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Shuping Zhang,1,* Yamei Ma,1,* Xiu Zang,2 Hao Heng,2 Xuekui Liu,2 Gangshan Peng,3 Ran Liu,3 Jun Liang,1,2,* Houfa Geng1,2,* 1Graduate School, Bengbu Medical University, Bengbu, Anhui, People’s Republic of China; 2Department of Endocrinology, Xuzhou Central Hospital, Xuzhou, Jiangsu, People’s Republic of China; 3The Affiliated Xuzhou Clinical College, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Houfa Geng; Jun Liang, Email genghoufa@xzhmu.edu.cn; liangjun@xzhmu.edu.cnAbstract: Maturity Onset Diabetes of the Young (MODY) is an autosomal dominant inherited disorder prevalent among adolescents. Typically, it manifests with hyperglycemia before the age of 25. MODY5 is attributed to a mutation in the Hepatocyte Nuclear Factor-1β (HNF-1β) gene. A complete absence of HNF-1β is observed in 50% of those with MODY5. The 17q12 microdeletion syndrome closely linked with MODY5. Its incidence in the general population is around 1 in 14,500 and is linked with facial deformities, diabetes, polycystic kidneys, pancreatic hypertrophy, liver anomalies, and neuropsychological impairments. The most primary clinical signs are predominantly associated with the HNF-1β gene deletion. We chronicle the case of a male of 19 years of age diagnosed with diabetes, who, alongside persistent liver damage and polycystic kidneys, was referred from a community hospital to the Xuzhou Central Hospital. His clinical presentation included diabetes, liver dysfunction, polycystic kidneys, lipid irregularities, insulin resistance, and fatty atrophy. Subsequent genetic screening unveiled a 17q12 chromosomal deletion and an absence of the Hepatocyte Nuclear Factor-1β (HNF-1β) gene. Hence, for adolescent patients lacking a familial diabetes history but exhibiting symptoms like polycystic kidneys, liver damage, lipid irregularities, and fatty atrophy, a thorough assessment for the 17q12 microdeletion syndrome becomes imperative.Keywords: 17q12 microdeletion syndrome, HNF-1β gene, special-type diabetes, MODY5, polycystic kidneys, liver damage

Xinran Yang,1,* Chenglin Yu,2,* Yixin Chen,1 Bin Nian,3 Min Chai,1 Dilimulat Maimaiti,4 Dahai Xu,1 Xiuxian Zang1 1Department of Emergency Medicine, The First Hospital of Jilin University, Changchun, Jilin, 130000, People’s Republic of China; 2Department of Emergency Medicine, Yanbian University Hospital, Yanji, Jilin, 133000, People’s Republic of China; 3Department of Ultrasonography, Yanbian University Hospital, Yanji, Jilin, 133000, People’s Republic of China; 4Department of Emergency Medicine, Seventh Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dahai Xu; Xiuxian Zang, Department of Emergency Medicine, The First Hospital of Jilin University, No. 1 Xinmin Street, Chaoyang District, Changchun, Jilin, 130000, People’s Republic of China, Tel +86-15043032548 ; +86-13596097922, Email xudahai0319@jlu.edu.cn; zangxx@jlu.edu.cnAbstract: Hemorrhagic fever with renal syndrome (HFRS), a naturally occurring epidemic disease, is primarily caused by hantaviruses. It frequently involves the lungs and is characterized by symptoms such as fever, hemorrhage, and renal failure. However, the occurrence of acute pancreatitis (AP) in HFRS patients can be neglected, and high intraocular pressure (IOP) is exceedingly uncommon. In this report, we discuss the case of a 30-year-old male who presented with fever, nausea, vomiting, and abdominal pain. Physical examination revealed extremity petechiae rashes and elevated IOP. Laboratory tests indicated coagulopathy and renal failure. A computed tomography scan confirmed AP. Further testing revealed a positive anti-hantavirus IgM antibody. The patient received supportive care, fluid hydration, hemofiltration, mannitol, brinzolamide, and brimonidine to reduce IOP. Three days post-admission, the patient developed shortness of breath and chest pain. Subsequent chest computed tomography revealed pulmonary edema and bilateral pleural effusion. Treatment included oxygen supply, respiratory support, and thoracentesis, with continued hemofiltration. The patient recovered, regaining normal pulmonary and renal functions and normalized IOP. This case underscores the importance of comprehensive evaluations and vigilant monitoring in HFRS patients, particularly measuring IOP in those with visual complaints, to save lives and reduce morbidity.Keywords: hemorrhagic fever with renal syndrome, acute pancreatitis, high intraocular pressure, pulmonary edema

