrast-associated acute kidney injury (CA-AKI) is a frequently observed complication in CKD patients undergoing coronary angiography (CAG), and both definitions of CA-AKI are significantly correlated with a poor long-term prognosis. Consequently, in the clinical management of CKD patients, it is crucial to prioritize CA-AKI, irrespective of the specific CA-AKI definition used.Keywords: contrast-associated acute kidney injury, chronic kidney disease, definitions, long-term mortality, population attributable risks

Jiwen Hou,1,2,&ast; Hua Jiang,1,&ast; Yan Han,1 Rong Huang,1 Xiang Gao,1 Wei Feng,1 Zongjun Guo2 1Department of Geriatrics, Affiliated Hospital of Chengdu University, Chengdu, People’s Republic of China; 2Department of Geriatrics, Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zongjun Guo, Department of Geriatrics, Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Qingdao, Shandong Province, People’s Republic of China, Tel +8618661808736, Email guozjj@163.comPurpose: This study assessed the influences of different lifestyle on mild cognitive impairment (MCI) progression and established a decision tree prediction model to analyse their predictive significance on MCI progression incidence.Patients and Methods: From October 2015 to February 2020,330 patients with MCI were recruited, and demographic and lifestyle information collected. They were followed up for 19.04 ± 10.227 months. Cognitive function was assessed using the Mini-Mental State Examination Scale every 6 months, and they were divided into MCI stable group and MCI progression group.Results: The Kaplan Meier survival analysis showed an overall cohort survival rate of 33.2%; the annual conversion rate of MCI progression was 20%. Physical exercise, social engagement, high-fat diet, age, napping, and tea drinking were decision tree prediction model nodes. Hobbies were the most important factor for predicting MCI progression. The MCI progression probability rates were: with hobbies 26.829% (44 cases), without hobbies 57.831% (96 cases); for those withot hobbies, with physical exercise 43.077% (28 cases) without physical exercise 72.340% (68 cases); for those without hobbies with physical exercise and social engagement 20.000% (4 cases), without social engagement 53.333% (24 cases); for those without hobbies, physical exercises and social engagement and with nap habits 48.485% (16 cases), without nap habits 66.667% (8 cases). The decision tree prediction model AUC for predicting the MCI progression receiver operating characteristic curve was 0.737 (95% confidence interval: 0.685– 0.785) (75.71% sensitivity, 71.75% specificity, P < 0.001.Conclusion: Hobbies, physical exercise, social engagement, napping, and drinking tea can help prevent MCI progression, while a high-fat diet may exacerbate MCI progression. In this study the rule with the lowest MCI progress probability for those who had hobbies, high-fat diet, and social engagement. And the decision tree model had good prediction efficiency.Keywords: lifestyle, mild cognitive impairment progression, survival analysis, decision tree prediction model

Ke Zhang,1 Songwei Feng,1 Yan Wang,1 Wen Feng,2 Yang Shen1,3 1Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Department of Gynecology, The First People’s Hospital of Lianyungang, Lianyungang, 222000, People’s Republic of China; 3Institute of Sports and Health, Nanjing, People’s Republic of ChinaCorrespondence: Wen Feng, Department of Gynecology, The First People’s Hospital of Lianyungang, Lianyungang, 222000, People’s Republic of China, Tel +86-0518-85452253, Fax +86-0518-85456700, Email fengw125@126.com Yang Shen, Department of Obstetrics and Gynaecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210096, People’s Republic of China, Email shenyang@seu.edu.cnObjective: The objective of this research was to determine the age cut-off for worse prognosis and investigate age-related differentially expressed genes (DEGs) in patients with advanced ovarian serous cystadenocarcinoma (AOSC).Methods: In this research, we included a cohort of 20,846 patients diagnosed with AOSC, along with RNA-seq data from 374 patients in publicly available databases. Then we used the X-tile software to determine the age cut-off and stratified the patients into young and old groups. We utilized propensity score matching (PSM) to balance baseline between the young and old groups. Furthermore, we conducted an enrichment analysis of DEGs between the two age groups using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and gene ontology (GO) to identify dysregulated pathways. To evaluate the potential prognostic value of the DEGs, we performed survival analysis, such as Kaplan-Meier analysis and Log rank test.Results: We stratified the patients into young group (n=16,336) and old group (n=4510) based on the cut-off age of 73 years by X-tile software. Age over 73 years was identified as an independent risk factor for overall survival (OS) and cancer-specific survival (CSS). Next, we identified 436 DEGs and found that the neurotrophin signaling pathway and translation factor activity were associated with prognosis outcomes. Among the top 10 hub genes (RELA, NFKBIA, TRAF6, IRAK2, TAB3, AKT1, TBP, EIF2S2, MAPK10, and SUPT3H), RELA, TAB3, AKT1, TBP, and SUPT3H were found to be significantly associated with poor prognosis in old patients with AOSC.Conclusion: Our study determined 73 years as the cutoff value for age in patients with AOSC. RELA, TAB3, AKT1, TBP, and SUPT3H were identified as age-related DEGs that could contribute to the poor prognosis of older patients with AOSC.Keywords: advanced ovarian serous cystadenocarcinoma, propensity score matching, prognosis, real-world study, age

