ObjectiveThe human angiotensin converting enzyme2 （hACE2） transgenic mouse model was used to clarify the antiviral efficacy of BD-77 against a novel coronavirus SARS-CoV-2 and explore the action mechanism of BD-77 against SARS-CoV-2. MethodSARS-CoV-2 Omicron and Delta variant strains-infected VeroE6 cell models were established and administered with BD-77 to observe the antiviral effect of BD-77 in vitro. A kit was used to detect the effect of BD-77 in vitro on the binding of spike S protein of SARS-CoV-2 virus （Delta/Omicron） to angiotensin converting enzyme2 （ACE2）. Chromatography was adopted to detect the binding of BD-77 to the S protein and N protein of the novel coronavirus. hACE2 transgenic C57BL/6 mice were divided into a blank control group， SARS-CoV-2 infection group， BD-77 administration groups of 37.5 mg·kg^-1 and 75 mg·kg^-1， with eight mice in each group. The pneumonia model of SARS-CoV-2-infected hACE2 transgenic mice was built to observe the survival of the mice， detect the virus titer of the lung tissue of the mice， and observe the lesions in the lung tissue. ResultBD-77 had a certain inhibitory effect on Omicron and Delta variant strains in vitro， with median inhibitory concentration （IC₅₀） of 526.3 mg·L^-1 and 653.0 mg·L^-1， respectively. BD-77 had no significant inhibitory effect on the binding of the S protein of WT， Omicron， and Delta variant strains of SARS-CoV-2 to ACE2 and had no binding effect with the S protein and N protein of the novel coronavirus. No mice in the blank group died， while the mortality rate of SARS-CoV-2-infected mice was 75%. There was a large amount of virus replication in the lung tissue of the mice and large areas of inflammatory infiltration in the lung tissue and interstitium. Compared with the model group， BD-77 administration groups of 37.5 mg·kg^-1 and 75 mg·kg^-1 could reduce the mortality of mice， significantly lower the virus titer in the lung tissue of mice （P<0.05）， and improve lung lesions. ConclusionBD-77 demonstrated significant inhibitory effects against SARS-CoV-2 virus in vitro and in vivo. However， its mechanism of action did not involve direct inhibition of the virus itself or intervention in the virus-host binding process. This finding suggests that the mechanism of action of BD-77 needs to be thoroughly investigated and elucidated by further experiments.

Objective:To evaluate the survival, complications and prognostic factors in patients with stageⅠb2 and Ⅱa2 cervical squamous cell carcinoma treated by primarily radical surgery with or without postoperative adjuvant therapy.Methods:The clinical and pathological data of patients with stageⅠb2 and Ⅱa2 cervical squamous cell carcinoma treated in the Cancer Hospital of the University of Chinese Academy of Sciences from January 2015 to January 2018 were retrospectively analyzed. All patients underwent Querleu-Morrow classification (Q-M classification) C2 radical surgery, including extensive hysterectomy+pelvic lymphadenectomy with or without adjuvant therapy based on postoperative risk factors. Survival rate was calculated by Kaplan-Meier method and survival curve was drawn. Univariate analysis was performed by using the log-rank test to analyze the clinicopathological factors related to the prognosis of patients. Multivariate analysis was performed by using Cox regression method to analyze independent risk factors affecting survival prognosis.Results:(1) The median age of 643 patients with cervical squamous cell carcinoma was 50 years old (45-58 years old). Clinical stage: 260 cases (40.4%, 260/643) of stage Ⅰb2, 383 cases (59.6%, 383/643) of stage Ⅱa2. (2) Among 643 cases underwent Q-M classification C2 surgery, 574 cases (89.3%, 574/643) of them received adjuvant therapy and 184 cases (28.6%, 184/643) of them had grade 3-4 complications after treatment, including 134 cases (20.8%, 134/643) early complications and 66 cases (10.3%, 66/643) late complications. The incidence of grade 3-4 complications in 574 patients received postoperative adjuvant therapy was 30.1% (173/574), which was significantly different from that in 69 patients who received surgery alone (15.9%, 11/69; χ2=6.08, P=0.014). (3) All 643 cases were followed up, and the median follow-up time was 40 months (3-76 months). During the follow-up period, 117 cases (18.2%, 117/643) recurred, including 45 cases (7.0%, 45/643) of local recurrence, 54 cases (8.4%, 54/643) of distant metastasis, and 18 cases (2.8%, 18/643) of local recurrence and distant metastasis. The 5-year progression-free survival (PFS) and 5-year overall survival (OS) rates of patients with stage Ⅰb2 and Ⅱa2 cervical squamous cell carcinoma were 79.9% and 85.5%, respectively. Univariate analysis showed that pelvic lymph node metastasis, para-aortic lymph node metastasis, deep stromal infiltration, and lymph-vascular space invasion were significantly associated with 5-year PFS in patients with stage Ⅰb2 and Ⅱa2 cervical squamous cell carcinoma (all P<0.05). The maximum diameter of tumor, pelvic lymph node metastasis and para-aortic lymph node metastasis were significantly associated with the 5-year OS of cervical squamous cell carcinoma in stages Ⅰb2 and Ⅱa2 (all P<0.05). Multivariate analysis showed that pelvic lymph node metastasis and para-aortic lymph node metastasis were independent factors affecting 5-year PFS and 5-year OS in patients with stage Ⅰb2 and Ⅱa2 cervical squamous cell carcinoma (all P<0.01). Conclusion:Radical surgery is a feasible and effective primary treatment for stagesⅠb2 and Ⅱa2 cervical squamous cell carcinoma, with a high 5-year survival rate and an acceptable complication rate.