Jingyi Zhou,* Kangkang Li,* Xinlong Zang, Yi Xie, Jinxiao Song, Xuehong Chen School of Basic Medicine, Qingdao University, Qingdao, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinlong Zang; Xuehong Chen, Email zangxinlong@126.com; chenxuehong@qdu.edu.cnBackground: Triple negative breast cancer (TNBC) is one of the most aggressive tumors with high metastasis and mortality, which constitutes 15~20% of all breast cancers. Chemotherapy remains main therapeutic option in the treatment of patients with TNBC.Methods: We developed reactive oxygen species (ROS)-responsive galactosylated nanoparticles (DOX@NPs) as an efficiently targeted carrier for doxorubicin (DOX) delivery to inhibit the growth of TNBC in vitro and in vivo. DOX@NPs were composed of polyacrylate galactose and phenylboronic derivatives conjugation. The in vitro cytotoxicity, cellular uptake, cell apoptosis and cycle distribution of tumor cells treated with different formulations were investigated. Meanwhile in vivo biodistribution and antitumor effects were investigated in a 4T1 tumor-bearing mouse model.Results: DOX@NPs showed good ROS responsiveness and rapid DOX release in the presence of H2O2. Furthermore, our data suggested that DOX@NPs could effectively trigger tumor cells apoptosis and cycle arrest, efficiently accumulate into tumor sites, and suppress tumor growth without adverse side effects.Conclusion: Our results suggested DOX@NP with potent potential as a promising nanocarrier for TNBC therapy, which deserved further investigation for other cancer treatment.Keywords: triple negative breast cancer, doxorubicin, ROS-responsive, drug delivery

Phytoene and astaxanthin are 2 important carotenoids in the green alga Haematococcus pluvialis. Under environmental stress, the synthesis of phytoene in H. pluvialis increases significantly, and phytoene is converted to astaxanthin through enzymatic catalysis. This paper analyzes the relationship between astaxanthin and phytoene accumulation in carotenoid synthesis pathways under different concentrations of sodium acetate (NaAc) by high-performance liquid chromatography. The highest concentrations of phytoene and astaxanthin were observed at the NaAc concentration of 6 g l-1 on the 12th day of induction. The highest astaxanthin concentration achieved was 2.26 ± 0.28%. Therefore, we concluded that 6 g l-1 NaAc and induction for 12 d provided the optimal inducing conditions for astaxanthin accumulation in H. pluvialis. psy, pds, lcyB, β-carotene ketolase crtw, and crtz, which are genes related to phytoene and astaxanthin synthesis, were cloned and studied at the transcriptional level. crtw and crtz were continuously up-regulated since the first day of induction, while psy, pds, and lcyB were continuously up-regulated starting on the 3rd day of induction. These findings are important for enhancing our understanding of the mechanism of accumulation of phytoene and astaxanthin in H. pluvialis and provide a foundation for identifying the induction conditions necessary for optimizing astaxanthin production and increasing astaxanthin yields.

Chengbao Feng,1 Jingjing Wang,1 Xue Yang,2 Xuefang Zang,1 Haikun Zhou,1 Erying Zhang,1 Haifei Li,1 Bo Liu,1 Shumin Chen,1 Ying Wang,1 Peng Wang,1 Lixue Gao,1 Jinyan Liu1 1Department of Medical Oncology, No. 2 Hospital of Baoding, Baoding City, People’s Republic of China; 2Baoding Children’s Hospital, Baoding City, People’s Republic of ChinaCorrespondence: Jinyan Liu Email movingwind@126.comObjective: The purpose of this study was to prepare and characterize a lipid magnetic ball modified with KRAS antibodies on the surface and to isolate circulating tumor cells of colorectal cancer with KRAS mutations.Methods: The microemulsion method was used to form lipid bilayers to encapsulate Fe3O4 nanoparticles with superparamagnetism to form lipid magnetic balls, and KRAS antibodies were formed on the surface to form KRAS immune lipid magnetic balls.Results: Compared with traditional EpCAM antibody-modified lipid magnetic balls, it can effectively improve the capture ability of colorectal cancer circulating tumor cells with KRAS mutation, the capture rate reaches 92.9%, and the capture results are consistent with clinical diagnosis and pathology.Conclusion: Our results showed that KRAS antibody-modified lipid magnetic balls can be used in the diagnosis and treatment of KRAS colorectal cancer.Keywords: colorectal cancer, circulating tumor cells, KRAS mutation, lipid magnetic balls

