ObjectiveTo investigate the effects of modified Ditan tang on genes related to the transcription-translation feedback loop （TTFL） of biorhythm in the rat model of non-alcoholic fatty liver disease （NAFLD） and its mechanism for prevention and treatment of NAFLD. MethodsSixty-five healthy SPF male SD rats were randomly assigned into blank （n=20）， model （n=15）， and low-， medium-， and high-dose （2.68， 5.36， and 10.72 g·kg^-1·d^-1， respectively） modified Ditan tang （n=10） groups. Other groups except the blank group were fed a high-fat diet for 12 weeks. The modified Ditan tang groups were treated with the decoction at corresponding doses by gavage， and the blank and model groups were treated with an equal volume of normal saline from the 9th week for 4 weeks. The levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） in the serum were measured by an automatic biochemical analyzer. TG and non-esterified fatty acid （NEFA） assay kits were used to measure the levels of TG and NEFA in the liver. The pathological changes in the hypothalamus and liver were observed by hematoxylin-eosin staining， and the lipid deposition in the liver was observed by oil red O staining. The levels of brain-muscle ARNT-like protein 1 （BMAL1/ARNTL） in the hypothalamus and liver were determined by immunohistochemical staining. The mRNA and protein levels of BMAL1， circadian locomotor output cycles kaput （CLOCK）， period circadian clock 2 （PER2）， and cryptochrome1 （Cry1） in the hypothalamus and liver were determined by Real-time PCR and Western blot， respectively. ResultsCompared with the blank group， the model group showed elevated levels of TG， TC， LDL-C， AST， and ALT （P<0.01） and a lowered level of HDL-C （P<0.05） in the serum， elevated levels of TG and NEFA in the liver （P<0.01）， pyknosis and deep staining of hypothalamic neuron cells， and a large number of vacuoles in the brain area. In addition， the model group showed lipid deposition in the liver， up-regulated mRNA and protein levels of CLOCK and BMAL1 （P<0.01）， and down-regulated mRNA and protein levels of Cry1 and PER2 （P<0.01） in the hypothalamus and liver. Compared with the model group， all the three modified Ditan tang groups showed lowered levels of TG， TC， LDL-C， ALT， and AST （P<0.05， P<0.01） and an elevated level of HDL-C （P<0.05） in the serum， and lowered levels of TG and NEFA （P<0.05， P<0.01） in the liver. Furthermore， the three groups showed alleviated pyknosis and deep staining of hypothalamic neuron cells， reduced lipid deposition in the liver， down-regulated mRNA and protein levels of CLOCK and BMAL1 （P<0.05， P<0.01）， and up-regulated mRNA and protein levels of Cry1 and PER2 （P<0.05， P<0.01） in the hypothalamus and liver. ConclusionModified Ditan tang can reduce lipid deposition in the liver and regulate the expression of CLOCK， BMAL1， Cry1， and PER2 in the TTFL of NAFLD rats.

Objective To analyze the risk factors of nosocomial infection among the patients in neuro-surgical ICU,and to construct the risk prediction model to provide reference for the prediction of nosocomial infection in neurosurgical ICU patients.Methods The clinical data of 280 patients admitted and treated in the neurosurgery ICU of this hospital from January 2021 to December 2022 were retrospectively analyzed.The pa-tients were divided into the infection group and non-infection group based on whether or not nosocomial infec-tion occurring,140 cases in each group.A total of 196 patients were extracted as the training set by a ratio of 7︰3 for constructing the model,while the remaining 84 patients served as the validation set for conducting the internal verification.The logistic regression was used to analyze the risk factors of nosocomial infection in the neurosurgery ICU patients,and a predictive model was established.The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive effect of the model.Results The multivariate logistic re-gression analysis indicated that old age,long surgery time,catheter use and glucocorticoids use were screened as the main risk factors of nosocomial infection occurrence in neurosurgery ICU patients.The nomogram mod-el was constructed based on the results of multivariate analysis,the area under the curve of training set and validation set were 0.796 and 0.875,respectively.The correcting model reflected good consistency between actual diagnosis and predictive diagnosis.Conclusion The model constructed in this study has the high predic-tive value for the nosocomial infection occurrence risk in the patients of the neurosurgery ICU.