Fenge Li,1,2,&ast; Yupeng Wang,1,&ast; Jin Yan,1,&ast; Huancheng Wu,3 Xueming Du,1 Weihong Feng,1 Xiaoqing Zhang,4 Yongming Xue,4 Huaqing Wang,5,6 Wenxin Liu7 1Department of Oncology, Tianjin Beichen Hospital Tianjin People’s Republic of China; 2Core Laboratory, Tianjin Beichen Hospital, Tianjin, People’s Republic of China; 3Department of Neurosurgery, Tianjin Beichen Hospital, Tianjin, People’s Republic of China; 4Department of Basic Research, Suzhou Lanma Biotechnology Co, Suzhou, People’s Republic of China; 5Department of Oncology, Tianjin Union Medical Center, Tianjin, People’s Republic of China; 6Department of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, People’s Republic of China; 7Department of Gynecological Oncology, Tianjin Medical Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenxin Liu, Department of Gynecological Oncology, Tianjin Medical Cancer Institute and Hospital, Huanhuxi Road, Tiyuanbei, Hexi District, Tianjin, People’s Republic of China, Tel +8618622221101, Email wenxin1973@163.com Huaqing Wang, Department of Translational Medicine, Tianjin Union Medical Center of Nankai University, Jieyuan Road No. 190, Nankai District, Tianjin, People’s Republic of China, Tel +8618622221223, Email huaqingw@163.comIntroduction: Tumor-infiltrating lymphocytes (TILs) therapy is one of the most promising adoptive T cell therapies, which has shown great clinical efficacy against several solid malignancies. Nevertheless, clinical response to TILs mono-therapy in Asian patients with recurrent cervical cancer has not been well reported.Case Presentation: Here, we report two patients who were diagnosed with metastatic cervical cancer and tumor progression following multiple conventional treatments. In particular, one of the patients has a history of severe myelosuppression after chemotherapy. The patients received lymphodepletion therapy, which consisted of cyclophosphamide (30mg/kg) for 2 days, followed by Fludarabine (25mg/m2) for 5 days, approximately 24 hr before receiving intravenous autologous TILs infusion. These two patients then received high doses of IL-2 for 10 days with the purpose of maintaining T cell survival and proliferation. Patient 1 experienced clinical partial response (PR) at 6 weeks post TILs infusion and a 33% tumor shrinkage at 12 weeks follow-up, and patient 2 was evaluated as stable disease (SD) at 6 weeks post treatment. Mild and manageable adverse events were observed and soon subsided after the TILs treatment. A time-course study examining the peripheral blood cell count and cytokine secretion demonstrated the persistence of infused TILs and long-term immune response.Conclusion: These results suggest that TILs mono-therapy can be a promising treatment strategy for Asian patients with late-stage metastatic cervical cancer even with severe myelosuppression. TILs infusion can induce persistence and a long-term systematic immune response that reversed peripheral CD4+T and CD8+T percentages implying that TILs infusion increased cytotic T cell responses, which is consistent with clinical responses in these patients. Trial registration number: NCT05366478.Keywords: tumor-infiltrating lymphocytes, clinical response, immune response, metastatic cervical cancer, treatment

