Abstract: Objective To investigate the influence of the variation of SARS-CoV-2 on the clinical feature, and to provide early warning signs for the variation of SARS-CoV-2 in clinical work. Methods From Jan 2, 2021 to Jun 30, 2021, a total of 105 COVID-19 patients were included in the study using a case-control method. Nasal swab samples were collected from the study subjects, the viral genes were sequenced, and patients were divided into Delta variant group and non-Delta variant group according to their gene sequences. Clinically relevant data were collected from the two groups, and indicators such as days of hospitalization, age distribution, lymphocytes, neutrophils, B lymphocytes, NK cells, IL-4, and IL-10 were compared; subgroup analysis was performed based on the number of days of viral negativity in the study subjects as the basis for grouping, and differences in immunological characteristics were compared, including lymphocytes, neutrophils, B lymphocytes, NK cells, IL-4, IL-10, etc. Results The theoretical hospitalization days of Delta variant group were (22.2±8.33) d, which were significantly longer than (17.6±10.50) d of non-Delta variant group (t=2.396, P<0.05). The total lymphocyte count and IL-4 of Delta variant group were (1.22±0.86) ×109/L and (0.80±0.23) ng/mL, which were significantly lower than corresponding (1.91±0.70) ×109/L and (1.59±0.59) ng/mL of non-Delta variant group (t=4.329, 9.072, P<0.05), while IL-10 was (7.16±7.77) ng/mL, which was significantly higher than (4.26±3.91) ng/mL of non-Delta mutation group (t=1.980, P<0.05). Subgroup analysis showed that the total lymphocyte count and IL-4 concentration in Delta variant group were (1.04±0.60) ×109/L and (0.74±0.25) ng/ml, which were significantly lower than corresponding (1.62±0.56) ×109/L and (1.56±0.52) ng/mL in non-Delta variant group, in patients with delayed discharge (P<0.05). Conclutions SARS-CoV-2 variant has an impact on clinical manifestations. The patient's B cell count and IL-10 concentration increased or IL-2 and IL-4 concentration decreased within 12 hours of admission indicated variant virus infection. The decrease of total lymphocyte count, especially T lymphocyte reduction, strongly suggests discharge delay due to viral clearance disorder.

Objective To observe the effects of carvedilol on renal function in mice with diabetic kidney disease(DKD)and to preliminarily study its mechanism of action.Methods C57BL/6J male mice were randomly divided into control group,model group and experimental group,with 10 mice in each group.The mouse model of type Ⅰ diabetes was established by intraperitoneal injection of 150 mg·kg-1 streptozotocin(STZ).After successful modeling,the experimental group mice were given 10 mg·kg-1·d-1 carvedilol by gavage,while the control group and model group were given equal amounts of 0.9％NaCl.During the experiment,the fasting blood glucose(FBG)of mice were monitored weekly.After 8 weeks of administration,the urinary albumin to creatinine ratio(UACR),uric acid(UA),and other contents in the urine of mice were detected,as well as the levels of iron(Fe),superoxide dismutase(SOD),and malondialdehyde(MDA)in the renal tissue.And hematoxylin-eosin(HE)and Masson staining were performed on the renal tissue to observe the pathological changes of the kidney.Results After 8 weeks of administration,the UACR of the control group,model group and experimental group were(12.43±1.13),(63.01±20.78)and(19.79±1.94)mg·mmol-1;the UA levels were(132.10±10.14),(174.40±7.06)and(135.00±3.95)μmol·L-1;the Fe levels were(7.49±0.81),(9.98±0.46)and(7.02±0.60)μmol·g prot-1;the SOD activities were(34.56±0.58),(30.27±1.22)and(34.43±1.36)U·mg prot1;the MDA contents were(5.49±0.31),(7.72±0.17)and(4.46±0.32)nmol·mg prot-1.The differences between model group and normal group were statistically significant(all P＜0.05);compared between experimental group and model group,the difference were significant(all P＜0.05).Conclusion Carvedilol can alleviate the damage of renal function in diabetes mice,and its mechanism may be related to inhibiting iron death and alleviating oxidative stress injury.

