BACKGROUND:Effects of different oxygen partial pressures on cytokine secretion of human adipose-derived stem cells have been differently reported. These differences may be caused by varying oxygen partial pressures.
OBJECTIVE:To investigate the influence of different oxygen partial pressures on cytokines secreted from human adipose-derived stem cells.
METHODS:Human adipose-derived stem cells were cultured in vitro and identified by its immunophenotype. Human adipose-derived stem cells were divided into five groups and cultured under different oxygen partial pressure conditions (1%, 3%, 5%, 10%, 21%) for 24 hours, respectively. With quantitative real-time PCR and enzyme linked immunosorbent assay, the secretion of cytokines, vascular endothelial growth factor, hepatocyte growth factor, nerve growth factor, keratinocyte growth factor, from human adipose-derived stem cells were analyzed on the gene and protein levels.
RESULTS AND CONCLUSION:Human adipose-derived stem cells were positive for CD71, CD73, CD90, CD105 and negative for CD34, CD45, CD54, HLA-DR. From the aspect of gene level, hypoxia (1%, 3%O 2 ) promoted the expression of vascular endothelial growth factor and nerve growth factor from human adipose-derived stem cells (P<0.01), and significantly elevated the expression of hepatocyte growth factor (P<0.05);however, there was no significant influence on keratinocyte growth factor under hypoxia (P>0.05). Based on the protein level, protein secretion of hepatocyte growth factor and vascular endothelial growth factor from human adipose-derived stem cells was increased under hypoxia (P<0.01), but no changes occurred in nerve growth factor and keratinocyte growth factor. After cultured under hypoxic environment, human adipose-derived stem cells were promoted to express gene vascular endothelial growth factor, hepatocyte growth factor and nerve growth factor, as wel as to secrete protein keratinocyte growth factor and vascular endothelial growth factor.

Objective To investigate the diagnostic significance of the difference values between Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA)in elderly patients with dementia.Methods 331 elderly patients with dementia were collected from outpatients in our hospital.There were 148 people with Alzheimer's disease (AD),87 cases with vascular dementia (VaD),44 cases with mixed dementia (MD),41 cases with frontotemporal dementia (FTD) and 11 cases with dementia with Lewy bodies (DLB).MMSE and MoCA were applied to test the cognitive impairment separately.Results The difference values between MMSE and MoCA was (3.3±1.7) points,(6.6±2.1) points,(6.6±2.1) points,(5.4±2.3) points,(6.1 ± 1.9) points in AD,VaD,MD,FTD and DLB group respectively,and there were statistical differences among the five groups (F=46.420,P=0.000).Statistical differences were found in the difference values between MMSE and MoCA between dementia patients with AD and non-AD (t=-13.429,P=0.000).According to receiver operating characteristic curve (ROC curve),the optimal cut off point of the difference values between MMSE and MoCA for differential diagnosis between AD and non-AD dementia was 5 points,with 79.8％ sensitivity and 78.4％ specificity,and area under the curve was 0.848 (95％CI:0.807-0.890).Conclusions The difference values between MMSE and MoCA may be one of parameters for differential diagnosis between AD and non-AD dementia.

