The outcome of transnasal endoscopic total maxillectomy in the treatment of sinonasal adenoid cystic carcinoma / 临床耳鼻咽喉头颈外科杂志

Objective:To assess the prognosis of sinonasal adenoid cystic carcinoma with hard palatine invasion treated by transnasal endoscopic total maxillectomy. Methods:Clinical data of twenty-six patients with sinonasal adenoid cystic carcinoma invading hard palatine treated by transnasal endoscopic total maxillectomy between May 2014 and December 2020 was analyzed retrospectively. Survival rate, local recurrence and distant metastasis were analyzed using Kaplan-Meier method. Cox regression was used to investigate the prognosis factors. Masticatory function after maxillectomy has also been assessed using the questionnaire of patients' satisfaction about masticatory function. Results:Margins in 8 patients（30%） were positive. The median time of follow-up was 38 months（6 to 85 months）. Twenty-five patients recurred. Four patients died of distant metastasis. The 5-year overall survival rate and relapse-free survival rate was 79.5% and 89.1%, respectively. Independent predictors of outcome on multivariate analysis were positive margin（P=0.018）, recurrence（P=0.006） and distant metastasis（P=0.04）. Conclusion:Transnasal endoscopic total maxillectomy could be performed for the treatment of the sinonasal adenoid cystic carcinoma with hard palatine invasion. Positive margin, local recurrence and distant metastasis were important predictors for patients' prognosis.

Efficacy of dupilumab in the treatment of moderate and severe atopic dermatitis in the elderly: a clinical observation / 中华皮肤科杂志

Objective:To evaluate clinical efficacy and safety of dupilumab in the treatment of moderate and severe atopic dermatitis (AD) in the elderly.Methods:An observational study was conducted, and a total of 42 elderly patients with moderate to severe AD were collected from Department of Dermatology, the First Affiliated Hospital of Soochow University from September 2021 to June 2022. These patients all received subcutaneous injection of dupilumab at an initial dose of 600 mg, followed by every-2-week injections at a dose of 300 mg, and the total course of treatment was 16 weeks. Clinical indicators, including eczema area and severity index (EASI) , numerical rating scale (NRS) , dermatology life quality index (DLQI) and investigator′s global assessment (IGA) , were recorded at weeks 0, 4, 8, 12 and 16, and the proportion of patients achieving more than 50% (EASI-50) and 75% (EASI-75) improvement in EASI scores were calculated; related laboratory indicators, including total serum immunoglobulin E (IgE) levels and eosinophil counts, were recorded at weeks 0, 4 and 16. During the treatment, adverse events were recorded. Statistical analysis was carried out by using chi-square test, one-way analysis of variance and t test with SPSS27 and GraphPad Prism 9.0 software. Results:Among the 42 patients, there were 25 males (59.5%) and 17 females (40.5%) , and their age was 71.82 ± 16.81 years. Among them, 17 patients (40.5%) presented with generalized eczema phenotype, 15 (35.7%) with flexor eczema phenotype, and 10 (23.8%) with prurigo nodularis phenotype. At weeks 4 and 16 after start of the treatment, the mean EASI score significantly decreased by 38.4% and 73.3% respectively, the mean NRS score significantly decreased by 53.0% and 77.4% respectively, and the mean DLQI score significantly decreased by 58.2% and 93.8% respectively compared with the corresponding scores before the treatment ( P < 0.05 or 0.001) . At weeks 4 and 16, the proportions of patients achieving an IGA score of 0 or 1 were 11.9% and 61.9% respectively, the proportions of patients achieving EASI-50 were 11.9% and 76.2% respectively, and the proportions of patients achieving EASI-75 were 2.4% and 57.1% respectively. Compared with the baseline levels, the mean total serum IgE level decreased by 23.1% and 38.2% at weeks 4 and 16 respectively ( P = 0.274, 0.395, respectively) , and the mean eosinophil count decreased by 24.4% and 37.5% at weeks 4 and 16 respectively ( P = 0.059, 0.735, respectively) . During the treatment, mild adverse events occurred in 6 (14.3%) patients, including conjunctivitis (3 cases) , fungal infection of the head and face (2 cases) , and psoriasiform dermatitis (1 case) , which subsided after symptomatic treatment. Conclusion:Dupilumab exhibited a rapid onset and marked efficacy in the treatment of moderate and severe AD in the elderly, with few and mild adverse events; however, some patients had not achieved EASI-50 or EASI-75 after 16-week treatment, and maintenance treatment was required.

