Objective To construct large medical model named by "Huaxi HongYi"and explore its application effectiveness in assisting medical record generation. Methods By the way of a full-chain medical large model construction paradigm of "data annotation - model training - scenario incubation", through strategies such as multimodal data fusion, domain adaptation training, and localization of hardware adaptation, "Huaxi HongYi" with 72 billion parameters was constructed. Combined with technologies such as speech recognition, knowledge graphs, and reinforcement learning, an application system for assisting in the generation of medical records was developed. Results Taking the assisted generation of discharge records as an example, in the pilot department, after using the application system, the average completion times of writing a medical records shortened (21 min vs. 5 min) with efficiency increased by 3.2 time, the accuracy rate of the model output reached 92.4%. Conclusion It is feasible for medical institutions to build independently controllable medical large models and incubate various applications based on these models, providing a reference pathway for artificial intelligence development in similar institutions.

Pulpitis is a common infective oral disease in clinical situations. The regulatory mechanisms of immune defense in pulpitis are still being investigated. Osteomodulin (OMD) is a small leucine-rich proteoglycan family member distributed in bones and teeth. It is a bioactive protein that promotes osteogenesis and suppresses the apoptosis of human dental pulp stem cells (hDPSCs). In this study, the role of OMD in pulpitis and the OMD-induced regulatory mechanism were investigated. The OMD expression in normal and inflamed human pulp tissues was detected via immunofluorescence staining. Intriguingly, the OMD expression decreased in the inflammatory infiltration area of pulpitis specimens. The cellular experiments demonstrated that recombined human OMD could resist the detrimental effects of lipopolysaccharide (LPS)-induced inflammation. A conditional Omd knockout mouse model with pulpal inflammation was established. LPS-induced inflammatory impairment significantly increased in conditional Omd knockout mice, whereas OMD administration exhibited a protective effect against pulpitis. Mechanistically, the transcriptome alterations of OMD overexpression showed significant enrichment in the nuclear factor-κB (NF-κB) signaling pathway. Interleukin-1 receptor 1 (IL1R1), a vital membrane receptor activating the NF-κB pathway, was significantly downregulated in OMD-overexpressing hDPSCs. Additionally, the interaction between OMD and IL1R1 was verified using co-immunoprecipitation and molecular docking. In vivo, excessive pulpal inflammation in Omd-deficient mice was rescued using an IL1R antagonist. Overall, OMD played a protective role in the inflammatory response via the IL1R1/NF-κB signaling pathway. OMD may optimize the immunomodulatory functions of hDPSCs and can be used for regenerative endodontics.
Pulpitis/metabolism* ; NF-kappa B/metabolism* ; Animals ; Signal Transduction ; Humans ; Mice ; Mice, Knockout ; Dental Pulp/metabolism* ; Disease Models, Animal ; Lipopolysaccharides

Objective:To investigate the accuracy, effectiveness and feasibility of MassARRAY genotyping assay in the diagnoses of neonatal genetic metabolic diseases.Methods:This is a retrospective study. From December 2016 to January 2020, newborns were screened by tandem mass spectrometry at the Zhejiang Newborn Screening Center, among which the data of 7 922 suspected positive cases of genetic metabolic diseases were collected. These patients were then tested for the common variants of 27 genetic metabolic diseases by MassARRAY genotyping assay, along with further testing using Sanger or next-generation sequencing used to verify and/or further search for potential variants.Results:A total of 1 408 cases were tested with MassARRAY. Among these, 307 cases were confirmed with certain genetic metabolic diseases. The detection rate of hyperphenylalaninemia was the highest, followed by primary carnitine deficiency, short acyl-coA dehydrogenase deficiency and methylmalonic acidemia. With these cases, the consistency of Sanger sequencing and MassARRAY was 100% (307/307). Another 287 cases were identified as carriers by MassARRAY with a 49.1% (141/287) consistency in reference to Sanger sequencing, mainly involving SLC22A5 and MCCC1 genes. Meanwhile, 50.8% (146/287) of these cases were found to have another variant mainly involving PAH, PTS and ACADS genes. The remaining 814 cases have no variants; 158 cases out of these patients have continuously abnormal amino acids, acyl carnitines, urine organic acid and/or other biochemical indices, and were tested by next-generation sequencing, among which 38% (60/158) were detected with two variants. In this study, a total of 513 patients with genetic metabolic disease were diagnosed, and the detection rate of MassARRAY was 59.8% (307/513). Conclusions:MassARRAY genotyping assay can be used as an early molecular screening method for neonatal genetic metabolic diseases. The detection rate is particularly high in diseases with a high concentration of hotspot variants, such as hyperphenylalaninemia and primary carnitine deficiency. The future application value of MassARRAY should be further improved by continuously optimizing its ability to identify new disease genes and potential variable sites.