Xuege Zang,1,* Zheng Feng,2,* Hui Qiao,1 Libo Wang,1 Chao Fu3 1Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Pediatrics, China-Japan Union Hospital of Jilin University, Changchun, People’s Republic of China; 3Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun, People’s Republic of China*These authors contributed equally to this workCorrespondence: Libo Wang; Chao Fu Email wanglibo20199@126.com; fc616@jlu.edu.cnAbstract: Vertebrobasilar dolichoectasia (VBD) can lead to cranial nerve symptoms. However, multiple cranial nerve symptoms associated with VBD in one case remain extremely rare. We here present the case of a 33-year-old male with VBD diagnosed by multimodality imaging, who developed simultaneous abducens and vestibulocochlear nerve symptoms and subsequently improved after blood pressure control treatment. To our knowledge, this is the first report of such a vascular disorder resulting in simultaneous symptoms of the abducens and vestibulocochlear nerves. This study highlights that such a vascular anomaly should be considered when cranial nerve symptom is encountered, especially when multiple cranial nerves involved. Meanwhile, radiological evaluation of such neurovascular conflict using three-dimensional constructive interference in steady-state imaging is recommended.Keywords: vertebrobasilar dolichoectasia, cranial nerve, abducent nerve, vestibulocochlear nerve, nerve compression syndrome

Xu Zhang,1,2,* Peng Zhang,1,* Meng Shao,1 Xueyan Zang,1 Jiayin Zhang,1 Fei Mao,1 Hui Qian,1,2 Wenrong Xu1,2 1Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China; 2Zhenjiang Key Laboratory of Gastrointestinal Cancer, Jiangsu University, Zhenjiang, Jiangsu 212013, China *These authors contributed equally to this work Background: Increasing evidence suggests that SALL4 plays oncogenic roles in cancer development and progression. We have previously shown that SALL4 is highly expressed in gastric cancer, and its upregulation is associated with lymph node metastasis and poor prognosis. The role of SALL4 in gastric cancer metastasis and the underlying mechanism remain unclear.Materials and methods: The biological roles of SALL4 in gastric cancer cell mobility, migration, and invasion were investigated by wound healing, transwell migration assay, and Matrigel invasion assay. The effects of SALL4 on epithelial–mesenchymal transition (EMT) in gastric cancer cells were examined by quantitative real-time PCR and Western blot. The downstream target genes of SALL4 were identified by microarray. The regulation of TGF-β1 by SALL4 in gastric cancer cells was analyzed by luciferase reporter assay and chromatin immunoprecipitation assay.Results: SALL4 knockdown inhibited, while SALL4 overexpression promoted the motility, migration, and invasion abilities of gastric cancer cells in vitro. SALL4 knockdown also suppressed the peritoneal metastasis of gastric cancer cells in nude mice. SALL4 knockdown suppressed, while SALL4 overexpression induced the activation of TGF-β/SMAD signaling pathway and triggered EMT in gastric cancer cells. TGF-β1 was identified as a direct target gene of SALL4. The results of chromatin immunoprecipitation study and luciferase reporter assay further confirmed that SALL4 bound to the promoter of TGF-β1 gene and activated its expression. TGF-β1 knockdown reversed SALL4-mediated promotion of gastric cancer cell motility, migration, and invasion, indicating that TGF-β1 acts as a downstream effector of SALL4. Furthermore, the expression of TGF-β1 was found to be closely associated with that of SALL4 in gastric cancer tissues.Conclusion: SALL4 promotes the metastasis of gastric cancer, at least partly, by directly activating TGF-β1, suggesting that SALL4 may serve as a new target for gastric cancer therapy. Keywords: gastric cancer, SALL4, TGF-β1, EMT, metastasis