Analysis of characteristics and influencing factors of cervical lymph node skip metastasis in papillary thyroid carcinoma / 国际外科学杂志

Objective:To analyze the characteristics and influencing factors of the patients with cervical lymph node skip metastasis of papillary thyroid carcinoma (PTC), as to guide the precise treatment of lateral area.Methods:The clinicopathological data of 237 patients with PTC initially diagnosed and treated in Xuanwu Hospital Capital Medical University from Feb 2014 to Mar 2022 were analyzed retrospectively. Among them, there were 217 positive in the central area, and 20 negative, with skip rate 8.4%. The age, sex, pathological type, glandular lobe involvement, tumor size, number of tumor lesions, primary lesion location, and capsule invasion were statistically compared. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the t test. The measurement data of non normal distribution are expressed by M( Q1, Q3), and the Mann Whitney U test is used for comparison between groups. Comparison between groups of count data was conducted using the chi-square test, correction chi-square or Fisher exact probability. Results:Multivariate analysis showed that age ≥ 55 years old( OR: 6.032, 95% CI: 1.692-21.504, P=0.006), female( OR: 23.459, 95% CI: 2.181-252.341, P=0.009), tumor ≤5 mm( OR: 79.453, 95% CI: 7.570-833.891, P<0.001)and located in the upper lobe( OR: 3.446, 95% CI: 1.325-8.962, P=0.011) were independent risk factors for skip metastasis. The patients with skip metastasis had a smaller total number of cervical lymph node metastases( Z=-2.81, P=0.005), smaller total number of neck dissection lymph nodes( Z=-6.62, P<0.001) and less lymph nodes metastases in level Ⅳ( Z=-2.54, P=0.011) than patients with non-skip metastasis. Conclusions:Skip metastasis often occurred with age ≥55 years, female, tumor size less than 5mm and located in the upper lobe. For these patients, careful evaluation for the lateral area is required.

Broad phenotypic alterations and potential dysfunctions of lymphocytes in COVID-19 recovered individuals

BackgroundLymphopenia is a typical symptom in the COVID-19 patients. While millions of patients are clinical recovered, little is known about the immune status of lymphocytes in these individuals. MethodsA clinical recovered cohort (CR) of 55 COVID-19 individuals (discharged from hospital 4 to 11 weeks), and 55 age and sex matched healthy donors cohort (HD) were recruited. Detailed analysis on phenotype of the lymphocytes in peripheral blood mononuclear cells (PBMCs) was performed by flow cytometry. FindingsCompared with cohort HD, the CD8+ T cells in cohort CR had higher Teff and Tem, but lower Tc1 (IFN-{gamma}+), Tc2 (IL-4+) and Tc17 (IL-17A+) frequencies. The CD4+ T cells of CR had decreased frequency, especially on the Tcm subset. Moreover, CD4+ T cells of CR expressed lower PD-1 and had lower frequencies of Th1 (IFN-{gamma}+), Th2 (IL-4+), Th17 (IL-17A+) as well as circulating Tfh (CXCR5+PD-1+). Accordingly, isotype-switched memory B cell (IgM-CD20hi) in CR had significantly lower proportion in B cells, though level of activation marker CD71 elevated. For CD3-HLA-DRlo lymphocytes of CR, besides levels of IFN-{gamma}, Granzyme B and T-bet were lower, the correlation between T-bet and IFN-{gamma} became irrelevant. In addition, taken into account of discharged days, all the lowered function associated phenotypes showed no recovery tendency within whole observation period. InterpretationThe CR COVID-19 individuals still showed remarkable phenotypic alterations in lymphocytes after clinical recovery 4 to 11 weeks. This suggests SARS-CoV-2 infection imprints profoundly on lymphocytes and results in long-lasting potential dysfunctions. FundingKunming Science and Technology Department (2020-1-N-037)

Impaired T cell functions along with elevated activated Tregs at the early stage of asymptomatic SARS-CoV-2 infection

BackgroundLimited data are available on the T cell responses for the asymptomatic SARS-CoV-2 infection case. MethodsAn imported SARS-CoV-2 infection case in Wuhan was admitted in hospital for quarantine and observation. The T cell responses were followed up by flow cytometry analysis of the peripheral blood nonnuclear cells (PBMCs) at days 7, 13, 22, and 28 after admission. FindingsWe found the imported SARS-CoV-2 infection in Wuhan is an asymptomatic case. His T cell differentiation, proliferation and activation matched the classical kinetics of T cell responses induced by viral infection, but the activation maintained at a relatively low level. Function analysis indicated frequencies of IFN-{gamma} producing CD4+ and CD8+ T cells were notably lower than that of the healthy controls (HC) at day 7, and then rebound gradually. But IFN-{gamma}+CD8+ T cells were detained at a significant lower level even at day 28, when the SARS-CoV-2 virus had already become undetectable for 3 weeks. Moreover, percentage of IL-17 producing CD4+ T cells was also detained constantly at a much lower level compared to HC. At day 7, although percentage of Tregs was in normal range, the frequency of activated Treg (aTreg) was remarkably as high as 4{middle dot}4-fold of that in HC. InterpretationThe T cell activation in the asymptomatic SARS-CoV-2 infection experienced a significant suppression and presented impairment of Th1/Th17 and CD8+ T cell functions. Early elevation of the aTregs might play role in the activation and function of T cells in the asymptomatic SARS-CoV-2 infection.