Objective:To investigate the effectiveness and advantage of visual laryngoscope in the treatment of patients with sudden cardiac arrest who need spontaneous respiration tracheal intubation.Methods:Totally 60 patients who suffered from cardiac arrest and needed spontaneous respiration tracheal intubation were enrolled from June 2020 to February 2021 in the Affilicated Hospital of Chifeng University. Theywere randomlydivided into two groups-traditional laryngoscope (TL) group and visual laryngoscope (VL) group, with30 patients in each group. Then the success rate of glottis exposure, the operative time, success rate and complication rate of tracheal intubation were compared between the two groups. Subgroup assessment between the junior emergency resident doctor (A group) and the senior emergency resident doctor (B group) was conducted.Results:According to Cormack Lehan grades, the success rate of glottis exposure in VL group was higher than that in TL group ( P>0.05), and the success rate of Grade I in VL group was significant higer than that in TL group: 56.70%(17/30) vs. 30.00%(9/30), P<0.05. The trial times of successful intubation cases and the operative time of successful intubation cases were significantly less than those in TL group (1.30 vs 1.67, P = 0.049) and (56.37 s vs 67.12 s, P<0.05). In the subgroup, the one-time success rate of tracheal intubation in A-TL group was significantly lower than that in B-TL group (4/15 vs. 11/15, P<0.05), while the one-time success rate of tracheal intubation in A-VL group was 60.00%, which is lower than that in B-VL group ( P>0.05). The operative time consumed for successful intubation in A-TL group was significantly longer than that in B-TL group: 78.00 s vs. 55.57 s, P<0.05, while the operative time in A-VL group was a little longer than that in B-VL group ( P>0.05). Conclusions:Visual laryngoscope used in spontaneous respiration tracheal intubation can not only increase the success rate of glottis exposure, decrease trial times and shorten operative time of intubation, but also improve the success rate and decrease the complication rate of emergency tracheal intubation.

There is no difference between breast conserving surgery (BCS) combined with radiotherapy and radical surgery in outcomes.However, comparing with the radical surgery, BCS has little trauma, less bleeding and lower infection rate, which makes patients′ quality of life improved.In the practice of BCS, due to the disease, patients, physicians, socio-economic, clinical, security and many other factors, there are still many controversial issuesin the doctor-patient communication, socio-economic, aesthetic, margins width, precision operation procedures of BCS.At the same time, new surgical techniques such as plastic breast conserving surgery, and new intraoperative assessment equipment such as MarginProbe system and other new technology development has brought us new ideas to solve these problems.

Although methyltransferase has been recognized as a major element that governs the epigenetic regulation of the genome during temozolomide (TMZ) chemotherapy in glioblastoma multiforme (GBM) patients, its regulatory effect on glioblastoma chemoresistance has not been well defined. This study investigated whether DNA methyltransferase (DNMT) expression was associated with TMZ sensitivity in glioma cells and elucidated the underlying mechanism. DNMT expression was analyzed by western blotting. miR-20a promoter methylation was evaluated by methylation-specific PCR. Cell viability and apoptosis were assessed using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and TdT-mediated dUTP-biotin nick end labeling assays, respectively. The results showed that compared with parental U251 cells, DNMT1 expression was downregulated, miR-20a promoter methylation was attenuated and miR-20a levels were elevated in TMZ-resistant U251 cells. Methyltransferase inhibition by 5-aza-2\'-deoxycytidine treatment reduced TMZ sensitivity in U251 cells. In U251/TM cells, DNMT1 expression was negatively correlated with miR-20a expression and positively correlated with TMZ sensitivity and leucine-rich repeats and immunoglobulin-like domains 1 expression; these effects were reversed by changes in miR-20a expression. DNMT1 overexpression induced an increase in U251/TM cell apoptosis that was inhibited by the miR-20a mimic, whereas DNMT1 silencing attenuated U251/TM cell apoptosis in a manner that was abrogated by miR-20a inhibitor treatment. Tumor growth of the U251/TM xenograft was inhibited by pcDNA-DNMT1 pretreatment and boosted by DNMT1-small hairpin RNA pretreatment. In summary, DNMT1 mediated chemosensitivity by reducing methylation of the microRNA-20a promoter in glioma cells.
Animals ; Antineoplastic Agents, Alkylating/*pharmacology/therapeutic use ; Apoptosis/drug effects ; Brain/drug effects/metabolism/pathology ; Brain Neoplasms/drug therapy/*genetics/pathology ; DNA (Cytosine-5-)-Methyltransferase/antagonists & inhibitors/*genetics/metabolism ; DNA Methylation ; Dacarbazine/*analogs & derivatives/pharmacology/therapeutic use ; Drug Resistance, Neoplasm ; Female ; Gene Expression Regulation, Neoplastic ; Glioma/drug therapy/*genetics/pathology ; Humans ; Mice, Inbred C57BL ; MicroRNAs/*genetics ; Promoter Regions, Genetic