Yajuan Zheng,1,&ast; Peipei Yuan,1,2,&ast; Zhenkai Zhang,1 Yang Fu,1,2 Saifei Li,1 Yuan Ruan,1 Panying Li,1 Yi Chen,1 Weisheng Feng,1– 3 Xiaoke Zheng1– 3 1College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450008, People’s Republic of China; 2The Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou, 450046, People’s Republic of China; 3Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan province & Education Ministry of P. R. China, Zhengzhou, 450008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weisheng Feng; Xiaoke Zheng, Email fwsh@hactcm.edu.cn; zhengxk.2006@163.comPurpose: Fatty oil of Descurainia Sophia (OIL) has poor stability and low solubility, which limits its pharmacological effects. We hypothesized that fatty oil nanoparticles (OIL-NPs) could overcome this limitation. The protective effect of OIL-NPs against monocrotaline-induced lung injury in rats was studied.Methods: We prepared OIL-NPs by wrapping fatty oil with polylactic-polyglycolide nanoparticles (PLGA-NPs) and conducted in vivo and in vitro experiments to explore its anti-pulmonary hypertension (PH) effect. In vitro, we induced malignant proliferation of pulmonary artery smooth muscle cells (RPASMC) using anoxic chambers, and studied the effects of OIL-NPs on the malignant proliferation of RPASMC cells and phospholipase C (PLC)/inositol triphosphate receptor (IP3R)/Ca2+ signal pathways. In vivo, we used small animal echocardiography, flow cytometry, immunohistochemistry, western blotting (WB), polymerase chain reaction (PCR) and metabolomics to explore the effects of OIL-NPs on the heart and lung pathological damage and PLC/IP3R/Ca2+ signal pathway of pulmonary hypertension rats.Results: We prepared fatty into OIL-NPs. In vitro, OIL-NPs could improve the mitochondrial function and inhibit the malignant proliferation of RPASMC cells by inhibiting the PLC/IP3R/Ca2+signal pathway. In vivo, OIL-NPs could reduce the pulmonary artery pressure of rats and alleviate the pathological injury and inflammatory reaction of heart and lung by inhibiting the PLC/IP3R/Ca2+ signal pathway.Conclusion: OIL-NPs have anti-pulmonary hypertension effect, and the mechanism may be related to the inhibition of PLC/IP3R/Ca2+signal pathway. Keywords: pulmonary hypertension, PLC/IP3R/Ca2+, nanoparticles, RPASMC, fatty oil

Abstract Amorphous carbon (a-C) has attracted considerable interest due to its desirable properties, which are strongly dependent on its structure, density and impurities. Using ab initio molecular dynamics simulations we show that the sp2/sp3 content and underlying structural order of a-C produced via liquid quenching evolve at high temperatures and pressures on sub-nanosecond timescales. Graphite-like densities ( $$\lesssim$$ ≲ 2.7 g/cc) favor the formation of layered arrangements characterized by sp2 disordered bonding resembling recently synthesized monolayer amorphous carbon (MAC), while at diamond-like densities ( $$\gtrsim$$ ≳ 3.3 g/cc) the resulting structures are dominated by disordered tetrahedral sp3 hybridization typical of diamond-like amorphous carbon (DLC). At intermediate densities the system is a highly compressible mixture of coexisting sp2 and sp3 regions that continue to segregate over 10’s of picoseconds. The addition of nitrogen (20.3%) (a-CN) generates major system features similar with those of a-C, but has the unexpected effect of reinforcing the thermodynamically disfavored carbon structural motifs at low and high densities, while inhibiting phase separation in the intermediate region. At the same time, no nitrogen elimination from the carbon framework is observed above $$\simeq$$ ≃ 2.8 g/cc, suggesting that nitrogen impurities are likely to remain embedded in the carbon structures during fast temperature quenches at high pressures.

DC microgrids have become a prevalent topic in research in part due to the expected superior efficiency of DC/DC converters compared to their AC/DC counterparts. Although numer-ous side-by-side analyses have quantified the efficiency benefits of DC power distribution, these studies all modeled converter loss based on product data that varied in component quality and operating voltage. To establish a fair efficiency comparison, this work derives a formulaic loss model of a DC/DC and an AC/DC PFC boost converter. These converters are modeled with identical components and an equivalent input and output voltage. Simulated designs with real components show AC/DC boost converters between 100 W to 500 W having up to 2.5 times more loss than DC/DC boost converters. Although boost converters represent a fraction of electronics in build-ings, these loss models can eventually work toward establishing a comprehensive model-based full-building analysis.

