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The article examines the features of the combustion process of hydrogen-containing gas (syn-gas) in the working cylinder of a spark-ignition internal combustion engine. The main objective of the study is to evaluate the heat release parameters of syngas. To achieve this goal, an exper-imental investigation was conducted to assess the nature of syngas combustion and establish its regularity. The most significant result is the derivation of dependencies for determining the cur-rent value of the combustion characteristic index m and the combustion duration φz in Professor I.I.Vibe's heat release model for spark-ignition engines operating on syngas, with an air excess ratio α ranging from 1.0 to 2.2 and hydrogen content in the fuel composition varying between 30% and 100% by volume. The significance of the obtained results lies in the establishment of the variability of the combustion index m (ranging from 1.6 to 5.5) in Professor I.I.Vibe's semi-empirical heat release model, which more closely corresponds to the actual heat release law ob-served in experimental studies. The proposed dependencies for determining m and φz allow for accounting the specific features of the syngas combustion process in spark-ignition engines, thereby significantly improving the accuracy of determining the indicated pressure in the work-ing cylinder (the relative root-mean-square error does not exceed 4.5%), which, in turn, enhanc-es the accuracy of assessing the engine's energy and economic parameters. The results of this study can be applied in the design and construction of new spark-ignition engines running on alternative fuel.

Ruiming Wang, Weiguo Kong, Wenhua Zhang Department of Neurology, Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, People’s Republic of ChinaCorrespondence: Wenhua Zhang, Department of Neurology, Hangzhou Traditional Chinese Medicine Hospital affiliated to Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China, Tel +86-571-85827888, Fax +86-571-85119481, Email zwhzxpz@hotmail.comObjective: This study aimed to explore the relationship between serum lipoprotein(a) (LP(a)) levels and early neurological deterioration (END) in patients with acute ischemic stroke (AIS) after thrombolysis.Methods: In total, 236 patients with AIS after thrombolysis were enrolled in this study. Serum LP(a) levels were measured on admission after thrombolysis. END was defined as an increase of at least two points in the NIHSS score within 48 hours after thrombolysis. Binary logistic regression analysis was used to assess the association between serum LP(a) levels and END.Results: Overall, patients with END had higher LP(a) than those without END (high LP(a): 38.3% vs 22.2%, intermediate LP(a): 40.3% vs 41.8%, low LP(a): 21.3% vs 36.0%, p< 0.005). In the multivariate analysis, high LP(a) (defined as LP(a) level≥ 300 mg/L) was an independent risk factor for END post-thrombolysis (OR=3.154, 95% CI=1.067– 9.322, p=0.038).Conclusion: Our findings demonstrated that LP(a) was an independent risk factor for END post-thrombolysis and that LP(a) level≥ 300 mg/L could be associated with END post-thrombolysis in this study population.Keywords: Lipoprotein(a), early neurological deterioration, acute ischemic stroke, thrombolysis

Chengran Wang,1,&ast; Yihong Zhang,1,&ast; Weihui Kong,2 Xin’ao Rong,1 Ziming Zhong,1 Lei Jiang,3 Shuhan Chen,1 Chuang Li,1 Fuqiang Zhang,1 Jinlan Jiang1 1Department of Scientific Research Center, China–Japan Union Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China; 2Department of Stomatology, the First Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China; 3Department of Geriatric Medicine, Changchun Central Hospital, Changchun, Jilin Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fuqiang Zhang; Jinlan Jiang, Department of Scientific Research Center, China–Japan Union Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China, Email zfqzhang@jlu.edu.cn; jiangjinlan@jlu.edu.cnAbstract: Osteosarcoma is the predominant primary malignant bone tumor that poses a significant global health challenge. MicroRNAs (miRNAs) that regulate gene expression are associated with osteosarcoma pathogenesis. Thus, miRNAs are potential therapeutic targets for osteosarcoma. Nanoparticles, widely used for targeted drug delivery, facilitate miRNA-based osteosarcoma treatment. Numerous studies have focused on miRNA delivery using nanoparticles to inhibit the progress of osteosarcoma. Polymer-based, lipid-based, inorganic-based nanoparticles and extracellular vesicles were used to deliver miRNAs for the treatment of osteosarcoma. They can be modified to enhance drug loading and delivery capabilities. Also, miRNA delivery was combined with traditional therapies, for example chemotherapy, to treat osteosarcoma. Consequently, miRNA delivery offers promising therapeutic avenues for osteosarcoma, providing renewed hope for patients. This review emphasizes the studies utilizing nanoparticles for miRNA delivery in osteosarcoma treatment, then introduced and summarized the nanoparticles in detail. And it also discusses the prospects for clinical applications. Keywords: osteosarcoma, MicroRNAs, nanoparticle delivery, molecular targeted therapy

Dongdong Li,1 Lijun Bian,1 Lili Cui,2 Jingying Zhou,1 Gaotian Li,1 Xiaoyan Zhao,1 Liao Xing,1 Jiaxing Cui,1 Bo Sun,1 Chunlai Jiang,1,3,4 Wei Kong,1,3,4 Yong Zhang,1,3,4 Yan Chen1,3,4 1National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, People’s Republic of China; 2Beijing Institute of Drug Metabolism, Beijing, People’s Republic of China; 3Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, People’s Republic of China; 4NMPA Key Laboratory of Humanized Animal Models for Evaluation of Vaccines and Cell Therapy Products, Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Yan Chen; Yong Zhang, National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130012, People’s Republic of China, Tel +86-431-85167751, Fax +86-431-85167674, Email chen_yan0417@126.com; zhypharm@jlu.edu.cnPurpose: Heterologous immunization using different vaccine platforms has been demonstrated as an efficient strategy to enhance antigen-specific immune responses. In this study, we performed a head-to-head comparison of both humoral and cellular immune response induced by different prime-boost immunization regimens of mRNA vaccine and adjuvanted protein subunit vaccine against varicella-zoster virus (VZV) in middle-aged mice, aiming to get a better understanding of the influence of vaccination schedule on immune response.Methods: VZV glycoprotein (gE) mRNA was synthesized and encapsulated into SM-102-based lipid nanoparticles (LNPs). VZV-primed middle-aged C57BL/6 mice were then subjected to homologous and heterologous prime-boost immunization strategies using VZV gE mRNA vaccine (RNA-gE) and protein subunit vaccine (PS-gE). The antigen-specific antibodies were evaluated using enzyme-linked immunosorbent assay (ELISA) analysis. Additionally, cell-mediated immunity (CMI) was detected using ELISPOT assay and flow cytometry. Besides, in vivo safety profiles were also evaluated and compared.Results: The mRNA-loaded lipid nanoparticles had a hydrodynamic diameter of approximately 130 nm and a polydispersity index of 0.156. Total IgG antibody levels exhibited no significant differences among different immunization strategies. However, mice received 2×RNA-gE or RNA-gE>PS-gE showed a lower IgG1/IgG2c ratio than those received 2×PS-gE and PS-gE> RNA-gE. The CMI response induced by 2×RNA-gE or RNA-gE>PS-gE was significantly stronger than that induced by 2×PS-gE and PS-gE> RNA-gE. The safety evaluation indicated that both mRNA vaccine and protein vaccine induced a transient body weight loss in mice. Furthermore, the protein vaccine produced a notable inflammatory response at the injection sites, while the mRNA vaccine showed no observable inflammation.Conclusion: The heterologous prime-boost strategy has demonstrated that an mRNA-primed immunization regimen can induce a better cell-mediated immune response than a protein subunit-primed regimen in middle-aged mice. These findings provide valuable insights into the design and optimization of VZV vaccines with the potentials to broaden varicella vaccination strategies in the future.Keywords: varicella-zoster Virus, mRNA vaccine, glycoprotein E, lipid nanoparticles, heterologous prime-boost, cell-mediated immunity