Objective:To investigate the sensitivity of tumor organoids derived from samples of colorectal cancer to lobaplatin and oxaliplatin hyperthermic perfusion in vitro and to assist clinical development of hyperthermic intraperitoneal chemotherapy. Method:Tumor samples and relevant clinical data were collected from patients with pathologically confirmed colorectal cancer in the Sixth Affiliated Hospital of Sun Yat-sen University from July 2021 to December 2022. Organoids were cultured and tumor tissue were passaged. In vitro hyperthermic perfusion experiments were performed on organoids with good viability. Firstly, 10 organoids were treated with oxaliplatin and lobaplatin at the following six concentrations: 1 000, 250, 62.5, 15.6, 3.9, and 0.98 μmol/L. The organoids were exposed to oxaliplatin at 42℃ for 30 minutes and to lobaplatin at 42℃ for 60 minutes. Dose-response curves of responses to in vitro hyperthermic perfusion with these two drugs were constructed and evaluated. Clinical doses of oxaliplatin and lobaplatin were further tested on 30 organoids. This testing revealed oxaliplatin was effective at 579 μmol/L at a hyperthermic perfusion temperature of 42℃ for 30 min and lobaplatin was effective at 240 μmol/L at a hyperthermic perfusion temperature of 42℃ for 60 minutes. Result:Thirty-two tumor organoids were cultured from samples of colorectal cancer. The median concentration required for oxaliplatin to eliminate 50% of tumor cells (IC50) was 577.45 μmol/L (IQR: 1846.09 μmol/L). The median IC50 for lobaplatin was 85.04 μmol/L (IQR: 305.01 μmol/L).The difference between the two groups was not statistically significant ( Z=1.784, P=0.084). In seven of 10 organoids, lobaplatin showed a greater IC50 after in vitro hyperthermic perfusion than did oxaliplatin. Testing of 30 organoids with clinical doses of oxaliplatin and lobaplatin revealed that oxaliplatin achieved an average inhibition rate of 39.6% (95%CI: 32.1%?47.0%), whereas the average rate of inhibition for lobaplatin was 89.7% (95%CI: 87.0%?92.3%): this difference is statistically significant ( t=?15.282, P<0.001). Conclusion:The rate of inhibition achieved by hyperthermic perfusion of lobaplatin in vitro is better than that achieved by hyperthermic perfusion with oxaliplatin. Lobaplatin is more effective than oxaliplatin when administered by hyperthermic intraperitoneal perfusion and therefore has the potential to replace oxaliplatin in this setting.

Objective:To study the effects of metformin on marginal bone resorption of implants in patients with type 2 diabetes melli-tus(T2DM)and exercise habit.Methods:63 cases with 73 implants were included.Among them,there were 41 cases(47 implants)without T2DM in group N,10 cases(13 implants)with T2DM and without exercise habit in group M,12 cases(12 implants)with T2DM and exercise habit in the MR group.The patients were followed up at 6 months,1 and 2 years after implantation.The marginal bone loss(MBL).Implantation success rate and peri-implantitis incidence rate were compared among the groups.Results:The bone resorption of the proximal and median margins of the long-term bone level of the implants in the N and MR groups were significantly lower than that in the M group(P=0.001 and P=0.000 5,respectively).The implant success rates of group N,MR and M were 95.74％,100％and 76.92％,respectively.The incidence of peri-implantitis of the three groups was 2.13％,0 and 15.38％,respec-tively.Conclusion:Metformin is more effective in the improvement of the long-term marginal bone resorption of implants,increase the success rate of implants,and reduce the incidence of peri-implantitis in patients with T2DM and exercise habit in the mandibular first molar area.