BACKGROUNDZhongfei Mixture (ZM), a traditional Chinese medicine, exploited from the clinical experience, has mainly been used for the treatment of advanced lung cancer since it was produced in 1983. However, little research has been conducted on its anti-tumor mechanism. In this study, we aimed to investigate the anti-tumor and apoptotic effects of ZM in vitro and in vivo.

METHODSThe growth inhibition effect of ZM on A549 cells was evaluated by MTT assay. Morphological observation and clone forming tests were performed to determine the effect of ZM on cell viability. Cell cycle distribution and apoptosis were analyzed by flow cytometry. In addition, the in vivo anti-proliferation activity of ZM was evaluated using mice bearing Lewis lung carcinoma. Further, the apoptosis of cells in tumor tissue was determined by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, and the expression of Ki-67 protein in tumor tissues was analyzed by En-Vision immuno-histochemistry staining.

RESULTSZM exerted an obvious inhibitory effect on proliferation of A549 cells. It arrested A549 cells in G(2)-M phase and induced apoptosis. Compared with 3.02% and 5.32% in control group, the percentages of cells arrested in G(2)-M phase were 19.20% and 19.58% in 7.94 mg/ml ZM treated A549 cells at 24 hours and 48 hours. Moreover, the apoptosis rate increased from 0.18% to 18.01% after ZM treatment for 48 hours. ZM also significantly inhibited tumor growth in the tumor-implanted mice. Compared with saline control group, the effects of ZM showed significant tumor growth inhibition (P < 0.05). Furthermore, ZM could down-regulate the expression of Ki-67 in tumor tissue in mice bearing Lewis lung carcinoma.

CONCLUSIONSOur results indicated that ZM has notable anti-tumor effect and the effects of ZM in moderate dose groups were superlative both in vitro and in vivo. The possible mechanism of ZM might be associated with arresting cell cycle in G(2)-M phase as well as down-regulating Ki-67 expression in tumor tissues.

Animals ; Antineoplastic Agents ; therapeutic use ; Apoptosis ; drug effects ; Cell Line, Tumor ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; methods ; Mice ; Xenograft Model Antitumor Assays

BACKGROUNDThe role of epigenetics in gene expression regulation and development significantly enhances our understanding of carcinogenesis. All the tumor related genes may be the target of epigenetical or genetic regulation. We selected some epigenetically regulated genes for cDNA array analysis and observed variability in the expression of the DICER1 gene in distinct stages of gastric cancer. The aim of this study was to assess the correlation between the expression of DICER1, an epigenetically regulated gene, and gastric cancer.

METHODSTo detect the expression of 506 tumor-associated genes, including DICER1, in the matched cancerous mucosa, pre-malignant lesion (adjacent mucosa), non-cancerous gastric mucosa and distant lymphocyte metastatic lesion in 3 cases of gastric cancers using cDNA array. DICER1 mRNA expression and DICER1 protein expression were further analyzed by Real-time PCR and Western blot in 32 cases of progressive gastric cancer. DICER1 protein expression was also detected in 33 early and 30 progressive gastric cancers by the immunohistochemistry (IHC) method.

RESULTSIn 3 cases of gastric cancer cDNA array showed dramatically decreased expression of DICER1 in pre-malignant lesion, cancerous mucosa and distant lymphocyte metastatic lesions compared with matched noncancerous gastric mucosa, pre-malignant lesion and cancerous mucosa. Real-time PCR results showed that the expression level of DICER1 mRNA in gastric cancer was significantly down-regulated compared to normal gastric tissue (P < 0.05). The IHC assay also showed that the expression of DICER1 was significantly decreased in progressive gastric cancer. Among the 63 cases of gastric cancers, 13/33 early (39.4%) and 19/30 (63.3%) progressive cancers showed negative expression of DICER1 (50.8%). The difference in expression of DICER1 between early and progressive gastric cancers was significant (P < 0.01). The result of Western blotting showed that DICER1 protein was down-regulated significantly in advanced gastric cancer (P < 0.05).

CONCLUSIONSDICER1 expression is decreased during the progression of gastric cancer, especially in progressive gastric cancers, which indicating DICER1 may play an important role in the development of cancer and the epigenetical regulation involved.