Objective:To establish and evaluate a new real-time quality control method that can identify the random errors by using the backpropagation neural network (BPNN) algorithm and taking blood glucose test as an example.Methods:A total of 219 000 blood glucose results measured by Siemens advia 2 400 analytical system from January 2019 to July 2020 and derived from Laboratory Information System of Beijing Chaoyang Hospital Laboratory Department was regarded as the unbiased data of our study. Six deviations with different sizes were introduced to generate the corresponding biased data. With each biased data, BPNN and MovSD algorithms were used and tested, and then evaluated by traceability method and clinical method.Results:For BPNN algorithm, the block size was pre-set to 10 and the false-positive rate in all biases was within 0.1%. For MovSD, however, the optimal block size and exclusive limit were 150 and 10% separately and its false-positive rate in all biases was 0.38%, which was 0.28% higher than BPNN. Especially, for the least two error factors of 0.5 and 1, all the random errors were not detected by MovSD; for the error factor larger than 1, random errors could be detected by MovSD but the MNPed was higher than that of BPNN under all deviations. The difference was up to 91.67 times. 460 000 reference data were produced by traceability procedure. The uncertainty of BPNN algorithm evaluated by these reference data was only 0.078%.Conclusion:A real-time quality control method based on BPNN algorithm was successfully established to identify random errors in analytical phase, which was more efficient than MovSD method and provided a new idea and method for the identification of random errors in clinical practice.

Objective:To investigate the application value of establishing the differential diagnosis model of pulmonary tuberculosis using routine laboratory data.Methods:The retrospective study was conducted. The routine laboratory data of newly diagnosed patients with pulmonary tuberculosis and other pulmonary diseases in Beijng Jishuitan Hospital and Beijing Hepingli Hospital from May 2015 to November 2021were collected. According to the random numbers showed in the computer, all the 11516 patients were divided into training dataset and test dataset with a ratio of 9∶1. Four machine learning algorithms, Support Vector Machine, Random Forest, K-Nearest Neighbor and Logistic Regression, were used to build models and select features. The diagnostic accuracy of each model was verified by using the 10-fold cross-validation method and the performance of each model was evaluated by using the receptor operator of characteristic (ROC) curve.Results:Random Forest was selected as the optimal machine learning algorithm to build the best feature model in the study. According to importance scale of factors, the differential diagnosis model of pulmonary tuberculosis consisting of 37 non-specific test indexes. In the validation set and test set the accuracy and area under curve (AUC) of the models were 0.747 and 0.736, the sensitivity, specificity and accuracy were 68.03% and 68.75%, 70.91% and 67.90%, 70.30% and 68.12%, respectively.Conclusion:A key tool in the differential diagnosis model of pulmonary tuberculosis was established by routine laboratory data in combination with machine learning. The results of this study need to be further verified by more data from medical institutions.