Xiangping Cheng,1,2,&ast; Boyu Chen,3,&ast; Xiaoyan Chen,4,&ast; Zhi Song,2 Jie Li,2 Jiacheng Huang,4 Weilin Kong,4 Jinglun Li1 1Department of Neurology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, People’s Republic of China; 2Department of Neurology, The Gulin People’s Hospital, Luzhou, Sichuan Province, People’s Republic of China; 3Department of Cerebrovascular Diseases, Qujing No. 1 Hospital, Qujing, Yunnan, People’s Republic of China; 4Department of Neurology, Xinqiao Hospital and the Second Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinglun Li, Department of Neurology, The Affiliated Hospital of Southwest Medical University, No. 25 Taiping Street, Jiangyang District, Luzhou City, Sichuan Province, 646000, People’s Republic of China, Email ljl031611@163.com Weilin Kong, Department of Neurology, Xinqiao Hospital and the Second Affiliated Hospital, Army Medical University (Third Military Medical University), No. 183 Xinqiao Main Street, Shapingba District, Chongqing, 400037, People’s Republic of China, Email kongweilin96@whu.edu.cnPurpose: Renal impairment (RI) is associated with unfavourable outcome after acute ischaemic stroke with anterior circulation large vessel occlusion. We assessed the association of RI with clinical outcomes in patients with acute basilar artery occlusion (ABAO), and the impact of RI on the effects of endovascular therapy (EVT) versus standard medical treatment (SMT).Patients and Methods: We used data from the BASILAR registry, an observational, prospective, nationwide study of patients with ABAO in routine clinical practice in China. Baseline estimated glomerular filtration rate (eGFR) was recorded at admission. The primary outcome was the modified Rankin Scale (mRS) score at 90 days. Secondary outcomes included favourable outcome (mRS score 0– 3), mortality, and symptomatic intracranial haemorrhage (sICH). Multivariate logistic regression was used to assess the association of RI with mortality and functional improvement at 90 days.Results: Among 829 patients enrolled, 747 patients were analysed. The median baseline eGFR was 89 mL/min/1.73m2 (IQR, 71– 100), and 350 (46.8%), 297 (39.8%), and 100 (13.4%) patients had baseline eGFR values of ≥ 90, 60– 89, and < 60 mL/min/1.73m2, respectively. RI was associated with increased mortality (adjusted odds ratio [aOR], 1.97; 95% CI, 1.15– 3.67) at 90 days and decreased survival probability (aOR 1.74; 95% CI, 1.30– 2.33) within 1 year. EVT was associated with better functional improvement (common aOR, 2.50; 95% CI, 1.43– 4.35), favourable outcome (aOR 5.42; 95% CI, 1.92– 15.29) and lower mortality (aOR 0.47; 95% CI, 0.25– 0.88) in ABAO patients with eGFR ≥ 90 mL/min/1.73m2. However, RI was not modified the relationship of EVT with functional improvement (common aOR, 3.03; 95% CI, 0.81– 11.11), favourable outcome (aOR 2.10; 95% CI, 0.45– 9.79), and mortality (aOR 0.56; 95% CI, 0.15– 2.06) by eGFR categories.Conclusion: RI is associated with reduced efficacy of EVT and worse functional outcome and higher mortality at 3 months and lower survival probability at 1 year in patients with ABAO.Keywords: ischemia stroke, basilar artery occlusion, renal impairment, endovascular therapy, glomerular filtration rate

A total of 60 isolates of Fusarium were isolated from fruit rot of banana (Musa spp.), papaya (Carica papaya) and guava(Psidium guajava). The most common species recovered from the fruit rot of the three fruit crops were F. semitectum(40 %), F. solani (38.3 %), F. verticillioides (11.7 %) and F. oxysporum (10 %). Fusarium semitectum was isolated from fruit rot of banana, papaya and guava; F. oxysporum from banana and papaya; F. solani from banana and guava and F.verticillioides from banana. From pathogenicity tests, F. solani and F. semitectum were pathogenic to both banana and papaya and F. verticillioides to banana. F. oxysporum was not pathogenic to banana and papaya and F. semitectum was not pathogenic to guava. The results of the present study showed the presence of several Fusarium spp. on fruit rot of banana, papaya and guava and several species are found to be pathogenic causing fruit rot on their hosts.

Zhiping Qi,1 Su Pan,1 Xiaoyu Yang,1 Renfeng Zhang,1 Cheng Qin,1 Hongye Yan,1 Longchuan Zhu,1 Weijian Kong2 1Department of Orthopedic Surgery, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of China; 2Department of Nuclear Medicine, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of ChinaCorrespondence: Weijian Kong; Longchuan Zhu, Email kongweijian0613@sina.com; zhulongchuan0504@163.comPurpose: Spinal cord injury (SCI) is an incurable and disabling event that is accompanied by complex inflammation-related pathological processes, such as the production of excessive reactive oxygen species (ROS) by infiltrating inflammatory immune cells and their release into the extracellular microenvironment, resulting in extensive apoptosis of endogenous neural stem cells. In this study, we noticed the neuroregeneration-promoting effect as well as the ability of the innovative treatment method of FTY720-CDs@GelMA paired with NSCs to increase motor function recovery in a rat spinal cord injury model.Methods: Carbon dots (CDs) and fingolimod (FTY720) were added to a hydrogel created by chemical cross-linking GelMA (FTY720-CDs@GelMA). The basic properties of FTY720-CDs@GelMA hydrogels were investigated using TEM, SEM, XPS, and FTIR. The swelling and degradation rates of FTY720-CDs@GelMA hydrogels were measured, and each group’s ability to scavenge reactive oxygen species was investigated. The in vitro biocompatibility of FTY720-CDs@GelMA hydrogels was assessed using neural stem cells. The regeneration of the spinal cord and recovery of motor function in rats were studied following co-treatment of spinal cord injury using FTY720-CDs@GelMA hydrogel in combination with NSCs, utilising rats with spinal cord injuries as a model. Histological and immunofluorescence labelling were used to determine the regeneration of axons and neurons. The recovery of motor function in rats was assessed using the BBB score.Results: The hydrogel boosted neurogenesis and axonal regeneration by eliminating excess ROS and restoring the regenerative environment. The hydrogel efficiently contained brain stem cells and demonstrated strong neuroprotective effects in vivo by lowering endogenous ROS generation and mitigating ROS-mediated oxidative stress. In a follow-up investigation, we discovered that FTY720-CDs@GelMA hydrogel could dramatically boost NSC proliferation while also promoting neuronal regeneration and synaptic formation, hence lowering cavity area.Conclusion: Our findings suggest that the innovative treatment of FTY720-CDs@GelMA paired with NSCs can effectively improve functional recovery in SCI patients, making it a promising therapeutic alternative for SCI.Keywords: spinal cord injury, carbon dots, FTY720, neural stem cells, hydrogel, GelMA, nerve damage repair