BACKGROUND:Biomimetic design of bioactive materials to restore,maintain or improve the function of tissue based on the understanding of anatomy on the function and structure of biological tissue is a research hotspot in the field of regenerative medicine at present. OBJECTIVE:To discuss the effect of mechanical properties,three-dimensional spatial structure,and biochemical activity of biomedical scaffolds on cell behavior and review the application of biomedical scaffolds in the field of tissue engineering. METHODS:The articles published in CNKI,Wanfang,Web of Science,and PubMed databases from January 2003 to April 2023 were searched by computer.The Chinese search terms were"extracellular matrix,tissue engineering,scaffolds,biomaterials,biomimetic structures,mechanical properties,three-dimensional structures,tendon-bone interface,osteochondral,neural conduits,artificial blood vessels".English search terms were"extracellular matrix,tissue engineering,scaffolds,biomimetic structures,biomaterials,tendon bone interfaces,osteochondral,neural conduits,artificial blood vessels". RESULTS AND CONCLUSION:Cells are in a complex and dynamic three-dimensional environment,so the extracellular matrix is the ultimate target of biomaterial simulation.The bionic structure of biomedical scaffolders needs to be similar to the real microenvironment,so that cells can stick to the wall,grow and migrate normally,and maintain their diverse physiological functions.Biomimetic design of extracellular matrix in terms of mechanical properties,three-dimensional spatial structure,and biochemical properties of biomedical scaffolds can play a decisive role in tissue repair,thus affecting the final result of tissue repair.Biomimetic biomedical scaffolds have been widely used in tendon-bone interface,bone cartilage interface,nerve,vascular regeneration,and other fields,providing a promising new idea in clinical practice.

Objective To summarize the clinical diagnosis and treatment of nodular regenerative hyperplasia of the liver. Methods Retrospective analysis was made on the clinical manifestations,imagings, laboratory tests, diagnosis, treatment and prognosis of 18 consecutive cases finally established as NRH during the past 26 years. Results 15 of the 18 cases showed portal hypertension, 4 cases showed mono or multiple occupations of the liver, 8 cases suffered from concurrent autoimmune diseases, 3 cases were suspected of blood diseases. Preoperatively, 13 cases were diagnosed as cirrhosis, 2 cases were diagnosed as liver cancer or focal nodular hyperplasia ( FNH). All cases were diagnosed by operative wedging biopsy. 3 cases received splenectomy, 4 cases received disconnection /Phemister surgery, 3 cases received liver occupation/liver lobe resection, 1 case received partial small bowel resection, and 1 case received spleen artery restrictive surgery. Postoperatively, symptoms of portal hypertension relieved obviously. Follow-up study showed most of the patients were stable and prognosis of the NRH was good.Conclusions NRH may relate to the disturbance of liver blood supply, and most common clinical manifestation is portal hypertension, and can combine with immune diseases, hematopathy also can present single or multiple liver occupations. Differential diagnoses include liver cirrhosis, FNH, idiopathic portal hypertension. Diagnosis of NRH relies on liver wedging biopsy. Surgery can relive concurrent portal hypertension.

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a serious global health threat.This raises an urgent need for the devel-opment of effective drugs against the deadly disease.SARS-CoV-2 non-structural protein 14 (NSP14)carrying RNA cap guanine N7-methyltransferase and 3'-5'exoribonuclease activities could be a potential drug target for intervention.NSP14 of SARS-CoV-2 shares 98.7％ of similarity with the one (PDB 5NFY) of acute respiratory syndrome (SARS) by ClustalW.Then,the SARS-CoV-2 NSP14 structures were modelled by Modeller 9.18 using SARS NSP14 (PDB 5NFY) as template for virtual screening.Based on the docking score from AutoDock Vina1.1.2,18 small molecule drugs were selected for further evaluation.Based on the 5 ns MD simulation trajectory,binding free energy (AG) was calculated by MM/GBSA method.The calculated binding free energies of Saquinavir,Hypericin,Baicalein and Bromocriptine for the N-terminus of the homology model were-37.2711 ± 3.2160,-30.1746 ± 3.1914,-23.8953 ± 4.4800,and-34.1350 ± 4.3683 kcal/mol,respectively,while the calculated binding free energies were-60.2757 ± 4.7708,-30.9955 ± 2.9975,-46.3099 ± 3.5689,and-59.8104 ± 3.5389 kcal/mol,respectively,when binding to the C-terminus.Thus,the compounds including Saquinavir,Hypericin,Baicalein and Bromocriptine could bind to the N-terminus and C-terminus of the homology model of the SARS-CoV-2 NSP14,providing a candidate drug against SARS-CoV-2 for further study.