Xinlong Zang,1 Huaiwei Ding,2 Xiufeng Zhao,3 Xiaowei Li,1 Zhouqi Du,1 Haiyang Hu,1 Mingxi Qiao,1 Dawei Chen,1 Yuihui Deng,1 Xiuli Zhao1 1Department of Pharmaceutics, School of Pharmacy, 2Department of Pharmaceutical Chemistry, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China; 3Hongqi Hospital affiliated to Mudanjiang Medical University, Mudanjiang, People’s Republic of ChinaAbstract: Therapeutic delivery of small interfering RNA (siRNA) is a major challenge that limits its potential clinical application. Here, a pH-sensitive cholesterol–Schiff base–polyethylene glycol (Chol–SIB–PEG)-modified cationic liposome–siRNA complex, conjugated with the recombinant humanized anti-EphA10 antibody (Eph), was developed as an efficient nonviral siRNA delivery system. Chol–SIB–PEG was successfully synthesized and confirmed with FTIR and 1H-NMR. An Eph–PEG–SIB–Chol-modified liposome–siRNA complex (EPSLR) was prepared and characterized by size, zeta potential, gel retardation, and encapsulation efficiency. Electrophoresis results showed that EPSLR was resistant to heparin replacement and protected siRNA from fetal bovine serum digestion. EPSLR exhibited only minor cytotoxicity in MCF-7/ADR cells. The results of flow cytometry and confocal laser scanning microscopy suggested that EPSLR enhanced siRNA transfection in MCF-7/ADR cells. Intracellular distribution experiment revealed that EPSLR could escape from the endo-lysosomal organelle and release siRNA into cytoplasm at 4 hours posttransfection. Western blot experiment demonstrated that EPSLR was able to significantly reduce the levels of MDR1 protein in MCF-7/ADR cells. The in vivo study of DIR-labeled complexes in mice bearing MCF-7/ADR tumor indicated that EPSLR could reach the tumor site rather than other organs more effectively. All these results demonstrate that EPSLR has much potential for effective siRNA delivery and may facilitate its therapeutic application. Keywords: siRNA, cationic liposome, pH sensitive, endosomal escape, anti-EphA10 antibody, gene silencing

Background: In the United States, Black and Hispanic/Latinx individuals continue to be disproportionately impacted by HIV. Applying a distributional cost-effectiveness framework, we estimated the distributional health impacts and cost-effectiveness of [...]

OBJECTIVE: This study aimed to compare the efficacy and safety between sintilimab combinations and single treatment in cancer patients, as well as identify biomarkers for selection of patients who might benefit from the combination treatments. MATERIALS AND METHODS: A search of randomized clinical trials (RCTs) comparing sintilimab combinations vs. single treatment in different tumors according to the PRISMA guidelines was performed. Selected endpoints included completion response rate (CR), objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), major adverse effects (AEs), immune-related adverse events (irAEs). Subgroup analyses based on different combination regimens, tumor type and basic biomarkers were included. RESULTS: Results reported from 11 RCTs involving 2,248 patients were included in this analysis. Pooled results indicated that both sintilimab plus chemotherapy and sintilimab plus targeted therapy significantly improved CR [RR=2.44, 95% CI (1.14, 5.20), p=0.021; RR=2.91, 95% CI (1.29, 6.57), p=0.010], ORR [RR=1.34, 95% CI (1.13, 1.59), p=0.001; RR=1.70, 95% CI (1.13, 2.56), p=0.011], PFS [HR=0.56, 95% CI (0.43, 0.69), p<0.001; HR=0.56, 95% CI (0.49, 0.64), p<0.001] and OS [HR=0.59, 95% CI (0.48, 0.70), p<0.001]. Subgroup analyses suggested that the sintilimab-chemotherapy group exhibited a superior PFS benefit than the chemotherapy alone group regardless of age, gender, EGOS PS, PD-L1 expression, smoking status, and clinical stage. There were no significant statistical differences in the incidence of any grade and grade 3 or worse AEs between the two groups [RR=1.00, 95% CI (0.91, 1.10), p=0.991; RR=1.06, 95% CI (0.94, 1.20), p=0.352]. While the incidence of any grade irAEs was higher with sintilimab plus chemotherapy as compared to chemotherapy alone (RR=1.24, 95% CI (1.01, 1.54), p=0.044), but no significant difference was found for grade 3 or worse irAEs (RR=1.11, 95% CI (0.60, 2.03), p=0.741). CONCLUSIONS: Sintilimab combinations brought benefits to a greater number of patients at the cost of a mild increase of irAEs. PD-L1 expression may not be used as a predictive biomarker, composite biomarkers consisting of PD-L1 and MHC class II expression are worth to be explored to enlarge the patient population that benefits from sintilimab combinations. [ABSTRACT FROM AUTHOR]