In recent decades, environmental problems have enforced designers to estimate the level of environmental emission of building design and reduce their environmental impact. On the premise of ensuring indoor comfort, the cost-effectiveness of solutions for reducing the building's greenhouse gas has become a critical issue. Based on the Life Cycle Assessment (LCA), this paper establishes a building performance trade-off framework for indoor thermal comfort, economics, and environmental implication. This framework consists of four parts: the establishment of the optimization model; sensitivity analysis; obtain of Pareto frontier solutions, and decision-making analysis. Optimization variables involve envelope type and some envelope physical parameters. The “design variables-building performances” database is obtained by using building simulation software combined with the Latin hypercube sampling algorithm. Sensitivity analysis is used to extract the key factors affecting building performance. The designer can prioritize these key factors and it can reduce the uncertainty of building performance. A multi-objective optimization method coupling Gradient Boosted Decision Tree (GBDT) and non-dominated sorting genetic (NSGA-II) algorithm is proposed to seek the trade-off between three performances (obtain Pareto frontier solutions). The Pareto solution provides a more comprehensive reference for the preferences of different stakeholders, and the set of alternative solutions is further shrunk. Finally, take a specific residential building in China's cold climate zone as a showcase of the trade-off framework. According to the obtained Pareto frontier solution, the solution set is shrunk to a certain range, and the distribution ranges of Life Cycle Costs, the greenhouse gas emissions, and the annual thermal discomfort hour ratio are 122.3–137.1 USD/m2, 15.6–44.8 kg CO2/m2, and 19.1–25.2%, respectively. The trade-off framework adopts the order of objective Pareto optimal and then subjective preference selection, narrowing the scope of alternatives for designers and saving time-cost of decision-making.

The performance of polymer:fullerene bulk heterojunction (BHJ) solar cells is significantly influenced by the morphology of electron donor and acceptor blends under the premise that electronic structure is complimentary regarding donor and acceptor materials. There are many cases where intimate mixing of donor and acceptor perturbs the electronic structure, which fundamentally changes the transport and photovoltaic characteristics. Here, we present the bimolecular crystal packing of polymers and fullerenes, and investigate the correlation between device performance and structural details. We find that bimolecular crystallization can reorganize polymer chain packing, leading to poor electron transport and device performance. The size compatibility and the passivation of entropy penalty led to cocrystallization instability, which was clearly seen byin situGIWAXS data. PC61BM is found to intercalate into side chains of PQT by reorganizing both PQT and PC61BM, forming stable, highly ordered bimolecular crystals. The poor electron transport in bimolecular crystal domain could account for the poor device performance in both perovskite and organic solar cells. Bis-PC61BM, on the other hand, only forms loosely packed aggregates in solution, and then rapidly phase separated into large domains with an edge-on interfacial orientation and performed poorly in solar cells.

Adjustment strategies including window ventilation and shading have important improvements in energy consumption, thermal and light environments, furthermore, the upper limit for improvement is affected by design parameters. However, studies incorporating adjustment strategies in the building design process are very limited. To address this research gap, we explore the effects of window ventilation and shading on building design performance from uncertainty analysis, sensitivity analysis, and multi-objective optimization. Furthermore, China's typical climate zones are compared given climate effects. Results indicate that (1) the uncertainty of total energy demand in the severe cold climate is most affected with the uncertainty increase rate being 32.0%, the uncertainty of thermal comfort ratio in the hot summer and cold winter climate and the hot summer and warm winter climate is most affected with the uncertainty increase rate being 16.3% and 14.0%, respectively. (2) the sensitivity analysis of the thermal comfort ratio is more sensitive to adjustment strategies than to total energy demand. The severe cold climate is more vulnerable than in other climates. (3) when multi-objective optimization is performed with maximum thermal comfort and minimum total energy demand when considering adjustment strategies, the severe cold climate has the greatest energy-saving potential (38.1%) and the hot summer and cold winter climate has the largest potential to improve thermal comfort (17.6%). More importantly, the light environment is within the comfort range from the daylight glare index, the illuminance, and illuminance uniformity ratios.