Objective:To investigate the levels of gross radioactivity in drinking water in Hangzhou city before and after Qiandao Lake as the water source to the main urban area of Hangzhou.Methods:Since 2012, water samples were collected from water source, factory water and peripheral water in rainy and dry seasons, respectively, to determine their gross α and β activity concentrations for comparison and analysis.Results:The gross radioactivity levels in drinking water in Hangzhou are lower than the limits specified in the national standard "Standards for drinking water quality" (GB 5749-2006), without statistically significant difference for these water sources between the rainy and dry season ( P>0.05). The gross α(0.008±0.000)and gross β(0.034±0.013)levels in Qiandao lake were both less than those in Qiantang river ( Z=-3.235, -4.058, P<0.05), with significant difference ( Z=-2.181, -4.577, P<0.05). There was no significant difference in gross α and gross β in factory water and peripheral water before and after the operation of Qiandao Lake water supply project ( P>0.05). Conclusions:The gross radioactivity in drinking water in downtown Hangzhou are low from 2012 to 2020. The gross radioactivity levels in Qiandao Lake are lower than in the lower reaches of Qiantang river and Dongtiao steam. No impact was generated on radioactivity levels in drinking water after Qiandao lake supplied water to Hangzhou.

OBJECTIVE To explore the value of providing pharmaceutical service related to risdiplam in direct-to-patient （DTP） pharmacies. METHODS The follow-up data of spinal muscular atrophy （SMA） patients who purchased and used risdiplam from Shangyao Yunjiankang Yiyao Pharmacy （Shanghai） Co.， Ltd. from May 2021 to January 2023 were collected. The medication information， therapeutic efficacy and the occurrence of adverse events were retrospectively analyzed. RESULTS A total of 42 prescriptions were checked by pharmacists in the DTP pharmacies， and 7 prescriptions were found to be unreasonable （16.7%， 7/42）， which were corrected after the timely intervention. During the follow-up management， pharmacists replied to 4 patients （9.5%， 4/42） regarding medication consultation about medication requirements and adverse events. Two patients with type Ⅰ SMA experienced adverse events： one of them presented with fever and the other presented with skin dryness with darkening. Both of them were grade Ⅰ toxic reactions and generally did not require clinical treatment. Considering that the patient sustained low-grade fever for a long time， the pharmacist suggested symptomatic treatment under the guidance of the doctor. CONCLUSIONS Pharmacists in DTP pharmacies conducting follow-up management of risdiplam use for rare disease SMA patients can help promote rational， standardized medication for patients.

As one of the hallmarks of cancer, metabolic reprogramming leads to cancer progression, and targeting glycolytic enzymes could be useful strategies for cancer therapy. By screening a small molecule library consisting of 1320 FDA-approved drugs, we found that penfluridol, an antipsychotic drug used to treat schizophrenia, could inhibit glycolysis and induce apoptosis in esophageal squamous cell carcinoma (ESCC). Gene profiling and Ingenuity Pathway Analysis suggested the important role of AMPK in action mechanism of penfluridol. By using drug affinity responsive target stability (DARTS) technology and proteomics, we identified phosphofructokinase, liver type (PFKL), a key enzyme in glycolysis, as a direct target of penfluridol. Penfluridol could not exhibit its anticancer property in PFKL-deficient cancer cells, illustrating that PFKL is essential for the bioactivity of penfluridol. High PFKL expression is correlated with advanced stages and poor survival of ESCC patients, and silencing of PFKL significantly suppressed tumor growth. Mechanistically, direct binding of penfluridol and PFKL inhibits glucose consumption, lactate and ATP production, leads to nuclear translocation of FOXO3a and subsequent transcriptional activation of BIM in an AMPK-dependent manner. Taken together, PFKL is a potential prognostic biomarker and therapeutic target in ESCC, and penfluridol may be a new therapeutic option for management of this lethal disease.