Objective:To investigate the sensitivity of tumor organoids derived from samples of colorectal cancer to lobaplatin and oxaliplatin hyperthermic perfusion in vitro and to assist clinical development of hyperthermic intraperitoneal chemotherapy. Method:Tumor samples and relevant clinical data were collected from patients with pathologically confirmed colorectal cancer in the Sixth Affiliated Hospital of Sun Yat-sen University from July 2021 to December 2022. Organoids were cultured and tumor tissue were passaged. In vitro hyperthermic perfusion experiments were performed on organoids with good viability. Firstly, 10 organoids were treated with oxaliplatin and lobaplatin at the following six concentrations: 1 000, 250, 62.5, 15.6, 3.9, and 0.98 μmol/L. The organoids were exposed to oxaliplatin at 42℃ for 30 minutes and to lobaplatin at 42℃ for 60 minutes. Dose-response curves of responses to in vitro hyperthermic perfusion with these two drugs were constructed and evaluated. Clinical doses of oxaliplatin and lobaplatin were further tested on 30 organoids. This testing revealed oxaliplatin was effective at 579 μmol/L at a hyperthermic perfusion temperature of 42℃ for 30 min and lobaplatin was effective at 240 μmol/L at a hyperthermic perfusion temperature of 42℃ for 60 minutes. Result:Thirty-two tumor organoids were cultured from samples of colorectal cancer. The median concentration required for oxaliplatin to eliminate 50% of tumor cells (IC50) was 577.45 μmol/L (IQR: 1846.09 μmol/L). The median IC50 for lobaplatin was 85.04 μmol/L (IQR: 305.01 μmol/L).The difference between the two groups was not statistically significant ( Z=1.784, P=0.084). In seven of 10 organoids, lobaplatin showed a greater IC50 after in vitro hyperthermic perfusion than did oxaliplatin. Testing of 30 organoids with clinical doses of oxaliplatin and lobaplatin revealed that oxaliplatin achieved an average inhibition rate of 39.6% (95%CI: 32.1%?47.0%), whereas the average rate of inhibition for lobaplatin was 89.7% (95%CI: 87.0%?92.3%): this difference is statistically significant ( t=?15.282, P<0.001). Conclusion:The rate of inhibition achieved by hyperthermic perfusion of lobaplatin in vitro is better than that achieved by hyperthermic perfusion with oxaliplatin. Lobaplatin is more effective than oxaliplatin when administered by hyperthermic intraperitoneal perfusion and therefore has the potential to replace oxaliplatin in this setting.

Humans ; Coronary Artery Disease/surgery* ; Percutaneous Coronary Intervention ; Heart ; Treatment Outcome ; Coronary Angiography

A series of new monobactam sulfonates is continuously synthesized and evaluated for their antimicrobial efficacies against Gram-negative bacteria. Compound 33a (IMBZ18G) is highly effective in vitro and in vivo against clinically intractable multi-drug-resistant (MDR) Gram-negative strains, with a highly druglike nature. The checkerboard assay reveals its significant synergistic effect with β-lactamase inhibitor avibactam, and the MIC values against MDR enterobacteria were reduced up to 4-512 folds. X-ray co-crystal and chemoproteomic assays indicate that the anti-MDR bacteria effect of 33a results from the dual inhibition of the common PBP3 and some class A and C β-lactamases. Accordingly, preclinical studies of 33a alone and 33a‒avibactam combination as potential innovative candidates are actively going on, in the treatment of β-lactamase-producing MDR Gram-negative bacterial infections.

Objective:To establish a simple and efficient clinical prediction model of moderate and severe obstructive sleep apnea hypopnea (OSAHS) in snoring patients based on the clinical data and morphological measurement data in order to increase the early diagnosis and then early intervention of OSAHS. The prediction model is evaluated by external validation.Methods:A total of 299 subjects from January 2015 to December 2018 were selected to perform polysomngraphy (PSG) in Yangpu Hospital, Tongji University School of Medicine. According to the PSG results, they were divided into moderate and severe OSAHS groups (143 cases) and control groups (156 cases). Clinical complications data and morphological measurement data were collected. The regression equation and ROC curve were established according to the Logistic regression method. Then, another 110 subjects from January 2019 to October 2019 were chosen as verified data group, and used to verify the accuracy of the prediction model. The data of 110 subjects were put into the equation according to risk factors and assignment. The ROC curve was drawn and the area under the curve was calculated. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value were calculated.Results:The predicted equation was: y = -10.707 86+0.589 60 × sex+ 0.141 61 × BMI+ 1.281 62 × tonsil size degree+ 1.807 43 × modified Mallampati degree′tongue position. The AUC of the ROC curve of prediction model in training set was 0.851(95% CI 0.807-0.895), the sensitivity was 83.9%, the specificity was 79.5%, and the cut-off value was 0.634.The AUC of the ROC curve in validation set was 0.827(95% CI 0.751-0.904) with a sensitivity of 73.3% and a specificity of 86.0%, and an accuracy of 79.1%. Its positive predictive value was 5.238, and negative predictive value was 0.310. Conclusions:The predictive model constructed by the combination of clinically accessible data (sex) and morphological measurement (BMI, tonsil size degree, modifiedMallampatidegree) has a relatively high predictive efficiency for screening snoring patients with moderate and severe OSAHS. The predictive model is proved with good forecast accuracy by the external verification method.

