AIM: To explore the efficacy of bilateral lateral rectus recession in the treatment of basic intermittent exotropia. METHODS: A prospective study was conducted on 104 patients with basic intermittent strabismus admitted to our hospital from October 2022 to October 2023, patients were randomly divided into a study group of 52 cases and a control group of 52 cases using a random number ranking method. The control group received unilateral recess-resect, while the study group received bilateral lateral rectus recession, the differences in surgical success rate, postoperative strabismus, and postoperative exotropia drift were compared between two groups.RESULTS: There was no statistically significant difference between the two groups at 1 d, 1, 3, and 6 mo after surgery(all P>0.05). The strabismus in the 6 m and 33 cm eye positions at 1, 3, and 6 mo after surgery were lower than those at 1 d after surgery(all P<0.05). However, there was no statistically significant difference in the strabismus in the 6 m and 33 cm eye positions between the two groups at 1 d, 1, 3, and 6 mo after surgery(all P>0.05), and there was statistical significant difference between the two groups in exotropia drift at different postoperative time points(all P<0.05). The exotropia drift of both groups increased at 3 and 6 mo after surgery compared to 1 mo after surgery, and the exotropia drift at 6 mo after surgery was greater than that at 3 mo after surgery(all P<0.05). However, the exotropia drift of the study group at 3 and 6 mo after surgery was lower than that of the control group(all P<0.001). CONCLUSION: Bilateral lateral rectus recession for the treatment of basic-type intermittent exotropia effectively reduces the amount of postoperative exotropia drift, and it has better long-term stability.

To evaluate the diagnostic performance of a three-gene (GBP5, DUSP3, and TBP) tuberculosis (TB) score in bacteriologically-negative pulmonary tuberculosis, and to develop and validate a discriminative diagnostic model by integrating inflammatory cytokines (IL-2, IL-5, IL-17, and IFN-γ). A prospective cohort study was conducted, a total of 238 patients admitted to the Affiliated Infectious Disease Hospital of Soochow University from May 2023 to May 2024 were enrolled, including 119 pathogen-negative pulmonary tuberculosis patients and 119 patients with other pulmonary diseases (OPD). The GeneXpert MTB-HR kit was used to detect the three-gene TB scores from residual blood routine samples. The diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis. Concurrent data on 12 inflammatory cytokines were collected from patients. Potential biomarkers were screened using univariate analysis and multivariate logistic regression, and selected features were incorporated into the construction of four machine learning models: logistic regression, support vector machine (SVM), K-nearest neighbors (KNN), and adaptive boosting (AdaBoost). The samples were randomly split into a training set (85%) and a test set (15%). The models were trained on the training set, and their diagnostic performance was validated using the test set. The predictive ability of each model was evaluated based on ROC curve parameters. The results showed that the three-gene TB score alone yielded an AUC of 0.539 (sensitivity: 50.94%, specificity: 60.50%) in distinguishing pathogen-negative pulmonary tuberculosis from OPD. Four non-col-linear inflammatory factors (IL-2, IL-5, IL-17, and IFN-γ) were selected and combined with the three-gene TB score to construct machine learning models. The AdaBoost model demonstrated the best performance, achieving an AUC of 0.893 (sensitivity: 85.4%, specificity: 73.0%) in the training set and an AUC of 0.873 (sensitivity: 88.2%, specificity: 72.2%) in the test set. In conclusion,the AdaBoost diagnostic model integrating the three-gene TB score with inflammatory factors (IL-2, IL-5, IL-17, and IFN-γ) exhibits superior discriminating performance for pathogen-negative pulmonary tuberculosis compared to OPD, significantly outperforming the three-gene TB score alone.