Lili Yuan,1,&ast; Lin An,1,&ast; Yandong Zhu,1 Chongling Duan,1 Weixiang Kong,1 Pei Jiang,2 Qing-Qing Yu1 1Jining NO.1 People’s Hospital, Shandong First Medical University, Jining, People’s Republic of China; 2Translational Pharmaceutical Laboratory, Jining NO.1 People’s Hospital, Shandong First Medical University, Jining, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing-Qing Yu, Jining No.1 People’s Hospital, Shandong First Medical University, Jining, 272000, People’s Republic of China, Email yuqingqing_lucky@163.com Pei Jiang, Translational Pharmaceutical Laboratory, Jining NO.1 People’s Hospital, Shandong First Medical University, Jining, 272000, People’s Republic of China, Email jiangpeicsu@sina.comAbstract: As a disease with high morbidity and high mortality, lung cancer has seriously harmed people’s health. Therefore, early diagnosis and treatment are more important. PET/CT is usually used to obtain the early diagnosis, staging, and curative effect evaluation of tumors, especially lung cancer, due to the heterogeneity of tumors and the differences in artificial image interpretation and other reasons, it also fails to entirely reflect the real situation of tumors. Artificial intelligence (AI) has been applied to all aspects of life. Machine learning (ML) is one of the important ways to realize AI. With the help of the ML method used by PET/CT imaging technology, there are many studies in the diagnosis and treatment of lung cancer. This article summarizes the application progress of ML based on PET/CT in lung cancer, in order to better serve the clinical. In this study, we searched PubMed using machine learning, lung cancer, and PET/CT as keywords to find relevant articles in the past 5 years or more. We found that PET/CT-based ML approaches have achieved significant results in the detection, delineation, classification of pathology, molecular subtyping, staging, and response assessment with survival and prognosis of lung cancer, which can provide clinicians a powerful tool to support and assist in critical daily clinical decisions. However, ML has some shortcomings such as slightly poor repeatability and reliability.Keywords: machine learning, computed tomography, lung cancer, artificial intelligence, diagnosis

Huimin Guo,1,&ast; Songkun Gao,2,&ast; Weimin Kong1 1Gynecology Department, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 2Gynecologic Oncology Department, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weimin Kong, Gynecology Department, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, 100006, People’s Republic of China, Email kwm1967@ccmu.edu.cnObjective: In current most observational studies, the prognosis of cervical adenocarcinoma is worse than that of cervical squamous cell carcinoma. However, most of the current studies are holistic and lack more detailed staging and grouping analysis of the prognosis of the two types of cervical tumors.Patients and Methods: Inclusion from the SEER database of stage IIB-IVA cervical squamous cell carcinoma and cervical adenocarcinoma patients who did not undergo surgery from 2000 to 2019, underwent radiotherapy/chemotherapy/radiotherapy and chemotherapy/no treatment, and then propensity score matching (PSM) was performed to eliminate confounding factors between cervical squamous cell carcinoma and cervical adenocarcinoma patients with the same stage and treatment method. After matching the original data and propensity score, logarithmic rank test and chi square test were used to evaluate the survival benefits of different stages and treatment methods for patients using Kaplan Meier curve. The prognosis of two types of cervical tumors under the same treatment method was compared, and factors that may cause poor prognosis were analyzed, excluding confounding factors.Results: A total of 10,057 patients were included in this study, and survival analysis showed a significant correlation between the treatment method used and patient prognosis (P< 0.05). However, for patients who received radiotherapy or no special treatment, OS and CSS were only related to tumor stage and not to tumor type. In patients undergoing radiotherapy and chemotherapy, the OS and CSS of stage IIIA and IVA patients are not related to tumor pathological characteristics, while the OS of stage IIB patients is not related to tumor properties after PSM.Conclusion: In patients undergoing radiotherapy and chemotherapy, the OS and CSS of stage IIIA and IVA patients were not related to histological type, while the OS of stage IIB patients was not related to histological type after PSM.Keywords: cervical squamous cell carcinoma, cervical adenocarcinoma, staging, prognosis, SEER

Cheng Qin, Zhiping Qi, Su Pan, Peng Xia, Weijian Kong, Bin Sun, Haorui Du, Renfeng Zhang, Longchuan Zhu, Dinghai Zhou, Xiaoyu Yang Department of Orthopedic Surgery, the Second Hospital of Jilin University, Changchun, 130041, People’s Republic of ChinaCorrespondence: Xiaoyu Yang, Department of Orthopedic Surgery, the Second Hospital of Jilin University, Changchun, TX, 130041, People’s Republic of China, Email yangxiaoy@jlu.edu.cnAbstract: Spinal cord injury (SCI) treatment represents a major challenge in clinical practice. In recent years, the rapid development of neural tissue engineering technology has provided a new therapeutic approach for spinal cord injury repair. Implanting functionalized electroconductive hydrogels (ECH) in the injury area has been shown to promote axonal regeneration and facilitate the generation of neuronal circuits by reshaping the microenvironment of SCI. ECH not only facilitate intercellular electrical signaling but, when combined with electrical stimulation, enable the transmission of electrical signals to electroactive tissue and activate bioelectric signaling pathways, thereby promoting neural tissue repair. Therefore, the implantation of ECH into damaged tissues can effectively restore physiological functions related to electrical conduction. This article focuses on the dynamic pathophysiological changes in the SCI microenvironment and discusses the mechanisms of electrical stimulation/signal in the process of SCI repair. By examining electrical activity during nerve repair, we provide insights into the mechanisms behind electrical stimulation and signaling during SCI repair. We classify conductive biomaterials, and offer an overview of the current applications and research progress of conductive hydrogels in spinal cord repair and regeneration, aiming to provide a reference for future explorations and developments in spinal cord regeneration strategies. Keywords: neural tissue engineering, electrical stimulation, electrical signal, conductive biomaterials, spinal cord injury microenvironment