Household fuel substitution has been a crucial step for controlling air pollution in China, but the performance evaluation of household fuel substitution policies is overlooked. This study capitalized on the opportunity to use data collected during the household coal-replacement program in North China to evaluate the effect of a mandatory policy on fuel substitution at the micro-level. The results indicate that there is a significant effect of the coal-replacement program on fuel substitution, as we expected. The coal-to-electricity policy is effective in achieving the goal of a clean winter but not a warm winter due to the decline of delivered energy, while the high-quality coal replacement policy results in better performance in delivered energy but no improvement in indoor air quality. It is recommended to prioritize supporting measures on both the supply and demand sides before implementation, along with undertaking differential measures during the implementation phase to better address energy inequality.

In analyses of urban environments, city-level sustainability assessments standards have received a lot of attention. Many countries, particularly in the developed world, have developed the standards to measure the performance of neighborhoods, districts, and cities in achieving sustainable development goals. In this study, four standards from China and the United States were selected and analyzed within the scope of green and sustainable development. China's new Assessment Standard for Green Eco-districts (ASGE) targets to support China's New-type Urbanization Plan from the conceptual stage to the concrete implementation. LEED® rating systems are one of the important references for the development of ASGE. By comparing ASGE with the advanced standards it draws from, this study aimed to evaluate ASGE's work in adapting to China's national conditions; pointing out the strengths and weaknesses and proposing improvements. The study results indicate that the rating systems of ASGE are in line with China's national conditions, and that some non-technical indicators are forward-looking, but that there is still room for improvement in terms of implementation paths, weight assignment, number of indicators, and index system. Based on these explorations, this study provides suggestions for aspects of principles and methods that could be used for the construction of similar standards in developing countries.

A carbon dioxide (CO2) based mixture was investigated as a promising solution to improve system performance and expand the condensation temperature range of a CO2 transcritical Rankine cycle (C-TRC). An experimental study of TRC using CO2/R134a mixtures was performed to recover waste heat of engine coolant and exhaust gas from a heavy-duty diesel engine. The main purpose of this study was to investigate experimentally the effect of the composition ratio of CO2/R134a mixtures on system performance. Four CO2/R134a mixtures with mass composition ratios of 0.85/0.15, 0.7/0.3, 0.6/0.4 and 0.4/0.6 were selected. The high temperature working fluid was expanded through an expansion valve and then no power was produced. Thus, current research focused on the analysis of measured operating parameters and heat exchanger performance. Heat transfer coefficients of various heat exchangers using supercritical CO2/R134a mixtures were provided and discussed. These data may provide useful reference for cycle optimization and heat exchanger design in application of CO2 mixtures. Finally, the potential of power output was estimated numerically. Assuming an expander efficiency of 0.7, the maximum estimations of net power output using CO2/R134a (0.85/0.15), CO2/R134a (0.7/0.3), CO2/R134a (0.6/0.4) and CO2/R134a (0.4/0.6) are 5.07 kW, 5.45 kW, 5.30 kW, and 4.41 kW, respectively. Along with the increase of R134a composition, the estimation of net power output, thermal efficiency and exergy efficiency increased at first and then decreased. CO2/R134a (0.7/0.3) achieved the maximum net power output at a high expansion inlet pressure, while CO2/R134a (0.6/0.4) behaves better at low pressure.

Building energy consumption prediction plays an irreplaceable role in energy planning, management, and conservation. Constantly improving the performance of prediction models is the key to ensuring the efficient operation of energy systems. Moreover, accuracy is no longer the only factor in revealing model performance, it is more important to evaluate the model from multiple perspectives, considering the characteristics of engineering applications. Based on the idea of model integration, this paper proposes a novel improved integration model (stacking model) that can be used to forecast building energy consumption. The stacking model combines advantages of various base prediction algorithms and forms them into “meta-features” to ensure that the final model can observe datasets from different spatial and structural angles. Two cases are used to demonstrate practical engineering applications of the stacking model. A comparative analysis is performed to evaluate the prediction performance of the stacking model in contrast with existing well-known prediction models including Random Forest, Gradient Boosted Decision Tree, Extreme Gradient Boosting, Support Vector Machine, and K-Nearest Neighbor. The results indicate that the stacking method achieves better performance than other models, regarding accuracy (improvement of 9.5%–31.6% for Case A and 16.2%–49.4% for Case B), generalization (improvement of 6.7%–29.5% for Case A and 7.1%-34.6% for Case B), and robustness (improvement of 1.5%–34.1% for Case A and 1.8%–19.3% for Case B). The proposed model enriches the diversity of algorithm libraries of empirical models.