Objective:To investigate the effects and mechanism of very long chain acyl-CoA dehydrogenase(VLCAD)on prolifera-tion,invasion and metastasis of oral squamous cell carcinoma cells.Methods:The expression levels of VLCAD and glucose trans-porter 1(GLUT1)in human normal oral epithelial cell line(HOEC cells)and human oral squamous cell carcinoma line(SCC25 cells)were determined by Western blot,and the expression levels of VLCAD and GLUT1 in oral squamous cell carcinoma patients and their correlation with pathological stages and prognosis were analyzed in the TCGA database.SCC25 cell lines with VLCAD over-expression and knockdown were constructed and the expression level of VLCAD and GLUT1,cell proliferation,migration,invasion ability,lactate dehydrogenase content and lactate production level were detected respectively.Results:The expression level of VL-CAD in SCC25 cells was significantly lower than that in HOEC cells.The expression level of GLUT1 in SCC25 cells was significantly higher than that in HOEC cells.There was a significant negative correlation between the two expression levels(P＜0.05).VLCAD overexpression significantly inhibited GLUT1 expression and aerobic glycolysis in SCC25 cells,and also inhibited cell proliferation,migration and invasion.VLCAD knockdown effectively reversed the antitumor effects of overexpression mediated by VLCAD(P＜0.05).Conclusion:VLCAD inhibits proliferation,invasion,and metastasis of oral squamous cell carcinoma SCC25 cells by down-regulating GLUT1 and inhibiting its mediated aerobic glycolysis.

Objective:To investigate the effects and mechanism of very long chain acyl-CoA dehydrogenase(VLCAD)on prolifera-tion,invasion and metastasis of oral squamous cell carcinoma cells.Methods:The expression levels of VLCAD and glucose trans-porter 1(GLUT1)in human normal oral epithelial cell line(HOEC cells)and human oral squamous cell carcinoma line(SCC25 cells)were determined by Western blot,and the expression levels of VLCAD and GLUT1 in oral squamous cell carcinoma patients and their correlation with pathological stages and prognosis were analyzed in the TCGA database.SCC25 cell lines with VLCAD over-expression and knockdown were constructed and the expression level of VLCAD and GLUT1,cell proliferation,migration,invasion ability,lactate dehydrogenase content and lactate production level were detected respectively.Results:The expression level of VL-CAD in SCC25 cells was significantly lower than that in HOEC cells.The expression level of GLUT1 in SCC25 cells was significantly higher than that in HOEC cells.There was a significant negative correlation between the two expression levels(P＜0.05).VLCAD overexpression significantly inhibited GLUT1 expression and aerobic glycolysis in SCC25 cells,and also inhibited cell proliferation,migration and invasion.VLCAD knockdown effectively reversed the antitumor effects of overexpression mediated by VLCAD(P＜0.05).Conclusion:VLCAD inhibits proliferation,invasion,and metastasis of oral squamous cell carcinoma SCC25 cells by down-regulating GLUT1 and inhibiting its mediated aerobic glycolysis.