Xueyuan Zhou, Yan Li, Jun Chen, Zhou Fang, Wei Kong, Ji Wen, Qiyao Zhang Reproductive Medical Center, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250000, People’s Republic of ChinaCorrespondence: Ji Wen; Qiyao Zhang, Reproductive Medical Center, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250000, People’s Republic of China, Tel +86 531-82436297, Email 72050580@sdutcm.edu.cn; qiyaozh@163.comPurpose: Transcutaneous electrical acupoint stimulation (TEAS) can be used in patients with infertility. This study explored the impact of TEAS on brain-derived neurotrophic factor (BDNF) levels and in-vitro fertilization (IVF) outcomes in patients with infertility.Patients and Methods: This quasi-experimental study included infertile women undergoing IVF and embryo transfer (IVF-ET) at one hospital between January 2018 and December 2021. The TEAS group received TEAS before IVF, while the placebo group received mock stimulation. The primary outcomes were serum and follicular fluid (FF) BDNF expression levels. Finally, 510 and 518 participants were included in TEAS and placebo groups.Results: The serum (P< 0.001) and FF (P< 0.001) BDNF expression levels were higher in the TEAS group than in the placebo group. The TEAS group had a lower total dose of gonadotropins (P=0.007), higher fertilization rates (P=0.006), higher high-quality embryo rates (P=0.013), and higher pregnancy rates per ET (P=0.031). The subgroup analysis showed that the Val/Val genotype was associated with the differences in serum and FF BDNF between the TEAS and placebo groups (all P< 0.05).Conclusion: In conclusion, TEAS might increase serum and FF BDNF expression levels and improve IVF embryological and clinical outcomes. Patients with the Val/Val genotype might be more likely to benefit from TEAS.Keywords: transcutaneous electrical acupoint stimulation, brain-derived neurotrophic factor, infertility, in-vitro fertilization, embryo transfer, quasi-experimental study

Tao Wang,1,2,&ast; Qianwen Yang,3,&ast; Yan Gao,2 Rongping Zhang,2 Chaoxin Zhou,2 Weifang Kong,1 Guojin Zhang,1 Xinyue Chen,4 Hong Pu,1 Lan Shang1 1Department of Radiology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2Department of Radiology, The First People’s Hospital of Liangshan Yi Autonomous Prefecture, Xichang, Sichuan, People’s Republic of China; 3School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 4CT Collaboration, Siemens-Healthineers, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Pu; Lan Shang, Department of Radiology, The First Department of Radiology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, No. 32, West Section 2, 1st Ring Road, Chengdu, Sichuan Province, 60072, People’s Republic of China, Tel +86 13882267217, Fax +86 87294280, Email ph196797@163.com; shanglan8282@163.comPurpose: This study aimed to investigate clinical features and computed tomography (CT) manifestations of rifampicin primary drug-resistant pulmonary tuberculosis in Liangshan Yi Autonomous Prefecture.Patients and Methods: A total of 100 inpatients with confirmed primary rifampicin-resistant pulmonary tuberculosis were recruited from January 2020 to December 2022 at an infectious disease hospital located in the Liangshan Yi Autonomous Prefecture. Additionally, 100 inpatients with confirmed drug-susceptible pulmonary tuberculosis during the same period were matched to the rifampicin-resistant group based on gender, age, and ethnicity. The clinical characteristics of the two groups were recorded separately. Furthermore, the CT manifestations in these patients were independently analyzed by three radiologists.Results: The results showed that comorbid diabetes mellitus was more prevalent in the drug-resistant tuberculosis (DR-TB) group than in the drug-susceptible tuberculosis (DS-TB) group (9% vs 0%, p=0.0032). In terms of imaging presentation, DR-TB patients exhibited a higher frequency of calcifications (55% vs 35.00%, p=0.0068), greater median number of cavities (5 vs 2, p=0.0027), and larger maximum cavity diameter (52.08± 25.55 mm vs 42.72± 17.48 mm, p=0.0097). Additionally, bilateral involvement was more common in DR-TB patients at the site of the lesion (89% vs 76%, p=0.0246), with a higher prevalence in the right middle (82% vs 68%, p=0.0332), right lower (82% vs 68%, p=0.0332), left upper (91% vs 77%, p=0.0113), and left lower lobes (92% vs 66%, p< 0.0001). Conversely, the involvement of only one lobe was less frequent in patients with DR-TB than in those with DS-TB (4% vs 13%, p=0.0398), whereas the involvement of all five lobes was more common (68% vs 51%, p=0.0209).Conclusion: Patients with DR-TB exhibit a higher prevalence of severe imaging manifestations, highlighting the importance of CT in the early detection and diagnosis of DR-TB.Keywords: drug-resistant tuberculosis, drug-susceptible tuberculosis, tuberculosis, comorbid diabetes mellitus

Xin Yao,1 Qingyu Wang,1 Changge Han,1 Jiaojiao Nie,1 Yaotian Chang,1 Lipeng Xu,1 Bingya Wu,1 Jingtian Yan,1 Zhiyuan Chen,1 Wei Kong,1,2 Yuhua Shi,1 Yaming Shan1,2 1National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin, 130012, People’s Republic of China; 2Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences, Jilin University, Changchun, Jilin, 130012, People’s Republic of ChinaCorrespondence: Yaming Shan, School of Life Sciences, Jilin University, 2699 Qianjin Street, Changchun, Jilin, 130012, People’s Republic of China, Tel +86 133 2446 4361, Email shanym@jlu.edu.cnIntroduction: Broadly neutralizing antibodies (bNAbs) have the ability to neutralize a considerable breadth of genetically diverse human immunodeficiency virus (HIV) strains. Passive immunization can potentially provide protection against HIV infection in animal models. However, the direct antibody infusion effect is limited due to the short half-life and deficient immunogenicity of the antibody. As an alternative strategy, we propose the use of nano viral vectors, specifically the adeno-associated virus (AAV), to continuously and systematically produce bNAbs against HIV.Methods: Plasmids expressing bNAbs PG9, PG16, 10E8, and NIH45-46 antibodies were constructed, targeting three different epitopes of HIV. Additionally, the bNAbs gene mediated by rAAV8 was administered to generate long-term expression with a single injection. We established both single and combined immunization groups. The neutralizing activity of antibodies expressed in mice sera was subsequently evaluated.Results: The expression of bNAbs in BALB/c mice can last for > 24 weeks after a single intramuscular injection of rAAV8. Further studies show that neutralization of the HIV pseudovirus by sera from co-immunized mice with rAAV8 expressing 10E8 and PG16 was enhanced compared with mice immunized with 10E8 or PG16 alone.Conclusion: The prolonged expression of neutralizing antibodies can be maintained over long periods in BALB/c mice. This combined immunization is a promising candidate strategy for HIV treatment.Graphical Abstract: Keywords: AAV delivery, HIV therapy, passive immunotherapy, combined immunotherapy