A deep learning algorithm using CT images to screen for Corona Virus Disease (COVID-19)

BackgroundThe outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) has caused more than 2.5 million cases of Corona Virus Disease (COVID-19) in the world so far, with that number continuing to grow. To control the spread of the disease, screening large numbers of suspected cases for appropriate quarantine and treatment is a priority. Pathogenic laboratory testing is the gold standard but is time-consuming with significant false negative results. Therefore, alternative diagnostic methods are urgently needed to combat the disease. Based on COVID-19 radiographical changes in CT images, we hypothesized that Artificial Intelligences deep learning methods might be able to extract COVID-19s specific graphical features and provide a clinical diagnosis ahead of the pathogenic test, thus saving critical time for disease control. Methods and FindingsWe collected 1,065 CT images of pathogen-confirmed COVID-19 cases (325 images) along with those previously diagnosed with typical viral pneumonia (740 images). We modified the Inception transfer-learning model to establish the algorithm, followed by internal and external validation. The internal validation achieved a total accuracy of 89.5% with specificity of 0.88 and sensitivity of 0.87. The external testing dataset showed a total accuracy of 79.3% with specificity of 0.83 and sensitivity of 0.67. In addition, in 54 COVID-19 images that first two nucleic acid test results were negative, 46 were predicted as COVID-19 positive by the algorithm, with the accuracy of 85.2%. ConclusionThese results demonstrate the proof-of-principle for using artificial intelligence to extract radiological features for timely and accurate COVID-19 diagnosis. Author summaryTo control the spread of the COVID-19, screening large numbers of suspected cases for appropriate quarantine and treatment measures is a priority. Pathogenic laboratory testing is the gold standard but is time-consuming with significant false negative results. Therefore, alternative diagnostic methods are urgently needed to combat the disease. We hypothesized that Artificial Intelligences deep learning methods might be able to extract COVID-19s specific graphical features and provide a clinical diagnosis ahead of the pathogenic test, thus saving critical time. We collected 1,065 CT images of pathogen-confirmed COVID-19 cases along with those previously diagnosed with typical viral pneumonia. We modified the Inception transfer-learning model to establish the algorithm. The internal validation achieved a total accuracy of 89.5% with specificity of 0.88 and sensitivity of 0.87. The external testing dataset showed a total accuracy of 79.3% with specificity of 0.83 and sensitivity of 0.67. In addition, in 54 COVID-19 images that first two nucleic acid test results were negative, 46 were predicted as COVID-19 positive by the algorithm, with the accuracy of 85.2%. Our study represents the first study to apply artificial intelligence to CT images for effectively screening for COVID-19.

An experimental study of the effect of extraction and retention of canine primary intruded teeth to the permanent successors / 中华口腔医学杂志

Objective@#To compare the influence of extraction and retention of the intruded dogs' teeth on permanent successors.@*Methods@#Nine healthy 45-days-old Chinese rural puppies were selected, and six were submitted to the intrusion of the bilateral canine. Intruded teeth on the left side were extracted 30 minutes later and the teeth on the right side were kept in their sockets. After 8 months, all dogs were sacrificed. General observation, periapical radiograph and cone beam CT were used to observe the preoperative and postoperative deciduous teeth, permanent germs and permanent teeth development. The structure and content of successors' enamel were observed by scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS).@*Results@#In the extraction groups, the enamel hypoplasia was found in 19 permanent successors, ectopic eruption in 2 cases and abnormal teeth were in 19 cases in total (79%). In the retention groups, enamel hypoplasia of the permanent successors occurred in 2 cases, root dilaceration in 6 cases, and ectopic eruption in 5 cases, retained deciduous teeth in 3 cases, and there were 22 abnormal teeth in total (92%). In blank control group, there was no abnormal teeth. The major effect of intruded deciduous teeth on the permanent successors exhibited enamel hypoplasia [85% (41/48)], presented as enamel coloration and enamel defect (P=0.416).@*Conclusions@#The intruded deciduous teeth should be removed early in order to reduce the effect on the permanent teeth.