To evaluate the diagnostic performance of a three-gene (GBP5, DUSP3, and TBP) tuberculosis (TB) score in bacteriologically-negative pulmonary tuberculosis, and to develop and validate a discriminative diagnostic model by integrating inflammatory cytokines (IL-2, IL-5, IL-17, and IFN-γ). A prospective cohort study was conducted, a total of 238 patients admitted to the Affiliated Infectious Disease Hospital of Soochow University from May 2023 to May 2024 were enrolled, including 119 pathogen-negative pulmonary tuberculosis patients and 119 patients with other pulmonary diseases (OPD). The GeneXpert MTB-HR kit was used to detect the three-gene TB scores from residual blood routine samples. The diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis. Concurrent data on 12 inflammatory cytokines were collected from patients. Potential biomarkers were screened using univariate analysis and multivariate logistic regression, and selected features were incorporated into the construction of four machine learning models: logistic regression, support vector machine (SVM), K-nearest neighbors (KNN), and adaptive boosting (AdaBoost). The samples were randomly split into a training set (85%) and a test set (15%). The models were trained on the training set, and their diagnostic performance was validated using the test set. The predictive ability of each model was evaluated based on ROC curve parameters. The results showed that the three-gene TB score alone yielded an AUC of 0.539 (sensitivity: 50.94%, specificity: 60.50%) in distinguishing pathogen-negative pulmonary tuberculosis from OPD. Four non-col-linear inflammatory factors (IL-2, IL-5, IL-17, and IFN-γ) were selected and combined with the three-gene TB score to construct machine learning models. The AdaBoost model demonstrated the best performance, achieving an AUC of 0.893 (sensitivity: 85.4%, specificity: 73.0%) in the training set and an AUC of 0.873 (sensitivity: 88.2%, specificity: 72.2%) in the test set. In conclusion,the AdaBoost diagnostic model integrating the three-gene TB score with inflammatory factors (IL-2, IL-5, IL-17, and IFN-γ) exhibits superior discriminating performance for pathogen-negative pulmonary tuberculosis compared to OPD, significantly outperforming the three-gene TB score alone.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Objective:To survey bone age, vitamin A, vitamin D and IGF-1 levels among stunted children, and to explore the clinical values.Methods:The experimental group was composed of 200 stunted children who visited the growth retardation clinic of Jiangning Hospital Affiliated to Nanjing Medical University between October 2017 and October 2019.The control group consisted of 200 children of normal height during the same period.The differences of developmental level, the qualified rates of serum vitamin A and vitamin D, and the number of the children whose serum IGF-1 at or above the median and their corresponding measurements were compared between the two groups.Results:Totally, 26% of the experimental group fell behind normal children by two years in their bone ages, as compared with 12% of control group.The differences in developmental levels of bone ages between the two groups were statistically significant( χ2=12.74, t=5.42、7.92, P<0.01). Compared with the control group, the experimental group had obviously lower rates of vitamin A and vitamin D levels( χ2=26.85、13.65, t=8.45、12.47, P<0.01). A total of 88 children (44%) of the experimental group had serum IGF-1 levels at or above the median, as compared with 138 children (69%) of the control group( χ2=25.43, t=32.31, P<0.01). Conclusion:This finding supports the potential use of the bone age, vitamin A and D status and IGF-1 levels in growth retardation screening among children.

Objective: To study the immune regulation function of high expressing interleukin-10 (IL-10) in B cells on CD4⁺T-cells in periodontitis mouse model. Methods: Twenty-four 7-weeks-old female C57BL/6 mice were randomly and equally assigned into 4 groups: the healthy control group (HC group, n=6), the ligation combined Porphyromonasgingivalis (Pg) infection group (P group, n=6), the ligation combined Pg infection with non-stimulated B cell transfer group (P+NSB group, n=6) and the ligation combined Pg infection with stimulated B cell transfer group (P+SB group, n=6). Ligation combined Pg infection of the maxillary second molar was used to induce periodontitis of mice. The exogenous non-stimulated B cells or stimulated B cells were injected into the palate gingivalat the 5th day after ligation, and all mice were sacrificed at the 14th day. HE stain was used to detect the histological of periodontal tissues, toluidine blue stain was used to analysis the alveolar bone loss, immunofluorescence stain was used to detect the expression of CD4⁺T-cell and IL-10, immunohistochemical was used to detect the expression of receptor activator of NF-κB ligand (RANKL) and IL-1β. Results: Results of HE staining showed that more hyperplasia of gingival epithelium and the alveolar bone resorption in P group, P+NSB group and P+SB group compared with HC group. Results of toluidine blue staining showed that the alveolar bone losses in P group [(0.668±0.041) mm²], P+NSB group [(0.750±0.039) mm²] and P+SB group [(0.517±0.038) mm²] were significantly increased compared with that in HC group [(0.336±0.029) mm²](F=146.051, P<0.01), and the alveolar bone resorption was significantly increased in P+NSB group compared with that in P group (F=146.051, P<0.01). However, compared with P+NSB group and P group, the alveolar bone loss in P+SB groupwas significantly decreased (F=146.051, P<0.01). Results of immunofluorescence staining showed that CD4⁺T-cells expressed in P group [(287.5±37.9) cell/mm²], P+NSB group [(314.6±53.3) cell/mm²] and P+SB group [(185.4±42.9) cell/mm²] were higher than that in HC group [(12.5±13.7) cell/mm²)(F=71.284, P<0.01). Compared with P group and P+NSB group, CD4⁺T-cells expression in group P+SB was decreased (F=71.284, P<0.01). IL-10 levels were increased in P group [(111.7±20.4) cell/mm²], P+NSB group [(126.7±15.1) cell/mm²] and P+SB group [(191.0±22.6) cell/mm²] compared with that in HC group [(22.7±4.3) cell/mm²] (F=98.516, P<0.01), and the IL-10 expressed in P+SB group was significantly higher than those in P+NSB group and P group. Results of immunohistochemical tests showed that RANKL expressions in gingival tissues among P group [(674.0±71.5) cell/mm²], P+NSB group [(831.0±97.5) cell/mm²] and P+SB group [(420.1±40.8) cell/mm²] were significantly higher than that in HC group [(69.3±29.1) cell/mm²] (F=154.886, P<0.01). However, it dramatically decreased in P+SB group compared with those in P group and P+NSB group.The IL-1βexpression in P group [(447.8±40.8) cell/mm²], P+NSB group [(512.5±38.2) cell/mm²] and P+SB group [(281.6±32.4) cell/mm²] were significantly higher than that in HC group [(50.8±20.9) cell/mm²], and it also higher in P+NSB group compared with in P group. However, it decreased in P+SB group compared with those in P group and P+NSB group (F=221.185, P<0.01). Conclusions High expression IL-10 in B cell smight inhibit alveolar bone loss, RANKL and IL-1β expressions and CD4⁺T-cell infiltration through IL-10.