Chen Wang,1 Jinqin Hou,2 Anning Li,3 Weimin Kong4 1Department of Perinatal Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 2Department of Special Education and Psychology, China National Academy of Educational Sciences, Beijing, People’s Republic of China; 3The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Gynecological Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, People’s Republic of ChinaCorrespondence: Weimin Kong, Department of Gynecological Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, No. 251, Yaojiayuan Road, Chaoyang District, Beijing, People’s Republic of China, Tel +8618611942798, Email kwm1967@ccmu.edu.cnPurpose: Few studies have explored the association between sleep quality and depressive symptoms in perinatal women from the second trimester to the postpartum period. This study aims to explore this relationship using a longitudinal design.Patients and Methods: Participants were enrolled at 15 gestational weeks. Demographic information was collected. Perinatal depressive symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS). Sleep quality was measured employing the Pittsburgh Sleep Quality Index (PSQI) at five timepoints from enrollment to three months postpartum. Overall, 1416 women completed the questionnaires at least thrice. A Latent Growth Curve (LGC) model was performed to identify the relationship between the trajectories of perinatal depressive symptoms and sleep quality.Results: Of the participants, 23.7% screened positive at least once on the EPDS. The perinatal depressive symptoms trajectory, fitted by the LGC model, decreased at early pregnancy and increased from 15 gestational weeks to three months postpartum. The intercept of sleep trajectory positively affected the intercept of perinatal depressive symptoms’ trajectory; the slope of sleep trajectory positively affected both the slope and the quadratic coefficient of perinatal depressive symptoms’ trajectory.Conclusion: The trajectory of perinatal depressive symptoms increased from 15 gestational weeks to three months postpartum following a quadratic trend. Poor sleep quality was associated with depression symptoms beginning at the onset of pregnancy. Moreover, rapidly declining sleep quality could be a significant risk factor for perinatal depression (PND). These findings call for greater attention to perinatal women who report poor and persistently deteriorating sleep quality. Additional sleep-quality evaluations, depression assessments, and referrals to mental health care providers may benefit these women and support PND prevention, screening, and early diagnosis.Keywords: perinatal depression, sleep quality, trajectory, latent growth curve model

An intensification of East Asian rainfall usually occurs in summers following El Niño. We propose that this teleconnection is mediated via the westerlies impinging on the Tibetan Plateau, through El Niño's control on tropical tropospheric temperature. This is distinct from previous studies that attribute the El Niño's influence to changes in the western Pacific subtropical anticyclone. The warming in the eastern equatorial Pacific leads to uniform warming of the entire tropical troposphere, which sharpens the temperature gradient between the tropics and the subtropics and shifts the westerlies southward. The westerlies impinge over the Tibetan Plateau for longer and, through interaction with the topography, induce intense and persistent extratropical northerlies downstream of the plateau that in turn intensifies the East Asian rainband. The rainband has previously been shown to intensify in a similar manner in a warming climate, suggesting that the El Niño response provides an analog for future changes.

The East Asian summer monsoon is unique among summer monsoon systems in its complex seasonality, exhibiting distinct intraseasonal stages. Previous studies have alluded to the downstream influence of the westerlies flowing around the Tibetan Plateau as key to its existence. We explore this hypothesis using an atmospheric general circulation model that simulates the intraseasonal stages with fidelity. Without a Tibetan Plateau, East Asia exhibits only one primary convective stage typical of other monsoons. As the plateau is introduced, the distinct rainfall stages—spring, pre-mei-yu, mei-yu, and midsummer—emerge, and rainfall becomes more intense overall. This emergence coincides with a pronounced modulation of the westerlies around the plateau and extratropical northerlies penetrating northeastern China. The northerlies meridionally constrain the moist southerly flow originating from the tropics, leading to a band of lower-tropospheric convergence and humidity front that produces the rainband. The northward migration of the westerlies away from the northern edge of the plateau leads to a weakening of the extratropical northerlies, which, coupled with stronger monsoonal southerlies, leads to the northward migration of the rainband. When the peak westerlies migrate north of the plateau during the midsummer stage, the extratropical northerlies disappear, leaving only the monsoon low-level circulation that penetrates northeastern China; the rainband disappears, leaving isolated convective rainfall over northeastern China. In short, East Asian rainfall seasonality results from the interaction of two seasonally evolving circulations—the monsoonal southerlies that strengthen and extend northward, and the midlatitude northerlies that weaken and eventually disappear—as summer progresses.

The sea surface temperature (SST) contrast between the Northern Hemisphere (NH) and Southern Hemisphere (SH) influences the location of the intertropical convergence zone (ITCZ) and the intensity of the monsoon systems. This study examines the contributions of external forcing and unforced internal variability to the interhemispheric SST contrast in HadSST3 and ERSSTv5 observations, and 10 models from phase 5 of the Coupled Model Intercomparison Project (CMIP5) from 1881 to 2012. Using multimodel mean fingerprints, a significant influence of anthropogenic, but not natural, forcing is detected in the interhemispheric SST contrast, with the observed response larger than that of the model mean in ERSSTv5. The forced response consists of asymmetric NH–SH SST cooling from the mid-twentieth century to around 1980, followed by opposite NH–SH SST warming. The remaining best-estimate residual or unforced component is marked by NH–SH SST maxima in the 1930s and mid-1960s, and a rapid NH–SH SST decrease around 1970. Examination of decadal shifts in the observed interhemispheric SST contrast highlights the shift around 1970 as the most prominent from 1881 to 2012. Both NH and SH SST variability contributed to the shift, which appears not to be attributable to external forcings. Most models examined fail to capture such large-magnitude shifts in their control simulations, although some models with high interhemispheric SST variability are able to produce them. Large-magnitude shifts produced by the control simulations feature disparate spatial SST patterns, some of which are consistent with changes typically associated with the Atlantic meridional overturning circulation (AMOC).

This study explores how the termination of the mei-yu is dynamically linked to the westerlies impinging on the Tibetan Plateau. It is found that the mei-yu stage terminates when the maximum upper-tropospheric westerlies shift beyond the northern edge of the plateau, around 408N. This termination is accompanied by the disappearance of tropospheric northerlies over northeastern China. The link between the transit of the jet axis across the northern edge of the plateau, the disappearance of northerlies, and termination of the mei-yu holds on a range of time scales from interannual through seasonal and pentad. Diagnostic analysis indicates that the weakening of the meridional moisture contrast and meridional wind convergence, mainly resulting from the disappearance of northerlies, causes the demise of the mei-yu front. The authors propose that the westerlies migrating north of the plateau and consequent weakening of the extratropical northerlies triggers the mei-yu termination. Model simulations are employed to test the causality between the jet and the orographic downstream northerlies by repositioning the northern edge of the plateau. As the plateau edge extends northward, orographic forcing on the westerlies strengthens, leading to persistent strong downstream northerlies and a prolonged mei-yu. Idealized simulations with a dry dynamical core further demonstrate the dynamical link between the weakening of orographically forced downstream northerlies with the positioning of the jet from south to north of the plateau. Changes in the magnitude of orographically forced stationary waves are proposed to explain why the downstream northerlies disappear when the jet axis migrates beyond the northern edge of the plateau.

