Objective : To explore the mechanism of isorhamnetin (Iso) in the treatment of oral squamous cell carcinoma (OSCC) using network pharmacology and molecular docking methods and to verify it in vitro. Methods : The key targets were obtained by constructing the PPI protein interaction network based on the common intersection targets of Iso-OSCC. At the same time, gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) were used to analyze the related signaling pathways of the intersection targets. Iso and core targets were also analyzed through molecular docking and visualization. Colony formation assay and Transwell assay were used to identify the effect of Iso on the proliferation and invasion of Cal-27 cells. Western blot was used to analyze the regulatory effects of different concentrations of Iso on estrogen receptor-1 (ESR1), phosphoinositide-3-kinase regulatory subunit-1 (PIK3R1), Src tyrosine kinase (SRC), and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway proteins. Results: A total of 269 potential intersection targets of Iso-regulated OSCC were obtained. According to the degree obtained by topological analysis, PIK3R1, AKT1, SRC, ESR1, and other core targets were screened out. KEGG analysis showed that 165 signaling pathways were enriched in the intersection targets of Iso-OSCC, among which the PI3K/AKT signaling pathway played an important role in the treatment of OSCC with Iso. Molecular docking results showed that the absolute value of binding energy between target proteins PIK3R1, AKT1, SRC, ESR1, and Iso was high. After Cal-27 cells were treated with Iso, the number of cell colony formations, the number of transmembrane cells, and the expression of PIK3R1, ESR1, SRC, p-PI3K, and p-AKT were negatively correlated with the increase in Iso concentration (P < 0.05). Conclusion Iso can inhibit PI3K/AKT signal transduction and influence the expression of PIK3R1, AKT1, SRC, and ESR1 proteins, thereby inhibiting the occurrence and development of OSCC.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Objective To investigate the mechanism of DNA methyltransferase 1(DNMT1)inhibitor combined with extracellular signal-regulated kinase 1(ERK1),homeodomain-interacting protein kinase 2(HIPK2),and glycogen synthase kinase 3 β(GSK3 β)inhibitors in synergistically inducing apoptosis and protein arrest in relapsed and refractory acute myeloid leukemia(AML)cells.Methods Three therapeutic targets,including ERK1,HIPK2,and GSK3β,were screened based on the Gene Expression Omnibus(GEO),The Cancer Genome Atlas(TCGA)database,and Ex-pression 2 Kinases database.Human AML cell line U937 cells were treated with DNMT1 inhibitor a-lone or combined with ERK1,HIPK2,or GSK3β inhibitors.Cell viability was detected using the CCK-8 method.Apoptosis rate was analyzed by flow cytometry,and cell cycle distribution was de-termined by propidium iodide(PI)staining.The mRNA expression levels of DNMT1,ERK1,HIPK2,and GSK3β were detected by real-time fluorescent quantitative reverse transcriptionpoly-merase chain reaction(RT-qPCR).Protein expressionlevels of DNMT1,ERK1,HIPK2,and GSK3β were detected by immunoblotting.Results DNMT1 inhibitor significantly inhibited the cell viability of U937 cells,and significantly induced apoptosis and cell cycle arrest in U937 cells(P＜0.05).When DNMT1 inhibitor was combined with ERK1,HIPK2,or GSK3β inhibitors,cell via-bility and apoptosis rate were significantly reduced(P＜0.05).DNMT1 inhibitor alone or its com-bination with ERK1,HIPK2,and GSK3β inhibitors induced U937 cell arrest in the G0/G,phase,with a significant increase in the proportion of cells in the G0/G1 phase in the combination group(P＜0.05).The combination of DNMT1 inhibitor with ERK1,HIPK2,and GSK3β inhibitors sig-nificantly reduced the mRNA expression levels in DNMT1,ERK1,HIPK2,and GSK3β in U937 cells(P＜0.05).Similarly,the combination therapy significantly reduced the protein expression levels of DNMT1,ERK1,HIPK2,and GSK3β in U937 cells(P＜0.05).Conclusion DNMT1 inhibitor combined with ERK1,HIPK2,and GSK3 β inhibitors can synergistically induce apoptosis and protein arrest in relapsed and refractory AML cells,providing a novel strategy for combined tar-geted therapy of AML.