Objective:To explore the clinical effect of R-MAD (rituximab, methotrexate, cytarabine, dexamethasone) regimen in the treatment of primary ocular adnexal double-expression diffuse large B-cell lymphoma (DLBCL).Methods:The clinical data of an elderly patient with primary ocular adnexal double-expression DLBCL who was treated with R-MAD regimen in June 2019 in Fujian Medical University Union Hospital was retrospectively analyzed. The clinical manifestations, diagnosis and treatment, prognosis were also analyzed, and the related literature was reviewed.Results:The patients was a 71-year-old male. After initial treatment of R-CHOP chemotherapy, the patient's eye mass did not shrink, the swelling and pain became worse, the curative effect was not good, and the disease progression continued. After the patient was given R-MAD chemotherapy for 3 courses, the eye swelling subsided and pain symptoms were significantly improved, satisfactory results were obtained, and no obvious adverse reactions occurred.Conclusions:R-MAD regimen has an ideal effect on the patient with primary ocular adnexal double-expression DLBCL, which can significantly improve symptoms, delay disease progression, and improve the quality of life of patients, but the prognosis still needs to be followed up in the long-term.

Virtual reality technology is a technology that creates a visual environment for people to experience through computer simulation, with features of immersion, interaction and imagination. This technology was used in engineering mechanics and urban planning in early times In medicine, diagnostics serves as a bridge for medical students to transit from basic medicine to clinical medicine. Using virtual reality technology to produce standardized patients (SPs) allows medical students to simulate the role of clinicians in the classroom, complete the diagnosis and treatment for virtual patients using various electronic media and the mastered theoretical knowledge of diagnostics, set up simulation training and online-and-offline teaching according to the diagnostic course standards which compensates the disadvantages in traditional medical teaching. Virtual reality technology has practical significances for cultivating medical students' clinical skills and thinking through procedural process evaluation, real-time feedback, etc.. This paper will discuss the prospect of virtual reality technology, its application as well as its advantages in diagnostic teaching.

[Objective] This prospective study was conducted to assess the influence of overnight orthokeratology (OK) on low,middle and high myopia in southern Chinese teenagers.[Methods] Fifty-four subjects (107 eyes,age 11.65 ± 2.44 years,mean±SD)who matched the inclusion criteria for OK were enrolled in the study.The subjects were divided into three groups according to the different refraction baseline (low myopia group:0.75 ～ 3.00 D,51 eyes;middle myopia group:3.25 ～ 5.00 D,36 eyes;high myopia group:5.25 ～ 9.00 D,20 eyes).Refraction,central corneal thickness,corneal keratometry,anterior chamber depth and axial length (AL) were measured at baseline and after 1 years using ocular biometry.The changes were evaluated and compared among the groups.Results were analyzed by SPSS 17.0 software.[Results] Fifty-four subjects (total 107 eyes) completed the 1-year follow-up examinations.At baseline,the spherical equivalent refractive error (SER) was-2.15 D ± 0.63 D,-4.20 D ± 0.54 D,and-6.63 D ±1.18 D in three groups.The axial length was (24.50-± 0.66) mm,(25.16-± 0.65) mm,and (26.35 ± 0.87) mm in the three groups,respectively.There were no significant differences among the groups in initial central corneal thickness,anterior chamber depth,central,flat and steep kerotometry.The increase in axial length during the 1-year study period was (0.22 ± 0.27) mm,(0.09-± 0.22)mm and (0.02-± 0.22) mm in three groups,respectively,and the difference was significant between low myopia group and middle myopia group (P =0.04),low myopia group and high myopia group (P =0.008),whereas no significant difference was found between middle myopia group and high myopia group (P =0.35).Spherical equivalence decreased dramatically in three groups after one year (all P ＜ 0.0001).And the difference was significant between low myopia group and middle myopia group (P ＜ 0.0001),low myopia group and high myopia group (P ＜ 0.0001).Central,flat and steep kerotometry after one year became flatten in all group (all P ＜0.0001).There were no significant differences in the change of central corneal thickness,anterior chamber depth and corneal diameter.[Conclusions] OK lens is more effective in middle and high myopia control than in the low myopia control.The change in corneal keratometry may be one of the main factors influencing the OK treatment effect.