Jianyi Li,1,&ast; Keke Li,2,&ast; Yukun Du,1,&ast; Xiaojie Tang,3,&ast; Chenjing Liu,1 Shannan Cao,3 Baomeng Zhao,2 Hai Huang,3 Hongri Zhao,3 Weiqing Kong,1 Tongshuai Xu,3 Cheng Shao,1 Jiale Shao,1 Guodong Zhang,4 Hongbo Lan,5 Yongming Xi1 1Department of Orthopaedic Surgery, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Yantai Campus of Binzhou Medical University, Yantai, People’s Republic of China; 3Yantai Affiliated Hospital of Binzhou Medical University, Yantai, People’s Republic of China; 4Tengzhou Central People’s Hospital, Tengzhou, People’s Republic of China; 5Shandong Engineering Research Center for Additive Manufacturing Qingdao University of Technology, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongming Xi, Department of Orthopaedic Surgery, the Affiliated Hospital of Qingdao University, Qingdao, 266071, People’s Republic of China, Email xym700118@163.com Hongbo Lan, Shandong Engineering Research Center for Additive Manufacturing Qingdao University of Technology, Qingdao, 266520, People’s Republic of China, Email hblan99@126.comBackground: Successful treatment of infectious bone defect remains a major challenge in the orthopaedic field. At present, the conventional treatment for infectious bone defects is surgical debridement and long-term systemic antibiotic use. It is necessary to develop a new strategy to achieve effective bone regeneration and local anti-infection for infectious bone defects.Methods: Firstly, vancomycin / poly (lactic acid-glycolic acid) sustained release microspheres (VAN/PLGA-MS) were prepared. Then, through the dual-nozzle 3D printing technology, VAN/PLGA-MS was uniformly loaded into the pores of nano-hydroxyapatite (n-HA) and polylactic acid (PLA) scaffolds printed in a certain proportion, and a composite scaffold (VAN/MS-PLA/n-HA) was designed, which can not only promote bone repair but also resist local infection. Finally, the performance of the composite scaffold was evaluated by in vivo and in vitro biological evaluation.Results: The in vitro release test of microspheres showed that the release of VAN/PLGA-MS was relatively stable from the second day, and the average daily release concentration was about 15.75 μg/mL, which was higher than the minimum concentration specified in the guidelines. The bacteriostatic test in vitro showed that VAN/PLGA-MS had obvious inhibitory effect on Staphylococcus aureus ATCC-29213. Biological evaluation of VAN/MS-PLA/n-HA scaffolds in vitro showed that it can promote the proliferation of adipose stem cells. In vivo biological evaluation showed that VAN/MS-PLA/n-HA scaffold could significantly promote bone regeneration.Conclusion: Our research shows that VAN/MS-PLA/n-HA scaffolds have satisfying biomechanical properties, effectively inhibit the growth of Staphylococcus aureus, with good biocompatibility, and effectiveness on repairing bone defects. The VAN/MS-PLA/n-HA scaffold provide the clinic with an application prospect in bone tissue engineering.Graphical Abstract: Keywords: osteogenesis, dual-nozzle 3D printing technology, drug-loaded microspheres, vancomycin, nano-hydroxyapatite

Peng Jiang,1 Wei Kong,1 Chunxia Gong,2 Yanlin Chen,3 Fenglian Li,1 Lingya Xu,1 Yang Yang,1 Shikai Gou,1 Zhuoying Hu1 1Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Obstetrics and Gynecology, Women and Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Pathology, Women and Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Zhuoying Hu, Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China, Tel +86 2389011092, Fax +86 2389011082, Email huzhuoying@sina.comObjective: The purpose of this study was to evaluate the prognostic value of hemoglobin, albumin, lymphocyte, and platelet (HALP) score in patients with operable cervical cancer, and on this basis, combined with classical clinicopathological parameters to predict the recurrence of patients.Methods: A total of 1580 patients with stage IA-IIA cervical cancer were randomly divided into training cohort (n=1054) and validation cohort (n=526) according to the predefined ratio of 2:1. In the training cohort, the receiver operating characteristic (ROC) curve and Youden index were used to determine the optimal threshold of HALP score for predicting cervical cancer recurrence. On this basis, the independent related factors with cervical cancer recurrence were screened through univariate and multivariate Cox regression analysis, and then a nomogram model was further established. The internal and external validation of the model was carried out in the training cohort and the validation cohort respectively through the consistency index (C-index) and calibration curve.Results: ROC curve and Youden index showed that the optimal threshold of HALP score for predicting cervical cancer recurrence was 39.50. Multivariate analysis confirmed that HALP score and some other classic clinicopathological parameters were independently associated with cervical cancer recurrence. Based on the results of multivariate analysis, a nomogram model for predicting cervical cancer recurrence was successfully constructed. The internal and external calibration curves showed that the fitting degree of the model was good, and the C-index (the C-index of the training cohort and the validation cohort were 0.862 and 0.847, respectively) showed that the prediction accuracy of the model proposed in this study was better than other similar models.Conclusion: HALP score may be a novel predictor for predicting the cervical cancer recurrence. Nomogram model based on HALP score and classical clinicopathological parameters can better predict the recurrence of cervical cancer.Keywords: HALP score, nomogram model, predict, cervical cancer, recurrence

Increased atmospheric moisture content and changing land-ocean thermal contrasts are usually implicated in the East Asian summer rainfall response to global warming. We highlight an additional influence whereby increased meridional stationary eddy circulation downstream of the Tibetan Plateau drives a stronger moisture flux convergence over southeastern China, intensifying the early summer rainband. This effect occurs robustly across the Community Earth System Model large ensemble Representative Control Pathway 8.5 simulations, and only for its pre-Meiyu stage (mid-May through late June). The westerly jet impinging on the Plateau is also enhanced, suggesting an orographic influence on the westerlies as the root cause. The increased westerlies result from warmer tropical tropospheric temperatures that enhance the meridional temperature gradient at the latitudes of the Plateau. Our results highlight the potential role of the westerlies in altering the East Asian early summer monsoon rainfall in the late 21st century.