Objective To investigate the effect of first aid nursing path under the center of chest pain on the diagnosis and treatment of patients with ST-segment elevation myocardial infarction (STEMI). Methods A total of 79 cases of STEMI patients who had been selected for emergency treatment after the establishment of the chest pain center were as the experimental group. The patient's first aid nursing path was used in the center of chest pain. A total of 159 cases of STEMI patients before the establishment of the chest pain center were as the control group, Application of traditional clinical pathway. Compared to the diagnosis and treatment effect of two groups of patients. Results The rate of completed the project within 10 min for the experimental group: the completion of electrocardiogram examination (91.1% vs 84.9% ), oral aspirin, clopidogrel, or lindinda (81.0% vs 75.5%), and laboratory medical order (79.7% vs 69.8%) were higher than those in the control group, and the difference was statistically significant (χ2=2.31, 1.68, 2.06, P < 0.05). The day of hospitalization in the experimental group was less than that of the control group (6.48±3.82 vs 9.76± 4.32), and the difference was statistically significant (t=-9.80, P < 0.05). The mortality rate during hospitalization was lower than that of the control group (5.66% vs 3.8% ), and the difference was statistically significant (χ2=-2.24, P<0.05). Conclusion The first aid nursing path in the center of chest pain can shorten the time of diagnosis and treatment of STEMI patients and improve the diagnosis and treatment effect of STEMI patients.

Objective To evaluate combined sampling at multiple sites of gastric mucosa for Helicobacter pylori (HP) culture.Methods A total of 258 patients with upper gastrointestinal symptoms received 13C-urea breath test between August 2014 and May 2015.During endoscopy,gastric mucosa biopsy samples from the lesser curvature of the antrum (A),the greater curvature of the antrum (B),gastric angle (C) and the body of the stomach (D) were collected to isolate HP strains.The positive rates of HP based on combined sampling and single site sampling were compared with a Nemenyi test.Results Consistency between 13C-urea breath test and HP culture was 82.56％.There was significant difference between the single site sampling and two-site sampling in the positive rate of HP,except for the body of the stomach (P＜0.05).There was significant difference in the positive rate of HP between the single site sampling and three-site sampling (P ＜ 0.05).There was no significant difference between any two-site sampling in the lesser curvature of the antrum and the body of the stomach,gastric angle and the body of the stomach,the greater curvature of the antrum and the body of the stomach,and any three-site sampling (P＞0.05).Conclusion The combined sampling of the lesser curvature of the antrum and the body of the stomach have the highest cost-effectiveness in HP culture compared with the single site sampling and three-site sampling.