Blotting, Western ; DEAD-box RNA Helicases ; analysis ; genetics ; physiology ; Endoribonucleases ; analysis ; genetics ; physiology ; Epigenesis, Genetic ; Humans ; Immunohistochemistry ; Oligonucleotide Array Sequence Analysis ; Polymerase Chain Reaction ; Ribonuclease III ; Stomach Neoplasms ; chemistry ; etiology ; genetics

OBJECTIVETo study the reasonable dosage for paraplatin according to different dosage calculations.

METHODSA prospective, randomized, single-blinded study on 54 patients with advanced non-small-cell lung cancer (NSCLC) treated with paraplatin was conducted. Patients were divided to 2 groups. In group A, paraplatin dosage was calculated according to patients' body surface, and in group B, it was calculated according to the area under the curve (AUS). Hematological toxicity, response rate and survival rate in the two groups of patients were compared.

RESULTSNeutropenia in group A and group B was seen in 77.8% and 37.0% (P < 0.05), and thrombocytopenia in 18.5% and 3.7% (P > 0.05) of patients, respectively. Hemoglobin decrease was seen in 48.2% of patients in both groups. The average quantity of paraplatin given in one cycle of treatment was 535.93 +/- 106.71 mg and 398.52 +/- 71.72 mg (P < 0.01) respectively. The average time interval between treatment cycles was 27.04 +/- 5.30 d and 22.85 +/- 2.80 d (P < 0.05). The response rate and survival rate of patients in group A and B were 22.2% versus 48.2% (P < 0.05), and 40.7% versus 44.4% (P > 0.05) respectively, but the median survival time was identical (12 months) in the two groups.

CONCLUSIONNSCLC patients given paraplatin with dosages calculated on the basis of AUC have higher response rate and less severe hematological toxicity than those given paraplatin with dosages on the basis of body surface. However, the median survival time and survival rate have no statistical differences between the two groups of patients.

Adenocarcinoma ; drug therapy ; Aged ; Antineoplastic Agents ; administration & dosage ; adverse effects ; Area Under Curve ; Carboplatin ; administration & dosage ; adverse effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Carcinoma, Squamous Cell ; drug therapy ; Female ; Humans ; Lung Neoplasms ; drug therapy ; Male ; Middle Aged ; Neutropenia ; chemically induced ; Prospective Studies ; Single-Blind Method ; Survival Rate ; Thrombocytopenia ; chemically induced

Amniotic Fluid ; metabolism ; Biomarkers ; metabolism ; Diagnosis, Differential ; Embolism, Amniotic Fluid ; metabolism ; pathology ; Female ; Humans ; Infant, Newborn ; Keratin-13 ; metabolism ; Pregnancy ; Respiratory Aspiration ; metabolism ; pathology

OBJECTIVETo study the emergency management principles of severe trauma in hospital (injury severity score larger than or equal to 16).

METHODSWe used "ATP principle" to manage severe traumatic patients. The ATP principle is composed of: 1) attending surgeons offering initial management (A); 2) teamwork commencement immediately after patients admitted to hospital (T); 3) parallel principle, ie, emergency resuscitation, evaluation and laboratory test performed simultaneously (P). Clinical effects before and after applying ATP principle were retrospectively analyzed and compared.

RESULTSDuring January 1, 2002 to December 31, 2003, 338 patients were treated without applying ATP principle, in which ISS was 25.9+/-6.4, 152 cases died with the mortality being 39.2%, and the time stayed in emergency department and the time to operation room after admission were (102.8+/-16.7) min, (140.3+/-20.6) min, respectively. During January 1, 2004 to December 31, 2005, 438 patients were treated based on ATP principle, in which ISS was 28.6+/-7.8, 87 cases died with the mortality being 19.9%, and the time in emergency department and the time to operation room after admission were (69.5+/-11.5) min, (89.6+/-9.3) min, respectively. ISS showed no significant difference between the two groups (P larger than 0.05) but the mortality, the time stayed in emergency department and the time to operation room after admission were greatly reduced and showed significant difference between the two groups (P less than 0.05).