Xiuhua Jiang,1,&ast; Shiqi Chai,1,&ast; Yan Huang,2,&ast; Zuxiong Huang,3,&ast; Wenting Tan,4,&ast; Yanhang Gao,5,&ast; Xiaobo Lu,6,&ast; Zhongji Meng,7,&ast; Huayou Zhou,8 Wenbing Kong,8 Xiaoting Tang,1 Yujun Tang,1 Tingting Qi,1 Chengjin Liao,2 Qiaorong Gan,3 Xiaomei Xiang,4 Yanan Zhang,5 Shuai Wang,6 Yuanyuan Chen,7 Jinjun Chen1,9 1Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 3Department of Hepatology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 4Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, People’s Republic of China; 5Department of Hepatology, the First Hospital of Jilin University, Changchun, People’s Republic of China; 6Infectious Disease Center, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 7Department of Infectious Diseases, Hubei Clinical Research Center for Precise Diagnosis and Treatment of Liver Cancer, Taihe Hospital, Hubei University of Medicine, Shiyan, People’s Republic of China; 8Department of Blood Transfusion, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 9Hepatology Unit, Zengcheng Branch, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinjun Chen, Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, No. 1838, Guangzhou Dadao Bei, Guangzhou, 510515, People’s Republic of China, Email chjj@smu.edu.cnBackground: Acute-on-chronic liver failure (ACLF) has high short-term mortality and lacks sufficient medical therapy. Available algorithms are unable to precisely predict short-term outcomes or safely stratify patients with ACLF as emergent liver transplantation candidates. Therefore, a personalized prognostic tool is urgently needed.Purpose: Platelet function and its clinical significance in ACLF patients with chronic hepatitis B virus (HBV) infection have not been investigated. This study aimed to assess changes in platelet function using thromboelastography (TEG) and platelet mapping (TEG-PM) in HBV-related ACLF patients.Methods: Chronic liver disease patients with acute decompensation or acute hepatic injury were recruited. The derivation cohort enrolled HBV-related patients at Nanfang Hospital. HBV-related and non-HBV-related patients were both enrolled in internal and external validation cohorts at seven university hospitals. TEG and TEG-PM were performed at baseline in the derivation cohort and baseline, day 7, and day 14 in the validation cohorts. The primary outcome was all-cause 28-day mortality. Status check and new-onset complications were recorded during the 3-month follow-up, but status check will extend to 5 years.Conclusion and Future Plans: In this study, 586 participants were enrolled, including 100 in derivation cohort, 133 in internal validation cohort, and 353 in external validation cohort. Biomaterials, including plasma, serum, urine, and some explanted liver tissues, were collected from these patients. A 3-month follow-up with survival status was completed. The baseline characteristics indicated that 51% of the patients had adenosine diphosphate (ADP)-hyporesponsive circulating platelets. The prognostic potential of platelet function will be explored in the derivation cohort (HBV-related ACLF patients) and further substantiated in the validation cohorts (HBV-related and non-HBV-related ACLF patients). Biosamples are currently used to explore the underlying mechanisms related to ADP-hyporesponsive platelets. The ongoing proteomic and metabolic analyses will provide new insights into the pathogenesis of extrahepatic organ failures in ACLF patients.Keywords: acute-on-chronic liver failure, coagulopathy failure, platelet function, thromboelastography, prognosis, study design

Ying Shi1– 3&ast;, Wenming Kong1 &ast;, Haiqin Jiang,2,3 Wenyue Zhang,2,3 Chen Wang,2– 4 Limei Wu,1 Yunliang Shen,1 Qiang Yao,1 Hongsheng Wang1– 3,5 1Department of Leprosy Control, Zhejiang Provincial Institute of Dermatology, Huzhou, People’s Republic of China; 2Hospital of Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, People’s Republic of China; 3National Centre for STD and Leprosy Control, China CDC, Nanjing, People’s Republic of China; 4Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China; 5Centre for Global health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China&ast; These authors contributed equally to this workCorrespondence: Qiang Yao, Department of Leprosy Control, Zhejiang Provincial Institute of Dermatology, St 61, Zhejiang, People’s Republic of China, Email 7793908@qq.com Hongsheng Wang, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 12 Jiangwangmiao Street, Nanjing, People’s Republic of China, Tel: +86 025 8547 8953, Email whs33@vip.sina.comPurpose: Reports on antimicrobial resistance (AMR) of Mycobacterium leprae (M. leprae) in Zhejiang Province are limited. Thus, this study aimed to investigate the drug resistance of new leprosy cases within several years and analyse the emergence of AMR mutations from Zhejiang Province.Methods: This study enrolled 34 leprosy cases in Zhejiang Province, China, from 2018 to 2021. Gene mutation of WHO-recommended DRDRs (folP1, rpoB and gyrA) and genes of compensatory AMR-associated DRDRs, including nth, rpoA, rpoC, gyrB and 23S rRNA, were detected by amplification. Clinical data analysis was performed to investigate the epidemiological association of leprosy.Results: Of the 34 samples, 2 (5.9%) strains showed drug resistance, which were mutated to dapsone and ofloxacin, separately. Two single mutations in gyrB were detected in different strains (5.9%), whereas one of the rpoC mutation was also detected in one strain each (2.9%), which were proved to be polymorphs. No correlation of drug resistance proportion was identified in male vs female, nerve vs no nerve involvement, deformity vs no deformity and reaction vs non-reaction cases.Conclusion: Results showed well control of leprosy patients in Zhejiang Province. Gene mutations of WHO-recommended DRDRs folP1 and gyrA confirmed the resistance to dapsone and ofloxacin. Compensatory AMR-associated mutations confirmed to be polymorphs still require further study to determine their phenotypic outcomes in M. leprae. The results demonstrated that drug-resistant strains are not epidemic in this area. Given the few cases of leprosy, analysing the AMR of M. leprae in Zhejiang Province more comprehensively is difficult. However, regular MDT treatment and population management in the early stage may contribute to the low prevalence of leprosy.Keywords: M. leprae, antimicrobial resistance, gene mutation

Despite important progress in understanding the influence of deforestation on the bacterial α diversity and community structure at local scales, little is known about deforestation impacts in terms of spatial turnover and soil bacterial community network interactions, especially at regional or global scales. To address this research gap, we examined the bacterial spatial turnover rate and the species networks in paired primary and secondary forest soils along a 3700-km north-south transect in eastern China using high-throughput 16S rRNA gene sequencing. The spatial turnover rate of bacterial communities was higher in primary forests than in secondary, suggesting deforestation increased biotic homogenization at a large geographic scale. Multiple regression on matrices analysis revealed that both geographic distance and soil properties (especially soil pH and organic matter availability) strongly affected bacterial spatial turnover. Through the phylogenetic molecular ecological network approach, we demonstrate that the bacterial network of primary forests was more intricate than in secondary forests. This suggests that microbial species have greater niche-sharing and more interactions in primary forests as compared to secondary forests. On the other hand, the bacterial network in secondary forests was more modular, and the taxa tended to co-occur, with positive correlations accounting for 82% of all potential interactions. In conclusion, our findings demonstrate that anthropogenic deforestation has clear effects on bacterial spatial turnover and network interactions, with potential for serious consequences such as microbial diversity loss in primary forests.