BACKGROUND:With the development of genetic engineering and tumor molecular biology, gene therapy for tumors has become a new treatment modality.
OBJECTIVE:To explore the effect of the KDR gene silencing on the proliferation and invasion capacity of breast cancer MCF-7 cel s.
METHODS:Interfering RNA (siRNA) sequences for smal molecule KDR gene was designed and transferred into human breast cancer MCF-7 cel s. Then, RT-PCR and western blot assay were used to detect the KDR mRNA and protein expression. Flow cytometry, cel counting kit-8 test and Transwel test were employed to detect the cel cycle, proliferative capacity and invasion capacity of breast cancer MCF-7 cel s after the KDR gene silencing.
RESULTS AND CONCLUSION:After 48 hours of KDR silencing, the mRNA and protein expressions of KDR in MCF-7 cel s were decreased obviously;MCF-7 cel s arrested at G0/G1 stage and the number of cel s at S stage was reduced. Cel proliferation was inhibited significantly. The amount of cel s passing through the filtering membrane became less. After KDR gene silencing, the proliferation and invasion of breast cancer MCF-7 cancer stem cel s were inhibited remarkably, indicating that KDR gene silencing may be a new target for the effective treatment of breast cancer.

Objective To evaluate the prognostic value of three different staging system based on positive lymph nodes,lymph node ratio and log odds of positive lymph nodes in breast carcinoma.Methods In 472 breast carcinoma patients,survival analysis was performed with Kaplan-Merier and COX regression model,the hazard ratio (HR) of the three staging system were compared.Results When more than 10 lymph nodes were dissected in the operation,there was statistical differences in survival among the staging systems based on lymph node ratio and log odds of positive lymph nodes (P ＜ 0.05),while the prognosis was highly homologous between the staging systems based on positive lymph nodes in stage N0 and N1.Univariate analysis showed age,tumor size,Her2 status,estrogen receptor status and the total lymph nodes dissected were related to overall survival (all P ＜ 0.05).COX multivariate analysis showed that the staging system based on lymph node ratio (5.495) and log odds of positive lymph nodes (4.662) had the higher HR than the N staging system (2.722).Conclusions Compared with the number of involved lymph nodes,the staging system based on lymph node ratio and log odds of positive lymph nodes were superior to the staging system based on positive lymph nodes for prognostic assessment of breast carcinoma.

Objective To observe the influence of insulin therapy on the short-term prognosis of patients with acute ST-elevation myocardial infarction (ASTEMI) complicated with hyperglycaemia.Methods A total of 128 patients with ASTEMI complicated with hyperglycaemia were randomized into 2 groups:treatment group and control group.There were 64 patients(50.0％ )in the treatment group and 64 patients(50.0％ ) in the control group.All of the patients were given anticoagulants,antiplatelet drugs,statins,beta-receptor blockers,nitrates and angiotensin-converting enzyme inhibitors (ACEI)or angiotensin receptor blocker (ARB) Moreover,the patients in the treatment group were given extra 50 U insulin ( Novolin R) in 50 ml saline by venous infusion.In the treatment group,Venous blood samples were obtained before and 7 days after treatment to determine the fasting blood glucose and hs-CRP in serum; the levels of fasting blood glucose and hs-CRP and short-term prognosis were compared between the 2 groups.ResultsThe levels of fasting blood glucose in the treatment group were decreased significantly after treatment ( [ 5.4 ± 0.8 ] mmol/L vs [ 11.6 ± 2.3 ] mmol/L,P ＜0.01),but there was no significant change in the control group( [ 10.7 ± 2.1 ] mmol/L vs [ 11.2 ± 2.7]mmol/L,P ＞ 0.05 ).The levels of hs-CRP in both groups were decreased significantly after treatment (P ＜0.05),but it was much more obvious in the treatment group( [ 6.2 ± 1.5 ] mg/L vs [ 8.7 ± 1.8 ] mg/L,P ＜0.05).The incidence of major adverse cardiac events(MACE) during a 3 months′ follow-up in the treatment group was significantly lower than that in the control group ( 12.50％ vs 34.38％,P ＜ 0.05 ).Conclusion Insulin therapy can improve the short-term prognosis in patients with ASTEMI complicated with hyperglycaemia.