Due to reducing the reliance of buildings on fossil fuels, Passive House (PH) is receiving more and more attention. It is important that integrated optimization of passive performance by considering energy demand, cost and thermal comfort. This paper proposed a set three-stage multi-objective optimization method that combines redundancy analysis (RDA), Gradient Boosted Decision Trees (GBDT) and Non-dominated sorting genetic algorithm (NSGA-II) for PH design. The method has strong engineering applicability, by reducing the model complexity and improving efficiency. Among then, the GBDT algorithm was first applied to the passive performance optimization of buildings, which is used to build meta-models of building performance. Compared with the commonly used meta-model, the proposed models demonstrate superior robustness with the standard deviation at 0.048. The optimization results show that the energy-saving rate is about 88.2% and the improvement of thermal comfort is about 37.8% as compared to the base-case building. The economic analysis, the payback period were used to integrate initial investment and operating costs, the minimum payback period and uncomfortable level of Pareto frontier solution are 0.48 years and 13.1%, respectively. This study provides the architects rich and valuable information about the effects of the parameters on the different building performance.

The energy crisis and environmental pollution pose great challenges to human development. Traditional vapor-compression cooling consumes abundant energy and leads to a series of environmental problems. Radiative cooling without energy consumption and environmental pollution holds great promise as the next generation cooling technology, applied in buildings mostly in indirect way. In this work, a temperature-regulating module was introduced for direct summer cooling and winter heating. Firstly, the summer experiments were conduct to investigate the radiative cooling performance of the module. And the results indicated that the maximum indoor temperature reached only 27.5 °C with the ambient temperature of 34 °C in low latitude areas and the air conditioning system was on for only about a quarter of the day. Subsequently, the winter experiments were performed to explore the performance of the module in cooling and heating modes. The results indicated that indoor temperature can reach 25 °C in the daytime without additional heat supply and about a quarter of the day didn't require heating in winter. Additionally, the transient model of the module and the building revealed that the electricity saving of 42.4% (963.5 kWh) can be achieved in cooling season with the module, and that was 63.7% (1449.1 kWh) when coupling with energy storage system. Lastly, further discussion about the challenges and feasible solutions for radiative cooling to directly combine with the buildings were provided to advance the application of radiative cooling. Furthermore, with an acceptable payback period of 8 years, the maximum acceptable incremental cost reached 26.2 $/m2. The work opens up a new avenue for the application mode of the daytime radiative cooling technology.

In this paper, the use of recycled aggregate concrete (RAC) for the upper slabs in steel-concrete composite beams is proposed. Perfobond rib connector (PBL), a relatively new type of shear connectors, has been widely used to ensure composite action between the steel and concrete elements in composite beams. For the past decades, several studies on assessing the performance of PBLs have been conducted, but very few focused on the PBLs that are embedded in RAC slabs. This paper presents results of an experimental and numerical simulation study that focused on characterizing the behavior of PBL fabricated using RAC. In the experimental program, a total of six standard push-out specimens, divided into three groups, were fabricated and loaded to failure. Test results indicated that the ductility of the PBLs using RAC materials decreased as the perforated steel plate thickness decreased, while the PBL ultimate strength increased by 4.3% and 12.8% for steel plate thicknesses of 10.0 mm and 12.0 mm, respectively, as compared to specimens with 8.0 mm steel plate thickness. Finite element (FE) models for PBLs embedded in RAC were developed, and numerical results were validated by corresponding experimental results. An extensive parametric numerical analysis was conducted to assess the effects of different parameters such as transverse steel rebar diameter and perforated steel plate strength and thickness on the performance of such connectors. Numerical simulation results showed that the PBL ultimate strength obtained based on the perforated plate fracture failure mode increases linearly as the steel rebar diameter increases. Also, numerical results indicated that as steel plate strength and thickness increase, failure mode changes from steel plate fracture to rupture of reinforced concrete dowels. Furthermore, existing published analytical formulas for predicting behavior of PBLs were assessed via a comparison with experimental and numerical results developed in this study. The outcomes of this study contribute in providing fundamental knowledge in a new sustainable application of PBL in steel-concrete composite beams with RAC slabs.