Objectives:Quantitative flow ratio(QFR)is a coronary angiography-derived functional test without the need of guidewire use.Fractional flow reserve(FFR)is used as the reference standard to verify the diagnostic value of QFR in patients with non-ST-segment elevation acute coronary syndrome(NSTE-ACS)with coronary critical lesion(40%-70%stenosis)and functional stenosis. Methods:This retrospective analysis included patients with NSTE-ACS who were admitted to Fuwai Central China Cardiovascular Hospital from June 1,2018 to February 1,2023 and underwent coronary FFR examination.QFR values of target vessels were analyzed offline by AngioPlus(Shanghai Pulsation Medical Imaging Technology Co.,LTD.),the second-generation QFR detector,and anatomical parameters of the diseased vessels were recorded as follows:minimal luminal diameter(MLD),percent diameter stenosis(DS%),minimal luminal area(MLA),percent area stenosis(AS%).Functional coronary artery stenosis is defined as FFR≤0.80. Results:Using FFR as the gold standard,the AUC values of contrast-flow QFR(cQFR)and fixed-flow QFR(fQFR)for identifying functional coronary artery stenosis in NSTE-ACS patients were 0.829(95%CI:0.773-0.885,P<0.001)and 0.821(95%CI:0.766-0.875,P<0.001),respectively.The diagnostic accuracy,sensitivity and specificity of cQFR and fQFR were 81.30%,56.00%,98.63%and 76.83%,59.00%,99.04%,respectively.DeLong test showed that diagnostic performance of cQFR was significantly better than fQFR in diagnosing functional stenosis of coronary critical lesions in patients with NSTE-ACS. Conclusions:With FFR as the gold standard,QFR(especially cQFR)has certain diagnostic value in patients with NSTE-ACS with functional stenosis of coronary critical lesions.

Tumor vaccine is a promising strategy for cancer immunotherapy by introducing tumor antigens into the body to activate specific anti-tumor immune responses. Along with the technological breakthroughs in genetic engineering and delivery systems, messenger ribonucleic acid (mRNA) technology has achieved unprecedented development and application over the last few years, especially the emergency use authorizations of two mRNA vaccines during the COVID-19 pandemic, which has saved countless lives and makes the world witness the powerful efficacy of mRNA technology in vaccines. However, unlike infectious disease vaccines, which mainly induce humoral immunity, tumor vaccines also need to activate potent cellular immunity to control tumor growth, which creates a higher demand for mRNA delivery to the lymphatic organs and antigen-presenting cells (APCs). Here we review the existing bottlenecks of mRNA tumor vaccines and advanced nano-based strategies to overcome those challenges, as well as future considerations of mRNA tumor vaccines and their delivery systems.

Objective To understand the epidemic status of biological stings on an island and the knowledge about environmental emergencies of personnel stationed on the island.Methods With convenience sampling,we investigated 270 personnel using a self-designed anonymous questionnaire based on clinical treatment situation and on-the-spot investigation of the island.Results A total of 270 questionnaires were distributed,and 254 valid questionnaires were returned,with an effective rate of 94.07％.A total of 164(64.57％)personnel had a history of stings,with median times of 2(0,5).The main clinical symptoms were local swelling and pain(142 cases,86.59％)and pruritus(110 cases,67.07％).The personnel scored 14(11,17)for the first aid knowledge about island environmental emergencies(the full score was 26).The vast majority of personnel(227 cases,89.37％)believed that it was necessary to learn the knowledge about island environmental emergencies,and the majority of personnel(186 cases,73.23％)hoped to learn through centralized teaching.Conclusion The environmental emergencies represented by biological stings are becoming increasingly serious,so it is necessary to carry out multiple prevention and environmental control measures,and to carry out regular and long-term training for personnel stationed on islands.

Objectives:To search, evaluate, and summarize the evidence related to the application management of over-the-counter (OTC) medications for constipation in the elderly, providing evidence-based support for the rational use of these medications.Methods:A systematic search was conducted through computerized decision support systems, guideline websites, professional association websites, and databases for clinical decisions, guidelines, evidence summaries, and expert consensus on the management of OTC medications for constipation in the elderly. The search period spanned from January 2018 to March 2023. The quality of the literature was independently assessed, and evidence was extracted. The 2014 version of the Joanna Briggs Institute (JBI) evidence grading system was used to determine the levels of evidence.Results:A total of 18 article were included, consisting of two clinical decisions, five guidelines, seven expert consensus statements, and four evidence summaries. These covered five areas: medication principles for elderly individuals with different characteristics, medication selection, medication monitoring, health education, and precautions, culminating in a total of 30 best evidence.Conclusions:This study summarizes the best evidence for the management of OTC medications for constipation in the elderly, providing evidence-based support for the rational application of these medications.