He Zhang, Weimin Kong, Chao Han, Tingting Liu, Jing Li, Dan Song Department of Gynecological Oncology, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Weimin KongDepartment of Gynecological Oncology, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Qihelou Street, Dongcheng District, Beijing, 100006, People’s Republic of ChinaTel +86 18801273620Email kwm1967@ccmu.edu.cnPurpose: This study aimed to investigate the association of metabolic factors with endometrial atypical hyperplasia and endometrial cancer, and to develop a nomogram model to predict the risk of developing endometrial cancer.Patients and Methods: We collected data of patients with endometrial atypical hyperplasia and endometrial cancer as the case group and then selected patients with simple hyperplasia or polypoid hyperplasia of the endometrium during the same period as the control group using the age-matched method. Laboratory results of metabolic factors were retrieved from the clinical data of the two groups of patients. Multivariable logistic regression analysis was used to determine the risk factors associated with endometrial malignant hyperplasia and to develop a nomogram prediction model of risk factors associated with endometrial malignant hyperplasia. Discrimination, calibration, and clinical usefulness of the prediction model were assessed using the C-index, calibration plot, and decision curve analysis.Results: Predictors included in the column line graph model were age, hypertension, diabetes, BMI, uric acid, and hyperlipidemia. We calculated the C-index of the model and performed bootstrap validation. Our nomogram model had good discriminatory power and was well calibrated. Decision curve analysis was also used to guide the practical application of this column line graph model.Conclusion: The development of endometrial malignant hyperplasia is significantly associated with metabolic factors: BMI > 25, hyperuricemia, and hyperlipidemia are the main risk factors. Hypertension, hyperglycemia and elevated CA199 were also associated with the development of endometrial malignant hyperplasia. The nomogram prediction model based on physical examination and laboratory testing developed in this study can be used as a rapid method for predicting the risk of endometrial malignancy development and screening for risk factors in a population of women with metabolism-related high-risk factors.Keywords: risk factors, gynecologic oncology, predictors, nomogram

The Holocene East Asian summer monsoon (EASM) was previously characterized as a trend toward weaker monsoon intensity paced by orbital insolation. It is demonstrated here that this evolution is more accurately characterized as changes in the transition timing and duration of the EASM seasonal stages (spring, pre-mei-yu, mei-yu, midsummer), and tied to the north-south displacement of the westerlies relative to Tibet. To this end, time-slice simulations across the Holocene are employed using an atmospheric general circulation model. Self-organizing maps are used to objectively identify the transition timing and duration of the EASM seasonal stages. Compared to the late Holocene, an earlier onset of mei-yu and an earlier transition from mei-yu to midsummer in the early to mid-Holocene are found, resulting in a shortened mei-yu and prolonged midsummer stage. These changes are accompanied by an earlier northward positioning of the westerlies relative to Tibet. Invoking changes to seasonal transitions also provides a more satisfactory explanation for two key observations of Holocene East Asian climate: the "asynchronous Holocene optimum" and changes to dust emissions. A mechanism is proposed to explain the altered EASM seasonality in the simulated early to mid-Holocene. The insolation increase over the boreal summer reduces the pole-equator temperature gradient, leading to northward-shifted and weakened westerlies. The meridional position of the westerlies relative to the Tibetan Plateau determines the onset of mei-yu and possibly the onset of the midsummer stage. The northward shift in the westerlies triggers earlier seasonal rainfall transitions and, in particular, a shorter mei-yu and longer midsummer stage.

A recent hypothesis holds that changes to the East Asian summer rainfall are characterized by changes in the timing and duration of its intraseasonal stages, controlled by the meridional position of the westerlies relative to the Tibetan Plateau. This hypothesis is examined in the context of the leading mode of East Asian summer (July–August) rainfall. One phase of this “tripole” mode—characterized by less rainfall over central eastern China and increased rainfall over northeastern and southeastern China—is tied to an earlier termination of Meiyu that results in a significantly shorter Meiyu and longer Midsummer stage. This phase also exhibits an earlier northward transition of the westerlies to the north of the Plateau, essentially mirroring the changes to precipitation seasonality. The reverse does not hold true for the opposite phase. Our results show direct observational evidence for the meridional position of the westerlies to control East Asian summer monsoon seasonality.

Weihao Kong,1,* Li Zhang,2,* Ran An,1,* Mingwei Yang,2 Hao Wang2 1Department of Emergency Surgery, Department of Emergency Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hao WangDepartment of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Avenue, Hefei, 230032, People’s Republic of ChinaEmail wanghaoayfy@163.comBackground: Previous studies have shown that D-dimer plays an essential role in the occurrence and development of various tumors, and its diagnostic value in gallbladder carcinoma (GBC) is unknown. Therefore, the purpose of our study was to explore the diagnostic value of D-dimer in distinguishing between gallbladder carcinoma and benign controls.Methods: We retrospectively included age and gender-matched patients with gallbladder carcinoma and benign gallbladder lesions, and analyzed the diagnostic value of inflammatory markers, D-dimers, and tumor biomarkers by receiver operating characteristic curves (ROC).Results: The area under the ROC curve of white blood cells (WBC), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), D-dimer, alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and carbohydrate antigen 19– 9 (CA19-9) were 0.600, 0.760, 0.729, 0.849, 0.502, 0.699, and 0.802, respectively. The combined diagnostic value of D-dimer and CA19-9 was 0.920, which was superior to other joint indicators.Conclusion: Serum D-dimer may be considered as a potential biomarker for detection of GBC. Moreover, the combined diagnosis of D-dimer and CA19-9 has excellent diagnostic value in gallbladder carcinoma.Keywords: D-dimer, CA19-9, diagnosis, gallbladder carcinoma

This study examined the drag reduction properties of cylindrical flows across various asymmetric notched structures through numerical simulation and particle image velocimetry. The focus was on investigating the influence of the number of asymmetric grooves on the drag characteristics, including the mean drag, spectral characteristics, time-averaged streamlines, separation point prediction, time-averaged pressure, wake vortex strength, Reynolds stress, and turbulent kinetic energy. The results showed that the presence of asymmetric grooves significantly influenced these flow parameters. Notably, the improvement was optimal in the four-groove configuration, evidenced by the lowest mean drag coefficient (0.804), vortex shedding frequency (2.74 Hz), recirculation area length (1.208D), and pressure difference across the cylinder (81.76). Moreover, this configuration resulted in the weakest trailing vortex, a 45% reduction in the maximum Reynolds stress (0.011), and a 40.5% decrease in the maximum turbulent kinetic energy (0.05). Thus, the presence of asymmetric grooves had a significant positive effect on the cylindrical flow properties, though the degree of improvement decreased with further increase in the number of grooves. [ABSTRACT FROM AUTHOR]

Insulin-like peptides (ILPs) play important roles in growth and metabolic homeostasis, but have also emerged as key regulators of stress responses and immunity in a variety of vertebrates and invertebrates. Furthermore, a growing literature suggests that insulin signaling-dependent metabolic provisioning can influence host responses to infection and affect infection outcomes. In line with these studies, we previously showed that knockdown of either of two closely related, infection-induced ILPs, ILP3 and ILP4, in the mosquito Anopheles stephensi decreased infection with the human malaria parasite Plasmodium falciparum through kinetically distinct effects on parasite death. However, the precise mechanisms by which ILP3 and ILP4 control the response to infection remained unknown. To address this knowledge gap, we used a complementary approach of direct ILP supplementation into the blood meal to further define ILP-specific effects on mosquito biology and parasite infection. Notably, we observed that feeding resulted in differential effects of ILP3 and ILP4 on blood-feeding behavior and P. falciparum development. These effects depended on ILP-specific regulation of intermediary metabolism in the mosquito midgut, suggesting a major contribution of ILP-dependent metabolic shifts to the regulation of infection resistance and parasite transmission. Accordingly, our data implicate endogenous ILP signaling in balancing intermediary metabolism for the host response to infection, affirming this emerging tenet in host-pathogen interactions with novel insights from a system of significant public health importance.