Objective:To explore the value of bedside chest radiograph in the diagnosis and follow-up of severe and critical COVID-19.Methods:Twenty-nine patients with severe or critical COVID-19 were collected from January 23 to February 23, 2020，from four COVID-19 designated hospitals in Guangdong Province. Bedside radiography was taken in all the 29 patients, ranged from 1 to 16 times for each patient. Twenty-seven patients underwent follow-up, and the number of re-examination ranged 1 to 15 times, and the interval of review is 1 to 8 days.The imaging findings of bedside chest radiography and the imaging changes on follow-up chest radiography were analyzed retrospectively.Results:Twenty-nine patients were collected. The radiography showed the lesions involved all more than 3 lung fields. The films showed consolidation shadow in 19 cases, multiple patches of shadow in 23 cases, reticular pattern in 12 cases, strips shadow in 14 cases, interlobar fissure thickening in 18 cases, and "white lung" in 4 cases.The complications included pleural effusion in 4 cases, pneumothorax in 2 cases, mediastinal and subcutaneous emphysema in 1 case. The radiography showed the lesions progressed in 15 cases, with expanded involvement of the lung.The increase of lesion density was found in 6 cases, new lesions were noted in 5 cases, while both of them were found in 4 cases. Nine cases showed improvement, with reduced range and decreased density. Patchy or consolidation shadow turned to strips shadow or articular pattern shadow in 8 cases.There was no significant change in 3 cases with large consolidation shadow.Conclusions:Bedside chest radiography has a good value in the follow-up of severely and critically ill patients with COVID-19, and can provide great help for clinicians to evaluate their condition.

OBJECTIVETo investigate the effect of low-molecular-weight heparin (LMWH) combined with paclitaxel (PTX) on the invasiveness and migration of nasopharyngeal carcinoma cells and explore the molecular mechanisms.

METHODSMTT assay was used to detect the growth inhibition induced by LMWH and PTX in CNE1 and CNE2 cells. Wound healing assay and Transwell migration assay were employed to assess the effects of the drugs on the cell migration, and Transwell invasion assay was used to evaluate the cell invasiveness. The cellular expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were analyzed by Western blotting. ELISA was used to determine the expression of heparanase (HPA) in the culture medium of the cells.

RESULTSMTT assay showed an obvious suppression of CNE1 and CNE2 cell proliferation in response to LMWH and PTX treatments. Treatment with 200 U·ml LMWH combined with 0.1 µmol·L PTX for 24 h resulted in the inhibition rates of migration of 66.70% and 70.53% in CNE1 and CNE2 cells, respectively significantly higher than the rates in cells with PTX treatment alone. The combined treatment with LMWH and PTX for 24 h also caused a significantly higher inhibition rate of cell invasion than LMWH and PTX alone. LMWH enhanced the down-regulation of MMP-9 and HPA induced by PTX.

CONCLUSIONLMWH can enhance the inhibitory effect of PTX on the migration and invasion of nasopharyngeal carcinoma cells, the mechanism of which may involve the down-regulation of MMP-9 and HPA expressions.

Carcinoma ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Glucuronidase ; metabolism ; Heparin Lyase ; metabolism ; Heparin, Low-Molecular-Weight ; administration & dosage ; pharmacology ; Humans ; Matrix Metalloproteinase 9 ; metabolism ; Nasopharyngeal Neoplasms ; pathology ; Paclitaxel ; administration & dosage ; pharmacology ; Tissue Inhibitor of Metalloproteinase-1 ; metabolism