CONCLUSIONSApplying ATP principle to treat severe traumatic patients can shorten emergency treatment time in hospital and decrease mortality.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; China ; Emergency Service, Hospital ; organization & administration ; Female ; Humans ; Injury Severity Score ; Male ; Middle Aged ; Patient Care Team ; Retrospective Studies ; Triage ; Wounds and Injuries ; classification ; mortality ; therapy

BACKGROUND: Rectal cancer (RC) is a malignant tumor that seriously threatens human health. Long non-coding RNAs (lncRNAs) play a vital role in tumor regulation. Nevertheless, their exact expression features and functions remain obscure, and therefore was the aim of the current study. METHODS: We utilized the Affymetrix human GeneChip to screen differentially expressed profiles of lncRNAs and mRNAs from the cancer tissues and matched paracancer tissues of 6 RC patients. Gene Ontology (GO) and pathway enrichment analyses identified crucial functions and pathways of the aberrantly expressed mRNAs. We used quantitative real-time polymerase chain reaction to verify the significant expression differences of 11 candidate lncRNAs between the cancer and paracancer tissues. LncRNA-mRNA coexpression networks were built by calculating the Pearson correlation value to identify significant correlation pairs. Online bioinformatics tools GEPIA2, ONCOMINE, and PROGgeneV2 were used to mine the expression and prognosis of three crucial mRNAs and six verified lncRNAs. Competing endogenous RNA networks were constructed by predicting microRNA response elements and calculating free energy. RESULTS: We found 1658 differentially expressed lncRNAs (778 up-regulated and 880 down-regulated) and 1783 aberrantly expressed mRNAs (909 up-regulated and 874 down-regulated). GO and pathway enrichment analyses revealed the vital functions of the differentially expressed mRNAs, including cell proliferation, cell migration, angiogenesis, and cellular response to zinc ion. The canonical signaling pathways mainly included the interleukin-17, cell cycle, Wnt, and mineral absorption signaling pathways. Six lncRNAs including AC017002.2 (P = 0.039), cancer susceptibility 19 (CASC19) (P = 0.021), LINC00152 (P = 0.013), NONHSAT058834 (P = 0.007), NONHSAT007692 (P = 0.045), and ENST00000415991.1 (P = 0.045) showed significant differences in expression levels between the cancer tissue and paracancer tissue groups. AC017002.2, NONHSAT058834, NONHSAT007692, and ENST00000415991.1 have not yet been reported in RC. The crucial mRNAs myelocytomatosis viral oncogene (MYC), transforming growth factor beta induced (TGFBI), and solute carrier family 7 member 5 (SLC7A5) were selected. AC017002.2 and LINC00152 were positively correlated with MYC, TGFBI, and cytochrome P450 family 2 sub-family B member 6 (All r > 0.900, P < 0.050). NONHSAT058834 was positively associated with MYC (r = 0.930, P < 0.001), and CASC19 was positively correlated with SLC7A5 (r = 0.922, P < 0.001). CONCLUSION This study offers convincing evidence of differentially expressed lncRNAs and mRNAs as potential biomarkers in RC.

Objective: To evaluate the prostate health index (PHI) as a tool for the diagnosis of PCa with a PSA level of 4－10 μg/L and determine the best cut-off value of PHI. METHODS: Fifty-eight patients with a PSA level of 4－10 μg/L underwent transrectal ultrasound-guided prostatic biopsy in our hospital between April 2017 and June 2019. We constructed receiver operating characteristic (ROC) curves for the relationship of the biopsy results with the level of PSA, the ratio of ［－2］ proPSA to fPSA and PHI, and calculated the area under the ROC curves (AUC). RESULTS: Prostatic biopsy revealed 18 cases of PCa in the 58 patients (31.0%). Statistically significant differences were observed between the PCa and non-PCa groups in ［－2］ proPSA, %［－2］ proPSA and PHI, but not in tPSA, % fPSA and PSA-density. The AUCs of PSA, % fPSA, PSA-density, ［－2］ proPSA, %［－2］ proPSA and PHI were 0.556, 0.407, 0.533, 0.746, 0.751 and 0.774, respectively. The specificity of PHI was 27.50% (95% CI: 14.6%－43.9%), the highest among the above predictors at 90% sensitivity. By applying PHI to this cohort, 13 cases (22.4%) of unnecessary biopsy could be avoided. CONCLUSIONS The application of PHI can increase the accuracy of PCa prediction and reduce unnecessary prostatic biopsy.、.
Asians ; Humans ; Macau ; Male ; Prostate ; Prostate-Specific Antigen ; Prostatic Neoplasms/diagnosis*

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.