Radiative cooling (RC) dissipates terrestrial heat to outer space through the atmospheric window, without external energy input and production of environmental pollutants. More and more efforts have been devoted to this clean promising cooling technology; thus diverse radiative coolers have emerged. However, the performance, cost, and effectiveness of various radiative coolers are not exactly the same. In addition, the large-scale application of RC technology is impeded by the low energy density, uncontrollable cooling power, and limited sky-facing area. Here, we critically review the recent progress of RC technology, evaluate the cooling performance of various radiative coolers, and discuss the challenges and feasible solutions to commercialize RC technology. Furthermore, valuable insights are provided to make new breakthroughs in this field.

Energy-saving technologies in buildings have received great attention from energy efficiency researchers in the construction sector. Traditional research tends to focus on the energy used during building operation and in construction materials production, but it usually neglects the energy consumed in the building construction process. Very few studies have explored the impacts of technological progress on energy efficiency in the construction industry. This paper presents a model of the building construction process based on Cobb-Douglas production function. The model estimates the effects of technological progress on energy efficiency with the objective to examine the role that technological progress plays in energy savings in China's construction industry. The modeling results indicated that technological progress improved energy efficiency by an average of 7.1% per year from 1997 to 2014. Furthermore, three main technological progress factors (the efficiency of machinery and equipment, the proportion change of the energy structure, and research and development investment) were selected to analyze their effects on energy efficiency improvement. These positive effects were verified, and results show the effects of first two factors are significant. Finally, recommendations for promoting energy efficiency in the construction industry are proposed.

Lin Cheng, Pu Yao, Hongping Wang, Qian Yuan, Xiaowen Wang, Wei Feng, Fengjun Sun, Qian Wang Department of Pharmacy, The First Affiliated Hospital of Third Military Medical University (Army Medical University), Chongqing, 400038, People’s Republic of ChinaCorrespondence: Qian Wang; Fengjun Sun, Email xqwq411@126.com; fengj_sun@163.comObjective: In this study, the Lactobacillus plantarum HFY15 (LP-HFY15) strain isolated from naturally fermented yak yogurt was investigated. An animal model of lupus nephritis was established by pristane to verify the interventional effect of LP-HFY15 on mouse lupus nephritis by regulating the transforming growth factor-β 1 (TGF-β 1) signaling pathway.Materials and Methods: Indexes in mouse serum and tissues were detected by kits, pathological changes in mouse kidney were observed by hematoxylin-eosin (H&E) staining, and quantitative polymerase chain reaction (qPCR) was used to detect TGF-β 1-related expression in mouse kidney tissue, which further elucidated the mechanism of LP-HFY15.Results: LP-HFY15 decreased the elevation of urinary protein and the levels of interleukin-6 (IL-6), IL-12, tumor necrosis factor alpha (TNF-α), and interferon γ (IFN-γ) in serum and kidney tissue. LP-HFY15 also reduced serum creatinine (SCr), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), and raised total protein (TP), and albumin (ALB) levels in mice with nephritis. In addition, LP-HFY15 inhibited the positive rate of double-stranded deoxyribonucleic acid (dsDNA) antibodies in mice with nephritis. The observation of H&E sections showed that LP-HFY15 alleviated the glomerulus morphological incompleteness and inflammatory infiltration caused by nephritis. Further results showed that LP-HFY15 downregulated the mRNA expression of TGF-β 1, vascular endothelial growth factor (VEGF), and nuclear factor kappa-B (NF-κB) in the kidneys of lupus nephritis mice, and the expression of inhibitor of NF-κB (IκB-α), copper/zinc superoxide dismutase (Cu/Zn-SOD), and manganese superoxide dismutase (Mn-SOD) was also upregulated.Conclusion: These results indicated that LP-HFY15 plays a significant role in experimental intervention for lupus nephritis. The effect of LP-HFY15 was positively correlated with its concentration, and the effect was similar to that of prednisone at 109 CFU/kg.Keywords: lactic acid bacteria, lupus nephritis, TGF-β 1, dsDNA, pristane