OBJECTIVETo study the promoter methylation status of SFRP genes and the effect of 5- aza- 2'- deoxycytidine (5- Aza- CdR)induced apoptosis via Wnt/β- catenin pathway by demethylation in Jurkat cells.

METHODSJurkat cells were treated with different concentrations of 5- Aza- CdR. The cell proliferation level of Jurkat cells was detected by MTT assay. Apoptosis was evaluated by flow cytometry. Methylation- spcific PCR (MSP) was used to determine the methylation status of SFRP genes. The expressions of SFRP genes were detected by real time fluorescence quantitative PCR. The mRNA expression levels of survivin, c- myc and cyclin- D1 were analyzed by RT- PCR. Western blot was used to detect the levels of β-catenin protein.

RESULTSCompared with control group, the different concentrations of 5-Aza-CdR could significantly inhibit the proliferation of Jurkat cells in a time-dose dependent manner (P<0.05). After being treated by 5- Aza- CdR for 48 hours, the cell early apoptosis rate in experiment group was significantly higher than that in control group (P<0.05). The promoters of SFRP1, SFRP2, SFRP4, SFRP5 genes were hypermethylation state in the control group, after being treated by 5-Aza-CdR for 72 hours, the brightness of SFRP1, SFRP2, SFRP4, SFRP5 genes' methylation strips weakened in a dose- dependent manner. SFRP mRNA expression increased (P<0.05) when 5- Aza- CdR concentration increased, and the level of β- catenin protein was dampened in a dose- dependent manner (P<0.05). As compared to the control group, the mRNA expressions of associated apoptosis genes survivin, c-myc and cyclin- D1, respectively were obviously down- regulated in a dose- dependent manner (P<0.05).

CONCLUSIONThe effect of demethylation could up- regulate SFRP genes expressions by reversing its hypermethylation and induced apoptosis by down-regulation of β-catenin and associated apoptosis genes.

Apoptosis ; Azacitidine ; analogs & derivatives ; pharmacology ; Cell Proliferation ; DNA Methylation ; Down-Regulation ; Gene Expression ; Humans ; Intercellular Signaling Peptides and Proteins ; genetics ; Jurkat Cells ; Membrane Proteins ; genetics ; Promoter Regions, Genetic ; Wnt Signaling Pathway ; beta Catenin ; metabolism

Objective To investigate the clinical features of patients with brucellosis in Fujian Province and to update the relevant physician's knowledge on brucellosis.Method Retrospective analysis of the epidemiological,clinical,laboratory,imaging,treatment and outcome data of 7 patients with brucellosis were carried out in Fujian Medical University Union Hospital between January 2011 and July 2015.Results Of the 7 patients with brucellosis,6 were males and 1 was female aged between 29 to 61 years old,and 6 cases had a history of contact with goat.The main clinical presentations were repeated limb pain in 6 cases,6 patients got fever,4 cases with hepatomegaly,6 cases splenomegaly,and 7 cases lung inflammation.Hematology examination results indicated that 4 cases were normal,1 case decreased and 2 cases increased in white blood cells.Six cases had a liver dysfunction and 4 cases with low albumin level.All patients were detected positive of Malta Brucella by blood culture or bone marrow culture.In 6 cases and 4 cases out of the 6 cases,splenomegaly and hepatomegaly were found through B ultrasonography,respectively.After treatment of the 7 cases by doxycycline combined with minocycline rifampicin,3 cases were recovered,2 cases were relapsed,and 2 cases were improved.Conclusions The clinical symptoms are typical in these brucellosis patients.What we need to do is focus on improving the clinical and related physician's awareness of brucellosis,collecting a comprehensive history,choosing suitable assistant examinations based on the conditions of patients,strengthening the contact between clinical departments and auxiliary departments,and timely diagnosis.

Bone Neoplasms ; pathology ; Carcinoma, Neuroendocrine ; pathology ; Humans ; Osteosarcoma ; pathology ; Ureter ; pathology ; Ureteral Neoplasms ; pathology