The prospect of chlorogenic acid in the treatment of glioma / 中国肿瘤临床

As a common primary intracranial tumor,malignant glioma accounts for 81% of all central nervous system malignancies.Af-ter standard treatment,such as surgery combined with external radiotherapy and chemotherapy,glioblastoma patients'survival is on-ly 14.4 months.Hence,the traditional treatment is difficult to meet patients'needs of survival and life quality.In recent years,chloro-genic acid(CGA),as plant extract polyphenols,has received widespread attention.Its antitumor properties,through its effects on the immune system,anti-oxidation properties,cell cycle regulation,and inhibition of tumor cell metastasis and invasion,have been exten-sively studied.This article will discuss the mechanisms involved in glioma treatment,synergism with other drugs,and metabolism in the human body,to provide a reference for the application of CGA in the treatment of the condition.

Comparative study of efficacy of different types of artificial liver treatments in management of hepatitis B-associated subacute severe hepatitis / 重庆医学

Objective To observe the clinical efficacy of plasma exchange(PE),PE combined with plasma bilirubin absorp-tion(PE+PBA),and PE combined with double plasma molecule absorption system(PE+DPMAS),to investigate the best treat-ment options for the patients of hepatitis B-associated subacute severe.Methods Totally 140 patients who had hepatitis B-associat-ed were randomly divided into a PE group,a PE+PBA group,and a PE+DPMAS group.The dinical symptoms and blood rontine, electrolytc and the main biochemical indexes were recorded both before and after treatment and compared among the three groups. Results The total effective rate was higher in the PE +DPMAS group than in the PE group and PE+PBA group,which were 70.8%,60.9%,67.4% respectively,but there was no significant difference(P >0.05).compared with before treatment,serum total bilirubin (TBIL),alanine aminotransferase (ALT),aspartic acid amino shift enzyme (AST),valley aminoacyl transfer peptidase (GGT),alkaline phosphatase (ALP),globulin (GLB)and other biochemical indexes decreased significantly after treatment in 3 groups (P 0.05).Serum K+ and Cl- was obviously declined after treatment in the PE group,there was significant difference(P <0.001).Serum Na+ was obviously declined after treatment between the PE + PBA and PE + DPMAS groups (P < 0.001 ),but the difference was no significant in the PE groups.Serum Ca2+ was significantly decreased in the three groups of patients after treatment(P <0.001).WBC,Hb and PLT were significantly statistical difference after treatment(P <0.05).Conclusion The three groups also can improve liver function and the treatment rate for the patients of subacute hepatitis B-associated severe hepatitis.PE+PBA and PE+DPMAS groups can effective-ly reduce two thirds of the overall usage of the plasma.PE+DPMAS groups that the quantity of Cl- ,Ca2+ ,Hb decline much least in the three groups show larger value in the clinical application.

Effect of ERK1/2 inhibitor AZD8330 on human Burkitt's lymphoma cell line Raji cells and its mechanism / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of ERK1/2 inhibitor AZD8330 on human Burkitt's lymphoma cell line Raji cells and its mechanism.</p><p><b>METHODS</b>Raji cells were treated with different concentrations of AZD8330. CCK-8 was used to detect the cell viability. The apoptosis rate of Raji cells was detected by flow cytometry using Annexin V/PI-staining. Real-time PCR was used to assess the expression of Bcl-2, Bcl-xl, caspase-3 and VEGF genes. The protein expression level of Bcl-2, Bcl-xl, caspase-3 and p-ERK1/2 was tested with Western blot.</p><p><b>RESULTS</b>The cell survival rate decreased to(62.09±0.86)%,(50.06±1.33)% and (39.13±2.34)% respectively after cells were treated with AZD8330 at 1.00 μmol/L in vitro for 24 h, 48 h and 72 h, and statistically significant differences were observed in groups with different time of treatment(P<0.05). Apoptosis of cells treated with AZD8330 at 0.10, 1.00, 10.00 μmol/L in vitro for 24 h, 48 h and 72 h was analyzed, and the statistically significant differences were observed in groups of different time and concentration treatment (P<0.05). AZD8330 induced Raji cell apoptosis and upregulated expression of Bcl-2, Bcl-xl, VEFG and decreased the expression of caspase-3 in a dose and time dependent manner, and statistically significant differences were observed in groups of different time and concentration treatment (P<0.05). At the same time, the Bcl-2, Bcl-xl and p-ERK1/2 proteins expression is suppressed obviously, but the expression of caspase-3 protein increased.</p><p><b>CONCLUSION</b>AZD8330 induces cell apoptosis by down-regulating the activation of ERK1/2 signal transduction pathway in Burkitt's lymphoma cell line Raji cells in a dose and time dependent manner.</p>