Objective:To investigate the clinical effect of turbocharged large free anterolateral thigh flaps (ALTF) by anastomosis with a superior perforator of the flap in reconstruction of large soft tissue defects of limbs.Methods:From June 2017 to June 2021, 6 patients with large soft tissue defects of limbs with exposed joints and tendons were treated in the Department of Hand and Foot Surgery of the Affiliated Hospital of Qingdao University with turbocharged large free ALTFs. The pressurised blood supply of ALTF was achieved by anastomosing a superior perforating branch carried in the flap. Such large and turbocharged ALTFs were used to repair large soft tissue defects with exposed joints and tendons in limbs. Of the 6 patients, there were 4 males and 2 females, and aged 32-60(46.0±8.1) years old. Cause of injury: 5 by traffic accident and 1 by machine crush. Four patients had soft tissue defects in lower limbs: 2 with open tibia and fibula fractures, 1 had patellar defect and fibula fracture, and 1 associated with fibula fracture. The other 2 patients had soft tissue defect in upper limbs with bone and tendon exposed but without fracture. The sizes of wound were 25.0 cm×12.0 cm-35.0 cm×19.0 cm. In the primary surgery, Vacuum sealing drainage (VSD) was applied. In the second stage, free ALTFs were used to cover the wound. The area of flap incision was increased by anastomosing the superior perforators and as the consequence, the size of flaps was achieved to 26.0 cm×13.0 cm-36.0 cm×15.0 cm. Donor site of 6 cases were reduced by direct suture, and the remaining wound was covered by free skin graft. Postoperative follow-ups were conducted at outpatient clinic reviews at 1, 2, 3 and 6 months after surgery, and followed by telephone or WeChat interviews. The results of the operation were evaluated according to the appearance, texture and sensory recovery of the flap.Results:All 6 flaps survived and the patients completed the postoperative follow-up that lasted for 6-24 (16.7±5.0) months. No necrosis of flap occurred after surgery. The appearance and texture of the flaps were satisfactory without wear and tear. Sensation recover was evaluated by the standered of British Medical Research Council (BMRC), 4 patients recovered to S 3 and 2 patients to S 2. The Mayo score of the elbow joint was good in 2 patient with upper extremity injuries. Of the other 4 patients with lower limb injuries, the knee function evalued by Hospital for Special Surgery(HSS) score were excellent in 3 patients and good in 1 patient, and the American Orthopedic Foot and Ankle Societ(AOFAS) ankle-hind foot function score was excellent in 2 patients and good in 2 patients. There was no infection or function loss at all donor sites. Conclusion:The perforator of an ALTF is relatively constant, and the flap can partially restore sensation. The superior perforator is reliable and the incision area of the flap can be enlarged by anastomosing the superior perforator vessels. It is a better way to reconstruct a large soft tissue defects in limbs.

Objective: To propose a digitally modified and guided bone regeneration technique supported by a nonabsorbable titanium plate and explore its effect on vertical bone regeneration. Methods: A total of 8 patients with severe vertical bone defects in the edentulous area who wanted to be treated with implants were included in this study. A digitally modified and guided bone regeneration technique supported by a nonabsorbable titanium plate (fence technique) was used for bone augmentation. The patient's jaw, dentition, and soft tissue data were obtained for prosthetically guided implantation and bone regeneration. After virtual bone augmentation, a model of the jaw was obtained through 3D printing technology, and the titanium plate was bent accordingly. The virtual design was transformed through the template (including the base template and the attachment of a periosteal screw and bone block), so the actual osteogenesis space consistent with the design could be realized in the operation. Guided bone regeneration was performed according to the improved procedure and technical process. After 6 ~ 8 months of bone augmentation, cone beam CT was taken to evaluate the effect of bone augmentation. The implant was implanted according to the initial implant design, and bone tissue was obtained for HE and Masson staining. Results: After 6 ~ 8 months of bone augmentation, the vertical linear bone increment reached (5.44 ± 1.73) mm. The implant was implanted according to the initial implant design, and the bone tissue was obtained for histological examination to show the formation of new bone. Conclusion Digital improved fence technique can simplify the preoperative and surgical procedures, and obtain good vertical bone augmentation results. In short, it is a kind of vertical bone augmentation technique worth popularizing and applying.

Objective: To explore the relationship between myopia and nutritional status among upper elementary students in Shanghai. Methods: A stratified cluster sampling method was used to select 5 576 fourth and fifth grade students from 16 districts in Shanghai, vision test, physical examination and questionnaire survey were administered. Two level multivariate Logistic regression and mixed linear models were used to analyze the relationship between myopia, spherical equivalent (SE) and nutritional status. Results: The detection rates of overweight and obesity were 17.0%(949) and 18.7%(1 042), respectively. There was a statistical difference in the proportion of the nutritional status in boys and girls( χ 2=210.94, P <0.01), with overweight and obesity in boys higher than those of girls. The overweight boys were more likely to have myopia (univariate analysis: OR=1.23, P =0.04; multivariate analysis: OR=1.21, P =0.06) than the normal weight boy. Overweight students tended to had more negative refractive than those with normal weight in both boys and girls(multivariate analysis, boys: β =-0.19, girls: β=-0.24, P <0.05). Myopia risk and refractive power in obese students showed no statistical difference with normal weight students( P >0.05). Conclusion Overweight students have lower SE than the normal weight among upper elementary students of Shanghai, more researches are needed to confirm this finding and to provide theoretical bases for myopia prevention and control.