Effect of Kechuanning Oral Liquid on Signal Transduction Pathway of PI3K in Asthma Rats Induced by Virus / 中国中医药信息杂志

Objective To observe the effect of Kechuanning Oral liquid on the expression of P13K in CD4+and CD8+T cells of asthma rats induced by respiratory syncytial virus (RSV), and explore its mechanism of preventing and treating asthma induced by virus. Methods SD rats were randomly divided into phosphate-buffered saline (PBS) control group, model group, dexamethasone and salbutamol group (positive drug group), and Kechuanning oral liquid group. Ovalbumin asthma rats model was built and induced by RSV. CD4+and CD8+T cells were separated by magnetic beads method. The expressive level of PI3K-110αin T cells was detected by immumofluorescence method with flow cytometry. Results Compared with PBS control group, positive drug group and Kechuanning oral liquid group, the CD4+and CD8+T cells percentage and the expression level of PI3K-110α in CD4+ and CD8+T cells of model group were significantly higher. The differences were statistically significant (P<0.01). The CD4+and CD8+T cells percentage was not associated with the expression level of PI3K-110α in CD4+ and CD8+T cells of each group by Pearson correlation analysis. Conclusion The CD4+ and CD8+T cells involve in the asthma immunity balanced modulation, and the level of PI3K expressed by CD4+ and CD8+T cells increase distinctly. Kechuanning oral liquid can restrain the expression of PI3K in CD4+ and CD8+T cells, which might be one of the immunologic mechanisms of treating asthma.

PIKA Provides an Adjuvant Effect to Induce Strong Mucosal and Systemic Humoral Immunity Against SARS-CoV / 中国病毒学·英文版

Severe Acute Respiratory Syndrome(SARS)is a deadly infectious disease caused by SARS Coronavirus(SARS-CoV).Inactivated SARS-CoV has been explored as a vaccine against SARS-CoV.However,safe and potent adjuvants,especially with more efficient and economical needle-free vaccination are always needed more urgently in a pandemic.The development of a safe and effective mucosal adjuvant and vaccine for prevention of emergent infectious diseases such as SARS will be an important advancement.PIKA,a stabilized derivative of Poly(I:C),was previously reported to be safe and potent as adjuvant in mouse models.In the present study,we demonstrated that the intraperitoneal and intranasal co-administration of inactivated SARS-CoV vaccine together with this improved Poly(I:C)derivative induced strong anti-SARS-CoV mucosal and systemic humoral immune responses with neutralizing activity against pseudotyped virus.Although intraperitoneal immunization of inactivated SARS-CoV vaccine alone could induce a certain level of neutralizing activity in serum as well as in mucosal sites,co-administration of inactivated SARS-CoV vaccine with PIKA as adjuvant could induce a much higher neutralizing activity.When intranasal immunization was used,PIKA was obligatorily for inducing neutralizing activity in serum as well as in mucosal sites and was correlated with both mucosal IgA and mucosal IgG response.Overall,PIKA could be a good mucosal adjuvant candidate for inactivated SARS-CoV vaccine for use in possible future pandemic.

Construction and expression of anti-clenbuterol single chain Fv recombinant vector / 生物工程学报

To construct the recombinant vector pBV220-scFv and express anti-clenbuterol (CBL) scFv antibody in Escherichia coli, we amplified the scFv gene using plasmid pCANTABSE-CBL as a template, recombined it with pPICZalphaA, then amplified the scFv-His-tag gene from plasmid pPICZalphaA-scFv and linked it with expression plasmid pBV220. We identified the recombinant plasmid by restrictive enzyme digestion, PCR amplification and sequence analysis. Finally, we transformed the recombinant vector into E. coli DH5alpha that was temperature-induced and expressed recombinant protein. We identified the recombinant protein by SDS-PAGE, Western blotting and indirect competitive ELISA. The results show that recombinant plasmid pBV220-scFv contained the inserted fragment with highest homology about 99.8%. The expression of scFv induced by temperature show 37 kD Mw and anti-His-tag mAb recognized-activity by SDS-PAGE and Western blotting respectively, and could competitively combine with CBL, the IC50 is 4.55 ng/mL. The recombinant plasmid pBV220-scFv is constructed and expresses the scFv gene of CBL in E. coli successfully. This study suggests the corresponding immunoassay methods could be set up by the recombinant scFv.